2013 Edition

September 2013

U.S. Department of Health and Human Services

Health Resources and Services Administration

WHIV covers 2012 Fin.indd 1 7
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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

The publication was produced for the U.S. Department of Health and Human Services, 

Health Resources and Services Administration by GEARS, Inc. under contract number 

HHSH25020110029C, by Management Solutions Consulting Group, Inc. under contract 

number HHSH250201000028C, and by Impact Marketing + Communications under 

contract number HHSH250200900041C.

This publication lists non-Federal resources in order to provide additional information 

to consumers. The views and content in these resources have not been formally 

approved by the U.S. Department of Health and Human Services (HHS) or

the Health Resources and Services Administration (HRSA). Listing these

resources is not an endorsement by HHS or HRSA.

A Guide to the Clinical Care of Women with HIV – 2013 Edition is not copyrighted. 

Readers are free to duplicate and use all or part of the information contained in this 

publication; however, the photographs and images may be copyrighted and permission 

may be required to reproduce them. Images include tables, charts, and graphs.

Suggested Citation:

U.S. Department of Health and Human Services, Health Resources and Services

A Guide to the Clinical Care of Women with HIV – 2013 Edition. Rockville, Maryland: 

U.S. Department of Health and Human Services, 2013.

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ii U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

U.S. Department of Health and Human Services

Health Resources and Services Administration

HIV/AIDS Bureau

Parklawn Building, Room 7-05

5600 Fishers Lane

Rockville, Maryland 20857

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Table of Contents

Preface........................................................................................................iv

Introduction..................................................................................................v

Contributing Authors ..................................................................................vi

Abbreviations and Acronyms...........................................................................................................................ix

1. Epidemiology and Natural History of HIV Infection in Women......................1

Ruth M. Greenblatt, MD

2. Approach to the Patient.................................................................................................................................19

Jean R. Anderson, MD

3. Prevention of HIV Infection.......................................................................................................................37

Jared M. Baeten, MD, PhD, and Connie Celum, MD, MPH

4. Primary Medical Care.......................................................................................................................................73

Judith Feinberg, MD

5. Adherence to HIV Treatment and Retention in Care..............................................133

Laura Armas-Kolostroubis, MD, and Laura Cheever, MD, ScM

6. Gynecologic Problems.................................................................................................................................151

Jean R. Anderson, MD

Color Plates.......................................................................................................................................................................215

7. Preconception Care and Contraception..................................................................................227

Erika Aaron, CRNP, MSN, and Jean R. Anderson, MD

8. HIV and Pregnancy.........................................................................................................................................263

Jean R. Anderson, MD

9. Psychosocial Issues, Mental Health, and Substance Abuse.........................339

Julie Barrosso, PhD, ANP, APRN, BC, FAAN

10. Adolescents...........................................................................................................................................................377

Donna Futterman, MD, and Anita Radix, MD, MPH

11. Palliative and Supportive Care.....................................................................................................397

Jessica S. Merlin, MD, MBA, and Rodney Tucker, MD, MMM

12. Occupational Exposure and Postexposure Management............................425

Mina Matin, MD, and Ronald H. Goldschmidt, MD

13. Pharmacologic Considerations in HIV-Infected Pregnant Patients....443

Paul Pham, PharmD, and Patricia Barditch-Crovo, MD

14. Quality Management................................................................................................................................515

Lori DeLorenzo, RN, MSN and Robin Bidwell, RNC, BSN, CCRC

15. Resources.................................................................................................................................................................531

Lori DeLorenzo, RN, MSN, and Skyler Sharp, RN, BSN

16. International Perspectives....................................................................................................................547

Stacie C. Stender, MSN, MSc ID, FNP-BC, and Kelley Curran

Index.........................................................................................................................................................................................569

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Preface

Recommendations change rapidly in HIV care, so the care provider is cautioned 

that this edition is dated November 2013. For the most current and continually 

updated HIV/AIDS treatment guidelines, contact AIDSinfo at:

http://www.aidsinfo.nih.gov

This Guide contains information relating to general principles of medical care 

that should not be construed as specific instructions for individual patients. 

Some of the information may cite the use of a particular drug in a dosage, 

for an indication, or in a manner other than recommended by the FDA. 

Therefore, the manufacturer’s package inserts should be consulted for complete 

prescribing information.

U.S. Department of Health and Human Services

Health Resources and Services Administration

HIV/AIDS Bureau

Parklawn Building, Room 7-05

5600 Fishers Lane

Rockville, Maryland 20857

http://www.hab.hrsa.gov

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Introduction

HIV/AIDS clinical care has improved dramatically over the past two decades as 

new and effective medications have become available. Over that same period, 

our understanding of how best to use antiretrovirals and deliver primary care to 

persons living with HIV/AIDS has deepened as well. Positive change on such a 

massive scale, however, brings with it new demands on clinicians.

Along with innovations in HIV drug therapies, HIV/AIDS care has become more 

complex than ever before due to increasing comorbidities that are attributable 

to HIV treatment and the aging of the HIV-infected population in the United 

States. Patient needs also have expanded across a broad spectrum of medical, 

psychological, behavioral, and social needs. Notably, significant numbers of 

infected individuals are identified and enter care late in the course of their 

HIV disease. Combined with the specific challenges faced by women with HIV 

infection, clinicians are confronted with complex care challenges.

A Guide to the Clinical Care of Women with HIV is a comprehensive clinical 

manual that addresses primary care needs unique to women living with HIV 

infection. The book’s target audiences are clinicians who provide primary care 

to women and those seeking a more in-depth understanding of how to care for 

women with HIV/AIDS. The 2013 edition of the guide, which was first published 

in 2001, has been updated, and chapters have been added on quality 

management and psychosocial, mental health, and substance abuse issues.

A manual devoted specifically to the care of women with HIV is important. 

Because women are often challenged by social isolation, poverty, 

discrimination, and lack of access to quality health care, they tend to be 

diagnosed later and to have poorer health status than men. They must often 

contend with vulnerability related to reproductive and gender issues and 

domestic violence. Finally, women living with HIV are usually relied upon to 

meet the care needs of children and other family members, many of whom are 

also HIV infected.

By presenting best practices in the clinical management of women with HIV/

AIDS disease, the Guide can help us continue the remarkable advances in HIV/

AIDS care that have made the Ryan White HIV/AIDS Program a model for 

health care delivery for our nation and for the world.

Laura Cheever, MD, ScM

Associate Administrator

HIV/AIDS Bureau

U.S. Department of Health and Human Services

Health Resources and Services Administration

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Editor

Jean R. Anderson, MD

Contributing Authors

Erika Aaron, RN, CRNP, MSN

Director of Women’s Services

Drexel University College of Medicine

Philadelphia, Pennsylvania

Jean R. Anderson, MD

Professor, Obstetrics and Gynecology

Johns Hopkins University School of Medicine

Baltimore, Maryland

Laura Armas-Kolostroubis, MD, AAHIVS

Associate Professor

University of Florida

Jacksonville, Florida

Jared M. Baeten, MD, PhD

Assistant Professor, Department of Global Health and Medicine

University of Washington

Seattle, Washington

Patricia Barditch-Crovo, MD

Clinical Associate

The Johns Hopkins University School of Medicine

Baltimore, Maryland

Julie Barroso, PhD, ANP, APRN, BC, FAAN

Associate Professor

Duke University School of Nursing

Durham, North Carolina

Robin Bidwell, RNC, BSN, CCRC

Performance Improvement Coordinator

Christiana Care Health Systems

Wilmington, Delaware

Connie Celum, MD, MPH

Professor, Department of Global Health and Medicine

University of Washington

Seattle, Washington

Laura Cheever, MD, ScM

Associate Administrator and Chief Medical Officer, HIV/AIDS Bureau 

Health Resources and Services Administration

Rockville, Maryland

Kelly Curran

Director, HIV and Infectious Diseases, Jhpiego

Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland

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Lori DeLorenzo, RN, MSN

Executive Director

Organizational Ideas

Blacksburg, Virginia

Judith Feinberg, MD

Professor of Medicine

University of Cincinnati College of Medicine

Cincinnati, Ohio

Donna Futterman, MD

Professor of Clinical Pediatrics

Einstein College of Medicine

Bronx, New York

Ronald H. Goldschmidt, MD

Director, National HIV/AIDS Clinicians’ Consultation Center

University of California, San Francisco

San Francisco, California

Ruth Greenblatt, MD

Professor of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics

University of California, San Francisco

San Francisco, California

Mina Matin, MD

Assistant Clinical Professor

University of California, San Francisco

San Francisco, California

Jessica S. Merlin, MD, MBA

Assistant Professor

University of Alabama Birmingham

Birmingham, Alabama

Paul Pham, PharmD

Research Associate

Johns Hopkins University School of Medicine

Baltimore, Maryland

Anita Radix, MD, MPH

Director of Research and Education

Callen-Lorde Community Health Center

New York, New York

Skyler Tyne Sharp, RN, BSN

Galax, Virginia

Stacie C. Stender, MSN, MSc ID, FNP-BC

Associate, Department of International Health

Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland

Rodney Tucker, MD, MMM

Associate Professor, Department of Medicine

University of Alabama Birmingham

Birmingham, Alabama

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The following experts reviewed chapters for the 2013 edition 

of this Guide:

Carla Alexander, MD

University of Maryland School of Medicine

Baltimore, Maryland

Magda Barini-Garcia, MD

Centers for Medicare & Medicaid Services

Baltimore, Maryland

Susan Buchbinder, MD

UCSF School of Medicine

San Francisco, California

David Cennimo, MD

University of Medicine and Dentistry of New Jersey School of Medicine

Newark, New Jersey

Rebecca Clark, MD, PhD

Louisiana State University School of Medicine – New Orleans

New Orleans, Louisiana

Susan Coffey, MD

UCSF School of Medicine

San Francisco, California

Audrey French, MD

Rush University, Rush Medical College

Chicago, Illinois

James L. Harmon, DNP, RN, ANP-BC, AAHIVS

Duke University School of Nursing

Durham, North Carolina

Mary Jo Hoy, RN, MSN

University of Medicine and Dentistry of New Jersey School of Nursing

Newark, New Jersey

Peter Oates, RN, MSN, NP-C, ACRN

University of Medicine and Dentistry of New Jersey School of Nursing

Newark, New Jersey

Robert Settles, LCSW

Health Resources and Services Administration HIV/AIDS Bureau

Rockville, Maryland

D. Heather Watts, MD

National Institutes of Health Eunice Kennedy Shriver National Institute of 

Child Health & Human Development

Bethesda, Maryland

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Abbreviations and Acronyms

3TC Lamivudine

5FC 5-flucytosine

5-FU 5-fluorouracil

AACTG Adult AIDS Clinical 

Trial Groups

AaDO2 Alveolar-arterial oxygen 

tension difference

AAHIVM American Academy of 

HIV Medicine

ABC Abacavir

AC/HS Differential 

agglutination test

ACE Angiotensin-convertingenzyme

ACOG

American Congress 

of Obstetricians and 

Gynecologists

ACRN AIDS certified 

registered nurse

ACT Artemisinin-based 

combination therapy

ADC AIDS dementia complex

ADR Adverse drug reaction

AEGIS AIDS Education Global 

Information System

AETC AIDS Education and 

Training Centers

AFASS

Acceptable, feasible, 

affordable, sustainable, 

and safe

AFB Acid-fast bacillus

AFI Amniotic fluid index

AFP Alpha-fetoprotein

AGC Atypical glandular cells

AGC-NOS Atypical glandular cells 

not otherwise specified

AGCUS

Atypical glandular 

cells of undetermined 

significance

AIDS Acquired immune 

deficiency syndrome

AIS Adenocarcinoma in situ

ALT Alanine aminotransferase

ANAC Association of Nurses in 

AIDS Care

ANC Absolute neutrophil count

APV Amprenavir

ARCHITECT® HIV Ag/Ab Combo assay

ARB Angiotensin II receptor 

blocker

ART Antiretroviral therapy

ARV Antiretroviral

ASC Atypical squamous cells

ASCCP

American Society for 

Colposcopy and Cervical 

Pathology

ASC-H

Atypical squamous cells, 

cannot rule out a high 

grade lesion

ASCUS

Atypical squamous 

cells of undetermined 

significance

ASCUS-H

Atypical squamous 

cells of undetermined 

significance – high-grade 

squamous intraepithelial 

lesion

ASIL Anal squamous 

intraepithelial lesions

AST Aspartate transaminase

ATV Atazanavir

ATV/r Ritonavir-boosted 

atazanavir

AUC

Area under the plasma 

drug concentration-time 

curve

AZT Zidovudine (also ZDV)

AZT/3TC Zidovudine/lamivudine

AZT/3TC/

ABC

Abacavir/lamivudine/

zidovudine)

B12 Vitamin B-12

BBP Bloodborne pathogen

BCA Bichloracetic acid

BCG Bacillus Calmette-Guérin

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bDNA Branched DNA

beta-hCG

Beta subunit of human 

chorionic gonadotropin 

(also HCG)

BF Breastfeeding

bid Twice per day

BMD Bone mineral density

BMGF Bill & Melinda Gates 

Foundation

BMI Body mass index

BP Blood pressure

BPI Brief Pain Inventory

BRCA-1; 

BRCA-2

Breast cancer gene 1; 

breast cancer gene 2

BUN Blood urea nitrogen

BV Bacterial vaginosis

bx Biopsy

CAPRISA

Center for the AIDS 

Programme of Research 

in South Africa

CATIE Canadian AIDS Treatment 

Information Exchange

CBC Complete blood count

CCR5 C-C chemokine receptor 

type 5

CDC U.S. Centers for Disease 

Control and Prevention

CDC NPIN CDC National Prevention 

Information Network

CHF Congestive heart failure

CIN Cervical intraepithelial 

neoplasia

CLIA

Clinical Laboratory 

Improvements 

Amendments

Cmax Maximum concentration

Cmin Minimum concentration

CMV Cytomegalovirus

CNS Central nervous system

CONRAD

Contraceptive Research 

and Development 

Program

COPD Chronic obstructive 

pulmonary disease

CPCRA Community Programs for 

Clinical Research on AIDS

CPK Creatine phosphokinase

CQI Continuous quality 

improvement

Cr Serum creatinine

CrCI Creatinine clearance

CS Cesarean section

CSF Cerebrospinal fluid

CST Contraction stress test

CT Computed tomography

CTL Cytotoxic T lymphocyte

Cu-IUD Copper intrauterine 

device

CV Cardiovascular

CVD Cardiovascular disease

CVA Cerebrovascular accident

CXCR4 C-X-C chemokine 

receptor type 4

CXR Chest x-ray

CYP Cytochrome P450

d Day

DBP Diastolic blood pressure

d/c Discontinue

d4T Stavudine

ddC zalcitabine

ddl Didanosine

DEET N,N-Diethyl-3-

methylbenzamide

DES Diethylstilbestrol

DHAP CDC Division of HIV/

AIDS Prevention

DHHS

U.S. Department of 

Health and Human 

Services (obsolete – 

see HHS)

DLV Delavirdine

DM Diabetes mellitus

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DMPA

Depotmedroxyprogesterone 

acetate

DNA Deoxyribonucleic acid

DOT Directly observed 

therapy

DRV Darunavir

DRV/r Ritonavir-boosted 

darunavir

DS Double strength

DSM-IV-TR

Diagnostic and Statistical 

Manual of Mental 

Disorders, 4th ed., 

Text Revision

DVT Deep venous thrombosis

EBV Epstein-Barr virus

EC

Emergency contraception 

(Ch. 7)

Enteric coated 

(Ch. 8, Ch. 13)

ECG Electrocardiogram

ED Erectile dysfunction

EE Ethinyl estradiol

EFV Efavirenz

EIA Enzyme immunoassay

ELISA Enzyme-linked 

immunosorbent assay

EKG Electrocardiogram

EMB Ethambutol

ENF Enfuvirtide

EOL End-of-life

ETG Etonogestrel

ETR Etravirine

EVG Elvitegravir

FDA U.S. Food and Drug 

Administration

FHI Family Health 

International

FI Fusion inhibitor

FPV Fosamprenavir

FPV/r Ritonavir-boosted 

Fosamprenavir

FSFI Female Sexual 

Function Index

FSH Follicle-stimulating 

hormone

FTA-ABS Fluorescent treponemal 

antibody absorption test

FTC Emtricitabine

G6PD

Glucose-6-phosphate 

dehydrogenase 

deficiency

GABA Gamma-aminobutyric 

acid

GBS Group B streptococcus

GC Gonorrhea culture

GCSF Granulocyte colonystimulating factor

GFR Glomerular filtration rate

GI Gastrointestinal

GNI Gross national income

gp Glycoproteins

GTT Glucose tolerance test

h Hour

H1 Histamine 1

H2 Histamine 2

HAART Highly active 

antiretroviral therapy

HAB HIV/AIDS Bureau

HAV Hepatitis A virus

Hb Hemoglobin

HbeAg+ Hepatitis B e antigen

HBIG Hepatitis B immune 

globulin

HBsAb Hepatitis B surface 

antibody

HBsAg Hepatitis B surface 

antigen

HBV Hepatitis B virus

HC Hormonal contraception

HCC Hepatocellular carcinoma

HCG

Human chorionic 

gonadotropin 

(also beta‐hCG)

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HCl Hydrochloride

HCV Hepatitis C virus

HD Hemodialysis

HDL High-density lipoprotein

HELLP

Hemolysis, elevated 

liver enzymes, and low 

platelet count syndrome

HERS HIV Epidemiology 

Research Study

HHS

U.S. Department of 

Health and Human 

Services

HIPAA

Health Insurance 

Portability and 

Accountability Act

HIV Human immunodeficiency 

virus

HIV Ab HIV antibody

HIVAN HIV-associated 

nephropathy

HIVMA HIV Medicine Association

HIV RNA HIV ribonucleic acid

HIV RNA 

PCR

HIV ribonucleic acid 

polymerase chain 

reaction

HLA Human leukocyte antigen

HLA-B5701 Human leukocyte antigen 

B*5701

HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme A

HMO Health maintenance 

organization

HPTN HIV Prevention Trials 

Network

HPV Human papillomavirus

HR Hazard ratio

HRSA U.S. Health Resources and 

Services Administration

HRT Hormone replacement 

therapy

hs At bedtime

hs-CRP High-sensitivity 

C-reactive protein

HSIL High-grade squamous 

intraepithelial lesion

HSR Hypersensitivity reaction

HSV Herpes simplex virus

HSV-2 Herpes simplex virus 2

HTLV Human T-cell 

lymphotropic virus

HTN Hypertension

HVTN HIV Vaccine Trials 

Network

IAS International AIDS Society

IC Inhibitory concentration

ICC Invasive cervical cancer

ICSI Intracytoplasmic sperm 

injection

IDSA Infectious Diseases 

Society of America

IDU Injection drug use/user

IDV Indinavir

IFA Immunofluorescence assay

IFN Interferon

IgA Immunoglobulin A (E, G, 

M, etc.)

IM Intramuscular

IMPAACT

International Maternal 

Pediatric Adolescent AIDS 

Clinical Trials Group

IND Investigational new drug

INH Isoniazid

INR International normalized 

ratio

INSTI Integrase strand transfer 

inhibitor

IP Intrapartum

iPrEX Pre-exposure prophylaxis 

initiative

IPV

Inactivated polio vaccine 

(Table 4-9)

Interpersonal violence 

(Ch. 9)

IQ Intelligence quotient

IRIS Immune reconstitution 

inflammatory syndrome

ITP

Idiopathic 

thrombocytopenic 

purpura

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IU International unit

IUD Intrauterine device

IUI Intrauterine insemination

IV Intravenous

IVF In vitro fertilization

KOH Potassium hydroxide

KS Kaposi’s sarcoma

LDL Low-density lipoprotein

LEEP Loop electrosurgical 

excision procedure

LFT Liver function test

LGV Lymphogranuloma 

venereum

LMIC Low- and middle-income 

countries

LMP Last menstrual period

LMWH Low-molecular-weight 

heparin

LNG Levonorgestrel

LNg-IUD Levonorgestrel-releasing 

intrauterine device

LPV Lopinavir

LPV/r Ritonavir-boosted 

lopinavir

LSIL Low-grade squamous 

intraepithelial lesion

MAC Mycobacterium avium 

complex

MCV Mean corpuscular volume

MCV4 Meningococcal 

conjugate vaccine

MDD Major depressive 

disorder

MDMA Methylenedioxymethamphetamine (“ecstasy”)

MDP Microbicides Development 

Programme

MDR Multi-drug resistant

MI Myocardial infarction

MIC Minimum inhibitory 

concentration

MMR Measles, mumps, 

and rubella

mo Month

MRI Magnetic resonance 

imaging

MSAFP Maternal serum alphafetoprotein

MSAS Memorial Symptom 

Assessment Scale

MSM Men who have sex 

with men

MTB Mycobacterium 

tuberculosis

MTCT Mother-to-child 

transmission

mtDNA Mitochondrial DNA

MTN Microbicide Trials 

Network

MVC Maraviroc

MY Measurement year

N-9 Nonoxynol-9

n/a Not applicable

NAAT Nucleic acid 

amplification test

NAPWA National Association of 

People with AIDS

NASBA Nucleic acid sequencebased amplification

NDVL Nondetectable viral load

NFV Nelfinavir

NGO Non-governmental 

organization

NIAID

National Institute of 

Allergy and Infectious 

Diseases

NICHD

The Eunice Kennedy 

Shriver National Institute 

of Child Health and 

Human Development

NIH National Institutes 

of Health

NNRTI Non-nucleoside reverse transcriptase inhibitor

NOS Not otherwise specified

nPEP Nonoccupational 

postexposure prophylaxis

NQC National Quality Center

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NQF National Quality Forum

NRTI Nucleoside reverse 

transcriptase inhibitor

NSAID Nonsteroidal antiinflammatory drug

NST Non-stress test

NTD Neural tube defect

NtRTI Nucleotide reverse 

transcriptase inhibitor

N/V Nausea/vomiting

NVP Nevirapine

OB Obstetric

OB-GYN Obstetrics and 

gynecology

OC Oral contraceptive

OI Opportunistic infection

OPV Oral polio vaccine

OR Odds ratio

OTC Over-the-counter

PACTG Pediatric AIDS Clinical 

Trials Group

PAIN Perianal dysplasia or 

intraepithelial neoplasia

PAPP-A Pregnancy-associated 

plasma protein A

PATH Program for Appropriate 

Technology in Health

PCN Penicillin

PCP

Pneumocystis jirovecii

[formerly carinii] 

pneumonia

PCR Polymerase chain 

reaction

PD Peritoneal dialysis

PEC Preeclampsia

pegIFN Pegylated interferon

PEP Postexposure prophylaxis

PEPFAR President’s Emergency 

Plan for AIDS Relief

PGL Persistent generalized 

lymphadenopathy

PHQ Patient Health 

Questionnaire

PI Protease inhibitor

PID Pelvic inflammatory 

disease

PI/r Ritonavir-boosted 

protease inhibitor

PK Pharmacokinetic

PML Progressive multifocal 

leukoencephalopathy

PMTCT Prevention of mother-tochild transmission

po By mouth

PPD Purified protein 

derivative

PPI Proton pump inhibitor

PPSV-23 Pneumococcal vaccine

PrEP Pre-exposure prophylaxis

PRN As needed

PT Prothrombin time

PTSD Post-traumatic 

stress disorder

pt-y Patient years

PTU Propylthiouracil

PZA Pyrazinamide

q Every

QA Quality assurance

qd Once per day

QI Quality improvement

qm Once per month

qod Once every other day

QTc Q-T corrected

qw Once per week

RTV 

(also /r) Ritonavir

RAL Raltegravir

RBC Red blood cell

RBT Rifabutin

RBV Ribavirin

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REACH

Reaching for Excellence 

in Adolescent Care 

and Health

RIBA Recombinant 

immunoblot assay

RIF Rifampin

RNA Ribonucleic acid

RPR Rapid plasma reagin

RPV Rilpivirine

RR Relative risk

RT Resistance testing

SAMHSA

Substance Abuse and 

Mental Health Services 

Administration

SBP Systolic blood pressure

SC Subcutaneous

SD Standard dose

sdNVP 

(also SDNVP) Single dose nevirapine

SIL Squamous 

intraepithelial lesion

SL Sublingual

SMX or SMZ Sulfamethoxazole

SQV Saquinavir

SQV/r Ritonavir-boosted 

saquinavir 

SS Single strength

SSRI Selective serotonin 

reuptake inhibitor

STD Sexually transmitted 

disease

STI Sexually transmitted 

infection

T-20 Enfuvirtide

TB Tuberculosis

TCA

Trichloroacetic acid 

(Ch. 6)

Tricyclic antidepressant 

(Ch. 13)

TdaP Tetanus-diphtheriapertussis vaccine

TE Toxoplasmic encephalitis

TDF Tenofovir

TDF/FTC/

EFV

Tenofovir/emtricitabine/ 

efavirenz

TDM Therapeutic drug 

monitoring

TG Triglycerides

tid Three times per day

tiw Three times per week

TMP Trimethoprim

TMP-SMX or 

TMP-SMZ

Trimethoprimsulfamethoxazole

TPV Tipranavir

TPV/r Ritonavir-boosted 

tipranavir

TQM Total quality management

TSH Thyroid-stimulating 

hormone

TSS Toxic shock syndrome

TST Tuberculin skin test

UCSF University of California, 

San Francisco

UFH Unfractionated heparin

UGT1 Uridine 5’-diphosphoglucuronosyltransferase 1

UNAIDS Joint United Nations 

Programme on HIV/AIDS

UNICEF United Nations 

Children’s Fund

USAID

U.S. Agency for 

International 

Development

USPHS U.S. Public Health Service

UTI Urinary tract infection

VAIN

Vaginal intraepithelial 

neoplasia (aka vaginal 

dysplasia)

Vd Volume of distribution

VDRL Venereal disease 

reaction level

VIA Visual inspection 

with acetic acid

VIN

Vulvar intraepithelial 

neoplasia (aka vulvar 

dysplasia)

VL Viral load

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VOICE

Vaginal and Oral 

Interventions to Control 

the Epidemic

VTE Venous thromboembolism

VVC Vulvovaginal candidiasis

VZIG Varicella-zoster 

immune globulin

VZV Varicella zoster virus

WBC White blood cell

WHO World Health 

Organization

WIHS Women’s Interagency 

HIV Study

WITS Women and Infant 

Transmission Study

WORLD

Women Organized 

to Respond to Lifethreatening Disease

wt Weight

y Year

ZDV Zidovudine

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Chapter 1:

Epidemiology and Natural History 

of HIV Infection in Women

Ruth M. Greenblatt, MD

Professor of Clinical Pharmacy, Medicine, Epidemiology 

and Biostatistics

University of California, San Francisco

The author declares no conflict of interest

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Chapter 1: Epidemiology and Natural History of HIV 

Infection in Women

Chapter 1 at a Glance

The Global Epidemic of HIV Among Women....................................................................3

Major Trends............................................................................................................................................................3

Prevalence...........................................................................................................................................................4

Aging........................................................................................................................................................................ 4

Demographics..................................................................................................................................................5

Patterns of Transmission........................................................................................................................6

Factors Influencing HIV Transmission in Women...........................................................8

HIV Mortality in Women..........................................................................................................................10

Leading Cause of Death...................................................................................................................10

Antiretroviral Therapy and Mortality..................................................................................10

Natural History of HIV Infection in Women.....................................................................11

Staging of HIV Infection in Women ......................................................................................11

Natural History of HIV Infection in the Absence 

of Antiretroviral Therapy.................................................................................................................15

Disease Progression in the Era of Antiretroviral Therapy .............................15

Influence of Pregnancy, Exogenous Steroids, and Aging...............................16

Case Detection in Women......................................................................................................................16

Unrecognized Risk....................................................................................................................................16

Summary...................................................................................................................................................................17

A Global Women’s Health Problem......................................................................................17

Autonomy is Key ........................................................................................................................................18

Routine HIV Screening Is Essential...........................................................................................18

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The Global Epidemic of HIV Among Women

In 2008, the Joint United Nations Programme on HIV/AIDS estimated that 15.7 

million women worldwide were living with HIV infection and that about half 

of all people living with HIV infection are women (Figure 1-1). Although HIV 

remains a major global health threat, the epidemic is highly regionalized in 

terms of overall prevalence, demographics, access to therapy, and modes of 

transmission. What follows is an overview of the epidemic, focusing on major 

trends, particularly trends among women.

Major Trends

Figure 1-1

Percentage of Women Aged ≥15 Years Living With HIV by 

Geographic Region, 1990–2007

Asia

Eastern Europe and 

Central Asia

Caribbean

15

25

35

45

55

65

20

30

40

50

60

’90 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ’00 ’01 ’02 ’03 ’04 ’05 ’06 ’07

Year

Sub-Saharan Africa

Global Latin America

% Female 

Source: UNAIDS/World Health Organization (WHO). AIDS Epidemic Update. 2009. 

Reprinted with permission.

Beyond the overall feminization of the HIV epidemic and the epidemic’s 

continued impact on years of life lost among women, several other trends are 

now obvious as well.

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Prevalence

The prevalence of HIV infection among women has increased in several 

regions, most notably sub-Saharan Africa, where almost 60% of cases occur 

in women and girls. However, at least seven African countries are meeting 

epidemic-control goals for the first time, with the prevalence of HIV infection 

among pregnant women aged 15–24 years now below 25%.

The worldwide HIV epidemic continues to afflict young women; at the same 

time, the number of women who acquired HIV infection at birth is slowly rising. 

In the United States, the largest number of new cases of HIV infection was 

in women and girls aged 13–29 years, but the highest prevalence of HIV 

infection was among women aged 30–39 years (Diagnoses of HIV Infection 

and AIDS in the United States and Dependent Areas, 2009. U.S. Centers for 

Disease Control and Prevention [CDC]; http://www.cdc.gov/hiv/surveillance/

resources/reports/2009report/. Accessed 7/31/2012).

HIV infection in children peaked between 2000 and 2002 and has slowly 

decreased since 2003, most dramatically in areas where screening and 

treatment of pregnant women are common (Diagnoses of HIV Infection and 

AIDS in the United States and Dependent Areas, 2009. CDC).

Focused or “concentrated” epidemics: In several regions, focused epidemics 

among injection drug users are expanding to include heterosexual women, a 

pattern of evolution that introduces HIV into a huge population pool in which 

individual behaviors may not be overtly high risk. In Eastern Europe and Russia, 

a rapidly growing HIV epidemic is linked to injection drug use (IDU) and is 

currently extending into heterosexual young women who often lack the skills 

needed to assess risk and advocate for themselves (J Urban Health 2009;86 

Suppl 1:121; Eur J Public Health 2011;21(5):613).

Declines in transmission: Recent declines in transmission to women have been 

clearly documented in three countries: the Dominican Republic, Tanzania, and 

Zambia (AIDS Epidemic Update. UNAIDS/World Health Organization (WHO). 

2009). However, the prevalence of risk behaviors such as sex with a person 

who was not a spouse or a coresident has increased in some locations; thus, 

sustained control of the HIV epidemic among women in high-prevalence regions 

is far from assured.

Aging

Numbers increasing: The number and proportion of HIV cases in people aged 

≥50 years has increased steadily since the introduction of potent antiretroviral 

therapy (ART) in high-resource areas. In the United States, before 2000, 

fewer than 10% of people living with HIV were aged ≥50 years; in 2007, 

however, 24% of those living with HIV infection were ≥50 and 16% of all 

HIV/AIDS diagnoses were made in that age group (calculations done on data 

in Diagnoses of HIV Infection and AIDS in the United States and Dependent 

Areas, 2009).

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The distribution of cases by race and location among older women is similar to 

that among women as a whole, although in the United States the prevalence of 

a history of IDU is lower among younger women living with HIV compared with 

older women. This pattern occurs in Europe as well; however, data documenting 

aging among HIV cases in resource-limited settings are sparse.

True incidence unknown: Although the number of infections identified in the 

≥50 age group has increased, as has the total number of persons with HIV 

who are living to ages ≥50, the true incidence of HIV infections among people 

aged ≥50 years is not known. When compared with younger people, however, 

those aged ≥50 years are more likely to have clinical AIDS at the time of HIV 

diagnosis and they tend to have a shorter survival after diagnosis.

Current U.S. screening guidelines recommend routine opt-out screening of 

people aged 13–64 years. This is important because risk-based screening 

will miss many asymptomatic older women with HIV, who often do not have 

recognized risk factors.

Menopause: The emergence of HIV cases among women who are progressing 

through menopause raises new issues for clinicians, researchers, and 

patients. Conditions related to aging that may be promoted by HIV, such as 

cardiovascular disease, must be managed, as must metabolic perturbations 

(e.g., diabetes, bone demineralization) and neurocognitive deficits. In women, 

the effects on immune function of hormonal changes or hormonal replacement 

therapy must also be monitored and managed.

Sexual activity: Compared with younger women, older women are less 

sexually active and are less likely to use condoms and other risk-reduction 

strategies (J Acquir Immune Defic Syndr 2003;33 Suppl 2:S122; Health Care 

Women Int 1997;18(4):343). With the availability of drugs that support 

sexual function in men, however, rates of sexual activity among older women 

may increase. Thus, although older sexually active women are at risk for HIV 

infection, the precise extent of that risk is not known.

Demographics

Greater diversity among women: In resource-rich countries, the demographic 

characteristics of HIV and AIDS cases have been heavily influenced by the 

large proportion of infections among men who have sex with men, many of 

whom are educated and economically stable. However, patterns of cases 

among women demonstrate a much greater representation of ethnic minorities 

and people who are poor, less educated, mentally ill, and/or drug dependent, 

all of which are factors that may limit personal autonomy when it comes to 

making key decisions, including decisions related to sexual behavior. Among 

new HIV diagnoses in US women in 2011 63% were black/African-Americans, 

17% Hispanic/Latino and 17% white; in the US population as a whole, 66% 

of women are white, 15% are Hispanic/Latino and 12% are black/African 

American (http://www.cdc.gov/hiv/library/slideSets/index.html) (accessed 

05/14/2013).

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In resource-limited countries, HIV cases among women can be linked with 

commercial sex work (often in an effort to support a family), social disruption, 

violent conflict, governmental policies, and/or local culture that tends to limit 

women’s economic or sexual autonomy. For example, in some locations, married 

women do not have the right to refuse sex. In other areas, social and economic 

sanctions associated with widowhood, divorce, or HIV infection can promote 

denial of infection or avoidance of testing. Lack of autonomy over key personal 

decisions is a common theme among populations of women affected by HIV.

Key Trends in HIV Epidemiology Among Women

• The proportion of HIV cases among women is increasing globally, led by 

increases in sub-Saharan Africa and the Caribbean region.

• Some countries have demonstrated decreases in the incidence of new HIV cases 

among young women and children, which indicates that intensive public health 

interventions can be effective.

• In areas in which IDU has been the major means of HIV transmission, new trends 

show extension of the epidemic to young, heterosexually active women.

• The largest number of new cases and the highest HIV prevalence rates are 

among young women in their childbearing years.

• Increased survival related to potent ART has resulted in a substantial increase 

in cases among women aged ≥50 years; the incidence of new infections among 

women in this age group is largely undefined.

HIV Transmission to Women

Patterns of Transmission

Although sexual intercourse is a common occurrence in the general population, 

the estimated average HIV transmission rate per intercourse event is low. 

Tracking studies indicate that the likelihood of transmission is highly variable 

among individuals and that high rates of transmission occur in specific 

situations. Table 1-1 summarizes the risk of HIV transmission to women through 

heterosexual intercourse in various situations. Epidemiologic patterns of HIV 

transmission are summarized in Table 1-2.

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Table 1-1

Risk of HIV Transmission to Women Per Sexual Contact Event 

Exposure Transmission Probability Per Act

Any male to female vaginal intercourse 0.124 (0.078-0.199)

No commercial sex, male to female intercourse 0.143 (0.088-0.233)

Commercial sex, male to female intercourse 0.051 (0.020-0.131)

High-income countries, male to female 

intercourse

0.081 (0.060-0.109)

Low-income countries, male to female 

intercourse

0.193 (0.086 – 0.433)

Source: Lancet Infect Dis 2009; 9:118

Table 1-2

Epidemiologic Patterns of HIV Transmission 

Pattern Unique 

Characteristics

Related Factors Regions

Epidemic* 

heterosexual

Risk often not 

recognized; often 

related to high-risk 

male partner

Poverty, lack of women’s 

sexual and economic 

autonomy, sex work

Worldwide

Endemic† 

heterosexual

Seen in highprevalence areas; 

affects general 

population of 

women

Poverty, lack of women’s 

sexual and economic 

autonomy, sex work

High-prevalence 

epidemics in subSaharan Africa, 

Caribbean, Asia

Drug use 

predominant

IDU is major 

factor; often 

coincides with 

high rates of viral 

hepatitis; often 

overlaps with 

sexual risk

Poverty and sex work; 

bridging to non-IDU, 

especially among young 

women

Worldwide, 

notably in Eastern 

Europe and 

Russia; current 

rapid expansion 

of epidemic

Perinatal Most common 

cause of HIV 

infection in 

children; some 

perinatally 

infected infants 

are now adults

Preventable with use 

of ART drugs; greatly 

diminished in highresource countries and 

some lower-resource 

countries; failure to 

screen pregnant women 

is major risk factor for 

ongoing transmission

Worldwide; large 

epidemic in subSaharan Africa

Occupational Usually 

preventable; PrEP 

is available

Rare; implementation 

of universal body fluid 

precautions can prevent 

most exposures

Worldwide

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Table 1-2

Epidemiologic Patterns of HIV Transmission 

Pattern Unique 

Characteristics

Related Factors Regions

Iatrogenic Related to poor 

medical practices 

(e.g., inadequate 

blood screening, 

unsafe injection 

practices)

Failure of adequate 

blood product handling, 

sterilization procedures; 

re-use of needles/

syringes for injections; 

children often affected

Often seen in 

local epidemics, 

primarily in 

Eastern Europe 

and sub-Saharan 

Africa; cannot 

sustain epidemic 

as single mode of 

transmission

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

* Epidemic: Cases exceed the expected pattern in a population over a defined time period

† Endemic: The habitual presence of a disease within a geographic area

(Epidemiology: An Introductory Text. Philadelphia: W.B. Saunders Company; 1974)

Factors Influencing HIV Transmission in Women

Partner infectivity: Infectivity is increased when male partners have a higher 

plasma viral load (VL), which has been linked to higher rates of HIV shedding 

in semen. Infectivity is highest during acute or recent HIV infection, when VL 

and viral shedding are maximal and host immune response is incomplete (AIDS

2007;21:1723). Exposure during early infection is estimated to account for half 

of all transmission events in North America (J Infect Dis 2007;195(7):951). Use 

of ART decreases the risk of HIV transmission between heterosexual partners; 

however, limited study size and infrequent events make precise assessment of 

the extent of protection difficult (AIDS 2009;23:1397). Results from HPTN 052, 

a randomized clinical trial designed to evaluate the efficacy of ART for the 

prevention of sexual transmission among serodiscordant couples, found that 

earlier initiation of ART, at CD4+ cell counts of 350–550 cells/mm3, reduced 

HIV transmission to the uninfected partner (N Engl J Med 2011;365(6):493).

Number of partners and commercial sex: It has been demonstrated in multiple 

settings that being paid for sex is associated with higher rates of HIV infection. 

In a systematic review of data from multiple sub-Saharan African countries, 

the odds ratio for HIV infection for women who reported being paid for sex 

was 2.29 compared with women who had never been paid for sex (PloS One

2007;2(10):e1001).

For women, having a larger number of male sexual partners is also 

consistently associated with an increased risk for HIV infection, with the effect 

size dependent on the number of partners, the region, and the population 

prevalence of HIV. Female sexual partners of women appear to present 

minimal risk of HIV transmission (AIDS 1998;12:450).

continued

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Genital tract infections: Many genital tract infections have been reported 

to increase both infectivity and susceptibility to HIV, including gonorrhea, 

Chlamydia trachomatis, bacterial vaginosis, trichomonal vaginitis, and 

human papillomaviruses (J Reprod Immunol 2008;77:32; PLoS One

2010;5(4):e10094). The most consistent and significant association is seen 

with genital ulcer diseases such as syphilis, chancroid, and genital herpes. 

Because genital herpes simplex is the most prevalent cause of genital ulcers 

and is a chronic infection, it likely has the strongest and longest duration 

of influence on an individual’s susceptibility to acquisition of HIV infection. 

Chen and colleagues, in a systematic review of published reports, found that 

having herpes simplex type 2 infection (usually genital) increased the odds 

of HIV infection 3.69-fold as compared with not having genital herpes (95% 

confidence interval, 2.78–4.89); the increase in the likelihood of infection was 

similar for both men and women (PloS One 2007; 2(10):e1001).

Region: Although significant regional differences exist in the predominant 

means and risk factors for HIV infection, all regions demonstrate multiple 

transmission modalities, which over time tend to extend into populations of 

young sexually active persons and often disproportionately afflict the poor.

Use of hormonal contraceptives or spermicides: Studies of the effects of 

hormonal contraceptives on susceptibility to sexually transmitted HIV infection 

have yielded mixed results (AIDS 2007;21:85; AIDS 2007;21:1771). A 

consensus is emerging, however, that oral estrogen-progestin contraceptives do 

increase susceptibility to HIV (Endocr Rev 2010;31(1):79). The evidence is even 

more consistent that depot medroxyprogesterone acetate (DMPA), an injectable 

progestin-only contraceptive, increases the risk of HIV acquisition. Studies of 

other progestin-only contraceptives and other delivery mechanisms are currently 

underway. Although further study is clearly warranted, hormonal contraception 

remains safe and highly effective for the prevention of unintended pregnancy 

and the promotion of reproductive autonomy, and the benefits are believed to 

strongly outweigh the risks. Use of the topical spermicide nonoxynol-9, which 

was evaluated as a candidate HIV microbicide, demonstrated a paradoxical 

increase in HIV susceptibility that was likely the result of increased genital tract 

inflammation (J Acquir Immune Defic Syndr 2005;40(1):1).

Pregnancy: Although the overwhelming volume of research and publications 

on pregnancy and HIV is focused on perinatal transmission, several studies 

indicate that pregnancy may be associated with increased rates of sexual HIV 

transmission to women (Lancet 2005;366:1182; J Clin Virol 2010; 48:180; 

AIDS 2009;23:1255), even when the analyses are controlled for sexual risk 

behaviors (Lancet 2005;366:1182). It is hypothesized that this heightened 

risk may be attributable to hormonal changes affecting the genital tract 

mucosa or immune responses. Condom use may also be less common during 

pregnancy, as many couples continue to view condoms primarily as a means 

of contraception. Healthcare providers must address appropriate preventive 

practices with at-risk pregnant women and be alert to signs and symptoms 

consistent with acute HIV infection during pregnancy. Surveillance for incident 

infections associated with pregnancy should extend to the postpartum period 

(BMC Public Health 2010;10:668) because women who are infected in late 

pregnancy may still be HIV seronegative at delivery.

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Because of the possibility of increased susceptibility to HIV infection during 

pregnancy, and with the recent encouraging results with antiretroviral-based 

preexposure prophylaxis, it is important that pregnant women in HIVdiscordant relationships be included in further testing of these interventions 

(see Chapter 7, Preconception Care and Contraception).

HIV Mortality in Women

Leading Cause of Death

Although the prevalence of HIV infection among women varies significantly by 

world region, AIDS remains a leading cause of death among women in many 

regions, including high-resource countries. Depending on age group, AIDS is 

among the top 10 causes of death for African-American and Hispanic women; 

among African-American women 25–54 years, HIV is the 4th leading cause of 

death (Natl Vital Stat Rep 2012;61(7):1).

AIDS deaths are a conservative indicator of the impact of HIV on women’s 

survival because they are derived from statistics on deaths directly due to 

AIDS-defining conditions and do not include excess deaths due to non-AIDS 

conditions that are associated with HIV, such as cardiovascular disease, 

metabolic diseases, and malignancies. In addition, HIV is a prominent cause of 

years of life lost for women in the years of prime economic and childrearing 

activity.

Antiretroviral Therapy and Mortality

The prominence of AIDS as a cause of death among women has emerged 

during an era in which ART is generally available, which tends to refute the 

notion that the existence of effective treatment has diminished the major threat 

to women’s health posed by HIV. Receipt of potent ART has been the strongest 

predictor of survival among women with HIV since those drugs were introduced 

in the 1990s. Even in populations with easy access to ART, however, excess 

deaths due to AIDS and non-AIDS conditions still occur among HIV infected 

patients, including women.

WIHS cohort: Sustained ART is associated with reduced AIDS and non-AIDS 

mortality. After the introduction of ART in the United States, the AIDS mortality 

rate within the WIHS, a large U.S. multisite observational cohort study of HIV 

in women, declined by almost 50%; however, HIV infection continued to be 

associated with AIDS deaths and with excess deaths due to heart disease and 

cancer (J Acquir Immune Defic Syndr 2009;51(4):399). Trauma/accidents/

suicide and liver disease remain prominent causes of death among HIV 

infected and high-risk HIV uninfected WIHS participants. During the pre-ART 

era, HIV infected women demonstrated a lower incidence of breast cancer 

than did uninfected women; in the era of potent ART, however, breast cancer 

rates are equal in the two groups, perhaps owing to increased survival or other 

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factors (Clin Infect Dis 2010; 51(8):957; J Natl Cancer Inst 2011;103(9):753; 

Breast J 2011;17(1):87). Use of alcohol and/or recreational drugs was also 

a predictor of mortality in WIHS participants (Clin Infect Dis 2007;44(2):287; 

Addiction 2005;100:990; AIDS 2008;22:1355).

Predictors of mortality: In the WIHS, CD4+ cell count below 200 cells/mm3, 

VL of ≥1000 copies/mL, hepatitis B surface antigenemia, body mass index 

(BMI) <18.5, and a high depressive symptom score were each independently 

associated with mortality (J Acquir Immune Defic Syndr 2009;51(4):399). 

Hepatitis C infection was a predictor of mortality after the use of potent 

ART became commonplace, which is consistent with other observations that 

liver disease has become a prevalent cause of mortality among U.S. women 

whose survival with HIV infection is extended by ART. In resource-limited areas, 

low BMI and anemia are leading predictors of mortality after ART (AIDS

2006;20:2355; S Afr Med J 2007;97:587). In these settings, HIV infection 

continues to be associated with AIDS and non-AIDS mortality, with tuberculosis 

and CNS infections being the leading causes of death (AIDS 2006;20:1181).

Sex differences: In both the pre-ART and potent ART eras, there have been 

indications that HIV infected women have higher mortality rates than do their 

male counterparts. These findings, which result from studies conducted in both 

resource-rich and resource-poor countries, are sometimes attributed to sex 

differences in access to treatment, although in some studies the results were 

independent of treatment utilization (J Infect Dis 2009;199(7):991; AIDS

2005;19:357). Several reports have identified a difference in age at death 

between males and females, with peak deaths in females occurring 5–10 

years earlier than in men (S Afr Med J 2007;97:587; Lancet 2008;371:1603); 

however, no clear independent sex difference in age at death has been seen 

in the setting of ART availability. Thus, although countered to some extent by 

studies that show no independent sex difference in survival among HIV infected 

adults in the ART era (Clin Infect Dis 2007;44(2):287; AIDS 2001;15:1115; 

AIDS Patient Care STDS 2007;21:321), the range of findings indicating higher 

mortality among women is cause for concern and warrants additional study.

Natural History of HIV Infection in Women

Staging of HIV Infection in Women

Case definitions for HIV infection—the criteria for diagnosis of HIV infection—

are now based largely on serologic screening tests. The CDC issued its last 

case definition for AIDS in 1994. That definition incorporated the opportunistic 

infections, cancers, and wasting conditions that are closely linked with HIV 

infection and disease progression as evidenced by CD4+ lymphocyte cell 

depletion. The case definition also included invasive cervical cancer, a femalespecific condition, as an AIDS-defining condition (in the presence of HIV 

infection) and chronic vaginal candidiasis and pelvic inflammatory disease as 

HIV-associated, but not AIDS-defining, conditions.

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The CDC has recently revised the staging system and surveillance case 

definitions into a single case defintion sytem for HIV because of diagnostic 

and treatment improvements and to make the system simpler and easier 

to use (MMWR 2008;57(RR10):1–8). Clinical categories A and B have 

been eliminated, since many of the clinical conditions listed under these 

categories were not discrete diseases, were not necessarily indicators of 

immunosuppression, poorly matched current treatment guidelines and were not 

integrated into routine surveillance practices; furthermore, the role of CD4+ 

cell counts/percentages are central in the new system, as objective measures 

of immunosuppression and are routinely used in care. As with the older system, 

HIV disease progression is classified from less to more severe, and once cases 

are classified into a surveillance severity stage, they cannot be reclassified into 

a less severe stage. This system is intended for public health surveillance and 

not as guide for clinical diagnosis or care.

The CDC HIV/AIDS disease staging system (Table 1-3) assesses disease 

severity by CD4+ cell counts and by the presence of specific HIV-related 

conditions. By contrast, the WHO clinical staging and disease classification 

system (Table 1.4) is based on clinical findings that guide the diagnosis, 

evaluation, and management of HIV/AIDS. This staging system is particularly 

useful in resource-limited settings in which CD4+ testing or other laboratorytesting methods are not readily available and is used in many countries to 

assess eligibility for antiretroviral therapy.

Table 1-3 

CDC Classification System for HIV-Infected Adults and Adolescents 

(2008)

Must meet laboratory criteria for HIV infection

Stage 1: no AIDS-defining condition and CD4+ cell count >/= 500 cells/microliter ot CD4+ % of total lymphocyte >/= 29%

Stage 2: no AIDS-defining condition and CD4+ cell count 200–499 cells/microliter or 

CD4+ % of total lymphocyte 14-28%

Stage 3 (AIDS): CD4+ cell count <200 cells/microliter or CD4+ % of total lymphocyte 

<14% or documentation of an AIDS-defining condition. Documentation of an AIDS-defining 

condition supersedes CD4+ cell count/%. 

Stage Unknown: documented HIV infection but no information available on CD4+ counts/% 

or AIDS-defining conditions.

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Table 1-3 

CDC Classification System for HIV-Infected Adults and Adolescents 

(2008)

†Category C AIDS-Indicator Conditions

• Candidiasis of the bronchi, trachea, or lungs

• Candidiasis, esophageal

• Cervical carcinoma, invasive, confirmed by biopsy

• Coccidioidomycosis, disseminated or extrapulmonary

• Cryptococcosis, extrapulmonary

• Cryptosporidiosis, chronic intestinal (>1 mo in duration)

• Cytomegalovirus disease (other than liver, spleen, or nodes)

• Cytomegalovirus retinitis (with loss of vision) (may be diagnosed presumptively)

• Encephalopathy, HIV-related

• Herpes simplex: chronic ulcers (>1 mo in duration), or bronchitis, pneumonitis, or 

esophagitis

• Histoplasmosis, disseminated or extrapulmonary

• Isosporiasis, chronic intestinal (>1 mo in duration)

• Kaposi sarcoma

• Lymphoma, Burkitt, immunoblastic, or primary central nervous system

• Mycobacterium avium complex or Mycobacterium kansasii, disseminated or 

extrapulmonary

• Mycobacterium tuberculosis, pulmonary or extrapulmonary

• Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

• Pneumocystis jirovecii (formerly carinii) pneumonia

• Pneumonia, recurrent

• Progressive multifocal leukoencephalopathy

• Salmonella septicemia, recurrent (non-typhoid)

• Toxoplasmosis of brain

• Wasting syndrome caused by HIV (involuntary weight loss >10% of baseline body 

weight) associated with either chronic diarrhea (≥2 loose stools per day for ≥1 mo) or chronic weakness and documented fever for ≥1 mo

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: MMWR 2008;57(RR10):1–8.

Table 1-4

World Health Organization HIV/AIDS Clinical Staging and Disease 

Classification System

Primary HIV Infection

• Asymptomatic

• Acute retroviral syndrome

Clinical Stage 1

• Asymptomatic

• PGL

continued

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Table 1-4

World Health Organization HIV/AIDS Clinical Staging and Disease 

Classification System

Clinical Stage 2

• Moderate unexplained weight loss (<10% of presumed or measured body weight)

• Recurrent respiratory infections (sinusitis, tonsillitis, otitis media, and pharyngitis)

• Herpes zoster

• Angular cheilitis

• Recurrent oral ulceration

• Papular pruritic eruptions

• Seborrheic dermatitis

• Fungal nail infections

Clinical Stage 3

• Unexplained severe weight loss (>10% of presumed or measured body weight)

• Unexplained chronic diarrhea for >1 mo

• Unexplained persistent fever for >1 mo (>37.6oC, intermittent or constant)

• Persistent oral candidiasis (thrush)

• Oral hairy leukoplakia

• Pulmonary tuberculosis (current)

• Severe presumed bacterial infections (e.g., pneumonia, empyema, pyomyositis, 

bone or joint infection, meningitis, bacteremia)

• Acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis

• Unexplained anemia (hemoglobin <8 g/dL)

• Neutropenia (neutrophils <500 cells/mcgL)

• Chronic thrombocytopenia (platelets <50,000 cells/mcgL)

Clinical Stage 4

• HIV wasting syndrome, as defined by CDC (see Table 1-3)

• Pneumocystis pneumonia

• Recurrent severe bacterial pneumonia

• Chronic herpes simplex infection (orolabial, genital, or anorectal site for >1 mo or 

visceral herpes at any site)

• Esophageal candidiasis (or candidiasis of trachea, bronchi, or lungs)

• Extrapulmonary tuberculosis

• Kaposi sarcoma

• Cytomegalovirus infection (retinitis or infection of other organs)

• CNS toxoplasmosis

• HIV encephalopathy

• Cryptococcosis, extrapulmonary (including meningitis)

• Disseminated nontuberculosis mycobacteria infection

• Progressive multifocal leukoencephalopathy

• Candida of the trachea, bronchi, or lungs

• Chronic cryptosporidiosis (with diarrhea)

• Chronic isosporiasis

• Disseminated mycosis (e.g., histoplasmosis, coccidioidomycosis, penicilliosis)

• Recurrent nontyphoidal Salmonella bacteremia

• Lymphoma (cerebral or B-cell non-Hodgkin)

• Invasive cervical carcinoma

• Atypical disseminated leishmaniasis

• Symptomatic HIV-associated nephropathy

• Symptomatic HIV-associated cardiomyopathy

• Reactivation of American trypanosomiasis (meningoencephalitis or myocarditis)

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: AIDS Education & Training Centers National Resource Center. HIV Classification: 

CDC and WHO Staging Systems. 2012

continued

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Natural History of HIV Infection in the Absence of 

Antiretroviral Therapy

Sex differences: Sex differences exist in CD4+ lymphocyte counts among 

HIV infected and uninfected individuals; when corrections can be made for 

differences in the extent of disease progression, females have CD4+ cell 

counts that are approximately 100 cells/mm3 higher than those of males early 

in HIV infection (Clin Infect Dis 2002;35(3):313). Assessing sex differences in 

rates of viral replication and plasma HIV RNA levels (VL) is more complex. 

Early in the course of HIV infection, females have lower HIV VLs than do 

males (AIDS 2007;21:835; Clin Infect Dis 2002;35(3):313). Because VL is a 

predictor of disease progression, a lower VL in females should be followed by 

slower progression as indicated by declines in CD4+ cell counts and clinical 

progression; however, no significant differences in rates of progression by sex 

have been identified (Am J Epidemiol 2008;168(5):532; AIDS 2003;17:353; 

J Infect Dis 1999;180:1018; Lancet 1998;352:1510). It appears, therefore, 

that females have better control of HIV replication than do males early 

in HIV infection, but lose this control later and progress more rapidly, thus 

catching up to their male counterparts. One clue to this loss of immunologic 

advantage was provided by Altfeld and colleagues, who reported that 

women have significantly more vigorous dendritic cell responses to HIV, which 

leads to greater CD8+ cell activation. CD8+ cell activation may result in 

the early control of HIV replication, but over time it could produce a chronic 

inflammatory state and increased lymphocyte loss (Nat Med 2009;15:955).

Host immune response: Variations in the pattern of HIV disease progression 

in the absence of ART are the focus of many studies that seek to characterize 

host immune responses to HIV. Much interest has been directed at HIV 

controllers or elite controllers, i.e., people whose CD4+ cells remain normal 

and stable and who have very low or undetectable VLs after HIV infection 

in the absence of ART. Because women tend to have higher CD4+ cell counts 

and lower HIV RNA levels than men, at least in the early stages after initial 

infection, one might expect sex differences in HIV control to exist. Such 

differences, however, have not been identified (J Virol 2009;83:329; Immunity

2007;27:406; AIDS Res Ther 2007;4:11), perhaps because natural HIV 

controllers are few in number and therefore studies of natural HIV control are 

small. Anecdotal reports indicate that sex differences exist in the prevalence 

of natural controllers, with a somewhat higher occurrence among women, but 

further study is needed.

Disease Progression in the Era of Antiretroviral Therapy

Sex differences in CD4+ cell counts persist after the initiation of ART; if these 

parameters form the basis for assessing ART outcome, women tend to fare 

better (AIDS 2007;21:835; J Antimicrob Chemother 2007;60(4):724; AIDS 

Res Hum Retroviruses 2010;;26:133). Most ART clinical trials, however, are not 

adequately powered to assess sex differences. The CASCADE Collaborative, 

which assessed sex differences in the survival of adult seroconverters in Europe, 

Canada, and Australia, concluded that ART increased the survival advantage 

of women, though sex differences existed in ART use and the results were not 

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adjusted for adherence (Am J Epidemiol 2008;168(5):532). In Europe, as in the 

United States, HIV risk factors and access to care appear to contribute to sex 

differences in HIV mortality during the ART era (Int J Epidemio1 2010;39:135; 

J Epidemiol Community Health 2004;58(11):944). In general, ART viral 

suppression does not differ by sex, and many reported sex differences in 

outcome disappear when the analysis is adjusted for treatment (Clin Infect 

Dis 2009;49:1570; Lancet 2003;362:1267; J Womens Health (Larchmt)

2007;16(7):1052). For both women and men, the use of ART is the strongest 

predictor of survival in HIV infection.

Influence of Pregnancy, Exogenous Steroids, and Aging

In both HIV infected and uninfected women, the absolute number of CD4+ 

lymphocytes temporarily declines during the third trimester of pregnancy as a 

result of hemodilution, but the CD4+ percentage remains relatively stable. No 

differences in overall HIV disease progression have been found to be related 

to pregnancy (AIDS 2005;19:357). Whether the use of hormonal contraception 

influences HIV disease acquisition or course is a controversial topic on which 

data conflict (see Chapter 7, Preconception Care and Contraception). Because 

sex steroids are important immune mediators, it is plausible that the changing 

hormone levels associated with menopause or hormone replacement therapy 

may influence the course of HIV infection. Data that might shed light on 

this issue are not currently available. Aging is associated with more rapid 

progression of untreated HIV disease, and sex differences in this phenomenon 

have not been reported (Am J Med 2008;121:1032; J Am Geriatr Soc

2009;57:2129).

Case Detection in Women

Unrecognized Risk

In resource-rich countries, most men with HIV report risk factors for infection 

such as sex with other men or parenteral drug use. For a woman, however, 

risk for HIV may be determined by the (often unknown) behavior of a male 

sexual partner or partners. In 2009, women accounted for 24% of new HIV 

infections in the United States, a figure that is likely to be artificially low 

because providers and patients underestimate the risk of HIV infection and 

may not test for it. For 2009, the CDC reported that heterosexual contact was 

the risk factor for 85% of women with HIV infection, IDU was associated with 

15% of cases, and less than 1% of cases had no clear risk factor (Diagnoses 

of HIV Infection and AIDS in the United States and Dependent Areas, 2009. 

CDC; http://www.cdc.gov/hiv/surveillance/resources/reports/2009report/. 

Accessed 7/19/12).

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The process of risk assignment in this report differed significantly from past 

years in that cases reported with no known risk factor were assigned a likely 

risk factor, which for most women is heterosexual contact. The revised data, 

however, should not be seen as indicating that HIV infected women are now 

more likely to be aware that they are at risk for heterosexually acquired HIV 

infection. Prior to the adoption of the imputation approach, 30%–40% of HIV 

infected women had no recognized HIV risk factor.

It is likely that women frequently are unaware of their risk for HIV infection 

because that risk is related to the drug use or sexual behaviors of a male 

sexual partner or partners. Without awareness of their risk for HIV infection, 

women often do not express concerns about HIV or seek out screening. Routine 

HIV screening, in which HIV testing is included as part of routine healthcare, 

is an important means of increasing case recognition and access to early HIV 

treatment among women. In the absence of routine screening, HIV cases in 

women tend to be detected at the time of pregnancy or presentation of an 

AIDS-defining condition. Both scenarios represent lost opportunities for early 

treatment and prevention of transmission to others, because women may be 

less likely than men to delay entry into care once HIV infection has been 

detected (AIDS Patient Care STDS 2009;23:765).

Key Points on Natural History of HIV in Women

• Among HIV infected adults, women have higher CD4+ cell counts than men.

• During early infection, women have lower VLs than men, but this difference 

disappears as infection continues. Differences in CD8+ cell activation may 

explain some of the sex differences in VL.

• Overall, the rate of progression of HIV disease appears to be similar in women 

and men.

• Receipt of ART is the strongest predictor of survival with HIV among both 

women and men.

• Women and men respond to ART similarly; differences in outcomes are often 

related to drug use and access to treatment.

Summary

A Global Women’s Health Problem

Even in resource-rich regions, HIV is a leading cause of death for women. 

Moreover, the number of HIV-related deaths among women is much higher 

when HIV-associated but non–AIDS-defining conditions are also considered. 

HIV kills women who are at the peak of their social and economic productivity. 

HIV, therefore, must be considered a major health concern for women.

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Autonomy is Key

Reducing the incidence of HIV infection in women and improving access to 

treatment requires increased autonomy among vulnerable women. Autonomy 

can be viewed broadly as control over one’s life and decision making, including 

decisions about sexuality and health, and depends on cultural factors, access 

to educational resources, and enlightened public policy. Women’s autonomy, 

especially in matters of sexuality and health, also requires the availability of 

resources such as drug and mental health treatment that can assist women in 

avoiding drug use, violence, and coercive sex. Autonomy is also related to the 

acquisition of personal skills that support young women’s ability to adhere to 

safe-sex practices and assess the risk of specific situations. Biological factors 

such as sexually transmitted infections and male-partner VL are important, but 

Dworkin and others have persuasively argued that the paradigm of risk for 

HIV infection in women should be extended to include social vulnerability (Am J 

Public Health 2010;100:435).

Routine HIV Screening Is Essential

Most women acquire HIV infection from a male sexual partner, and this trend 

is increasing. Furthermore, because many women are not aware that a male 

partner is HIV infected or at risk, risk-based screening is likely to miss cases 

of HIV among women. Making HIV screening a routine part of medical and 

reproductive healthcare for adolescents and adults is an important way to 

improve the ability to identify and provide care and treatment to women early 

in the course of HIV infection. Achievement of this goal is crucial for control of 

the HIV epidemic in women.

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Chapter 2:

Approach to the Patient

Jean R. Anderson, MD

Director, The Johns Hopkins HIV Women’s Health Program

Professor, Gynecology and Obstetrics

The Johns Hopkins Medical Institutions

The author declares no conflict of interest

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Chapter 2: Approach to the Patient

Chapter 2 at a Glance

The Woman With HIV Infection.......................................................................................................21

General Guidelines........................................................................................................................................21

Communication.............................................................................................................................................21

Respect.................................................................................................................................................................22

Sensitivity...........................................................................................................................................................22

Confidentiality.............................................................................................................................................23

Evaluation of the HIV Infected Woman.................................................................................23

Team Approach..........................................................................................................................................23

HIV Experience............................................................................................................................................24

Cultural Sensitivity....................................................................................................................................25

Special Circumstances..........................................................................................................................25

Spirituality........................................................................................................................................................25

Identifying Support Systems and Disclosure................................................................26

Education and Counseling................................................................................................................27

Medical Evaluation..................................................................................................................................28

Family-Centered Care........................................................................................................................29

Access to Care.............................................................................................................................................29

Limited-Resource Settings.................................................................................................................29

The Chronic Care Model for HIV .................................................................................................30

Community Resources and Policies..........................................................................................31

Organization of the HIV Healthcare System..............................................................31

Decision Support........................................................................................................................................32

Healthcare Delivery System Design......................................................................................32

Patient Self-Management Support........................................................................................32

Clinical Information Systems..........................................................................................................33

Quality Management...........................................................................................................................34

Effectiveness of the Chronic Care Model........................................................................34

From Research to Practice.....................................................................................................................35

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The Woman With HIV Infection

She could be any woman: The woman with HIV infection is not distinguishable 

from most women seen in primary care today. She may be any age or color, 

live anywhere, have any cultural background, and have any level of education 

and income. She has all the health and lifestyle concerns that any other woman 

has. She is often asymptomatic, and she may not know she is infected. Often, 

she is a mother and a caretaker for other family members.

HIV is just one part of her life: The issues most important to the woman with 

HIV will be shaped by her personal circumstances. HIV is just one aspect of 

an infected woman’s life; the perception of its role in her life will vary from 

woman to woman and from time to time. The healthcare provider–patient 

relationship begins with the particular circumstances and needs of each 

individual woman. To be most effective, that relationship must become a 

partnership based on mutual trust and respect.

This chapter reviews general guidelines for healthcare provider interactions 

with all patients, highlighting points that are particularly relevant to women 

with HIV infection. It also provides an overview of the initial and ongoing 

medical and psychosocial evaluation of women with HIV and discusses the 

changes in models of care as HIV has evolved into a chronic disease.

General Guidelines

Communication

Clear and nonjudgmental: The initial interaction of patient and provider 

should begin with introductions, and ensuing communications should be clear 

and nonjudgmental. The care provider’s language and terminology should 

be sensitive, inoffensive, and easily understood by the patient. A patient’s 

ability to understand what is being said to her will vary according to her 

age, cultural background, and level of education. Translation (of written 

materials) and/or interpretation (of speech) will be needed for women 

who are not able to understand or express themselves adequately in the 

language of the medical provider.

Whenever possible, questions should be asked in an open-ended manner, 

including questions about behavior and treatment adherence, and the patient 

should be given permission to be honest and to acknowledge failure with 

regard to relapse or nonadherence. She should be given adequate time and 

opportunity to ask questions and express concerns.

Written instructions: Patients should be given written instructions that detail how 

to make appointments and how to reach the care provider when there is a 

problem or when the patient has questions. Whenever possible, patients should 

be provided with written information about HIV and its treatment as well as 

with information about other health issues to supplement face-to-face discussions.

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Communication for the gynecologic exam: Women undergoing gynecologic 

exams may feel especially anxious, vulnerable, or embarrassed, or they may 

fear discomfort or the discovery of pathology. This anxiety and vulnerability 

may be particularly pronounced in women with a history of sexual abuse, 

rates of which are greater in some populations of women living with HIV. If a 

woman needs additional time to develop trust and overcome anxiety, then the 

gynecologic exam may have to be postponed until a subsequent visit.

Adequate preparation for the exam is important. The care provider should 

explain what will be done and why, and he or she should explain the amount 

of discomfort the woman may experience. The process may be demystified by 

showing the patient charts, models, or equipment (such as specula). During the 

exam, before doing anything, the care provider should tell the patient what is 

going to happen next, and then describe what s/he sees or feels during the 

exam. The patient should be reassured when findings are normal.

Nonverbal communication: The importance of nonverbal communication should 

not be underestimated. Facial expression and body posture often convey 

far more than words. The most effective care providers are sensitive to these 

cues and use their own body language with care. Maintaining frequent eye 

contact encourages the patient’s candor, builds rapport and trust, helps allay 

embarrassment and fear, and conveys a care provider’s interest and attention.

Respect

Every patient deserves respect: Care providers should never be 

condescending, patronizing, or judgmental toward patients. Under no 

circumstances should a patient be treated as a sexual object. Although 

different circumstances may dictate different levels of formality, addressing a 

patient by her first name (without her express consent) or, especially, by terms 

of endearment (e.g., “honey” or “dear”) is usually inappropriate and offensive.

Respect for the patient includes respect for her beliefs and values. The use of 

complementary therapies among HIV infected patients is common and should 

be respected, not ridiculed. This respect should be maintained even if a care 

provider must discourage potentially harmful remedies and emphasize the 

proven effectiveness of currently recommended regimens.

Sensitivity

Essential to effective care: Sensitivity is essential to a care provider’s ability 

to gather and impart important information, foster trust, and ensure ongoing 

follow-up. It requires attention to how words are used, how questions are 

asked, and what body language and other unspoken aspects of communication 

convey. Responding to a patient’s fear, anxiety, denial, or anger is an 

inevitable part of the health provider’s role, and it requires consideration of 

the whole person and the entire context of her life, not just of her disease 

process. Any chronic and life-threatening disease carries with it an enormous 

burden of vulnerability and loss of control. Anything a care provider can 

do to give back some control to the woman will help ease that burden. The 

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importance of adherence to antiretroviral therapy (ART) regimens for optimal 

effectiveness and for reduced potential for drug resistance has been well 

established. Taking into account a patient’s values and lifestyle (e.g., work 

schedule, child care obligations) when choosing a treatment regimen may 

enhance adherence. In addition, understanding a woman’s cultural background 

will enhance a care provider’s sensitivity. For example, among Hispanic women, 

it is often important and reassuring when a patient’s spouse or mother is 

involved during visits.

Confidentiality

Confidentiality is a cornerstone of the therapeutic relationship. It carries 

special meaning for HIV infected individuals, who may have experienced 

discrimination in the workplace and other settings, stigmatization, or even 

abandonment by friends or family. HIV infected women may be particularly 

vulnerable to the effects of stigma because of lower economic status, cultural 

traditions, general societal beliefs about the role of women, minority status, 

and child care or other caretaking responsibilities. Information about a 

patient’s HIV status or details about her medical condition should be kept 

strictly confidential by providers and shared only with the express permission 

of the patient. At the same time, the patient should be encouraged and 

assisted in disclosing her status to others who need to know, such as sexual 

partners and healthcare providers.

Reporting: All States require reporting of AIDS cases, and in all 50 

States, the District of Columbia, and six dependent areas, HIV cases are 

reported confidentially by name. The need to report and the safeguards 

of confidentiality that are in place should be discussed with each woman. 

The Health Insurance Portability and Accountability Act (HIPAA) of 1996 

furthermore provides a federal mandate and standards for the protection of 

certain health information, addressing the use and disclosure of individuals’ 

health information and standards for individuals’ privacy rights to understand 

and control how their health information is used (See: http://www.hhs.gov/ocr/

privacy/hipaa/understanding/summary/index.html).

Evaluation of the HIV Infected Woman

Team Approach

A complex disease: Because HIV disease is medically and socially complex, 

a team approach is essential to the care of women with HIV, and care should 

be coordinated and integrated with all members of the team. Moreover, as 

the time that primary care providers have available to spend with individual 

patients grows ever more limited, the role of other team members in educating 

and supporting women with HIV is becoming more important.

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Multispecialty care: The expertise needed to provide care for women with 

HIV includes specialists in HIV medicine (including management of ART), 

gynecology, nursing, pharmacy, counseling, and social service assistance and 

case management. Primary medical management of HIV may be provided by 

physicians and, increasingly, by nurse practitioners or physician assistants with 

appropriate training and supervision. Throughout the course of HIV infection, 

multidisciplinary medical collaborations should be available for evaluation 

and management of the varied medical problems associated with HIV. As HIV 

has become a chronic disease, the inclusion of the patient and her family or 

other personal supporters as part of the team is ever more important. The 

involvement of peer counselors may be especially useful for helping women 

deal with the complexities of negotiating safer sexual practices, contraception 

and other reproductive concerns, medication adherence, and other issues where 

similar cultural background and personal experience with HIV may facilitate 

candid discussion and education.

HIV Experience

HIV expertise improves outcomes: Patients have better outcomes when their 

care, including ART, is managed by healthcare providers with expertise in 

treating HIV. Care provider experience is one of the few factors (specific 

to either providers or healthcare systems) that has been shown over time to 

increase the likelihood that a patient will receive effective ART and to prolong 

the life of people with HIV infection (N Engl J Med 1996; 334:701; AIDS

1998;12:417; Arch Intern Med 2005;165:1133). Care provider experience is 

increasing in importance as antiretroviral (ARV) management becomes steadily 

more complicated. Awareness of drug interactions and the ability to prevent 

and manage ARV-related adverse effects and drug resistance have significant 

effects on the short- and long-term health of HIV infected patients.

Role of primary care providers: As women with HIV infection live longer, the 

role of their primary care provider in treating other medical conditions is 

critical. When a woman must be referred to an HIV expert, it is important that 

her primary care provider assure the patient that she is not being abandoned. 

Primary care providers who have little or no experience treating patients 

with HIV, including providers in communities or geographic areas where there 

is a shortage of HIV expertise, should make referrals to and consult with 

HIV experts to ensure optimal patient care. Part C & D of the Ryan White 

HIV/AIDS Program funds clinics that can serve as resources for identifying 

experienced HIV providers and healthcare sites. The list of Ryan White–funded 

programs, including Part C & D programs, can be found at the website 

http://hab.hrsa.gov/.

HIV specialist care: Current U.S. Public Health Service (USPHS) treatment 

guidelines can be accessed at www.aidsinfo.nih.gov; many of these guidelines 

are living documents that are updated regularly online. The Health Resources 

and Services Administration also supports the AIDS Education and Training 

Centers warmline (800-933-3413), which is a resource for clinicians who need 

expert consultation. The HIV Medicine Association of the Infectious Diseases 

Society of America has outlined several qualifications that HIV physicians should 

meet to demonstrate appropriate experience, including direct care of at least 

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25 HIV infected patients over 36 months and completion of at least 10 hours 

of Category 1 continuing medical education credits per year. The American 

Academy of HIV Medicine offers HIV specialist certification to MDs, DOs, nurse 

practitioners, and physician assistants who have at least 20 HIV patients, have 

acquired at least 30 HIV-related educational credits over the previous 24 

months, and pass an examination every 2 years (www.aahivm.org).

Cultural Sensitivity

Cultural sensitivity is essential to a clinician’s ability to provide optimal 

patient care and is addressed in more detail in Chapter 9, Psychosocial 

Issues, Mental Health, and Substance Abuse. It is important that the provider 

recognize and understand the factors, including culture, that influence and 

guide a patient’s behavior and decisions. A woman’s traditions and beliefs 

affect her understanding of health and disease as well her acceptance of 

conventional medical treatment and reliance on alternative or complementary 

therapies. Her background shapes her view of herself as a woman, her role 

and responsibilities in society, and her beliefs and practices with regard to 

childbearing and contraception. Other factors may create barriers to care, 

as when a patient who has difficulty speaking, understanding, or reading 

English and receives care from a provider who can communicate only in English. 

Immigration status, as well as culturally based fears and mistrust of the U.S. 

healthcare system, also may impede care.

Special Circumstances

Many life circumstances may necessitate special approaches to care and 

unique sensitivity on the part of the care provider, as may be the case in 

treating women who are incarcerated, are victims of domestic or other 

violence, are addicted to alcohol or drugs, or have a psychiatric illness. 

Lesbians and transgender women also may require special sensitivity for 

treatment to be effective.

Some patient circumstances may arouse strong emotions in a care provider 

because of the provider’s background or beliefs. It is essential that providers 

be willing and able to separate themselves from any personal connotations or 

associations they may assign to a patient’s lifestyle or circumstances. They must 

provide care that is unbiased, sensitive, kind, and empathetic. If doing so is 

not possible, then the provider should refer the patient to a provider who can 

remain unbiased.

Spirituality

The spiritual dimension of a woman’s life encompasses her beliefs and values 

and may give her life meaning and a sense of wholeness (J Palliative Care

2000;3:129). Spirituality is important throughout life, during periods of health 

and of illness, and a patient’s beliefs and values can have a profound effect 

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on the way she views illness and its treatment. For instance, some women may 

view HIV as a punishment, and this belief may lessen their acceptance of 

treatment or put them at risk of nonadherence.

Major spiritual questions that often arise during illness may include the 

following:

• What gives my life meaning?

• Why is this happening to me?

• How will I survive this loss?

• What will happen to me when life ends?

It is important that the healthcare provider consider spirituality an essential 

component of a woman’s physical, emotional, and mental health and that 

the provider learn about a patient’s beliefs and what is important to her. A 

spiritual history should include specific questions about the patient’s faith or 

beliefs, their importance and influence in her life, her involvement in a spiritual 

or religious community and its importance to her, and ways in which the 

healthcare provider may be able to help the patient integrate her beliefs and 

spiritual concerns into her care.

An ongoing concern: Spirituality may affect patient health outcomes 

directly or indirectly. Recent studies involving primary care and oncology 

patients found that spiritual well-being was positively associated with several 

outcomes relating to healthcare utilization and life satisfaction (Ann Fam Med

2008;6:412) and to quality of life (Psychooncology 2008;17:1121).

Spirituality should be addressed throughout a patient’s care. Referrals to 

ministers, priests, rabbis, other spiritual guides, and community resources can 

be an important component of care. A care provider’s personal spiritual 

beliefs may be a source of strength and may enhance the patient–provider 

relationship, but they should not be imposed on patients; the patient’s beliefs 

should be recognized and respected.

Identifying Support Systems and Disclosure

During the initial evaluation, the HIV infected woman’s social and emotional 

support system should be identified and reinforced; this information should be 

updated at each visit. The care provider also should ask about disclosure—

to whom has the patient disclosed her HIV status, and what response(s) has 

she experienced? Many HIV infected women experience feelings of guilt 

and shame or fear violence or abandonment, and they are reluctant to trust 

anyone with knowledge of their infection or to share their feelings about 

it. Many communities still attach enormous stigma to HIV. A woman’s fears 

about ostracism and abandonment should be addressed openly; a sense of 

isolation may harm a patient’s physical and emotional well-being and lead to 

avoidance of clinic visits and nonadherence to drug therapy. Peer advocates 

and support groups may help many women with HIV cope with these fears and 

other issues on an ongoing basis.

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Disclosure to sexual partners, children, and other healthcare providers may 

require careful attention and assistance. A woman should be encouraged to 

disclose her status to partners and others who may be or have been at risk 

of HIV transmission; barriers to disclosure, such as fear of violence, should 

be identified and addressed. The care provider should offer assistance with 

disclosure when appropriate. A mother’s decision to disclose or not disclose her 

HIV status to children, who may or may not be infected themselves, should be 

honored. The timing of a mother’s disclosure to her perinatally infected child 

can be especially difficult and may reinforce a mother’s feelings of guilt. The 

care provider should discuss the variety of considerations inherent in these 

decisions and offer the patient assistance if she needs it.

Education and Counseling

Despite dramatic advances in therapy, significant decreases in mortality and 

hospitalizations, and overall improvement in quality of life, HIV remains a 

life-threatening and often life-ending disease, and no cure is on the horizon. 

For women, life with HIV infection often is enveloped by poverty; isolation; 

personal, partner, or community drug use; and the competing priorities of 

children and family. Mental illness, substance abuse, or domestic violence may 

complicate a woman’s clinical picture. Personal management of HIV disease 

now requires that a patient have a basic understanding of HIV infection and 

intense involvement in her own care.

Early and often: When encountering a woman newly diagnosed with HIV, care 

providers should be certain to educate the patient about the infection—natural 

history; clinical, immunologic, and virologic monitoring; and treatment—and 

about her medical condition in particular, including CD4+ cell count, clinical 

stage, and her need for treatment. The critical importance of adherence to 

care and to ART should be explained early and often. Barriers to care and to 

ART adherence, such as medication side effects and disclosure issues, should be 

assessed and addressed proactively.

Lifelong learning: Unlike patients with most other chronic medical conditions, 

those with HIV remain infectious for the rest of their lives and must learn about 

and become empowered to change behaviors that put themselves or others 

at risk (i.e., “prevention for positives”). Doing so successfully entails ongoing, 

lifelong learning and requires continual reinforcement. Perhaps the most 

important intervention for reducing sexual transmission to others is the use of 

effective ART. Observational studies and a meta-analysis have demonstrated 

decreased rates of HIV transmission among heterosexual serodiscordant 

couples on ART (particularly with fully suppressed HIV-RNA levels) as 

compared to those not on therapy (AIDS 2009;23:1397). Recent data from 

HPTN 052, a randomized clinical trial designed to evaluate ART as prevention 

of sexual transmission among serodiscordant couples, found that earlier 

initiation of ART (at CD4+ cell counts 350–550/mm3) reduced HIV transmission 

to the uninfected partner by 96%. (N Engl J Med 2011; 365:493-505). Preexposure prophylaxis (PrEP) (see Chapter 3) is an additional option that can 

be considered to help protect HIV-uninfected partners.

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Providers’ ongoing patient education efforts should aim to correct 

misconceptions and uncover myths. Relapses in unsafe sexual or drug-using 

behaviors and at least episodic problems with adherence should be recognized 

as the norm rather than the exception. Patients also should be counseled 

about health-promoting practices in general (e.g., smoking cessation, exercise, 

nutrition) and about other personally relevant issues when appropriate 

(e.g., substance abuse, domestic violence). Education and counseling must 

be provided throughout the course of a patient’s care, as knowledge and 

disease management change and the patient’s life circumstances evolve. Peer 

advocates (HIV-affected women from similar cultural backgrounds) can be 

effective members of the clinical team to help educate patients, advocate for 

them, and provide counseling as needed.

Medical Evaluation

Several closely spaced visits: The initial medical evaluation of an HIV infected 

woman should include a comprehensive medical and psychosocial history and 

physical examination. It should also include gynecologic history—menstrual 

history, sexual practices (including genital, oral, and anal sex), contraception 

and condom use history, previous sexually transmitted and other genital 

tract infections, prior abnormal Pap smears, and other gynecologic illnesses 

or symptoms—as well as pelvic examination and recommended laboratory 

testing. This initial assessment should take place over several closely spaced 

visits. This approach will allow the woman and her clinical care team to 

become familiar with one another and to develop the trust and partnership 

that will form the foundation of the woman’s ongoing care. It is particularly 

important for a woman newly diagnosed with HIV, who may be struggling with 

the shock, fear, denial, and despair that accompany the discovery of a lifethreatening illness, to be given the opportunity to assimilate information about 

HIV and her own clinical status in small bites.

The intervals at which follow-up visits are scheduled should be based on the 

patient’s HIV clinical, immunologic, and virologic status as well as other medical 

or comorbid conditions (e.g., substance abuse, mental illness) and her counseling 

or psychosocial support needs. At each visit, the patient should be questioned 

about new symptoms and side effects, her adherence with medications, and 

psychosocial issues and concerns. Her last menstrual period, current sexual 

activity, and use and consistency of use of condoms and contraception should 

be documented. Risk behaviors should be reassessed at regular intervals 

because sexual and drug-use patterns may change over time. Safe practices 

should be reinforced through positive prevention counseling (MMWR 2003;52 

RR12:1). Pelvic examination should be repeated at least annually and should 

take place more frequently if gynecologic signs or symptoms develop or if 

the patient has a history of abnormal Pap smears, or current or recent unsafe 

sexual practices, or exposure to sexually transmitted infections. Medical and 

gynecologic evaluation of HIV infected women is described in more detail in 

Chapter 4, Primary Medical Care, and Chapter 6, Gynecologic Problems.

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Family-Centered Care

HIV is a disease of families. An infected woman’s husband or partner and 

her children also may be living with HIV. Even when other family members 

are not infected, a woman is likely to be deeply affected by the presence 

of chronic and life-threatening illness within the family; she may be fearful of 

HIV transmission, and she may fear or face stigma. An HIV infected woman 

may neglect her own care while providing care to sick family members or to 

her children. The provider should encourage all HIV infected family members 

to receive appropriate care and should enlist family support for the infected 

woman by providing the family with information and education about HIV 

along with updates on the woman’s condition (with her permission). The care 

provider also may help by identifying support systems for the entire family.

Access to Care

Two studies conducted at several multistate primary and specialty HIV care 

sites in different geographic regions highlighted persistent gender disparities 

in care by demonstrating that women were less likely to receive effective ART 

(J Acquir Immune Defic Syndr 2005;38:96) and had higher hospitalization 

rates (Med Care 2005;43 suppl 9:40). If women with HIV are to benefit 

equally from the advances in understanding and management of this disease, 

then attention must be paid at the individual, community, and societal levels 

to the many factors that continue to hinder equal access to care. Such factors 

include lack of empowerment; difficulty accessing child care, transportation, 

and insurance coverage; stigma and isolation; violence against women; and 

the competing concerns that many women face when they are responsible 

for providing food, housing, and care for other family members while caring 

for themselves. It is important to create appropriate linkages to services not 

available at the primary site of care, including substance abuse treatment, 

food and housing assistance, and additional medical expertise.

Limited-Resource Settings

(see also Chapter 16, International Perspectives)

In limited-resource settings, great progress has been made in scaling up access 

to HIV testing and counseling, ART, interventions to prevent mother-to-child 

transmission, and treatment of TB and other HIV-related infections, largely 

because of resources committed to the Global Fund to Fight AIDS, Tuberculosis, 

and Malaria; the U.S. President's Emergency Plan for AIDS Relief (PEPFAR); 

and other international organizations. Increasingly, HIV education and training 

is being integrated into medical, nursing, and midwifery school curricula to 

prepare new generations of healthcare providers for the ongoing pandemic. 

Moreover, task-shifting strategies have been implemented in many countries to 

expand the human resource pool rapidly and to use scarce human resources 

more efficiently. (Task shifting entails assigning specific tasks to less specialized 

healthcare workers, such as shifting responsibility for HIV testing and counseling 

to community workers or assigning nurses to prescribe and dispense ART.)

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In settings with few resources, issues of cost, accessibility, stigma, and 

laboratory and healthcare infrastructure limit the use of ARVs; moreover, 

as new infections continue to occur, they threaten to overwhelm any fragile 

progress that has been made. Increasingly, attention is turning to the need for 

robust prevention programs and the use of biomedical prevention tools, such as 

male circumcision, in addition to—and integrated with—treatment resources. 

A new focus on integration and coordination of HIV prevention, care, and 

treatment with broader global health efforts, including linkage to women and 

children's health programs, has developed. Community involvement, laboratory 

infrastructure, and patient and provider education are interrelated and 

essential to all levels of HIV care. These components of the healthcare system 

must exist and must be strengthened if prevention, care, and treatment services 

are to succeed and ART is to reach those most in need.

The Chronic Care Model for HIV

With the advent of effective ART, life expectancy for HIV infected persons 

has been significantly extended and symptoms and disability related to HIV 

have decreased. This shift has required replacement of the acute and terminal 

illness model of care with a chronic care model. Analysis of a multinational 

cohort found that the average life expectancy for a 20-year-old with HIV who 

started ART between 2003 and 2005 is now extended to 49 years (Lancet

2008;372:293). However, a recent analysis based on HIV surveillance data 

from 25 States found that life expectancy improved less for women after a 

diagnosis of HIV from 1996 to 2005 than it did for men (J Acquir Immune Defic 

Syndr 2010;53:124). As people with HIV live longer, they are also subject to 

the same chronic illnesses as the general population. In some cases, they may 

be at increased risk for certain chronic diseases, such as cardiovascular and 

metabolic syndromes (see Chapter 4, Primary Medical Care).

Chronic disease criteria: HIV meets several chronic disease criteria. It has an 

uncertain course and a prescribed treatment regimen; it requires self-care and 

carries some degree of stigma; it brings about changes in identity, roles, and 

relationships; and it may cause psychological distress (AIDS 2002;16 suppl 

4:s69). As more HIV infected persons around the world have access to ART and 

are living longer, chronic disease management programs have become a global 

priority (UNAIDS 2008).

Objectives of chronic disease care: The objectives of chronic disease care 

include management of physical symptoms, maintenance or improvement 

of independence, and increased quality of life (Psychology and Psychiatry: 

Integrating Medical Practice. Chichester, UK: John Wiley & Sons; 2001; Public 

Health 2002;119:1130). The Chronic Care Model (www.improvingchroniccare.

org) illustrated in Figure 2-1 was developed and refined by experts in chronic 

illness management to encourage high-quality integrated chronic disease care. 

It can be applied to a number of chronic illnesses, including HIV/AIDS. The 

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model identifies key elements in a system of care that can help patients to be 

healthier, providers to be more satisfied, and cost reductions to be realized 

throughout the system.

Figure 2-1

The Chronic Care Model

Community

Resources and Policies

Health Systems

Organization of Health Care

Self-Management 

Support

Delivery System 

Design

Decision 

Support

Clinical Information 

Systems

Improved Outcomes

Productive Interactions

Prepared, 

Proactive 

Practice Team

Informed, 

Activated 

Patient

Source: Eff Clin Pract 1998;1:2. Copyright © 1998 by the American College of Physicians. 

Reprinted with permission.

Community Resources and Policies

Community programs can support and extend care for patients with HIV/AIDS. 

They can provide resources, fill gaps in needed services, promote better selfcare, and play a broad role in advocating for patients and promoting health 

policies that can better sustain the lives of people living with HIV/AIDS.

Organization of the HIV Healthcare System

In delivering care for patients with HIV/AIDS, the healthcare system 

should be organized to promote safe and high-quality care. It should be 

flexible and nimble (i.e., able to change), offer appropriate resources 

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and support for providers and patients, and emphasize prevention and 

health maintenance rather than crisis-oriented care. The system also 

should encourage open and methodical handling of errors and quality 

problems and should promote effective improvement strategies aimed at 

comprehensive system change. Coordination of care within and across health 

system components, including coordination with primary and specialist clinical 

care, as needed, should be facilitated.

Decision Support

Because of the rapid advancements in knowledge about HIV and changes 

in clinical practice, HIV care providers need ongoing education and training 

to remain current. Treatment decisions should be founded on evidence-based 

guidelines. Primary care providers also should be kept informed and involved 

when patients are referred for specialist care. The USPHS has supported 

the development of evidence-based guidelines for HIV prevention and care 

(available at www.aidsinfo.gov).These and other high-quality online and 

consultative resources (e.g., warmlines, hotlines) are available to assist HIV 

providers in ensuring that care is based on the most current information and 

recommendations (see Chapter 15, Resources).

Healthcare Delivery System Design

The healthcare delivery system should be proactive and focused on keeping 

patients as healthy as possible. This approach requires determining what 

care is needed, delineating roles clearly among care team members, 

ensuring that team members have current information about patient status, 

and facilitating follow-up as a part of standard care. When necessary, care 

should be coordinated and integrated across different clinical settings, and 

access to community resources should be facilitated. Attention should be given 

to patient understanding of care, and care should be sensitive to a patient’s 

cultural background and belief system. Case management services—defined 

as intensive, individually tailored, goal-oriented care—that are planned, 

coordinated, and managed by a single individual (case manager) or members 

of a team also should be provided.

Patient Self-Management Support

Successful HIV care depends on a well-informed and motivated patient. 

Although care providers are responsible for prescribing ARVs appropriately 

and can facilitate adherence, a woman with HIV is ultimately responsible for 

taking her medications properly and returning for regular care and follow-up. 

It is essential that patients be given tools to help them care for themselves, 

including information about how to take medications, recognize adverse effects, 

and minimize or prevent side effects. Patients often need help with developing 

problem solving, coping, and assertiveness skills. Finally, a woman should have 

a central role in making decisions about her care and in problem solving, 

both of which will help foster personal responsibility and a collaborative and 

trusting relationship with her care provider.

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A patient’s ability to engage in self-management of her HIV infection depends 

on specific knowledge and behaviors (AIDS Care 2009;21:1321), listed below 

and illustrated in Figure 2-2:

• Understanding illness and wellness in the context of HIV, including 

understanding the need for ART to strengthen the immune system and 

the importance of adherence to reduce risk of resistance

• Engaging in behaviors that promote personal health and prevent 

transmission to others, such as safer sexual and drug injection 

practices and substance abuse treatment

• Accessing appropriate treatment and other services, such as regular 

HIV care and other needed clinical care

• Attending to psychological health, which may include developing 

an improved sense of control over one’s life and actions, working to 

accept HIV as a part of life, and managing stress

• Developing a healthy focus on social relationships, which may include 

coping with stigma and decision making about disclosure, developing 

collaborative relationships with healthcare professionals, and seeking 

out supportive and affirming social networks.

Figure 2-2

Elements of Self-Management of HIV Infection

Elements of 

Self-Management 

of HIV Infection

Engaging in behaviors 

that promote personal 

health and prevent 

transmission to others

Understanding illness 

and wellness in the 

context of HIV

Accessing appropriate 

treatment and other 

services

Attending to 

psychological health

Developing a 

healthy focus on 

social relationships

Clinical Information Systems

Information systems, such as electronic health records, are essential for tracking 

individuals and populations of patients with HIV/AIDS and can be used for 

both clinical and quality management purposes. They can facilitate efficient, 

coordinated, and effective care by supporting the sharing of patient information 

among care providers. Increasingly, telemedicine capabilities are being used to 

complement and extend standard care delivery by enabling greater exchange 

Source: AIDS Care 2009;21:1321

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of information among providers and with patients, virtual consultations, and 

telepharmacy for sending e-scripts, among other innovations (Int J Med Inform

2006;75:638). Clinical information technology can help prevent serious errors in 

care, such as medication errors (JAMA 1998;280:1311), and can provide timely 

reminders for providers and patients.

Quality Management

As the care of individuals with HIV has become increasingly complex and 

multifaceted, the importance of care monitoring to ensure quality and 

comprehensiveness has been highlighted. For instance, the American Medical 

Association recently led a collaborative initiative to explore opportunities to 

improve the quality of outpatient chronic care (Jt Comm J Qual Patient Saf

2009;35:248). That effort focused on incorporating validated and nationally 

endorsed performance measures and tools into clinical care. Performance 

measures specific to the care of patients with HIV have been developed as 

well (see Chapter 14, Quality Management) and can be used as both clinical 

aids by providers and quality measures in auditing comprehensiveness and 

effectiveness of care.

Effectiveness of the Chronic Care Model

To date, no studies have assessed the effects of implementing the chronic care 

model specifically in HIV care. However, a recent review of the model’s use in 

the care of patients with other chronic illnesses found that multidisciplinary care, 

care coordination, patient self-management, and provider education had the 

greatest and most consistent effects on both clinical outcomes and process-ofcare measures, such as increased provider adherence to treatment guidelines 

(Intern Med J 2008;38:427). In addition, patient self-management has been 

shown to reduce emergency and other outpatient visits, decrease health 

distress, and improve self-efficacy (JAMA 2002;288:2469). Some studies also 

indicate that decision support and feedback for healthcare providers, as well 

as case management and telemonitoring or telephone support for patients, 

confer clinical benefit (Intern Med J 2008;38:427).

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From Research to Practice

Community-based participatory research is an emerging model that involves 

community members and patients to enhance ongoing clinical research. 

A practice-based research network is a group of care practices committed 

to patient care and to investigation of questions related to communitybased practice and to improvement of outcomes and quality of care. 

These new research models are well positioned to examine such issues as 

healthcare disparities, prevention, chronic disease management, and mental 

health. The melding of the two research models has great potential for 

solving intractable problems, ensuring that studies match the needs of all 

stakeholders, and allowing rapid translation of results into clinical practice 

(Exp Biol Med 2010;235:290).

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Chapter 3:

Prevention of HIV Infection

Jared M. Baeten, MD, PhD

Assistant Professor, Departments of Global Health and Medicine

Adjunct Assistant Professor, Department of Epidemiology

University of Washington

Connie Celum, MD, MPH

Professor, Departments of Global Health and Medicine

Adjunct Professor, Department of Epidemiology

University of Washington

The authors declare no conflicts of interest

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Chapter 3: Prevention of HIV Infection

Chapter 3 at a Glance

Introduction: A Global Public Health Priority.................................................................39

Daunting Challenges..............................................................................................................................39

HIV Risk Assessment and Risk Reduction Counseling........................................40

Practical Approaches to Risk Reduction Counseling.............................................42

Prevention Messages for HIV Infected Women........................................................45

What Works in HIV Prevention........................................................................................................45

Knowledge of Serostatus..................................................................................................................45

Behavioral Interventions.....................................................................................................................49

Use of Condoms.........................................................................................................................................50

Risk Reduction for Injection Drug Users..............................................................................54

Male Circumcision.....................................................................................................................................54

What Has Not Worked in HIV Prevention...........................................................................56

Nonspecific Vaginal Microbicides...........................................................................................56

HIV Vaccines...................................................................................................................................................57

Treatment of Sexually Transmitted Infections.............................................................59

Antiretroviral-Based HIV Prevention Strategies...........................................................61

ART for Prevention...................................................................................................................................61

Nonoccupational Postexposure Prophylaxis...........................................64

Possibilities and Challenges of ART-Based Prevention......................................70

Combination Strategies for HIV Prevention.....................................................................71

Conclusion...............................................................................................................................................................72

Prevention of HIV Remains a Critical Priority.............................................................72

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Introduction: A Global Public Health Priority

Women account for half of the 33 million adults living with HIV worldwide and 

more than half of new infections in global settings with the highest rates of HIV. 

Prevention of HIV infection in women is a global public health priority for the 

health of women, their sexual partners, and their children.

This chapter discusses HIV prevention with a focus on risk assessment, what 

does and does not work in prevention, and strategies in the research pipeline 

that may hold promise.

Daunting Challenges

Nearly three decades into the HIV epidemic, scientists and clinicians working 

to prevent HIV continue to face daunting challenges. Measures that women can 

take to prevent HIV acquisition are well known—abstaining from intercourse, 

selecting low-risk partners, negotiating mutual monogamy, and using condoms. 

However, high rates of HIV among women in many parts of the world are a 

testament to the barriers that women may face in successfully implementing 

effective prevention strategies.

Multiple vulnerabilities: Women are often not aware of their partners’ infection 

status or level of risk, and in many cases, they may not be able to negotiate 

sexual safety. Young women often face particularly high HIV risk because of 

emotional and physiological immaturity. In many areas of the world, risk is 

magnified by poverty and social vulnerability, leading to a greater likelihood 

of engaging in sexual relationships that lead to HIV exposure.

Risk magnified by disempowerment: Women in economically disadvantaged 

nations and in socially marginalized groups in the industrialized world may 

have less access to medical care for treatment of sexually transmitted infections 

(STIs) and contraception. They may not feel empowered to negotiate condom 

use, abstinence, or monogamy within their sexual relationships or to initiate 

HIV testing for themselves or their partners. An important issue is that fertility 

desires may overwhelm HIV prevention intentions, particularly condom use, 

even for women who perceive HIV risk.

Interventions for behavioral and biologic risk factors: Women who use 

injection drugs and some noninjection drugs (e.g., methamphetamine, cocaine) 

are at higher risk of HIV and need counseling that addresses both safe sexual 

practices and harm-reduction strategies related to drug use. Culturally sensitive 

interventions that target both behavioral and biologic risk factors for HIV 

are necessary to reduce transmission to women and girls. There remains, as 

well, a critical need to address the complex forces that fuel the HIV epidemic 

in women, including poverty, migration of populations, social and cultural 

disruption, gender discrimination, and stigma about STIs and HIV.

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HIV Risk Assessment and Risk Reduction Counseling

Given that many patients will not voluntarily discuss their sexual activity or 

potential risk of HIV or STIs, it is incumbent on health care providers to ask a 

few open-ended questions in a comfortable, nonjudgmental manner. Otherwise, 

providers enable avoidance of discussion of sensitive sexual behavioral and 

HIV risks (e.g., “I won’t ask; they won’t tell”). Suggestions for risk assessment 

and patient-centered counseling are provided in the sections that follow.

Risk assessment for every patient: Just as most people would find celibacy an 

impractical means of reducing sexual risk, many individuals may find changing 

other specific sex behaviors difficult or unappealing. Although some sexual 

behaviors may be less mainstream than others, remember that participation in 

such behaviors reflects not a lack of morals or willpower but rather differing 

perceptions of what is enjoyable. Moreover, sexually active women may 

not realize that they are practicing behaviors that put them at risk for HIV 

infection. Guidelines for physicians and other healthcare providers recommend 

that HIV and STI risk assessment be conducted for every patient, ideally 

on a regular basis; however, most primary care physicians do not routinely 

incorporate questions about sexual behavior into routine patient care.

Managing provider discomfort: Clinician discomfort and fear of embarrassing 

or offending a patient when discussing sex may be impediments to effective 

risk assessment. In such circumstances, a clinician may find it more acceptable to 

frame the discussion by explaining the routine nature of such questions, thereby 

demonstrating that the patient is not being singled out because of mannerisms, 

appearance, or ethnicity. One effective approach may be to emphasize the 

importance of the discussion to the patient’s care: “To be able to provide 

the best care for you today, we need to understand your risk for certain 

infections by talking about your sexual practices.” Another may be to allude 

to the universality of many concerns: “Many women find it difficult to get their 

partners to wear condoms. Has this been a problem for you?” As with any type 

of medical history taking, open-ended questions probably serve as the most 

effective means of eliciting information when taking a sexual history. Language 

should be clear, easy to understand, and nonjudgmental.

Low threshold for recommending HIV testing: Some HIV risk factors for women 

can be derived from epidemiologic studies, such as history of gonorrhea or 

syphilis, crack cocaine use, and injection drug use (IDU). Increased risk with 

drug use is often mediated through both exposure to infected blood (especially 

with IDU) or through association with unsafe sexual practices. However, 

sometimes women are at risk through monogamous relationships with their HIV 

infected husbands. Factors that may increase risk in women, such as a history of 

unwanted pregnancy or an incarcerated sex partner, are not well recognized 

among healthcare providers. Therefore, identifying risk behaviors in women 

requires care and attention on the part of the provider. In many cases, a low 

threshold for recommending HIV testing is necessary. Important risk topic areas 

to cover are listed in Table 3-1 and can be ascertained through a written or 

computerized patient-administered questionnaire.

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Table 3-1

Risk Assessment for STI/HIV for Women

Number of sex partners: ___ previous year ___ lifetime

Sex partners: ___ men ___ women ___ both

Sexual practices: ___ vaginal intercourse ___ anal intercourse

 ___ oral sex ___ sex toys ___ other (specify) ______________________

Consistent condom use: ___ yes ___ no

Use of: ___ injection drugs ___ crack cocaine ___ crystal methamphetamine

Patient perceives sex partner(s) to be at risk: ___ yes ___ no

Patient feels that sex partner(s) put her at risk: ___ yes ___ no

How does patient protect herself from HIV? _____________________________

________________________________________________________________

________________________________________________________________

How does the patient protect herself from unplanned pregnancy? ____________

________________________________________________________________

________________________________________________________________

History of abnormal PAP smear? ___ yes ___ no

History of STI? ___ yes ___ no

History of sex partner who was incarcerated? ___ yes ___ no

History of alcohol or drug abuse? ___ yes ___ no

History of: ___ injection drug use ___ sharing needles

___ crack cocaine use ___ crystal methamphetamine use

History of sexual, physical, or psychological abuse? ___ yes ___ no

Is there anything else that she feels she should mention to ensure good 

medical care? ____________________________________________________

________________________________________________________________

________________________________________________________________ 

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Practical Approaches to Risk Reduction Counseling

Individualize to the patient: Risk reduction counseling may seem overwhelming 

to a healthcare provider who has no special training in behavioral theory. 

However, the underlying principle is one that can be applied by any 

practitioner in any setting: Counseling should be individualized to the person 

receiving the counseling, and any attempt to individualize is superior to simply 

providing a didactic message.

Practical aspects of counseling:

• Focus the counseling session on risk reduction topics.

• Listen and react to the patient.

• Do not stick to a practiced script.

• Avoid overambitious risk reduction plans; focus on 

realistic goals.

• Give the patient written documentation of the risk 

reduction plan.

• Use culturally sensitive and ethnicity-specific language and 

terminology, when available and appropriate.

• Consider issues specifically relevant to women.

Focus the session: The cornerstone of the counseling session is to focus the 

session on a patient’s recent sexual activities, her perception of their risk, and 

her motivation to reduce her risk of HIV/STI exposure. The provider should 

redirect the patient to this topic whenever necessary. Clinicians and counselors 

may become distracted by providing excessive information about scientific 

data and principles in response to patient questioning. Such information is 

probably more effectively dispensed in pamphlet form or by referral to 

other patient information sources. In addition, women at risk for STIs, including 

HIV, often come to clinic with multiple complicating issues, including poverty, 

domestic violence, substance abuse, and child care problems. A counselor may 

begin to feel responsible for addressing all of these issues and discouraged by 

what seems to be a host of insurmountable problems. Moreover, because the 

patient may be uncomfortable discussing her own risk, she may be emotionally 

invested in distracting the counselor from that subject. For these reasons, the 

counselor should remember that, during a limited period of interaction with a 

woman, the primary goal is to directly address and, ideally, have an impact on 

risky sexual behavior.

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Appropriate objectives of risk reduction counseling 

(Adapted from Kamb ML, 1998):

• Enhance the patient’s self-perception of risk: Identify risk 

behavior; assess level of concern; identify ambivalent 

feelings about risk.

• Explore specifics of the patient’s most recent risk:

Identify specific risk details; address ability to 

communicate with partner(s).

• Assess the patient’s patterns of risk behavior: Identify 

situations that make the patient vulnerable to risk and 

triggers of high-risk behavior.

• Review previous risk reduction experience: Identify 

successful attempts at risk reduction and obstacles 

to risk reduction; summarize, reflect, and synthesize 

patient risk patterns.

• Address risk in the context of the patient’s life: Convey 

concerns and urgency regarding risk; support and 

encourage the patient to action.

Other longstanding issues may not be easily solvable and may be more 

appropriately referred to a social worker, substance abuse counselor, or 

mental health counselor.

Listen and react: While trying to convey prevention messages it is important 

to listen and react to the patient. It is a human quality that we enjoy talking 

and thinking about ourselves. The counseling technique of summarizing a 

patient’s descriptions and viewpoints about her risk is an extremely effective 

communication tool. In an effort to be nonjudgmental, counselors may find 

themselves nodding supportively to just about any statement that the patient 

may make. Instead, direct and clear feedback from the counselor about 

self-destructive behavior may communicate more effectively the importance 

of reducing risk. For example, if a patient is describing an evening during 

which she had sex with multiple men while using crack cocaine, it may be 

more appropriate for the counselor to respond with emphasis that such 

behavior is dangerous. It would also be important to explore the emotional or 

physical needs leading to such risky sexual behavior and to identify potential 

alternatives to fulfilling such needs.

Avoid overambitious risk reduction plans: The most common error made by 

counselors is developing an overambitious risk reduction goal, particularly 

during sessions in which good rapport has been established. In many cases, 

a counselor may be convinced that a woman has acknowledged her risk to 

such a degree that she is now ready to eliminate any subsequent episodes 

of unprotected sex. Such goals are likely unrealistic. Behavioral specialists 

favor extremely concrete goals, such as “On Friday night I am going to ask 

my partner to wear a condom.” Even modest goals, such as stopping at a 

drugstore and purchasing condoms on the way home from the session, may be 

suggested. Other possible goals are listed in Table 3-2.

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Table 3-2

Examples of Concrete Individualized Risk Reduction Plans

Type of Plan Patient Actions

Patient will talk about 

HIV/STI concern/risk to 

partner/friends.

• Disclose or communicate with partner, peers, 

and others

Patient plans to get 

herself tested or have 

partner(s) tested for HIV/

STIs before having sex.

• Get tested again to ensure she is not infected

• Have partner(s) tested for HIV/STI

• Use condoms until partner(s) tested for HIV/STI

• Abstain from sex until partner(s) is tested for HIV/STI

Patient plans to reduce, 

change, or eliminate 

at-risk partner(s).

• Break up with high-risk partner(s)

• Eliminate a particular type of high-risk partner 

(e.g., prostitutes, anonymous partners)

• Have fewer partners

Patient will change the 

type of partners she has. • Get to know partners better before having sex

• Remain monogamous with one partner for 3 mo

• Abstain from sex for 3 mo

Patient plans to change 

use of alcohol and drugs. • Decrease or eliminate alcohol and drug use when 

having sex

• Generally decrease or eliminate a specific 

drug or alcohol

• Will not share needles (she will exchange or 

obtain new)

• Use clean needles or only share needles with partners 

known to be HIV uninfected

• Seek medication-assisted therapy if addicted to 

heroin or other opiates

Patient plans to increase 

condom use or increase 

situations in which she uses 

condoms.

• Talk to partner(s) about using condoms

• Buy condoms or have them more available

• Have sex with condom use more often

• Use condoms with all partners (vaginal and anal sex)

• Use with all non main partners (vaginal and anal sex)

• Use condoms with main partner (vaginal and 

anal sex)

Patient plans to change 

the kind of sex she will 

have.

• Have oral sex instead of vaginal or anal sex

• Engage in mutual masturbation or petting (no 

penetrative sex)

Patient plans to make 

changes in the situations 

that are associated with 

risky behavior.

• Eliminate going to particularly risky place 

(e.g., bar, clubs)

• Reduce frequency of going to a particularly 

risky place

• Substitute behavior—go to gym, movies, etc., instead

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Adapted from JAMA 1998;280(13):1161 and from Beth Dillon, Project RESPECT training 

materials

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Prevention Messages for HIV Infected Women

Important for women already infected with HIV: Although this chapter 

focuses on factors that may increase a woman’s risk of acquiring HIV, 

prevention messages are equally important for women who are already 

HIV infected. Studies have shown that women with HIV are concerned 

about factors that may increase their infectiousness to their sexual partners 

and children. In general, the central messages for preventing sexual HIV 

transmission apply to HIV infected women as well as to those who are not 

infected but are at risk through their or their partners’ behaviors. Important 

messages include the importance of knowing one’s HIV status and that of 

one’s sexual partner(s), the effectiveness of behavioral change in preventing 

transmission, and the potential role of consistent condom use in significantly 

reducing risk of HIV transmission.

What Works in HIV Prevention

Knowledge of Serostatus

Essential to prevention: Knowledge of one’s HIV serostatus is the starting point 

for HIV prevention. An HIV-seropositive woman must know her status to prevent 

transmission to her infant and her partner(s) and so she can seek medical 

care for herself. For a seronegative woman, HIV testing is an opportunity 

for risk reduction counseling and strategizing on ways to remain uninfected. 

Unfortunately, most women at risk for HIV infection remain unaware of their 

HIV status, in part because they are often unaware of their partners’ risks.

Routine provision of HIV testing recommended: Selective HIV screening — 

i.e., targeting patients at highest risk, such as intravenous drug users, men who 

have sex with men (MSM), and STI clinic attendees—has long been central 

as a strategy for HIV testing. The advantage of selective screening is cost 

savings, particularly in low-prevalence settings. However, selective screening 

has the potential to miss many people with HIV infection, particularly women, 

who may not possess traditional risk factors for HIV or who may not recognize 

their own HIV risk, and experts have increasingly favored recommendations 

for universal HIV screening. Estimates are that 1 in 5 HIV infected persons in 

the United States is unaware of his or her HIV serostatus. Universal screening 

offers several important advantages, including increased detection rates 

and, potentially, increased test acceptance, as universal screening reduces 

the stigma of HIV testing by eliminating testing based on sexual orientation, 

socioeconomic status, or race.

In the United States, the Centers for Disease Control and Prevention (CDC) 

recommends an opt-out approach to HIV screening, in which testing will be 

performed unless a patient declines. To increase routine HIV testing as a part 

of routine medical practice, the target populations for opt-out testing are 

broad: all pregnant women, everyone aged 13–64 years seeking health 

care (e.g., in primary care or emergency room settings, unless the prevalence 

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of undiagnosed HIV in that community has been documented to be <0.1%), 

everyone initiating TB treatment, and everyone seeking treatment for STIs 

(MMWR 2006;55:1). Making HIV testing routine and universal is cost effective 

(N Engl J Med 2005;352:586). The evidence is insufficient to determine 

optimum time intervals for HIV screening. One reasonable approach would be 

one-time screening of adolescent and adult patients to identify persons who 

are already HIV-positive, with repeated screening of those who are known to 

be at risk for HIV infection, those who are actively engaged in risky behaviors, 

and those who live or receive medical care in a high-prevalence setting. 

Minimizing operational barriers to testing: Separate written consent for HIV 

testing should not be required unless mandated by local jurisdiction. Instead, 

general consent for medical care should be considered sufficient to encompass 

HIV testing. Rapid tests should be used to increase the likelihood that patients 

will receive their results. Unfortunately, routine HIV testing, particularly for 

hospitalized patients and those presenting to emergency care settings, 

has not yet been adopted widely, despite CDC guidelines. Some of the 

barriers to implementation of routine HIV testing include healthcare provider 

misconceptions about the amount of time testing requires, stigma associated 

with HIV/AIDS, and lack of reimbursement by some healthcare insurers.

In higher prevalence countries outside the United States, multilayered 

national programs have been initiated to increase universal knowledge of 

HIV serostatus, including widespread voluntary testing and counseling; optout testing in antenatal clinics; and door-to-door, home-based HIV counseling 

and testing, which rapidly increases knowledge of serostatus within a 

community and among families. Opt-out testing significantly increases HIV 

testing rates among pregnant women and is a key strategy in increasing 

uptake of antiretroviral (ARV) medications for prevention of mother-to-child 

HIV transmission.

Recommendations for counseling: In recognition that written consent and 

extensive pre- and posttest counseling reduced health care provider willingness 

to recommend and offer HIV testing, the 2006 CDC guidelines indicated 

that prevention counseling should not be required as part of HIV screening 

programs in healthcare settings. Prevention counseling is strongly encouraged 

for people at high risk for HIV, such as those seen in STI clinics.

Brief information about HIV tests should be provided with routine HIV testing, 

including the need for confirmatory tests if a rapid HIV test is positive. Patients 

at ongoing risk of HIV exposure should be counseled about risk reduction, and 

a concrete plan for reducing risk should be established by the patient. The 

need for annual HIV testing also should be communicated.

Table 3-3 describes appropriate goals for posttest counseling. For people 

who learn that they are HIV infected, disclosure to partners and the 

importance of linkage to care and antiretroviral therapy (ART) should be 

emphasized. Given that a substantial proportion of newly identified HIV 

infected persons do not follow up with care, it is important to obtain a CD4+ 

cell count, provide active referrals, and follow up with newly identified HIV 

positive persons within 2–4 weeks to determine whether they have had 

clinical follow-up with an HIV care program.

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Table 3-3

Goals of HIV Posttest Counseling

Test Result Counseling Messages

HIV 

seronegative • Readdress and reinforce risk reduction plan.

• Discuss need for repeat testing for people with recent (<3 mo) exposure or ongoing sexual and/or drug using risk behavior.

• Discuss disclosure of results to sexual and drug-using partners.

Indeterminate 

HIV-1 Western 

blot

• Discuss prevalence of and risk factors for indeterminate 

test results.

• For patients with p24 bands and those with high-risk behavior, 

discuss possibility of acute HIV infection.

• Arrange for repeat testing in 1 mo and perform HIV DNA or 

RNA PCR to confirm infection status.

HIV 

seropositive • Differentiate between being HIV infected and having AIDS.

• Emphasize importance of early clinical intervention and 

make medical referral.

• Discuss ways to avoid transmitting HIV to others.

• Discuss disclosure of results to sexual and drug-use 

partners and offer assistance with disclosure, if needed.

• Assess need for psychological support and provide 

referral if appropriate.

• Assess possibility of domestic violence and provide 

referral if necessary.

• Ensure patient has follow-up care.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Rapid HIV testing: HIV testing is of value only if patients return for their test 

results; however, low return rates have been described in the United States and 

in many developing countries. Many U.S. testing programs use an ELISA with 

confirmation through Western blot. Rapid testing for HIV yields substantial cost 

savings and avoids high patient nonreturn rates for test results.

A number of rapid tests—defined as requiring less than 2 hours—are 

approved by the U.S. Food and Drug Administration (FDA) and available 

in the United States (Table 3-4). Some tests require as little as 5 minutes, 

use blood obtained from a fingerstick, and can be performed easily 

by clinical staff using only minimal laboratory facilities. Some have 

been approved by the FDA with a waiver from the Clinical Laboratory 

Improvements Amendments (CLIA) regulations; such waivers allow trained 

but nonprofessional staff to use the tests outside of traditional laboratory 

settings. Experience from CDC-led demonstration projects of rapid testing 

has been encouraging, and the assays have been found to have high 

sensitivity and specificity (AIDS 2006;20:1655). An increased rate of false 

positive results (<2%) with tests that use oral fluid rather than blood has 

been reported; positive results require confirmatory testing.

Patients who test negative can be given a definitive result without a return 

visit. Patients who test positive should be informed that their screening test was 

positive and that they should return to receive a confirmed test result.

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In July 2012 the FDA approved the OraQuick In-Home HIV Test, a rapid 

home-use HIV test kit that provides a test result in 20–40 minutes and 

is approved for sale in stores and online to those 17 years and older. 

As with other rapid tests, positive tests must be confirmed by follow-up 

laboratory-based testing. (http://www.fda.gov/NewsEvents/Newsroom/

PressAnnouncements/ucm310542.htm )

Table 3-4

Rapid HIV Tests Approved by the FDA

Test Manufacturer Specimen 

Type

Sensitivity (%) Specificity (%)CLIA 

Waived

Clearview 

COMPLETE 

HIV 1/2

Inverness Medical

Professional Diagnostics

www.

invernessmedicalpd.com

Whole 

blood*

99.7 99.9 Yes

Serum/

plasma

99.7 99.9 No

Clearview 

HIV 1/2 

STAT-PAK

Inverness Medical

Professional Diagnostics

www.

invernessmedicalpd.com

Whole 

blood*

99.7 99.9 Yes

Serum/

plasma

99.7 99.9 No

Multispot 

HIV-1/

HIV-2 

Rapid Test

BioRad Laboratories

www.biorad.com

Serum 100 99.9 No

Plasma 100 99.9 No

OraQuick 

ADVANCE 

Rapid 

HIV-1/2 

Antibody 

Test

OraSure 

Technologies, Inc.

www.orasure.com

Oral 

fluid

99.3 99.8 Yes

Whole 

blood*

99.6 100 Yes

Plasma 99.6 99.9 No

Reveal 

G-3 Rapid 

HIV-1 

Antibody 

Test

MedMira, Inc.

www.medmira.com

Serum 99.8 99.1 No

Plasma 99.8 98.6 No

Uni-Gold 

Recombigen 

HIV

Trinity Biotech

www.unigoldhiv.com

Whole 

blood*

100 99.7 Yes

Plasma/

serum 100 99.8 No

OraQuick 

In-Home HIV 

Test

Orasure Technologies, 

Inc., www.orasure.com

oral fluid 99.3 99.8 Yes

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

*e.g., fingerstick

Adapted from FDA-Approved Rapid HIV Antibody Screening Tests. February 4, 2008

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Settings where rapid tests are valuable: Rapid testing is particularly 

valuable in areas of high prevalence where clinic return rates are low (e.g., 

STI clinics, emergency departments, nonmedical venues) or when an HIV 

diagnosis will influence immediate management decisions (e.g., postexposure 

prophylaxis, unknown HIV status in a pregnant woman presenting for 

labor and delivery). Rapid testing also has proven especially valuable in 

economically disadvantaged countries where HIV seroprevalence is high; 

laboratory resources are limited; and patient travel to and from clinic may be 

inconvenient, difficult, or too expensive.

Counseling remains the same: Some have expressed concern that rapid HIV 

testing may not offer patients sufficient time to digest counseling information 

and to decide whether they truly desire to know their HIV status. The 

principal components of HIV counseling remain the same for rapid testing 

as for traditional screening programs. Regardless of how HIV testing is 

performed, patients must be informed of the nature of the test and the risks 

and benefits of knowing their HIV status. They should consent voluntarily to the 

testing procedures, be informed that they can refuse testing, and have their 

confidentiality strictly preserved. Finally, they should be told that refusal of 

testing will not lead to denial of usual clinical services.

Does knowledge of HIV status change behavior? The literature in this area is 

difficult to synthesize, largely because of evolving counseling practices, varying 

lengths of follow-up, and few randomized trials with well-defined endpoints. 

A large study conducted in Kenya, Tanzania, and Trinidad randomly assigned 

individuals and couples to either voluntary HIV counseling and testing or basic 

health information (Lancet 2000;356:103). This trial found that counseling 

and testing resulted in a significant decline in unprotected intercourse with 

nonprimary partners by both male and female study participants. Newly 

identified HIV infected participants were more likely than HIV-uninfected 

participants to reduce episodes of unprotected intercourse. Among couples, 

unprotected intercourse was reduced more in those in which one or both 

members were diagnosed with HIV than in couples in which both members 

were HIV uninfected.

An ongoing randomized trial, Project Accept (HPTN 043), is evaluating whether 

community mobilization and mobile HIV testing reduce HIV incidence in South 

Africa, Tanzania, Thailand, and Zimbabwe. Studies have demonstrated the 

potential of HIV testing in couples with mutual disclosure of results. Among 963 

HIV serodiscordant couples from Zambia, condom use increased from <3% 

to >80% after joint voluntary counseling and testing (AIDS 2003;17:733). 

Counseling and testing for couples should be a top HIV prevention priority, 

because it facilitates mutual disclosure of HIV serostatus between partners in 

the presence of a trained counselor.

Behavioral Interventions

Knowledge alone does not motivate change: Several well-designed 

randomized controlled trials have been conducted to assess the efficacy of 

various behavioral intervention strategies. Most of the studies conclude that 

such interventions result in decreased sexual risk taking (primarily unprotected 

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sex); some indicate decreased STI and HIV incidence. In contrast to didactic 

education sessions, behavioral interventions focus on recognizing risk and 

formulating effective risk reduction strategies. However, knowledge alone does 

not motivate change. To translate this concept into an issue many of us have 

experienced, consider the issue of weight reduction and diet modification. 

Despite widespread knowledge about the adverse health effects of eating 

fatty foods, adhering to a diet is notoriously difficult. Similarly, knowledge 

about STIs and HIV is not enough to implement change in sexual behavior, 

which involves changes in behavior for two people.

Brief counseling sessions may be effective: The 20-minute Project RESPECT 

counseling sessions may be most applicable to busy practitioners interested 

in conducting effective behavioral counseling (JAMA 1998; 280:1161). This 

study demonstrated that individual brief counseling, involving two sessions of 

20 minutes each, was as effective in reducing STI incidence as four enhanced 

60-minute sessions. Both intervention arms—the two 20-minute and four 

60-minute counseling sessions—were superior to a didactic message.

The first of the two brief 20-minute sessions focused on recognizing HIV 

risk and barriers to risk reduction. After working with the client to agree 

on an achievable risk reduction plan, the counselors concluded the sessions 

by identifying a small risk reduction step that could be achieved before 

the second session. At the second session, counselors reviewed progress and 

barriers in achieving the behavioral goal and helped clients develop a longterm risk reduction plan.

Although the four 60-minute enhanced sessions also included recognizing 

risk and formulating risk reduction plans, more energy was focused on 

key theoretical behavioral elements, such as self-efficacy, attitudes, and 

social norms underlying risk behavior. The fact that the two brief 20-minute 

counseling sessions demonstrated efficacy equivalent to four 60-minute 

sessions is encouraging for healthcare providers who would like to integrate 

effective HIV counseling into busy clinical settings. Busy clinicians who cannot 

afford to offer even two 20-minute counseling sessions should determine 

whether referrals may be made to community-based organizations or to case 

managers who can provide brief client-centered counseling.

Use of Condoms

Effective for prevention: The National Institutes of Health (NIH) reviewed 

the scientific evidence and concluded that consistent use of latex condoms 

reduces a woman’s risk of HIV by at least 85% (www.niaid.nih.gov/about/

organization/dmid/documents/condomreport.pdf). Polyurethane condoms 

are thought to be as effective as latex condoms for preventing HIV. Natural 

skin condoms, however, are not effective in preventing transmission of HIV. 

Transmission of HIV that occurs with use of latex male condoms is likely due 

to technical failures or improper usage rather than to manufacturing defects. 

Studies reporting higher breakage rates tended to include populations from 

underdeveloped areas or those who participated in anal intercourse. Given the 

higher condom slippage and breakage rate with anal sex, use of water-based 

lubricants in conjunction with latex condoms is recommended for anal sex.

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More control with female condoms: The female condom, made of 

polyurethane or nitrile, has been available for use in the United States since 

1993; this device offers women more control over its use than does the male 

condom. The female condom is a sheath, closed at one end, with flexible rings 

at both ends. The FC2 device (shown in Figures 3-1 and 3-2) is inserted into 

the vagina by compressing the closed-end ring and pushing against the cervix; 

the outer ring covers the labia.

Results from a viral penetration study indicated that the physical-barrier 

properties of the FC2 Female Condom should provide adequate protection 

against viral particles (FDA Summary of Safety and Effectiveness Data. 2008; 

available at http://www.accessdata.fda.gov/cdrh_docs/pdf8/P080002b.

pdf. Accessed 9/25/2012). New female condom prototypes have been 

developed; the development process included substantial evaluation of 

women’s preferences and acceptability. The new devices are designed to 

address user complaints about the noise, appearance, and lubricant of the 

initial commercially available female condoms. When counseled about condom 

use, women should be advised to avoid simultaneous use of a female and 

a male condom, because doing so could increase the risk of slippage or 

breakage. Counseling messages about correct storage and use of condoms are 

important as well (see Table 3-5).

Figure 3-1

FC2 Female Condom

Source: © The Female Health Company. Chicago, 

IL. Reprinted with permission.

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Figure 3-2

FC2 Female Condom Insertion and Positioning

Step 1 

Inner ring is squeezed 

for insertion.

Step 2 

Sheath is inserted, 

similarly to a tampon.

Step 3 

Inner ring is pushed 

up as far as it can 

go with index finger, 

behind the pubic bone 

and over the cervix.

Step 4 

Female condom 

is in place.

Source: © The Female Health Company. Chicago, IL. Adapted with permission.

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Table 3-5

Proper Storage, Use, and Lubricants for Condoms

Condom Storage • Store in cool, dry place, such as a bedroom drawer.

• Avoid excessive humidity (e.g., don’t store in 

a bathroom).

• Avoid excessive heat (e.g., don’t carry in wallet in 

trouser pocket).

• Avoid exposure to direct sunlight.

Proper Use Lubricant • Use appropriate water-based lubricant that 

does not contain nonoxynol-9.

• Avoid use of compounds that contain mineral oil, such 

as petroleum jelly, cooking oils, shortening, or lotions, 

because they can weaken latex.

Male 

Condom • Use at onset of male arousal, before penetration.

• Hold tip of condom to create air-free 

reservoir for semen.

• Make sure that condom is unrolled to extend 

completely to the penis base, leaving the reservoir.

• Use enough lubrication to prevent excessive friction 

that might lead to breakage.

• Hold condom at base during withdrawal to 

prevent slippage.

Female 

Condom • Inner ring must be placed completely onto 

cervix, or condom may twist.

• Additional lubrication may be needed to prevent 

condom from twisting.

• Care must be taken not to insert the penis between 

condom and vaginal wall.

• The outer ring may need to be held in place to keep 

condom from slipping into vagina or anus.

• Use of male and female condoms together is not 

recommended due to higher failure rate.

• During anal intercourse, it may be advisable to 

remove inner ring to reduce likelihood of rectal 

bleeding.

Condom acceptability: Factors that influence condom use are complex and 

often differ between men and women. Surveys have shown that both men and 

women are influenced by perceived social norms and attitudes about condom 

use and by the recognition that condoms may prevent HIV and STIs. Ability 

to obtain condoms without excessive cost or embarrassment, ease of use, and 

preservation of pleasurable sexual sensation are clearly concerns for both men 

and women.

Acceptability of the male condom for both men and women is increased by 

normal appearance and feel, lack of odor, lack of slippage, the presence of 

a reservoir tip, and spermicidal lubrication. A man may be more likely to use 

the male condom if he feels that a woman may perceive him as being more 

sensitive and caring if he uses one. Conversely, women have complained that 

the interruption of foreplay has a negative effect on acceptability of both 

male and female condoms.

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Both men and women have complained about the aesthetic appearance of the 

external ring of the female condom and the noise it creates during intercourse. 

Interestingly, in several surveys more women have said that they would be 

likely to use the female condom again than have said they liked using it, 

suggesting that women may be willing to sacrifice comfort and pleasure during 

sex for protection against HIV, STIs, and pregnancy. Many women have also 

expressed a strong preference for a female-controlled device to prevent STIs, 

even though the female condom cannot be used secretly.

Considerations for women who have sex with women: Discussion of 

recommended protective sexual practices should not be limited exclusively 

to heterosexual women. Sexual transmission of HIV between women has 

been described (Clin Infect Dis 2003; 36:e40). The use of barriers, such as 

cellophane or latex dental dams, should be recommended for oral–genital 

contact, particularly in HIV-discordant relationships. Sexual activity should be 

avoided during menstruation or when there are symptoms of genital tract 

infection. The sharing of sex toys contaminated with blood was implicated in at 

least one case of female-to-female sexual transmission of HIV.

Risk Reduction for Injection Drug Users

Drug abuse treatment is effective HIV prevention: Substance abuse treatment 

often removes HIV risk that accompanies sharing of contaminated syringes 

while reducing sexual transmission risks. For people who cannot or will not stop 

injecting drugs, provision of single-use sterile needles and syringes is a highly 

effective HIV prevention strategy. Syringes that have been cleaned with bleach 

or other disinfectants likely reduce HIV risk, but not nearly as well as sterile 

equipment. Other important strategies for reducing HIV risk in injection drug 

users include preventing initiation of drug injection, providing HIV prevention 

programs to drug users (including on the streets and in jails and prisons), and 

making risk reduction counseling and HIV testing available to drug users and 

their sex partners.

Male Circumcision

Benefits for men: In three landmark clinical trials, adult male circumcision was 

conclusively demonstrated to reduce men’s susceptibility to HIV (PLoS Med

2005; 2:e298; Lancet 2007; 369:657; Lancet 2007; 369:643). Conducted 

in Kenya, South Africa, and Uganda, the studies together randomly assigned 

>11,000 uncircumcised HIV seronegative men to immediate versus delayed 

circumcision, then followed participants for HIV seroconversion for up to 2 

years. Each study found a statistically clear 50%–60% reduction in HIV risk 

among men who were circumcised. In addition, the studies found direct benefits 

for the female partners of circumcised men in reduced rates of STIs, including 

genital ulcer disease, vaginitis, and HPV.

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Adverse events associated with the circumcision procedure were rare. Sex 

should be deferred until complete healing of the glans is observed, because 

early resumption of sexual activity could increase risk of HIV acquisition if 

exposure occurs. Another significant finding is that concurrent research found 

no increase in risk-taking behaviors among men who underwent circumcision, 

suggesting that participants did not compensate for a perceived reduction in 

HIV risk by relaxing condom use and other behavioral prevention strategies.

More than 20 years of epidemiologic evidence, including more than a dozen 

prospective cohort studies, preceded the trial results. These epidemiologic 

studies generally compared HIV rates in men who were circumcised as infants 

or children with those who remained uncircumcised. Infant circumcision is 

technically easier than adult male circumcision and carries a lower risk of 

complications. Many countries are including infant circumcision promotion in their 

national rollout programs as part of an effort to decrease HIV transmission 

into the future. Biologic plausibility supports the association between a lack 

of circumcision and HIV risk—the foreskin contains large numbers of HIV 

target cells poorly protected by thin keratinized epithelium, and micro- and 

macroulceration of the foreskin may provide a portal of HIV entry.

Indirect benefits for women: Mathematical modeling studies suggest that 

widespread male circumcision will translate indirectly into substantial 

reductions in HIV among women in areas where male circumcision is 

uncommon. Acceptability surveys have found that a majority of women (69% 

across studies) favor circumcision of their male partners, and anecdotal 

reports suggest that women’s positive opinions about circumcision have 

enhanced male uptake in areas in which rollout of the procedure has begun. 

In the United States, 79% of men are circumcised; prevalence of circumcision 

is lower in men of color.

Studies of circumcised HIV infected men have not shown conclusive evidence 

of protection from HIV transmission for women, and sex during wound healing 

after circumcision may increase the risk of a transmission from a man to his 

female partner. Nonetheless, circumcision substantially reduces HIV acquisition 

among men, thereby potentially decreasing the likelihood that a woman will 

encounter an HIV infected male partner. To the extent that this is true, make 

circumcision could translate into reduced risk for women, but it does not lead to 

a direct reduction in male-to-female HIV transmission. Finally, remember that 

circumcision is only partially protective against HIV for men; behavioral change, 

and particularly consistent condom use, should be emphasized for circumcised 

men to further reduce HIV risk for themselves and their partners.

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What Has Not Worked in HIV Prevention

Nonspecific Vaginal Microbicides

Disappointing trial results: The concept of a topical microbicide—a vaginal or 

rectal gel, foam, or ring containing an active agent that protects against HIV 

infection—has been a topic of considerable interest. Microbicides hold great 

appeal because they can be female controlled, may be used without male 

partner knowledge, and would be active directly at the site of HIV exposure. 

To date, clinical trials have been completed for microbicide products that 

are designed to interfere with HIV through nonspecific mechanisms, such as 

by acting as a surfactant and disrupting the viral structure. Unfortunately, no 

product has shown encouraging protective results despite demonstrated high 

antiviral activity in laboratory studies and good safety profiles in early clinical 

studies (Table 3-6). Current attention in the microbicide field is being directed 

to ARV-containing products, which have the potential to target the virus 

specifically (discussed below). An important challenge in conducting microbicide 

research has been achieving high adherence to daily or coitally dependent 

products; future studies will explore novel ways to promote and accurately 

measure adherence. Community engagement has been particularly central to 

efforts to develop vaginal microbicides against HIV.

ARV-based microbicides: In July 2010, encouraging results from the first ARVbased topical microbicide, 1% tenofovir gel, were reported from the CAPRISA 

004 trial (Science 2010; 329:1168). The risk of HIV acquisition was reduced 

by 39% among women randomized to use 1% tenofovir gel twice within 24 

hours of having sex compared with women who used a placebo gel. Notably, 

there was higher efficacy among women who reported >80% adherence in 

use of the gel. In addition, a significant reduction in incidence of herpes simplex 

virus type 2 (HSV-2), the etiologic agent of genital herpes, occurred among 

women who used the tenofovir gel. The CAPRISA 004 results have invigorated 

the microbicide field, and multiple ARV-based compounds and delivery systems 

(e.g., vaginal rings) are in clinical development and undergoing evaluation. 

Disappointingly, in the VOICE study, a multi-country, multi-arm Phase IIb study 

of vaginal and oral PrEP in women at high risk of acquiring HIV, 1% TDF gel 

used daily was no better than placebo at reducing HIV transmission. (see 

Table 3-9).

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Table 3-6

Completed Clinical Trials of Nonspecific Vaginal Microbicides

Product Sponsor; 

Trial Location(s)

Outcome

Nonoxynol-9 

sponge

University of 

Washington; Kenya

Trend for increased risk of HIV acquisition 

among women randomized to nonoxynol-9 

compared with placebo (RR 1.7)

Nonoxynol-9 

film

FHI; Cameroon No effect on HIV acquisition

Nonoxynol-9 

gel

UNAIDS; Benin, 

Côte d’Ivoire, South 

Africa, Thailand

Increased HIV incidence among 

nonoxynol-9 users compared with placebo 

users (HR 1.5); greater among women who 

used the product more than the mean of 

3.5 times per day

Savvy (1% 

C31G) gel

FHI; Ghana, 

Nigeria

Two Phase III trials discontinued 

prematurely for futility because of lower 

than anticipated HIV incidence in the trial 

population. No evidence for protection 

against HIV or for harm

Carraguard gel Population Council;

South Africa

No statistically significant reduction in HIV 

incidence among women randomized to 

active product vs. placebo

Cellulose 

sulfate gel

CONRAD; Benin, 

India, Uganda, 

South Africa

FHI; Nigeria

Two Phase III trials stopped when 

independent data and safety monitoring 

board of one study detected a trend 

toward increased HIV risk among women 

randomized to cellulose sulfate compared 

with placebo; no increased risk was 

observed at the time in the other study

PRO 2000 gel NIH; Malawi, South 

Africa, United 

States, Zambia, 

Zimbabwe

MDP; South Africa, 

Tanzania, Uganda, 

Zambia

Smaller Phase IIb study (NIH) suggested 

potentially 30% reduced HIV risk as a 

result of 1% PRO 2000 gel, but larger 

Phase III trial (MDP) subsequently found no 

reduction in risk

Buffergel NIH; Malawi, South 

Africa, United 

States, Zambia, 

Zimbabwe

No statistically significant reduction in HIV 

incidence among women randomized to 

active product vs. placebo

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

HIV Vaccines

No efficacy yet: The search for a vaccine that protects against HIV acquisition 

has been challenging and has yielded surprising and sometimes perplexing 

results. Initial strategies focused on candidate vaccines that would elicit 

neutralizing antibodies, such as recombinant gp120, to envelope glycoproteins, 

a strategy that was tested through two parallel trials for subtype B and E 

infections in North America and Thailand, respectively (Table 3-7). No efficacy 

in reducing HIV acquisition was seen in either trial.

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Table 3-7

Completed Efficacy Trials of Candidate HIV Vaccines (Through 2009)

Trial Candidate 

Vaccine

Population Outcome Comments

AIDSVAX 

003 and 

004

Recombinant 

gp120 

(subtypes B 

and E)

MSM in North 

America and 

IDUs in Thailand

No reduction 

in HIV-1 

acquisition

STEP Adenovirus 

serotype 5 

vector with 

HIV-1 gag/pol/

nef inserts

3,000 highrisk MSM and 

women in North 

and South 

America and 

Caribbean

1.2-fold 

increased 

risk of HIV 

acquisition 

in vaccine 

recipients

Trial stopped 

at first interim 

analysis

Increased 

risk of HIV 

associated 

with lack of 

circumcision; 

no significant 

association 

with adeno-5 

seropositivity 

among MSM

75% of vaccine 

recipients 

developed a 

CTL response, 

as determined 

on the basis 

of gamma 

interferon 

response by 

ELISpot.

Ongoing 

studies to assess 

mucosal immune 

response in 

uncircumcised 

men

RV144 Canarypox vector 

(vCP1251) with 

recombinant 

AIDSVAX 

subtype B/E 

gp120 boost

Low-risk 

population 

in southern 

Thailand

Vaccine efficacy 

31% (95% CI 

1–51%) in 

modified intentto-treat analysis 

(nonsignificant 

trend of 26% 

efficacy in 

per protocol 

analyses)

First potential 

efficacy 

“signal” in HIV 

vaccine trial, 

although low 

efficacy

No difference 

in viral set-point 

in breakthrough 

infections

No humoral 

or cellular 

correlate in 

initial immune 

correlate 

assays; 

additional 

studies 

underway

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

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The vaccine field moved to candidate immunogens that would stimulate a 

cellular and humoral immune response, including an HIV-specific CD8 T-cell 

response that might lower viral load in early HIV infection and thus reduce HIV 

infectiousness and disease progression in people who became infected in spite 

of the vaccine. Merck developed a trivalent HIV candidate vaccine by inserting 

three HIV gene constructs (gag/pol/nef) from subtype B into an adenoviral 

serotype 5 vector (MRK Ad5). The vaccine was tested through the NIH’s HIV 

Vaccine Trial Network (HVTN), in the STEP trial. The STEP trial was stopped 

after the first interim analysis, when a modest increased risk of HIV acquisition 

was observed in the vaccine arm in modified intent-to-treat analyses. This 

result was surprising and disappointing, given promising nonhuman primate 

studies and high immunogenicity in the human trials, in which 75% of 

vaccine recipients had a cytotoxic T-cell response to HIV immunogens (Lancet

2008;372:1881&1894). Among MSM vaccine recipients, uncircumcised men 

had a 2.5-fold increased risk, but this risk was not seen in placebo recipients.

Another study, called Phambili, of the trivalent MRK Ad5 vaccine in a 

heterosexual population in South Africa was stopped soon after the surprising 

STEP results. A study of the MRK Ad5 vaccine (HVTN 505) is being conducted 

among circumcised, Ad5 seronegative MSM to determine whether the MRK 

Ad5 vaccine is safe and immunogenic and reduces viral set point in patients 

with breakthrough HIV infections.

Some renewed optimism: The most recently completed HIV vaccine efficacy 

trial, RV144, was conducted in a low-HIV-prevalence setting in Thailand and 

utilized a prime-boost approach, with a viral vector (canarypox) to stimulate 

a T-cell response, followed by antibody boosting with recombinant gp-120. 

This is the first HIV-1 vaccine study to demonstrate efficacy, albeit modest, with 

just a 31% reduction in HIV-1 acquisition risk in the primary modified intent-totreat analysis (p = .04) and 26% reduction in the per-protocol analysis (N Engl 

J Med 2009;361:2209). A surprising finding was the suggestion of increased 

efficacy among lower risk participants, although subgroup findings should 

be interpreted with caution given the relatively modest number of endpoints 

(51 and 74 endpoints in the vaccine and placebo arms, respectively), which 

limits the ability to evaluate the heterogeneity of vaccine protection. Initial 

analyses of potential immunologic correlates of protection have not identified 

a correlate.

The Thai RV144 trial has stimulated renewed optimism in the HIV vaccine field 

and identified multiple questions for research, including additional analyses 

of other potential immune correlates. Future priorities for the HIV vaccine 

field include evaluation of new HIV vaccine constructs, such as DNA, modified 

vaccinia vectors, and adenoviral mosaic vectors (e.g., Ad 25/35). Online 

updated lists of trials of HIV vaccines are maintained by the International AIDS 

Vaccine Initiative (www.iavi.org) and the HVTN (www.hvtn.org).

Treatment of Sexually Transmitted Infections

Increased susceptibility to HIV: STIs and other genital tract infections increase 

susceptibility to HIV. That STIs are important cofactors for HIV acquisition 

has been established by prospective studies from a variety of populations 

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examining risk factors for seroconversion. In such studies, women with genital 

ulcer disease, gonococcal or chlamydial cervicitis, or trichomoniasis were 

at twofold to fourfold increased risk for HIV infection. Several studies have 

demonstrated that disturbances in the normal microbial flora of the vagina—

including bacterial vaginosis and vaginal candidiasis—may increase HIV risk, 

but randomized trials of vaginal infection treatment with an HIV endpoint have 

not been attempted to date. Even the best designed prospective studies have 

not been able to distinguish among STIs acquired at the same time as HIV 

infection and those already present that could have increased susceptibility.

STI interventions important to reduce risk, but treatment trials disappointing:

Community trials of STI treatment have not found clear HIV reductions. Because 

of obvious ethical limitations, randomized trials that deny participants STI 

treatment cannot be conducted. As a result, community intervention trials of 

improved STI services or mass STI treatment have been conducted to determine 

the impact of STIs on population wide HIV transmission. Unfortunately, only one 

of six trials implementing STI treatment has shown a reduction in community HIV 

incidence. One principal reason is likely related to the stage of the epidemic: 

STIs play the greatest role in promoting HIV on a community level in early 

stages of an epidemic, when a core group of highest risk individuals, who are 

most likely to have concurrent STIs, contributes most to community HIV spread. 

Nevertheless, STIs clearly increase individual-level risk of HIV acquisition, and 

STI interventions should remain an important part of reducing HIV risk for 

individuals and populations, even where HIV is already well established.

Measures to reduce STIs:

• Encourage male and female condom use.

• Encourage early medical care for diagnosis and treatment 

of genital tract symptoms.

• Provide routine screening for genital tract infections among 

sexually active women.

• Discourage douching, which increases risk of bacterial 

vaginosis (BV) and pelvic inflammatory disease PID.

• Teach patients how to recognize genital herpes recurrences 

and prodromes; offer treatment to shorten/suppress 

recurrences.

For HIV infected persons, STI screening and treatment may reduce HIV 

infectiousness among those who are not taking ART and among those who are 

on therapy, because those infections may stimulate genital viral replication 

even in the context of good systemic HIV suppression.

Does suppression of HSV-2 reduce HIV transmission? Genital herpes may 

contribute substantially to HIV spread, but interventions to interrupt an effect 

of herpes on HIV risk have proved elusive. HSV-2 is common worldwide: 

Prevalence is approximately 20% among U.S. women and 50% or higher 

among populations in sub-Saharan Africa. A meta-analysis concluded that 

HSV-2 infection increased women’s risk for HIV three-fold (AIDS 2006;20:73). 

Among HIV infected persons, symptomatic and asymptomatic HSV-2 

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reactivation increases HIV concentrations in the blood and genital tract, 

suggesting that HSV-2 activity enhances HIV infectiousness. Strong biologic 

plausibility exists for HSV-2 to enhance HIV susceptibility and infectiousness: 

HSV-2 causes genital ulcers that may serve as a portal for HIV entry or exit, 

and asymptomatic HSV-2 reactivation (occurring on average on 20% of days, 

without genital ulcers) may draw HIV target cells to the genital tract.

Acyclovir and the related compounds valacyclovir and famciclovir are routinely 

used as episodic treatment for symptomatic genital ulcer disease due to HSV-2 

and as daily suppressive therapy to decrease the frequency of symptomatic 

HSV-2 reactivation and asymptomatic genital HSV-2 shedding. Unfortunately, 

two randomized trials of daily acyclovir HSV-2 suppressive therapy to 

reduce HIV acquisition and one trial of suppressive therapy to decrease 

HIV transmission from HIV infected persons to their sexual partners failed to 

demonstrate a protective effect of HSV-2 treatment. The results of these trials 

suggest that more potent and long-lasting HSV-2 suppressive therapies or, 

ultimately, a prophylactic HSV-2 vaccine might be needed to intervene in the 

relationship between HSV-2 and HIV.

While awaiting new HSV-2 prevention modalities, women with a history of 

genital herpes or with serologic evidence of HSV-2 infection should be taught 

how to recognize prodromes and recurrences. Suppressive herpes antiviral 

therapy should be considered in women with frequent recurrences, including 

those who report high-risk sexual behavior.

Antiretroviral-Based HIV Prevention Strategies

The role of ART in HIV prevention is a topic of significant public health interest. 

ART for HIV prevention comprises both treatment of HIV infected persons to 

decrease their infectiousness and post- or pre-exposure prophylaxis (PEP and 

PrEP, respectively) by HIV uninfected persons to prevent acquisition. Studies 

have now established potential efficacy for each of these approaches, 

although there is debate about how to implement preventive ART if it is proven 

to reduce HIV risk. Nonetheless, scientists and public health officials worldwide 

anticipate that ART-based prevention strategies may prove to be successful 

new ways to prevent HIV spread.

ART for Prevention

ART reduces HIV transmission risk: The amount of HIV in plasma is a primary 

determinant of the risk of sexual HIV transmission. In most people, ART reduces 

HIV plasma concentrations to undetectable levels within 6 months of initiation, 

and seminal and cervicovaginal HIV concentrations are also reduced to 

undetectable levels in most people as well. Use of ART during pregnancy, 

labor, and for the newborn has been responsible for the remarkable success in 

virtually eliminating mother-to-child HIV transmission in the United States.

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Substantial reduction in the quantity of plasma and genital HIV in persons 

initiating ART translates into markedly reduced risk of HIV transmission to 

sexual partners. A meta-analysis of data from five prospective observational 

studies of HIV serodiscordant couples, some unpublished, found only five cases 

of HIV transmission to sexual partners in 1,098 person-years from HIV infected 

persons receiving ART; this finding is consistent with an infection rate of <1% 

per year (AIDS 2009:23:1397). Community-level data from Vancouver, British 

Columbia, has shown a significant decline in new HIV cases coincident with 

increased ART use (Lancet 2010;376:532).

Data from HPTN 052, a randomized clinical trial designed to evaluate 

ART for prevention of sexual transmission among serodiscordant couples, 

found that earlier initiation of ART (at CD4+ counts 350–550 cells/mm3) 

reduced HIV transmission to the uninfected partner by 96%. (N Engl J 

Med 2011;365(6):493–505). This study has major implications for the use 

of ART for prevention among serodiscordant couples, particularly those 

wishing to conceive or unable/unwilling to use safer sexual practices. The 

U.S. Department of Health and Human Services guidelines now recommend 

ART for all HIV-infected individuals for the prevention of transmission of HIV 

(both for heterosexual transmission and for other transmission risks). (Panel on 

Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 

antiretroviral agents in HIV-1-infected adults and adolescents. Department of 

Health and Human Services. Available at http://aidsinfo.nih.gov/ContentFiles/

AdultandAdolescentGL.pdf. Section accessed 5/16/13) 

In the observational studies that have been reported to date, the follow-up 

time on ART was short relative to the lifetime duration of treatment that will 

be required of persons who start ART. Most patients who initiated ART did so 

at CD4+ counts <200 cells/mm3, when clinical symptoms may have provided 

a greater impetus for adherence. It is essential to obtain reliable information 

about the comparative long-term transmission benefits and behavioral risks 

associated with ART, particularly when it is initiated at higher CD4+ cell levels. 

ART does not eliminate transmission risk: An important research finding 

is that genital HIV shedding may not be fully suppressed among people 

receiving ART, even those with undetectable plasma viral loads, suggesting 

that ART may not completely eliminate transmission risk. In addition, the 

phenomenon of nonadherence means that not everyone prescribed ART will 

achieve reduced infectiousness. Healthcare providers should counsel patients 

on ART that the risk of transmission is not zero and that patients on ART have 

transmitted HIV to a partner, even when the patients had undetectable plasma 

HIV levels. Recommendations to women with HIV should stress the importance 

of consistent condom use to decrease HIV transmission risk.

Pre-exposure prophylaxis (PrEP) (see Table 3-9): The rationale for PrEP grows 

out of successful HIV prevention with use of ART prophylaxis for infants born 

to HIV-1–infected women and from nonhuman primate studies demonstrating 

that ARVs given prior to high-dose mucosal simian HIV challenge can provide 

partial or even full protection against infection (PLoS Med 2008:5:e28). PrEP 

offers advantages over post-exposure prophylaxis (PEP) for sexual and IDU 

exposures, because the efficacy of PEP declines rapidly if not initiated within 

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1 to 2 days after an exposure, and PEP is likely impractical for highest risk 

individuals (e.g., sex workers, members of HIV serodiscordant couples), who 

may have repeated exposures. 

Providing ARVs orally to an uninfected female partner may offer some 

additional protection against HIV transmission from an infected male partner 

during attempts to conceive, but study results to date have been mixed.

A Phase III study of daily oral TDF/FTC in uninfected MSM (iPrEX) reported a 

44% overall reduction in HIV acquisition compared with placebo; effectiveness 

was significantly affected by adherence (N Engl J Med 2010;363(27):2587; 

N Engl J Med 2010;363(27):2663). In the Partners PrEP study, conducted 

in Kenya and Uganda among more than 1400 HIV-serodiscordant couples, 

the use of daily TDF or daily TDF/FTC by the uninfected partner was found 

to have efficacy of 67% and 75%, respectively, compared with placebo 

in reducing HIV transmission (with reported 97% adherence by returned 

pill count, but only 81% of those assigned to the active-treatment arm had 

detectable blood levels of the study drug) (N Engl J Med 2012;367(5):399). 

Within a subgroup of those who received TDF/FTC and whose plasma drug 

levels were tested, measurable concentrations of TDF were associated with 

a 90% reduction in risk compared with placebo. In the TDF2 trial, conducted 

in Botswana, TDF/FTC given to 1200 HIV uninfected heterosexual men and 

women reduced transmission by 62% compared with placebo, with 84% 

adherence by returned pill count (N Engl J Med 2012;367(5):423). 

However, the FEM-PrEP clinical trial conducted in high-risk uninfected 

African women, found no efficacy with daily oral TDF/FTC (N Engl J Med

2012;367(5):411; Microbicide Trials Network; 2011. Available at http://www.

mtnstopshiv.org/node/3619. Accessed 9/3/2012). Medication adherence 

was very low in the FEM-PrEP trial; the study drug was detected in the blood 

of <27% of women who acquired HIV and in <38% of matched uninfected 

controls. 

The VOICE (Vaginal and Oral Interventions to Control the Epidemic) Study was 

designed as a five-arm, double-blinded study in which heterosexually-active 

women were first randomized to receive either gel or oral PrEP, and then within 

each group, randomly assigned to either tenofovir 1% topical gel or placebo 

gel; or to oral TDF, oral TDF/FTC or oral placebo. Unfortunately, no study drug 

significantly reduced the risk of HIV acquisition and again adherence was low; 

detectable drug levels were found in less than one-third of those tested and 

randomized to active drug. (20th Conference on Retroviruses and opportunistic 

Infections, Atlanta, GA,Abstract 26LB, 2013; Microbicide Trials Network; 2011. 

Available at http://www.mtnstopshiv.org/node/3619. Accessed 9/3/2012). 

Therefore, it is likely that adherence is a key factor in the discrepant results of 

these studies (AIDS 2012;26(7):F13).

In studies of PrEP to date, safety and tolerability were excellent (although 

nausea and vomiting were more common in the first 1–2 months among 

those taking TDF/FTC) and limited resistance was observed in seroconverters. 

Twice-weekly and coital dosing of TDF/FTC, as well as longer-acting 

formulations, intravaginal rings, and new candidate ARVs, are currently being 

evaluated for PrEP.

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In July 2012 the FDA approved a label indication for TDF/FTC for reduction of 

risk for sexual acquisition of HIV infection among adults, including heterosexual 

women. In August 2012 the CDC issued the following interim guidance for 

clinicians considering the use of PrEP for HIV prevention in heterosexually 

active adults, particularly those with known HIV-infected partners (MMWR

2012; 61(31):586): 1) TDF/FTC is contraindicated for PrEP in persons with 

unknown or positive HIV status; 2) in women and men at very high risk for 

acquiring HIV from penile-vaginal sex, daily doses of TDF/FTC can be safe 

and effective in reducing the risk of HIV infection; 3) PrEP use may be one 

of several options to help protect the HIV-negative partner in serodiscordant 

couples during attempts to conceive (Am J Obstet Gynecol 2011;204:488); 

and 4) women of reproductive age should have a documented pregnancy test 

before beginning PrEP and at regular intervals while being prescribed PrEP. If 

women become pregnant while being prescribed PrEP, providers should discuss 

currently available information regarding the potential risks and benefits of 

continuing PrEP to enable informed decision making. If a woman takes PrEP 

while pregnant, providers are encouraged to prospectively and anonymously 

submit information about the pregnancy to the Antiretroviral Use in Pregnancy 

Registry (http://www.apregistry.com/who.htm; accessed 9/4/2012). In 

addition, providers should counsel patients that the efficacy of PrEP is highly 

dependent on adherence and that its long-term safety in HIV-uninfected adults 

or following fetal exposure has not yet been determined.

PrEP should be delivered as part of a comprehensive set of prevention 

services, including risk-reduction and ready access to condoms. Table 3-10 

summarizes current CDC guidance to health care providers providing PrEP for 

heterosexually active adults. 

Nonoccupational Postexposure Prophylaxis

PEP may reduce likelihood of HIV infection after a high-risk exposure.

Theoretically, PEP can prevent HIV transmission either by blocking initial viral 

infection of cells or by inhibiting viral dissemination, thereby allowing for 

immune clearance of a small number of already-infected cells. The data for 

efficacy of ARVs as PEP come primarily from a single case-control study of 

healthcare workers who experienced occupational HIV exposures, mostly 

through needlestick injuries. Those who received zidovudine had an 80% 

lower likelihood of becoming infected; this study, however, was limited by a 

small sample size, retrospective design, and other potential sources of bias. 

The rationale for PEP after sexual exposure is largely that the probability 

of infection after a single unprotected sexual exposure is similar to that 

after a needlestick exposure (i.e., ~0.1%; slightly higher for receptive anal 

intercourse). Animal models suggest that PEP may be effective for mucosal 

and needle exposures, particularly when used within 24–48 hours. Ethical 

and pragmatic considerations make it unlikely that a randomized trial of PEP 

will be conducted. The effectiveness of PEP is likely to be influenced by time 

to initiation of treatment, duration of treatment, size of inoculum, and drug 

resistance profile of the virus in the source individual. Although the risks and 

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benefits of PEP for sexual exposure remain to be fully defined, studies suggest 

that provision of PEP for nonoccupational exposures is feasible (J Infect Dis

2001;183:707).

Considerations: If approached by anxious patients who have recently had a 

high-risk sexual exposure, the healthcare provider must weigh the likelihood 

of HIV infection in the contact, ART history if the contact is known to be HIV 

infected, the specific nature and timing of the exposure (initiation of PEP within 

48 hours is important, given findings from animal studies and breakthrough 

infections with later initiation), and the possible risks of drug toxicity or 

side effects. CDC guidelines recommend two or three ARV medications, 

depending on the intensity of the exposure, for 4 weeks for occupational 

and nonoccupational exposures having at least moderate HIV risk (Table 3-8 

and MMWR 2005;54:1). Other considerations should include evaluation and 

consideration of empiric treatment for other STIs, emergency contraception 

when appropriate, and possible indication for hepatitis B vaccination. Informed 

consent is recommended when administering PEP.

Table 3-8

Elements of NonOccupational Postexposure Prophylaxis 

Against HIV Infection

Factors to 

Assess

Considerations Recommendations

Exposure 

risk

Substantial risk for HIV 

exposure, defined as exposure 

of vagina, rectum, eye, mouth, 

nonintact skin, or percutaneous 

contact with blood, semen, 

vaginal secretions, rectal 

secretions, breast milk, or any 

bodily fluid contaminated with 

blood

Negligible risk of HIV exposure 

if exposing fluid is urine, nasal 

secretions, saliva, sweat, or tears

nPEP recommended for 

exposures with substantial risk 

from a known HIV infected 

source

nPEP not recommended for 

exposures with negligible 

risk, regardless of known or 

suspected HIV status of the 

source

Source of 

exposure

HIV infected vs. unknown HIV 

status (unknown HIV status of 

source frequently reported by 

persons seeking nPEP).

nPEP assessment on case-bycase basis for exposures with 

substantial risk from a source of 

unknown HIV status

Timing nPEP efficacy for preventing 

HIV likely declines substantially 

as time since exposure elapses. 

Animal models indicate initiation 

should occur within 48–72 h

nPEP not recommended >72 h 

after exposure occurs

Table 3-8 continues on the next page

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Table 3-8

Elements of NonOccupational Postexposure Prophylaxis 

Against HIV Infection

Factors to 

Assess

Considerations Recommendations

Initiate 

ARV nPEP

No evidence indicates that 

specific ARV agents improve 

efficacy for HIV prevention.

In addition, no evidence 

indicates whether combinations 

of 2 vs 3 medications have 

different efficacy for preventing 

HIV.

Recommended ARV medications 

for nPEP have been chosen 

on the basis of adherence 

and tolerability, subsequent 

to experience with their use 

for treatment of HIV infected 

persons.

Commonly used agents include

• Efavirenz + lamivudine or 

emtricitabine + tenofovir or 

zidovudine

• Atazanavir + lamivudine or 

emtricitabine + tenofovir (with 

ritonavir) or zidovudine

• Lopinavir/ritonavir + 

lamivudine or emtricitabine + 

zidovudine

Testing HIV testing at baseline is 

essential to confirm whether the 

person initiating nPEP is already 

HIV infected; however, nPEP 

should be initiated before results 

of HIV testing are obtained.

HIV testing, including viral load 

and resistance testing of source, 

if available, should be done as 

well.

HIV testing at nPEP initiation and 

4–6 wk, 3 mo, and 6 mo after 

exposure.

Laboratory assessment of 

safety (complete blood count, 

liver enzymes, creatinine, as 

well as pregnancy testing) 

recommended at time of nPEP 

initiation and during nPEP.

Additional testing for hepatitis B 

and C infection and STIs should 

be done.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Not a substitute for risk reduction: PEP should not be administered for 

exposures with low transmission risk or when care is sought beyond the period 

of 72 hours postexposure. PEP should be considered strongly for persons who 

have been sexually assaulted or when a condom break during sex occurs 

in an HIV serodiscordant couple (especially if the positive partner is not on 

antiretroviral treatment or does not have an undetectable viral load). PEP 

is not a substitute for risk reduction and should not be considered a form of 

primary HIV prevention. Patients presenting for possible PEP should have 

reinforcement of the importance of initiating, resuming, or improving risk 

reduction activities.

continued

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Table 3-9

Efficacy Trials of Oral and Topical Pre-Exposure Prophylaxis

Study 

Population Location Intervention Outcome Comments

CAPRISA 

004

900 sexually 

active women

South 

Africa

1% topical 

TFV gel (dosed 

coitally)

39% 

protection 

with TFV gel

54% 

effectiveness 

with >80% 

gel adherence; 

high 

vaginal TFV 

concentrations 

needed at 

exposure 

(Lancet 2011;

378:279)

TDF2 1219 sexually 

active adults; 

55% male, 

45% female; 

94 % unmarried; 

approximately 

90% age 21–29 

years

Botswana Daily oral 

TDF/FTC

63% 

protection

>30% did 

not complete 

study; cannot 

draw definitive 

conclusions for 

women and 

men separately

Partners 

PrEP

4758 

heterosexual 

serodiscordant 

couples; 38% 

negative-female, 

68% negativemale partner; 

98% married; 

median age 33 

years

Botswana, 

Kenya, 

Rwanda, 

South 

Africa, 

Tanzania, 

Uganda, 

Zambia

Daily oral TDF 

or TDF/FTC

67% 

protection 

with TDF 

alone; 75% 

protection 

with TDF/

FTC

Discordant 

couples may 

be a distinct, 

unique 

population

FEM-PrEP 1951 

heterosexual 

women at high 

risk of infection 

aged 18–35 

years

Kenya, 

South 

Africa, 

Tanzania

Daily oral 

TDF/FTC

Trial 

discontinued 

for futility in 

April, 2011

Adherence 

assessment with 

monthly clinical 

samples to 

measure drug 

concentration is 

pending

VOICE 

(MTN003)

5029 

heterosexual 

women aged 

18–45 years 

in highprevalence 

areas

Uganda, 

South 

Africa, 

Zimbabwe

Daily oral TDF 

or daily oral 

TDF/FTC or 

daily topical 

TFV gel

No study 

drug 

significantly 

reduced the 

risk of HIV 

acquisition: 

HIV 

incidence 

was 5.7 per 

100 person 

years. 

Effectiveness 

was 

–48.8% for 

TDF; –4.2% 

for TDF/

FTC; and 

14.7% for 

TDF gel. 

Adherence to 

study drugs 

was low: TFV 

was detected 

in 30% of the 

oral TDF arm; 

29% in the 

oral TDF/FTC 

arm; and 25% 

in the TDF gel 

arm.

Table 3-9 continues on the next page

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Table 3-9

Efficacy Trials of Oral and Topical Pre-Exposure Prophylaxis

Study 

Population Location Intervention Outcome Comments

HPTN 

052

1763 

heterosexual 

serodiscordant 

couples; 50% 

negative-female, 

50% negativemale partner; 

94% married; 

61% aged 

26–40 years

Botswana, 

Kenya, 

Malawi, 

South 

Africa, 

Zimbabwe, 

Brazil, 

India, 

Thailand

Immediate or 

delayed ART 

in HIV-infected 

partner

96% 

protection

Suppression 

of viraemia 

on therapy 

assured 

by routine 

monitoring

TDF = tenofovir disoproxil fumarate. TFV = tenofovir. TFV-DP = tenofovir diphosphate. FTC 

= emtricitabine. ART = antiretroviral therapy.

Adapted from Panel on Treatment of HIV-Infected Pregnant Women and Prevention 

of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant 

HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV 

Transmission in the United States. (Note: only trials including women were included).

continued

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Table 3-10

Interim guidance for provision of PrEP for the prevention of HIV 

infection in heterosexually active adults who are at ongoing, very 

high risk for sexual acquisition of HIV infection* 

Before initiating PrEP 

Determine eligibility 

• Document negative HIV antibody test immediately before starting PrEP medication. 

• Test for acute HIV infection if patient has symptoms consistent with acute HIV 

infection or reports unprotected sex with an HIV-positive person in the preceding 

month. 

• Determine if women are planning to become pregnant, are currently pregnant, or 

are breastfeeding. 

• Confirm that patient is at ongoing, very high risk for acquiring HIV infection. 

• If any sexual partner is known to be HIV-infected, determine whether receiving 

antiretroviral therapy; assist with linkage to care if not in care or not receiving 

antiretroviral therapy. 

• Confirm that calculated creatinine clearance is ≥60 mL per minute (CockcroftGault formula). [Nephron 1976;16:31]).

Other recommended actions 

• Screen for hepatitis B infection; vaccinate against hepatitis B if susceptible, or treat 

if active infection exists, regardless of decision regarding prescribing PrEP. 

• Screen and treat as needed for sexually transmitted infections (STIs). 

• Disclose to women that safety for infants exposed during pregnancy is not fully 

assessed but no harm has been reported. 

• Do not prescribe PrEP to women who are breastfeeding. 

Beginning PrEP medication regimen 

• Prescribe TDF/FTC (300 mg/200 mg) daily 

• In general, prescribe no more than a 90-day supply, renewable only after HIV 

testing confirms that patient remains HIV-uninfected. For women, ensure that 

pregnancy test is negative or, if pregnant, that the patient has been informed 

about use during pregnancy. 

• If active hepatitis B infection is diagnosed, consider using TDF/FTC, which may 

serve as both treatment of active hepatitis B infection and HIV prevention. 

• Provide risk-reduction and PrEP medication–adherence counseling and condoms. 

Follow-up while PrEP medication is being taken 

• Every 2–3 months, perform an HIV antibody test (or fourth generation antibody/

antigen test) and document negative result. 

• At each follow-up visit for women, conduct a pregnancy test and document results; 

if pregnant, discuss continued use of PrEP with patient and prenatal-care provider. 

• Evaluate and support PrEP medication adherence at each follow-up visit, more 

often if inconsistent adherence is identified. 

• Every 2–3 months, assess risk behaviors and provide risk-reduction counseling and 

condoms. Assess STI symptoms and, if present, test and treat for STIs as needed. 

• Every 6 months, test for bacterial STIs, even if asymptomatic, and treat as needed. 

• Three months after initiation, then every 6 months while on PrEP medication, check 

serum creatinine and calculate creatinine clearance. 

Table 3-10 continues on the next page

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Table 3-10

Interim guidance for provision of PrEP for the prevention of HIV 

infection in heterosexually active adults who are at ongoing, very 

high risk for sexual acquisition of HIV infection* 

On discontinuing PrEP (at patient request, for safety concerns, or if HIV 

infection is acquired) 

• Perform HIV test(s) to confirm whether HIV infection has occurred. 

• If HIV-positive, order and document results of resistance testing, establish linkage 

to HIV care. 

• If HIV-negative, establish linkage to risk reduction support services as indicated. 

• If active hepatitis B is diagnosed at initiation of PrEP, consider appropriate 

medication for continued treatment of hepatitis B infection. 

• If pregnant, inform prenatal-care provider of TDF/FTC use in early pregnancy 

and coordinate care to maintain HIV prevention during pregnancy and 

breastfeeding. 

*E.g., those with partners known to have HIV infection.

MMWR 2012;61(31);586–589

Possibilities and Challenges of ART-Based Prevention

A question of resources: During the past decade, ART has become available 

to populations worldwide—a tremendous health advance that has resulted 

in substantial decreases in morbidity and mortality risk for those on therapy. 

Nonetheless, in 2006, for each person started on ART worldwide, four were 

newly infected. Moreover, finite resources have limited ART availability 

worldwide, even for infected persons with clinical AIDS, who are most 

desperately at need. Implementing ART-based prevention strategies will 

require sufficient resources and targeted delivery to achieve a population-level 

impact. Pharmacovigilance systems to monitor ARV resistance will be critical for 

persons who become infected despite PEP or PrEP and might develop resistant 

virus and for those who are nonadherent to PrEP or ART.

continued

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Combination Strategies for HIV Prevention

Maximizing prevention efforts: No single standalone HIV prevention 

intervention is a panacea, and in the absence of a fully protective prophylactic 

vaccine, it is not likely that a single intervention will reverse the global 

epidemic. However, a number of HIV prevention strategies have been 

demonstrated to provide some protection against infection, thereby offering 

the possibility that combining several partially protective strategies might have 

additive or synergistic effects in reducing HIV on a population level. Analogous 

to the need for combination ART for treatment, researchers and clinicians are 

increasingly recognizing that combination HIV prevention strategies might 

maximize HIV prevention effects. Multicomponent packages of evidence-based 

biomedical, behavioral, and structural interventions must be appropriate, 

acceptable, and deliverable to priority subpopulations.

Population-level prevention: A core tenet of combination HIV prevention is 

that understanding the patterns and risks for HIV transmission at a population 

level guides the design of an optimal package of prevention interventions. On 

a population level, a combination prevention package that brings together 

interventions that target both HIV uninfected persons (e.g., behavioral risk 

reduction) and HIV infected persons (e.g., ART initiation and adherence) may 

achieve the greatest benefits. A key component of combination HIV prevention 

is increasing knowledge of HIV serostatus. For HIV infected persons, a strategy 

combining universal HIV testing with immediate linkage to ART has been named 

Test and Linkage to Care.

Interest in this approach was stimulated in large part by publication of a 

hypothetical modeling exercise in a high-prevalence African country. The 

results indicated that near-universal uptake of ART and optimal adherence, 

regardless of CD4+ cell levels, could reduce HIV incidence to <1 case per 

1,000 population within 10 years of full implementation of the strategy and 

reduce HIV prevalence to <1% within 50 years (Lancet 2009;373:48).The 

feasibility of implementing such an approach and the realism of the original 

model’s assumptions have been widely debated, given the challenges to date 

in (1) achieving high testing rates, particularly among some hard-to-reach 

populations; (2) addressing barriers to linking patients with HIV care; and (3) 

finding resources for increased testing and ART. Ongoing HIV epidemics in 

the United States and other high-income countries that have approximately 

15 years of widely available ART are a reminder of the continued need to 

identify barriers to reaching HIV infected individuals who are not aware of 

their status. Also needed is a focus on secondary transmission risk behaviors, 

because ART availability alone will not curb the epidemic. Demonstration 

projects to increase HIV testing and triage to HIV care on a population scale 

are being evaluated in the Bronx, NY, and Washington, DC, as well as in 

international settings.

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Conclusion

Prevention of HIV Remains a Critical Priority

The most effective available strategies for prevention are HIV counseling and 

testing, behavioral interventions that support abstinence or reduce risk taking, 

and condom use. While new strategies are being tested, healthcare providers 

must continue to assess and identify women at risk for acquiring or transmitting 

HIV and assist them in reducing their risk by setting and following through on 

achievable risk reduction plans.

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Chapter 4:

Primary Medical Care

Judith Feinberg, MD

Professor of Medicine

University of Cincinnati College of Medicine

The author declares no conflict of interest

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Chapter 4: Primary Medical Care

Chapter 4 at a Glance

Essential Principles of Care for the HIV Infected Woman................................75

Initial and Ongoing Evaluation......................................................................................................75

History and Counseling/Education .........................................................................................75

Physical Examination.............................................................................................................................79

Laboratory Testing and Other Monitoring..........................................................................81

Initial HIV Diagnosis...............................................................................................................................81

Baseline and Interval Laboratory Evaluation .............................................................84

Other Laboratory Testing.................................................................................................................97

Antiretroviral Therapy................................................................................................................................97

Goals of Antiretroviral Therapy...............................................................................................98

When to Initiate Antiretroviral Therapy...........................................................................98

Choosing an Initial Regimen......................................................................................................100

Antiretroviral Agents.........................................................................................................................101

Adherence....................................................................................................................................................103

Adverse Events Associated with Antiretroviral Therapy ..............................104

Management of the Treatment-Experienced Patient......................................107

Resistance Testing..................................................................................................................................110

Treatment of Acute HIV Infection.........................................................................................112

Treatment in Pregnancy.................................................................................................................112

Alternative or Complementary Therapy......................................................................112

Presentation and Management of Opportunistic Infections 

and Other Conditions Associated with HIV/AIDS ................................................113

Prophylaxis of Opportunistic Infections.........................................................................115

Common Opportunistic Infections and Other Conditions 

Associated with HIV...........................................................................................................................119

Pneumocystis jirovicii Pneumonia..................................................................................120

Candidiasis.........................................................................................................................................120

Cryptococcal Meningitis........................................................................................................121

Toxoplasmosis..................................................................................................................................122

Tuberculosis........................................................................................................................................123

Herpes Simplex Virus...................................................................................................................124

Cytomegalovirus...........................................................................................................................124

Disseminated Mycobacterium avium Complex...............................................125

Cryptosporidiosis and Microsporidiosis................................................................125

HIV-Associated Dementia (HAD) and HIV Encephalopathy............126

Wasting Syndrome (aka “Slim Disease”)...........................................................126

Central Nervous System Lymphoma........................................................................127

Progressive Multifocal Leukoencephalopathy................................................127

Systemic Lymphoma..................................................................................................................127

Chronic Hepatitis B and Hepatitis C........................................................................128

HIV-Associated Nephropathy .........................................................................................130

Cardiovascular Disease........................................................................................................130

Malignancies.....................................................................................................................................131

Anemia....................................................................................................................................................131

Opportunistic Disease in the Era of Antiretroviral Therapy....................132

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Essential Principles of Care for the HIV Infected Woman

This chapter focuses on the essential principles of care for the HIV infected 

woman. Cutting-edge treatment strategies currently being studied will be 

mentioned but not described in detail. To be truly useful, we indicate the 

general directions in which this field is moving and how to access updated 

information.

Several studies have demonstrated that positive clinical outcomes are a function 

of the clinician’s experience in caring for HIV infected patients (Cochrane 

Database Syst Rev 2011;6:CD003938). Nonspecialists are urged to seek 

expert advice and consultation whenever there is any question about the best 

way to manage a specific patient. This is especially important in the settings of 

antiretroviral (ARV) treatment failure and advanced HIV disease when patients 

are vulnerable to multiple simultaneous opportunistic processes.

There is as yet no compelling evidence that the clinical course of HIV infection 

in women differs significantly from that in men, with the obvious exception 

of the associated gynecologic conditions and obstetric issues (described in 

Chapters 6 and 8). Although recent data have indicated that women may 

have lower HIV viral loads (VLs) than men with an equivalent degree of 

immunosuppression, this does not appear to confer benefit in terms of either 

overall survival or complication-free survival. At present, the approach to the 

management of HIV infected women is the same as for men. With prolonged 

survival now possible, general preventive and health maintenance strategies, 

such as smoking cessation, control of hypertension, reduction of cardiovascular 

(CV) risk factors, and routine screening for malignancy (cervical, breast, colon), 

are all part of routine care for HIV infected women.

Initial and Ongoing Evaluation

History and Counseling/Education

A comprehensive database is valuable to the primary caregiver in assessing a 

patient’s current status and in formulating a management plan. At their initial 

encounter for HIV care, most patients are anxious and frightened. The ability 

to empathize, share knowledge without being patronizing, provide reassurance, 

and remain nonjudgmental are essential to gaining a patient’s trust and 

obtaining accurate information (see Chapter 2, Approach to the Patient). The 

areas of exploration detailed in Table 4-1 are of particular importance in 

caring for patients with HIV disease and deserve special attention.

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Table 4-1

Initial HIV History

Areas of Focus Areas of Exploration and Key Points 

HIV diagnosis • When was first positive HIV test? Why was test done?

• Can source of HIV infection be identified? Has source patient 

been treated for HIV? If so, are HIV medicines known? 

(Valuable if patient has acquired drug-resistant infection)

• IDU? Sex with IDU or bisexual male? Trading sex for drugs, 

money, or shelter? Current partner(s) HIV infected or at risk? 

(Many women are unaware of partner’s risk or HIV status.)

• Previously tested for HIV? If prior test(s) negative, look for 

evidence of acute seroconversion syndrome within past 6–9 mo 

(e.g., flu-like syndrome, rash, lymphadenopathy).

HIV treatment 

history • Pre-therapy CD4+ cell count and HIV RNA PCR quantification 

(i.e., VL)

• Specific treatment history, including during pregnancy: specific drugs and regimen changes (when/why), problems with 

adherence, response to therapy, adverse effects, history of 

treatment-limiting tolerance to any agent, other barriers to 

taking ARVs, treatment interruptions (including after delivery)

• History of resistance testing and availability of results

• Past OI prophylaxis

• HIV-related hospitalizations or any HIV-associated diagnoses

Other infectious 

diseases history • Identify history of STIs: syphilis, gonorrhea, chlamydia, HSV, 

PID, trichomoniasis, anogenital warts

• Identify history of other infectious diseases: TB, HAV, HBV, HCV, 

history of chicken pox or shingles

• Vaccination history: usual childhood illnesses, HAV and/or HBV, 

pneumococcal infection and influenza, HPV

OB-GYN history

(see Chapter 6)

• Date of most recent evaluation and results

• Pap smear: history of abnormal results, date of most recent

• Menstrual history/LMP

• History of gynecologic problems (e.g., fibroids, endometriosis, 

recurrent yeast infections), previous gynecologic surgery (e.g., 

hysterectomy, tubal ligation, LEEP, cervical conization)

• History of infertility or difficulty getting pregnant

• OB history: dates and outcomes of pregnancies, OB complications, future childbearing plans and/or desires

• Menopause: vasomotor symptoms, vaginal dryness, postmenopausal bleeding

• Last mammogram, history of abnormal mammogram

Other pertinent 

medical history • Hypertension

• Chronic kidney disease

• Diabetes

• Cardiovascular disease

• Thromboembolic disease

• Asthma or COPD

• Premalignant or malignant conditions (e.g., cervical, breast, 

colon, ovary)

• Osteopenia and/or osteoporosis

Surgical history • Prior surgical procedures, indications, complications 

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Table 4-1

Initial HIV History

Areas of Focus Areas of Exploration and Key Points 

Sexual practices • Use of condoms (male and/or female)

• Use of contraception other than condoms

• Consistency of use of condoms and other contraception

• Number of current sexual partners and their HIV status (if 

known)

• Sexual activity with men, women, or both

• History of anal sex

Current 

medications • Prescription

• OTC remedies

• History of and attitude toward regular medication use

• Use of nontraditional medications for HIV or other conditions

• Drug allergies

Mental health 

history • Past and current problems

• Depression (trouble sleeping, early awakening, change in 

appetite, loss of interest in usual activities, anhedonia)

Family history • Age and health of children, including HIV test results, if 

performed

• HIV in other family members

• Other medical diagnoses in family (see above list)

Social history • Where was patient born and raised?

• Where and with whom does patient live? Relationship to others 

in the household?

• Food or housing insecurity

• Childcare responsibilities

• History of or current domestic violence

• Presence of pets, especially reptiles (salmonellosis) and kittens 

(toxoplasmosis)

• Extent of formal education

• Occupational history and potential toxic exposures

• Travel history

• Cigarette, alcohol, and illicit drug use, past and current; misuse 

of prescription drugs

Sources of 

support • To whom has the patient disclosed her diagnosis? What were 

the reactions?

• Does the patient have friends or family to whom disclosure 

seems possible either now or in the future?

• Other HIV infected family members or friends?

• Are family or friends able to care for the patient’s children in 

the event of acute illness?

• Is the patient employed, and, if so, full or part time? Able to 

confide in supervisor?

• Does the patient have health insurance?

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

continued

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Counseling and education are important elements of the therapeutic bond; 

the information about HIV that the clinician shares with the patient is just 

as important as the information the clinician learns about the patient in the 

history-taking process. Because education about HIV entails conveying a large 

amount of information, it is best broached initially and then reintroduced and 

reinforced at appropriate intervals. Many patients are in a state of shock 

following their diagnosis or may be suffering from situational depression or 

fear of a partner’s response. Clinicians should be kind and patient and should 

take adequate time with the patient; schedule at least an hour for the initial 

visit and schedule an early second visit. Assure patients that they will be 

supported and cared for. Encourage patients to develop good relationships 

with the office or clinic nurse and ensure that patients are able to reach 

someone when they have questions, complaints, or symptoms, especially when 

starting antiretroviral therapy (ART). Convey information in lay language at 

a level of complexity appropriate to the patient’s ability to comprehend. 

Remember that a patient’s formal educational level may not necessarily 

correlate with her ability to understand complicated medical concepts. 

Concepts of particular importance for review with a new patient are described 

in Table 4-2.

Table 4-2

HIV Information for New Patients

Topic Areas of Discussion

HIV pathogenesis • What are CD4+ lymphocytes and why are they important?

• How does HIV infection affect CD4+ cells?

Natural history 

of HIV disease • How is “AIDS” different from “HIV infection” or “HIV disease”?

• Without therapy, what is the typical time course between 

acquisition of HIV and the development of HIV-associated 

problems and/or AIDS?

Monitoring 

activity of HIV 

disease

• What do CD4+ cell counts and HIV VL tests measure?

• How are they used and how often will they be repeated?

Goals of 

HIV disease 

management

• What does “maintain or improve the immune system” mean 

and why is it a goal of therapy?

• How is HIV replication controlled and why is this important?

• How can medication side effects be avoided or minimized?

• What are OIs and how are they prevented or treated?

Principles of HIV 

treatment • Describe the value of combination therapy in preserving health 

and prolonging life

• Underscore the importance of adherence to avoid treatment 

failure and the development of resistance

• Discuss decision-making about starting treatment

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Table 4-2

HIV Information for New Patients

Topic Areas of Discussion

Preventing 

spread of HIV 

infection

• Notification of sexual partners and drug use contacts

• Practicing safe sex

• Safer injection drug use practices, including needle exchange 

programs and the use of diluted bleach to sterilize injection 

equipment

• Be informed of the prevention benefit of ART, namely, that if 

taken as prescribed it can substantially reduce their risk of 

transmitting uninfected sexual (and likely also needle-sharing) 

partners 

• Be informed about PEP and PrEP for HIV-uninfected sexual 

partners and under what circumstances they might consider 

employing either strategy

“Prevention for 

Positives” • Keep bleach readily available in the household to clean up 

blood from accidents

• Describe appropriate wound care for injuries

• Reassure the patient about the difficulty of transmitting HIV 

to casual contacts and to family members, even in the close 

context of everyday family life

Health 

maintenance • Cancer screening (Pap smear, mammogram, colonoscopy)

• Immunizations

• TB screening

• Smoking cessation

• Lipid screening

• Diet, exercise, weight management

• Dental and eye care

• Bone density screening

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Lastly, because HIV is a chronic, life-threatening disease that still carries a 

social stigma, the clinician plays a key role in exploring mental health and 

psychosocial needs; helping patients identify potential sources of support; and 

referring patients for additional medical, psychiatric, and/or social services.

Depending on the initial history, a variety of issues may need to be explored 

in an ongoing fashion (at each visit or periodically). Such issues include new 

or worsening symptoms; interval sexual practices and other risk behaviors; 

interval menstrual history; a review of all medications, including complementary 

or over-the-counter products; adherence to ART; disclosure and/or social 

support issues; and others as indicated.

Physical Examination

The examination may yield clues to specific HIV-associated conditions. Perform 

a complete physical examination and track vital signs, particularly temperature 

and weight. Pay special attention to the areas outlined in Table 4-3.

continued

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Table 4-3

Physical Examination of the HIV Infected Woman

Area Key Focal Points

General • Evidence of wasting, often prominent at the temples

• Fat redistribution syndromes, including buffalo hump, fatty 

deposits in neck, enlarged breasts, and truncal (visceral) 

obesity; may coexist with or be separate from marked 

subcutaneous fat loss in the extremities, face, and buttocks

Eyes • Purplish spots of KS on conjunctival surfaces (rare in women)

• Petechiae

• Funduscopy: “cotton wool” spots, i.e., microinfarcts of the retinal 

nerve fiber layer due to occlusion of retinal capillaries

• CMV retinitis: typical “eggs and ketchup” appearance of 

infiltrates and hemorrhages in advanced HIV disease

• Visual-field deficits, common in CMV retinitis, may be 

uncovered with simple field testing by confrontation

Oropharynx • No examination of an HIV infected person, regardless of 

disease stage, should be considered complete without a careful 

oral exam, which often yields the earliest physical evidence of 

HIV infection

• Thrush: white plaques on buccal mucosa, palate, tongue, or 

posterior pharynx that are readily scraped off with tongue 

blade

• Oral hairy leukoplakia: furry white plaques most often found on 

the lateral margins of the tongue that cannot be scraped off

• Purplish spots or plaques on mucosal surfaces consistent with KS 

and with bacillary angiomatosis

• Ulcers (HSV, CMV, aphthous)

Lymph nodes • Generalized adenopathy: nontender or minimally tender; may 

wax and wane; most often related to HIV infection itself, but 

may also indicate lymphoma or disseminated OIs

• Localized adenopathy: may be sign of malignancy or infection, 

e.g., enlarged axillary nodes in breast cancer, inguinal 

adenopathy in vulvar cancer or LGV

• MAC

• Extremely tender or unilaterally enlarged lymph nodes: should 

trigger an evaluation for specific etiology

Heart • S3 gallop: may indicate heart failure, possible cardiomyopathy

Lungs • Fine, dry “cellophane” rales: classic for PCP, but are a late 

finding and may be absent

Abdomen • Organomegaly: may reflect disseminated infection with MAC, 

TB, disseminated endemic mycoses such as histoplasmosis, or 

lymphoma

• Splenomegaly: may be associated with ITP

Pelvic 

examination 

(including digital 

rectal exam)

(see Chapter 6)

• Genital ulcers: may reflect HSV; syphilis; other infections, 

including CMV, TB; aphthous or invasive vulvar cancer

• Genital warts: HPV

• Abnormal vaginal discharge: generally caused by infectious 

vaginitis (candidiasis, bacterial vaginosis, trichomoniasis)

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Table 4-3

Physical Examination of the HIV Infected Woman

Area Key Focal Points

Neurologic • Motor deficits: may reflect space-occupying lesions of the 

CNS, e.g., toxoplasmosis, CNS lymphoma, PML; may be due to 

neurosyphilis

• Symmetrical, distal sensory deficits (especially decrease or loss 

of vibratory or proprioceptive sensation): typically affect feet 

more than hands; indicate peripheral neuropathy due to either 

HIV disease or drug toxicity from some nucleoside analogs 

(e.g., ddI or d4T)

• Poor short-term memory, diminished concentration, sensorimotor 

retardation: hallmarks of AIDS dementia complex (HIV 

encephalopathy)

• Dysphoric mood and flat affect: may be signs of depression

Skin • Careful examination of skin often yields early clues about HIV 

infection and should be performed regularly

• Pruritic papular eruptions: early manifestation; may be sign of 

bacterial folliculitis, eosinophilic folliculitis, or scabies

• Pearly papules with central umbilication: typical of Molluscum 

contagiosum

• Painful vesicular rash: may be HSV; in a dermatomal distribution 

is usually shingles (VZV)

• Seborrheic dermatitis: may be severe; appears as greasy, scaly white, and/or erythematous areas on face, especially nasolabial 

fold and eyebrows; may be confined to scalp and hairline

• Psoriasis: common scaling lesion

• Purplish macules or plaques: may be either KS or bacillary 

angiomatosis; similar to appearance on mucosal surfaces; in 

dark-skinned individuals KS may appear more brown than 

purple

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Laboratory Testing and Other Monitoring

Initial HIV Diagnosis

The U.S. Centers for Disease Control and Prevention (CDC) recommends that 

voluntary, opt-out HIV testing be made a routine part of medical care for all 

patients aged 13–64 years who have been sexually active (MMWR Recomm 

Rep 2006;55(RR-14):1). Under current CDC recommendations, a separate 

signed consent and more extensive pretest counseling are not considered 

necessary. These changes are meant to simplify the process and promote 

universal testing; however, the need for specific consent or counseling is 

ultimately determined by relevant state laws.

continued

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HIV antibody tests: Standard HIV screening involves detecting antibodies 

to HIV, generally with an enzyme immunoassay (EIA). A reactive EIA should 

be followed by a confirmatory test, most commonly Western blot or, less 

commonly, immunofluorescence assay (IFA), which detects specific antibodies 

to HIV-1 proteins. CDC criteria for a positive Western blot are a band 

pattern indicating antibodies to two of the following proteins: p24, gp41, and 

gp120/160. A final diagnosis of HIV should not be given unless both screening 

and confirmatory tests are positive or reactive; with EIA alone the falsepositive rate is 2%. In patients with infection >12 weeks after transmission, 

the sensitivity of this screening algorithm is 99.5%; specificity is 99.99% (Am J 

Med 2000;109(7):568).The average time from transmission to a reactive EIA is 

10–14 days; seroconversion may be delayed to 3–4 weeks or longer in rare 

circumstances, but essentially all HIV-1 infected patients will seroconvert within 

6 months (Am J Med 2000;109(7):568). A false-negative test can occur if 

testing is performed in the window period (i.e., after infection occurs but prior 

to the development of detectable antibodies). Agammaglobulinemia is a rare 

cause of a false-negative test.

The test may be reported as indeterminate if the EIA is positive but only a 

single band is detected by Western blot. Although the logical concern is that 

this result represents testing during the process of seroconversion, in most 

cases—particularly in low-risk individuals and low-prevalence areas—it 

represents the presence of cross-reactive nonspecific antibodies. With evolving 

seroconversion, antibody to p24 is usually the first to appear; in its absence, 

seroconversion is unlikely. Causes of indeterminate test results include

• Seroconversion, which can be confirmed by a quantitative virologic 

test with a PCR-based assay (see below);

• Advanced HIV infection with decreased titers of p24 antibodies 

(seroreversion is rare);

• Autoantibodies due to autoimmune or collagen vascular diseases or 

malignancy;

• Cross-reactive allo-antibodies from pregnancy, blood transfusions, or 

organ transplantation; and

• Previous receipt of an experimental HIV vaccine.

For a woman with indeterminate test results, repeat serology at 1, 2, and 6 

months is recommended. Until seroconversion is ruled out, precautions should be 

taken to prevent HIV transmission to others. Typically, a woman in the process 

of seroconversion will develop a positive Western blot within 1 month. In highrisk patients or in other situations where acute infection is suspected, HIV RNA 

level (i.e., VL) should be obtained; this test has high sensitivity because of the 

generally high levels of viremia during acute infection.

HIV antigen/antibody tests: Two combination HIV antigen/antibody tests 

(ARCHITECT and Bio-Rad GS) have now been licensed by the U.S. Food and 

Drug Administration (FDA), and may be used for this purpose.

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Rapid tests: Six FDA-approved rapid serologic tests are now available 

and usually provide results within 15–30 minutes (FDA-Approved Rapid HIV 

Antibody Screening Tests. CDC. 2008; http://www.cdc.gov/hiv/topics/testing/

rapid/rt-comparison.htm. Accessed 8/1/2012). Three of the rapid tests are 

Clinical Laboratory Improvement Amendment (CLIA) waived, allowing pointof-care testing in clinical settings, which is particularly useful in settings where 

patients typically do not return for results, such as sexually transmitted infection 

(STI) clinics and emergency rooms, and during labor and delivery. Sensitivity 

and specificity are consistently >99% but positive predictive value varies 

depending on HIV prevalence. For this reason, positive results are considered 

preliminary and should always be confirmed with Western blot or IFA. For 

women who present to labor and delivery with undocumented HIV status and 

positive rapid test results, however, ARV prophylaxis should be given without 

delay to reduce the risk of perinatal transmission (ACOG Committee Opinion 

No. 418; Obstet Gynecol 2008;112(3):739).

In July 2012 the FDA approved the OraQuick In-Home HIV Test, a rapid 

home-use HIV test kit that provides a test result in 20–40 minutes and 

is approved for sale in stores and online to those 17 years and older. 

As with other rapid tests, positive tests must be confirmed by follow-up 

laboratory-based testing. (http://www.fda.gov/NewsEvents/Newsroom/

PressAnnouncements/ucm310542.htm ) (http://www.oraquick.com/)

Urine test: The only currently available urine test (Calypte HIV-1 Urine EIA) is 

licensed for screening only and must be administered by a physician; a positive 

result requires confirmation by another method.

Virologic tests: Nucleic acid amplification tests—HIV DNA (qualitative) or HIV 

RNA (quantitative)—are used to diagnose acute HIV infection, confirm the 

diagnosis during the window period, and diagnose neonatal infection. HIV 

RNA testing is not recommended as a routine screening test for HIV because 

2%–9% of people without HIV infection will have false-positive results, 

virtually always with low HIV RNA levels (i.e., <10,000 copies/mL [c/mL]) (Ann 

Intern Med 1999;130(1):37). Patients with acute HIV infection diagnosed by 

a virologic test while still antibody negative or indeterminate should undergo 

confirmatory serologic testing over the next 3 months. (See further discussion of 

HIV RNA testing on p. 92.)

Acute HIV infection should be suspected in patients with typical symptoms, 

including fever, pharyngitis, lymphadenopathy, and rash, particularly if these 

symptoms are accompanied by a high-risk exposure during the previous 

3–4 weeks. Women may be less likely to perceive an exposure as high risk, 

particularly if they are in what they believe to be a mutually monogamous 

relationship.

There is evidence that pregnancy may be a time of increased risk for HIV 

acquisition (Lancet 2005;366(9492):1182). Obstetrical providers should 

therefore have a low threshold for retesting in pregnancy when there is 

concern for possible acute HIV infection. In this situation both HIV VL and 

HIV serology should be obtained because serology may be negative or 

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indeterminate. An antibody/antigen test would be appropriate to use in this 

circumstance as well, since the woman may be antibody negative but antigen 

positive.

• HIV DNA is a qualitative test used to detect intracellular virus; it is 

used primarily to diagnose neonatal infection. Sensitivity is >99% at 

all stages of infection and specificity is approximately 98%.

• Viral isolation: qualitative or quantitative cultures have been used 

primarily to diagnose neonatal HIV infection, but they are expensive 

and labor intensive and have been largely replaced by HIV DNA or 

HIV RNA assays.

Baseline and Interval Laboratory Evaluation

Baseline laboratory evaluation is used to establish the stage of HIV disease 

and determine exposure to other infectious diseases, need for vaccinations, 

and the presence of comorbidities that may affect the choice of HIV therapy 

or require specific management. Ongoing laboratory testing is needed to 

assess the response to therapy and monitor for adverse effects. A flow sheet, 

whether part of an electronic or paper health record, is an essential tool 

for tracking important test results and key clinical data over time. Table 4-4 

outlines baseline and interval laboratory and other monitoring for women with 

HIV infection.

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Table 4-4

Baseline and Interval Laboratory and Other Monitoring for Women with HIV Infection

Entry 

Into 

Care

Before 

Initiating 

ART

ART Initiation 

or Change

2–8 Wks 

After ART 

Initiation/ 

Change

Every 

3–6 Mo

Every 

6 Mo

Every 

12 Mo

Treatment 

Failure

Clinically 

Indicated

Comments

HIV DISEASE TESTSCD4+ cell count X q 3–6 mo X X q 6–12 mo in 

clinically stable 

patients with NDVL

X X

HIV RNA (VL) X q 3–6 mo X X X X X X If VL is detectable at 2–8 wk, repeat 

q 4–8 wk until <200 c/mL, then q 3–6 mo. Interval for monitoring can be extended to q 6 mo if patient is ART adherent, has NDVL, and is clinically and immunologically stable for >2–3 y.

Resistance testing

X X X X If RT is performed at entry into care, 

repeat testing is optional if patient is ART naïve. RT is not possible with viral suppression and an ART switch that is due only to toxicity or for convenience.

Tropism testing X X X Perform if considering CCR5 antagonist 

therapy or for failure of CCR5 antagonist therapy

SAFETY/TOXICITY MONITORINGCBC w/differential

X q 3–6 mo X If on ZDV X X

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Table 4-4

Baseline and Interval Laboratory and Other Monitoring for Women with HIV Infection

Entry 

Into 

Care

Before 

Initiating 

ART

ART Initiation 

or Change

2–8 Wks 

After ART 

Initiation/ 

Change

Every 

3–6 Mo

Every 

6 Mo

Every 

12 Mo

Treatment 

Failure

Clinically 

Indicated

Comments

Electrolytes, BUN, creatinine

X q 3–6 mo X X X X Some experts recommend phosphorus 

measure while on TDF. Renal function assessment should include estimation of CrCl or GFR.

ALT, AST, bilirubin

X q 3–6 mo X X X X

Fasting glucose or hemoglobin A1C

X If normal, 

q 12 mo

X If last 

measure 

abnormal

If last 

measure 

normal

X See Diabetes Care 2006;29:1963 for 

consensus guidelines for management of hyperglycemia in Type 2 DM

Fasting lipid profile

X If normal, 

q 12 mo

X Consider 

4–8 wk 

after 

starting 

new ART

If last 

measure 

abnormal

If last 

measure 

normal

X

Urinalysis: RBC, WBC, proteinuria, sediment levels

X X If on TDF X X More-frequent monitoring indicated for 

patients with increased risk of renal insufficiency (e.g., DM, HTN)

Calculated creatinine clearance

X Prior to 

initiating TDF 

or IDV

X Consider at baseline, especially in 

Black patients, due to increased risk of HIVAN

Albumin level X q 12 mo X X

continued

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Table 4-4

Baseline and Interval Laboratory and Other Monitoring for Women with HIV Infection

Entry 

Into 

Care

Before 

Initiating 

ART

ART Initiation 

or Change

2–8 Wks 

After ART 

Initiation/ 

Change

Every 

3–6 Mo

Every 

6 Mo

Every 

12 Mo

Treatment 

Failure

Clinically 

Indicated

Comments

Alkaline phosphatase level

X q 12 mo X X

Pregnancy test If starting EFV XG6PD X Screen for deficiency in appropriate 

racial or ethnic groups

HLA-B*5701 testing

If considering 

ABC

COINFECTION AND COMORBIDITY TESTINGViral hepatitis screening (HAV, HBV, HCV)

X If not 

performed 

at entry; if 

patient is not 

HBV immune or 

vaccinated

X If HBV nonimmune, administer HBV 

vaccine series. Administer HAV vaccine if patient has HBsAg+ or HCV infection, is planning travel to endemic areas, is IDU, or in presence of HAV community outbreaks.

TB screening X X X Test with PPD or interferon-gamma 

release assay; no need to repeat if prior (+) PPD. Other testing may be indicated with potential exposure.

Syphilis serology

X X X More-frequent testing may be 

indicated if patient engages in highrisk behavior

continued

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Table 4-4

Baseline and Interval Laboratory and Other Monitoring for Women with HIV Infection

Entry 

Into 

Care

Before 

Initiating 

ART

ART Initiation 

or Change

2–8 Wks 

After ART 

Initiation/ 

Change

Every 

3–6 Mo

Every 

6 Mo

Every 

12 Mo

Treatment 

Failure

Clinically 

Indicated

Comments

CMV and other herpes virus screening

X CMV screening if at low risk for 

CMV; VZV screening if no history of chicken pox or shingles. Some experts recommend HSV-2 screening.

Toxoplasma serology

X

STI screening (GC, chlamydia, trichomoniasis) (see http:// www.cdc.gov/ mmwr/preview/ mmwrhtml/rr5212a1.htm for detail on indications for more frequent testing and which testing modalities to use)

X X X More-frequent testing may be 

indicated if patient engages in highrisk behavior

Chest X-ray X X Indicated for patients with positive TB 

screening results. Consider at baseline in presence of underlying lung disease.

HEALTH MAINTENANCE SCREENINGCervical cytology

X 2x in first 

y of care

X More-frequent screening is indicated if 

abnormal results are obtained and/or after treatment

continued

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Table 4-4

Baseline and Interval Laboratory and Other Monitoring for Women with HIV Infection

Entry 

Into 

Care

Before 

Initiating 

ART

ART Initiation 

or Change

2–8 Wks 

After ART 

Initiation/ 

Change

Every 

3–6 Mo

Every 

6 Mo

Every 

12 Mo

Treatment 

Failure

Clinically 

Indicated

Comments

Anal cytology/ digital rectal exam

X 2x in first 

y of care

X Not currently considered standard of 

care, but some experts recommend a screening schedule similar to that for cervical cytology. Consider anal Pap smear in women with genital warts or abnormal cervical cytology. Evaluate abnormal results with high-resolution anoscopy.

Ophthalmologic screening

Perform dilated 

exam q 6–12 mo 

in patient with 

CD4+ cell count 

<50 cells/mm3

X

Depression screening

X X X

Domestic violence screening

X X X

Alcohol and drug use

X X X

Tobacco use X X X

continued

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Table 4-4

Baseline and Interval Laboratory and Other Monitoring for Women with HIV Infection

Entry 

Into 

Care

Before 

Initiating 

ART

ART Initiation 

or Change

2–8 Wks 

After ART 

Initiation/ 

Change

Every 

3–6 Mo

Every 

6 Mo

Every 

12 Mo

Treatment 

Failure

Clinically 

Indicated

Comments

Colonoscopy X X Initiate screening at age 50; perform 

every 10 y, but earlier or more often if indicated by family history or prior findings

Mammography X X Baseline screening at age 40 and 

annually thereafter (ACOG Practice Bulletin #122; Obstet Gynecol2011;118(2 Pt 1):372). Perform individualized, periodic assessment of breast cancer risk.

Bone densitometry

X Initiate screening at age 65; consider 

at age 50+ if patient has one or more risk factors for premature bone loss. Perform periodically based on prior results and ongoing risk factors for bone loss.

Global assessment for frailty, functionality, fall risk

X X X Initiate screening at age 65

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixSource: Adapted from Primary Care Guidelines for the Management of Persons Infected With Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association 

of the Infectious Diseases Society of America (Clin Infect Dis 2009;49:651)

continued

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CD4+ lymphocyte count (CD4+ % and absolute CD4+ cell count): This 

is a key indicator of immune function in HIV infected patients. The normal 

laboratory range for the CD4+ lymphocyte percentage is 33%–60% and a 

normal CD4+ cell count is 700–1400 cells/mm3. CD4+ cell counts often drop 

precipitously at the time of primary HIV infection, then usually rebound to 

near-baseline levels. The natural history of HIV infection, illustrated in Figure 

4-1, involves a progressive loss of CD4+ cells (approximately 60 cells per 

year), with the risk of opportunistic infections (OIs) increasing as CD4+ cell 

counts decrease. An adequate CD4+ response to therapy is defined as an 

increase in the range of 50–150 cells/mm3 per year until a steady-state level 

is reached. If therapy is initiated at a low CD4+ cell count or at an older age, 

the increase may be blunted, even with appropriate virologic suppression.

Figure 4-1

Natural History of HIV Infection without the Use of Antiretroviral 

Therapy

Source: © N Engl J Med 1993;328:327. Reprinted with permission.

The baseline CD4+ cell count is important in decisions regarding the initiation 

of ART and the need for prophylaxis against specific OIs. Follow-up CD4+ 

cell count testing is important for determining when to start ART in untreated 

patients, assessing the immunologic response to ART, and informing decisions 

about the initiation or discontinuation of OI prophylaxis.

Because the CD4+ percentage is measured directly and the absolute CD4+ 

cell count is a calculated value, it is more useful and accurate when assessing 

trends over time to focus on changes in the CD4+ percentage. Most clinicians, 

however, use the absolute CD4+ cell count in clinical decision making.

Several factors may cause decreases in the absolute CD4+ cell count, including 

pregnancy (due to hemodilution; the CD4+ percentage remains relatively 

stable), corticosteroid use, intercurrent illness, bone-marrow suppressive 

medications, and recent vaccination. HTLV-1 infection may increase the CD4+ 

cell count.

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In general, the same laboratory should be used for serial CD4+ measurement 

and any value that indicates a change in patient management should trigger 

a retest. A 30% change in the absolute CD4+ cell count or a 3-point change 

(increase or decrease) in the CD4+ percentage between one test and the next 

is significant (i.e., a change of two standard deviations or more).

Plasma HIV RNA (VL): At baseline, VL reflects the rapidity with which HIV 

disease is likely to progress. Higher VLs have been repeatedly associated with 

a more rapid rate of disease progression.

VL is used routinely to monitor a patient’s response to treatment of HIV 

infection, with the goal of achieving and maintaining an undetectable VL as 

measured by ultrasensitive assays (<20–75 c/mL, depending on the assay); 

however, isolated “blips” (i.e., VLs transiently detectable at low levels) can 

be seen in successfully treated patients and are not thought to represent 

viral replication or to predict virologic failure (JAMA 2001;286(2):171). A 

repeat test should be performed as quickly as possible if a patient on ART 

with previously undetectable VL suddenly has quantifiable virus. The U.S. 

Department of Health and Human Services (DHHS) Guidelines for the Use of 

Antiretroviral Agents in HIV-1-Infected Adults and Adolescents defines virologic 

failure as a confirmed VL of >200 c/mL, which eliminates most cases of 

apparent viremia caused by blips or assay variability (http://www.aidsinfo.

nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/.

Accessed 5/16/2013).

Acute illness (e.g., bacterial pneumonia, tuberculosis (TB), herpes simplex 

virus (HSV), Pneumocystis jirovecii pneumonia [PCP]) and immunizations can 

cause transient increases in plasma HIV RNA for 2–4 weeks; testing should 

not be performed during this time. Plasma HIV RNA results usually should be 

verified with a repeat determination before making changes in therapy. The 

most frequent reason for an increase in viral load is poor adherence and any 

increase in viral load should prompt assessment of the patient’s adherence to 

the prescribed ART regimen. Recent studies have shown that women have lower 

VLs than men at comparable CD4+ cell counts, although these VL differences 

tend to disappear several years after seroconversion and have not been 

associated with slower disease progression or longer survival (see Chapter 1, 

Epidemiology).

Several different VL assays and methodologies (e.g., reverse transcriptase 

PCR, branched DNA, nucleic acid sequence-based amplification) are available. 

The variability of VL assays is 0.3–0.5 log. Although the results of different 

assays correlate, absolute values differ and no standard multiplication factor 

exists to translate among different assays. For this reason, the same VL assay 

should be used to follow an individual patient longitudinally.

HIV drug-resistance testing (see also p. 110): Genotypic and phenotypic 

resistance assays are used to provide information on resistance to nucleoside 

reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase 

inhibitors (NNRTIs), and protease inhibitors (PIs); tests for integrase and 

fusion inhibitor resistance are available separately from several commercial 

laboratories. A genotypic tropism assay for predicting HIV co-receptor usage 

is now commercially available and may be used as an alternative to a 

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phenotypic tropism assay before initiation of a CCR5 antagonist-containing 

regimen and for evaluation of virologic failure while taking CCR5 inhibitors. 

The purpose of resistance assays is to inform treatment decisions in the 

case of possible transmitted drug resistance, virologic failure, or suboptimal 

VL reduction.

Resistance testing should be performed in the following circumstances:

• With acute HIV infection; 6%–16% of transmitted virus is resistant to 

at least one ARV, and 3%–5% is resistant to drugs from more than 

one ARV class (AIDS 2010;24(8):1203; HIV Clin Trials 2007;8(1):1)

• At entry into HIV care; some drug-resistance mutations can remain 

detectable for years in untreated infected patients (Clin Infect Dis

2005;40(3):468; J Virol 2008;82(11):5510)

• Upon initiation of ART, because of the possibility of superinfection 

(optional)

• At entry into prenatal care; test prior to the initiation of ART and in 

patients who are on therapy and have detectable VL

• If virologic failure occurs, test before or within 4 weeks of 

discontinuing the failing drug regimen

• If VL reduction if suboptimal

In most situations, genotypic testing is preferred over phenotypic testing 

because of faster turnaround time, lower cost, better sensitivity for detecting 

mixtures of wild-type and resistant virus, and relative ease of interpretation. 

Adding phenotypic to genotypic testing is generally preferred for patients with 

known or suspected complex drug-resistance mutation patterns, particularly to 

PIs. In general, resistance testing should be performed with VL >1000 c/mL. 

With VL >500 but <1000 c/mL, testing may be unsuccessful but should still be 

considered. Testing is not recommended with VL <500 c/mL because resistance 

assays cannot be performed consistently at such low VLs.

Hematology and chemistry panels: The effects of HIV, associated conditions, 

and adverse effects of drugs may involve hematologic, renal, or hepatic 

abnormalities.

• Complete blood count (CBC): look for leukopenia, anemia, and 

thrombocytopenia; lymphocyte count is needed to calculate the 

absolute CD4+ cell count

• Serum creatinine: increased levels may indicate HIV-associated 

nephropathy (HIVAN) or drug toxicity

• Abnormal liver function tests (LFTs): may reflect viral hepatitis, 

alcohol abuse, or drug toxicity. Abnormalities may have an impact 

on options for ART.

Syphilis serology: High rates of coinfection necessitate routine testing in all 

HIV infected patients. A reactive nontreponemal assay (rapid plasma reagin 

[RPR] or venereal disease reaction level [VDRL]) must be confirmed with a 

treponemal-specific assay (fluorescent treponemal antibody absorption test 

[FTA] or methoxy trifluoromethyl phenyl acetic acid).

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Toxoplasmosis serology (MMWR Recomm Rep 2009;58(RR-4):1): Latent 

toxoplasmosis infection, as indicated by the presence of Toxoplasma gondii

immunoglobulin G (IgG), may be relevant to decisions on prophylaxis and 

avoidance of exposure in those who are IgG negative (e.g., avoiding raw or 

undercooked meat, cat litter). Repeat serology is recommended in patients who 

were previously IgG negative and have immune reconstitution to a CD4+ cell 

count >100 cells/mm3. Also repeat with a decrease in the CD4+ cell count to 

100 cells/mm3, especially if the patient is not receiving Pneumocystis jirovecii

pneumonia (PCP) prophylaxis, which is active against toxoplasmosis. The 

prevalence of latent toxoplasma infection varies significantly worldwide; in the 

United States, the rate is approximately 30%.

CMV serology (IgG): Most HIV infected adults have latent cytomegalovirus 

(CMV) infection. Knowledge of CMV antibody status can guide the clinician 

to use CMV-negative blood products if the patient is CMV IgG negative and 

transfusions are required. Check serology in patients at lower risk for CMV 

(e.g., non-injection drug users [IDUs]) upon initiation of care (MMWR Recomm 

Rep 2009;58(RR-4):1).

Varicella serology (IgG): Check serology in patients who do not have a 

history of chicken pox or shingles. If the patient is varicella IgG-negative and 

is subsequently exposed, administer postexposure prophylaxis with varicella 

immune globulin (MMWR Recomm Rep 2009;58(RR-4):1). Consider varicella 

vaccination for seronegative patients at increased risk for exposure to VZV.

Hepatitis A, B, C serology (MMWR Recomm Rep 2009;58(RR-4):1): Hepatitis 

A and B serologies will identify those who are not immune and are therefore 

candidates for vaccination. Laboratory tests for the hepatitis viruses are listed 

in Table 4-5.

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Table 4-5

Laboratory Tests for Hepatitis Viruses

Hepatitis 

Virus

Laboratory Test Interpretation

A HAV IgM Ab Current or recent HAV infection

HAV IgG Ab Immunity to HAV (past infection or after 

vaccination)

B HBsAg Current (acute or chronic) HBV infection

HBeAg Current HBV infection with high risk of 

infectivity

HBcAb Past or present HBV infection

HBsAb Immunity to HBV (past infection or after 

vaccination)

C HCV IgG Ab (ELISA) Past or present HCV infection

HCV IgG Ab (RIBA) Confirms HCV ELISA

HCV RNA PCR 

(qualitative, 

quantitative)

Current HCV infection

HCV genotype in 

PCR+s

Useful in determining prognosis, duration of 

treatment of anti-HCV therapy

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Recommendations are as follows:

Hepatitis A

• Vaccinate HAV Ab-negative IDUs, women with chronic liver disease, 

and patients infected with hepatitis B or C

• Consider vaccine for all other HIV infected patients without prior 

exposure by serology

• Vaccine may not produce an adequate immune response in patients 

with CD4+ cell counts <350 cells/mm3

Hepatitis B

• Provide vaccine for patients who are susceptible to infection (i.e., 

patients who are negative for the hepatitis B surface antigen 

(HbsAg), surface antibody (HbsAb), and core antibody (HBcAb)

• Offer vaccine to sex partners of persons who are HBsAg positive

• Vaccine may not produce an adequate immune response in patients 

with CD4+ cell counts <350 cells/mm3

• Consider HBV DNA PCR for patients who are HBcAb positive but 

HBsAg and/or HBsAb negative. Most of those with isolated HBcAb 

are not immune and should receive a complete primary vaccination 

series.

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• Choose ART or other potentially hepatotoxic agents carefully for 

women with chronic HBV (i.e., HBsAg positive or HBsAg negative 

but HBcAb positive with detectable HBV DNA) infection because of 

potential increased hepatic toxicity and the need for more-frequent 

assessment of LFTs

• For patients who are HBsAg positive, ART should include TDF + (FTC 

or 3TC) to treat both HIV and HBV infections

• In patients with HBV infection and documented cirrhosis, perform 

alpha-fetoprotein (AFP) and hepatic ultrasound annually to screen 

for hepatocellular carcinoma

Hepatitis C

• Infection status is needed to guide therapeutic decisions for possible 

HCV treatment

• Perform HCV antibody test at initiation of care and confirm positive 

HCV Ab with quantitative HCV RNA

• HIV/HCV coinfected patients may not manifest HCV antibody; 

consider a qualitative HCV RNA PCR test when HCV is suspected 

(i.e., with abnormal LFTs and negative serology)

• Women with detectable HCV should be tested for the HCV genotype

• Choose ART or other potentially hepatotoxic agents carefully for 

women with chronic HCV infection because of potentially increased 

hepatic toxicity and the need for more frequent assessment of LFTs

• Infants born to HCV infected women should be tested for HCV

• In patients with HCV infection and documented cirrhosis, perform 

an annual AFP and hepatic ultrasound to screen for hepatocellular 

carcinoma

Tuberculosis testing (MMWR Recomm Rep 2009;58(RR-4):1): A baseline 

purified protein derivative (PPD) or interferon-gamma release assay should 

be obtained for all patients who do not have a past history of a positive PPD. 

Patients who do have a history of a positive PPD should get a baseline chest 

X-ray (CXR). Note the following:

• A positive PPD in the setting of HIV infection is defined as >5 mm 

induration

• Anergy testing is not recommended

• Prior bCG vaccination is not a contraindication for PPD but may 

produce a positive PPD. Evaluate the patient for active TB and 

consider therapy for latent infection.

• With a positive PPD or interferon-gamma release assay, treat for 

latent TB after excluding active TB

• Repeat testing in patients with advanced HIV who were initially PPD 

negative but have subsequent immune reconstitution to a CD4+ cell 

count >200 cells/mm3

• Close contacts of persons with active TB should be treated for latent 

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TB, regardless of PPD results or prior treatment for TB, but active TB 

must first be ruled out

Other Laboratory Testing

Glucose-6-phosphate dehydrogenase deficiency: A relative deficiency of 

glucose-6-phosphate dehydrogenase (G6PD) may be found in up to 2% of 

African Americans and is not usually clinically significant. An absolute G6PD 

deficiency is occasionally found in women of Mediterranean ancestry and 

predisposes to hemolytic anemia with the use of certain medications, including 

dapsone and sulfonamides. Baseline testing will permit safe use of these drugs 

when needed.

Fasting blood sugar or hemoglobin A1C and lipid profile (total cholesterol, 

triglycerides, high-density lipoprotein, low-density lipoprotein): Both HIV and 

many ARVs have been associated with the development of hypertriglyceridemia 

and hypercholesterolemia; PIs have been linked to both new onset of and 

worsening of existing diabetes. Abnormal lipids should trigger a review of 

diet and exercise and the patient should be encouraged to make appropriate 

lifestyle changes. Also consider a change of HIV medications and/or anti-lipid 

therapy. (See Circulation 2005;112:3184 for the most recent recommendations.)

Urinalysis/calculated creatinine clearance: Because of an increased risk of 

HIV-associated nephropathy, this test is particularly important for Black HIV 

infected patients and patients with advanced disease or comorbid conditions. 

Perform prior to initiating TDF, IDV, ATV or other drugs with potential for 

nephrotoxicity.

Pap smear/STI screening: A Pap smear should be obtained (along with 

screening for gonorrhea, chlamydia and trichomoniasis) at baseline and 

periodically, with intervals based on prior results and/or treatment for an 

abnormal Pap, risk behaviors, and signs or symptoms or a diagnosis of STI 

(see Chapter 6, Gynecologic Problems).

Antiretroviral Therapy

DHHS supports several working groups of the Office of AIDS Research Advisory 

Council to develop and continuously update ARV treatment guidelines for adults 

and adolescents, children, and pregnant women. Updated recommendations 

are available at http://www.aidsinfo.nih.gov. The primary areas of attention 

in the adult and adolescent guidelines include baseline assessment, treatment 

goals, indications for initiation of ART, choice of the initial regimen in ART-naïve 

patients, drugs or combinations to be avoided, management of adverse effects 

and drug-drug interactions, management of treatment failure, and special ARTrelated considerations in specific patient populations.

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This section provides an overview of the general principles of ARV treatment; 

current evolution of and rationale for recommendations for earlier initiation of 

ART; current recommendations for initiating therapy in ART-naïve individuals, 

with special considerations for women; and management of ART-experienced 

patients. For detailed information on specific ARV agents now available in the 

U.S., see Table 8-7 (pp. 285–298 in Chapter 8, Pregnancy) and Tables 13-7 to 

13-9 (pp. 491–512) in Chapter 13, Pharmacology).

Goals of Antiretroviral Therapy

Eradication of HIV infection cannot be achieved with currently available 

ARV drug regimens, largely because a pool of latently infected CD4+ 

cells is established very early after acute infection (Proc Natl Acad Sci USA

1998;95(15):8869) and persists despite prolonged suppression of plasma 

viremia (Nat Med 2003;9(6):727; Nat Med 1999;5(5):512). Therefore, the 

primary goals of ART are to 1) reduce morbidity and mortality associated 

with HIV infection and improve quality of life; 2) restore and preserve 

immune function; 3) maximally and durably suppress HIV VL; and 4) prevent 

HIV transmission (DHHS Guidelines for the Use of Antiretroviral Agents in HIV1-Infected Adults and Adolescents; http://www.aidsinfo.nih.gov/guidelines/

html/1/adult-and-adolescent-treatment-guidelines/0/. Accessed 8/25/2012).

Three characteristics of HIV infection have significant implications for ART:

• Progressive immune damage: Between the time of initial infection 

and the development of clinical disease, progressive immune-system 

damage occurs, as evidenced by a decline in CD4+ lymphocyte 

counts as well as by ongoing inflammation and immune activation. 

These changes ultimately result in vulnerability to OIs and other 

AIDS-defining conditions as well as in higher rates of cardiovascular 

and other end-organ damage. Interrupting this progression provides 

a major rationale for the early initiation of ART.

• Rapid viral replication: The half-life of HIV in plasma is less than 48 

hours and turnover occurs at a rate of up to 1 billion virions per day 

(Nature 1995;373(6510):123). Lifelong therapy must be maintained 

to suppress viral replication and prevent disease progression.

• High degree of inherent genetic mutability: Mutations may develop 

rapidly when patients are not adherent to therapy; single mutations 

may confer high-level resistance to some ARV drugs and/or drug 

classes. Combination ART, consisting of at least two and preferably 

three active drugs from at least two drug classes, has been shown 

to have superior effectiveness in controlling viral replication, limiting 

the emergence of resistant virus, and reducing the risk of HIV 

progression and death.

When to Initiate Antiretroviral Therapy

It is now recommended that ART be initiated in all HIV-infected individuals 

regardless of CD4 cell count to reduce the risk of disease progression ART 

and to prevent of transmission of HIV. These recommendations are based on 

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the results of randomized controlled trials and cumulative observational cohort 

data that demonstrate the benefits of ART in reducing AIDS and non-AIDS 

associated morbidity and mortality as well as on increasing awareness that 

HIV-related morbidity and mortality result not only from immune deficiency 

but also from both the direct effects of HIV on specific organs and the indirect 

effects of HIV-associated inflammation on those organs. The benefit of ART in 

reducing transmission to others should also be considered in decisions about 

when to initiate therapy. The benefits of starting ART with high CD4+ cell 

counts and/or low viral set points should be balanced against considerations of 

short- or long-term adverse drug effects and the need for good adherence to 

lifelong therapy to prevent the development of resistance (DHHS Guidelines for 

the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents; http://

www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatmentguidelines/0/. Accessed 5/16/2013).

Available data indicate the following:

• Untreated HIV infection may have detrimental effects at all stages 

of infection

• Treatment is beneficial, even when initiated later in infection; 

however, later initiation may not fully reverse damage related to 

viral replication in the early stages of infection

• Earlier treatment may prevent the damage associated with HIV 

replication in early infection

• Earlier ART treatment is associated with reduced transmission to 

uninfected partners (N Engl J Med 2011; 365:493)

• Sustained viral suppression and maintenance of higher CD4+ cell 

counts may delay or prevent some HIV-associated but non-AIDS 

defining complications. Complications that may be delayed or 

prevented with ART include the following:

- HIVAN: ART is associated with preserved renal function and 

prolonged survival (Nephrol Dial Transplant 2006;21(10):2809; 

AIDS 2008;22(4):481; J Am Soc Nephrol 2005;16(8):2412)

- Progression of HBV/HCV infection (Hepatology 2009;50:1056; 

BMC Res Notes 2008;1:46; Hepatology 2008;48:1062)

- CV disease: Several studies suggest that untreated HIV and 

viral replication may be associated with endothelial dysfunction 

and inflammation; that increased markers of inflammation and 

coagulation, as well as risk of CV events, occur with treatment 

interruption; and that CV disease is associated with CD4+ 

cell depletion. Evidence also suggests that ART may result in 

significant improvement of parameters associated with CV 

disease, including markers of inflammation, high-sensitivity 

C-reactive protein, and endothelial dysfunction (J Acquir Immune 

Defic Syndr 2009;52(1):25; AIDS 2009;23:929; J Am Coll 

Cardiol 2008;52:569; PLoS Med 2008;5:e203; N Engl J Med

2006;355:2283; AIDS 2009;23:1743; AIDS 2008;22:2409).

- Cancer: Incidence of AIDS- and non-AIDS malignancies is increased 

as CD4+ cell count decreases to <350–500 cells/mm3. Regardless 

of CD4+ cell count, there appears to be a protective effect of 

ART for HIV-associated malignancies (J Acquir Immune Defic Syndr

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2009;52(1):25; AIDS 2009;23:1743; AIDS 2008;22:2143; Clin 

Infect Dis 2009;49:1109; Lancet Oncol 2009;10:1152).

- Neurocognitive decline: CD4+ cell count <350 cells/mm3 is 

associated with higher risk for HIV-associated dementia and moresevere neurologic complications (Ann Neurol 2008;63:213; AIDS 

2007;21:1915-1921; AIDS Res Hum Retroviruses 2008;24:1301)

Current recommendations for ART initiation (adapted from DHHS Guidelines 

for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents;

http://www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arvguidelines/10/initiating-art-in-treatment-naive-patients. Accessed 5/16/2013):

• Antiretroviral therapy (ART) is recommended for all HIV-infected 

individuals to reduce the risk of disease progression. The strength 

and evidence for this recommendation vary by pretreatment CD4 

cell count: CD4 count <350 cells/mm3 (strong recommendation); 

CD4 count 350–500 cells/mm3 (strong recommendation); CD4 count 

>500 cells/mm3 (moderate recommendation).

• ART also is recommended for HIV-infected individuals for the 

prevention of transmission of HIV (strong recommendation). 

• Patients starting ART should be willing and able to commit to 

treatment and understand the benefits and risks of therapy and 

the importance of adherence (strong recommendation). Patients 

may choose to postpone therapy, and providers, on a case-by-case 

basis, may elect to defer therapy on the basis of clinical and/or 

psychosocial factors.

Choosing an Initial Regimen

Factors to consider include the following (DHHS Guidelines for the Use of 

Antiretroviral Agents in HIV-1-Infected Adults and Adolescents):

• Comorbid conditions (e.g., cardiovascular disease, chemical 

dependency, liver disease, psychiatric disease, renal diseases, TB)

• Potential adverse drug effects

• Potential drug interactions with other medications

• Pregnancy or pregnancy potential

• Results of genotypic drug-resistance testing

• Female gender and pretreatment CD4+ cell count if considering NVP

• HLA-B*5701 testing if considering ABC

• Coreceptor tropism assay if considering MVC

• Patient adherence potential

• Convenience (e.g., pill burden, dosing frequency, food and 

fluid considerations)

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The current guidelines for managing HIV in adults and adolescents offer four 

preferred regimens for initial therapy in ARV-naïve patients:

• Efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC)

• Ritonavir-boosted atazanavir + tenofovir/emtricitabine 

(ATV/r + TDF/FTC)

• Ritonavir-boosted darunavir + tenofovir/emtricitabine (DRV/r 

+ TDF/FTC)

• Raltegravir + tenofovir/emtricitabine (RAL + TDF/FTC)

The DHHS guidelines also describe alternative and acceptable regimens, as 

well as combinations for which more data are needed and combinations that 

should be avoided. Chapter 8 of the current book covers recommendations 

for ART in pregnancy. Consultation with an HIV specialist is recommended for 

questions about treatment in specific patient situations.

In an ART-naïve patient, VL reduction to levels below the limits of assay 

detection usually occurs within the first 12–24 weeks of therapy. Predictors of 

virologic success include use of a high-potency ARV regimen, patient adherence 

to the treatment regimen, low baseline VL, higher baseline CD4+ cell count 

(>200 cells/mm3), and rapid reduction of VL in response to treatment.

In general, studies to date have not shown differences in the virologic efficacy 

of ART by gender (AIDS 2007;21(7):835; HIV Med 2006;7(8):520; Ann Intern 

Med 2010;153(6):349), although several studies have suggested that gender 

may influence the frequency, presentation, and severity of selected ARVrelated adverse events (Expert Rev Anti Infect Ther 2005;3(2):213). Although 

data are limited, evidence also suggests that women may metabolize and 

respond to specific medications, including ARV drugs, differently from men 

(Annu Rev Pharmacol Toxicol 2004;44:499; Pharmacol Res 2008;58(3-4):173; 

Gend Med 2007;4(2):106).

Results of a few studies examining metabolic complications associated with 

ARV use indicate that HIV infected women on ART are more likely than men 

to experience increases in central fat deposition and less likely than men to 

have triglyceride elevations (HIV Med 2001;2(2):84; J Acquir Immune Defic 

Syndr 2003;34(1):58). Compared with men, women have an increased risk of 

osteopenia and/or osteoporosis, particularly after menopause, and this risk may 

be exacerbated by HIV and ART (Osteoporos Int 2005;16(11):1345; AIDS

2007;21(13):1830). None of these differences, however, currently requires a 

change in the recommendations for treatment or monitoring in women.

Antiretroviral Agents

See Table 8-7 in Chapter 8, HIV and Pregnancy, for ARVs (including 

co-formulations) currently licensed in the United States, including formulations, 

dosing, and adverse effects. See Chapter 13, Pharmacologic Considerations in 

HIV Infected Pregnant Patients, for drug interactions and recommended dose 

adjustments with ARVs.

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ARVs are now divided into six classes on the basis of their mechanism of 

action: NRTIs, NNRTIs, PIs, fusion inhibitors (FIs), CCR5 antagonists, and 

integrase strand transfer inhibitors (INSTIs). It is helpful to understand how these 

drug classes inhibit HIV as components of a successful combination regimen.

Nucleoside reverse transcriptase inhibitors: NRTIs were the first class of agents 

shown to be effective in the treatment of HIV infection. The target enzyme 

for this group of drugs is HIV reverse transcriptase, an RNA-dependent DNA 

polymerase. Class-wide adverse effects include lactic acidosis, which appears 

to have a female predominance. Lactic acidosis is a rare but potentially 

life-threatening toxicity thought to be due to mitochondrial toxicity and 

associated with prolonged exposure to NRTIs. It is most common with stavudine, 

didanosine, and zidovudine; however, it can occur with other NRTIs (AIDS

2007;21(18):2455).

Non-nucleoside reverse transcriptase inhibitors: NNRTIs noncompetitively 

inhibit HIV reverse transcriptase by binding to a site distant from the enzyme’s 

active site. There are three first-generation NNRTIs: nevirapine, delavirdine, 

and efavirenz. The two second-generation agents, etravirine and rilpivirine, 

work against HIV that has developed some mutations to the older drugs in 

this class. NNRTIs are both metabolized by and induce the hepatic cytochrome 

P450 (CYP) enzyme system, resulting in multiple drug-drug interactions. All 

NNRTIs are associated with potential rash, which typically appears in the 

second week of dosing, usually around days 9–11. Dosing can be continued 

unless there is mucosal involvement, and the rash will resolve. NVP has been 

associated with an increased risk of symptomatic, potentially fatal, and 

often rash-associated liver toxicity among ARV-naïve individuals; women 

with higher CD4+ cell counts (>250 cells/mm3) and/or elevated baseline 

transaminases appear to be at the greatest risk (J Acquir Immune Defic Syndr

2004;35(5):538; Clin Infect Dis 2008;46(6):933; Clin Infect Dis 2004;38 Suppl 

2:S80; J Infect Dis 2005;192(3):545). It is not generally recommended that 

NVP be prescribed for ARV-naïve women who have CD4+ cell counts >250 

cells/mm3 unless there is no alternative and the benefit from NVP outweighs 

the risk of hepatotoxicity.

Protease inhibitors: PIs prevent maturation of virus proteins by competitively 

inhibiting HIV protease, an enzyme essential for cleavage of the HIV 

polyprotein into its separate active structural proteins; three viral enzymes 

(reverse transcriptase, integrase, and protease); and surface glycoproteins. 

When this enzyme is blocked, immature, noninfectious virus particles are 

produced. The other important properties of PIs are limited CNS penetration; 

metabolism by and complex effects on the CYP enzyme system, resulting in 

multiple drug-drug interactions; and an increased incidence of new diagnoses 

of diabetes or worsening of pre-existing diabetes.

Ritonavir, an early PI that was very difficult to tolerate at full dose, has 

more recently been used to enhance or boost the pharmacokinetic profiles 

of other PIs and other ARVs primarily metabolized by CYP 3A4, such as the 

CCR5 antagonist maraviroc, because it is such an effective inhibitor of CYP 

3A4. RTV-boosted PI regimens that permit fewer doses and/or fewer pills 

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per day while achieving high PI drug levels are preferred over unboosted 

dosing regimens. Boosting thus facilitates adherence and helps prevent the 

development of resistance.

All PIs are associated with variable degrees of gastrointestinal adverse effects 

(nausea, diarrhea, abdominal discomfort), hyperlipidemia, hyperglycemia, 

and fat maldistribution (central adiposity and/or peripheral lipoatrophy). All 

boosted PIs should be taken with food.

Fusion inhibitors: FIs interact with HIV directly, rather than with the host cell. 

This interaction prevents the fusion of HIV to the cell. Because it is a protein, 

enfuvirtide, the first drug in this class, must be given by subcutaneous injection 

twice daily. The most common side effect is local injection-site reactions.

CCR5 antagonists: This is the only drug class that targets a host cellular protein 

rather than a viral protein. To gain access to a CD4+ cell, HIV must first bind 

to the CD4+ receptor, undergo a conformational change, and then bind to the 

CCR5 coreceptor as a prelude to virus-cell fusion. MVC, the first drug in this 

class, is very well tolerated but is effective only against virus that solely utilizes 

CCR5; it is not effective against virus that can bind to both CCR5 and the CXC 

chemokine receptor type 4 (CXCR4), or solely to CXCR4. A tropism assay can 

determine whether MVC will be effective.

Integrase strand transfer inhibitors: This is the most recently approved class 

of ARVs. INSTIs prevent the covalent integration of proviral DNA into cellular 

DNA, thus preventing the manufacture of the constituent parts of new virions 

by an infected cell. Raltegravir, the first drug in this class, is well tolerated 

and at a dose of 400 mg twice daily produces a very rapid decrease in 

HIV VL within the first few weeks of treatment. It has no effect on CYP 450 

and therefore produces minimal drug-drug interactions. It inhibits another 

hepatic enzyme, UGT1, that is involved in glucuronidation. A second INSTI, 

elvitegravir, has been FDA approved for ART-naïve patients; it is available in a 

co-formulated tablet with FTC, TDF and cobicistat (a pharmokinetic enhancer) 

and is given once daily. Approval of a third INSTI, dolutegravir, is anticipated 

in the near future.

Adherence

Medication adherence is the crucial element in successful HIV treatment. (See 

Chapter 5, Adherence.) Studies have shown that healthcare professionals are 

poor judges of who will and will not be adherent. For this reason, all patients 

initiating therapy should be educated about the importance of adherence, 

and adherence should be discussed repeatedly over the course of treatment 

to offset the effects of treatment fatigue. The most frequent reason for an 

increase in viral load is poor adherence and any increase in viral load should 

prompt assessment of the patient’s adherence to the prescribed ART regimen. 

A potential reason for poor adherence in pregnancy is concern on the patient’s 

or the provider’s part that ARV drugs are dangerous in early pregnancy. 

Although multiple strategies have been employed to support and promote 

adherence, no data indicate which strategies are most effective.

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Adverse Events Associated with Antiretroviral Therapy

Complications of particular clinical significance or concern are included in Table 

4-6, with additional key information noted below. In general, decisions about 

management, including changes in ART, should be made in consultation with an 

HIV specialist.

Table 4-6

Antiretroviral Therapy-Associated Common and/or 

Severe Adverse Effects

Adverse Effect Antiretroviral Agent(s)

Bleeding events • All PIs:  spontaneous bleeding

• TPV: Reports of intracranial hemorrhage. Risk factors include 

CNS lesions; trauma; surgery; hypertension; alcohol abuse; 

coagulopathy; use of anticoagulant or antiplatelet agents, 

including vitamin E.

Bone marrow 

suppression • ZDV: Anemia, neutropenia

Cardiovascular 

disease • ABC and ddI: Associated with MI in some cohort studies. 

Risk greatest among those with traditional CVD risk factors.

• PIs: Associated with MI and stroke in some cohort studies. Risk 

greatest among those with traditional CVD risk factors. Limited 

data on newer PIs (ATV, DRV, TPV).

• SQV/r, ATV/r, and LPV/r: PR interval prolongation. 

Risks include structural heart disease, conduction system 

abnormalities, cardiomyopathy, ischemic heart disease, and 

coadministration with other drugs that prolong PR interval.

• SQV/r: QT interval prolongation in a study of healthy 

volunteers. Risks include underlying heart conditions, preexisting prolonged QT or arrhythmia, or use with other 

QT-prolonging drugs. ECG is recommended prior to SQV 

initiation and should also be considered during therapy.

CNS effects • d4T: Associated with rapidly progressive ascending 

neuromuscular weakness resembling Guillain-Barré syndrome 

(rare)

• EFV: Somnolence, insomnia, abnormal dreams, dizziness, 

impaired concentration, depression, psychosis, suicidal 

ideation. Most symptoms subside or diminish after 2–4 wk. 

Bedtime dosing may reduce symptoms. Risk factors include 

history of psychiatric illness, concomitant use of agents with 

neuropsychiatric effects, and  plasma EFV concentrations due 

to genetic factors or absorption (i.e., with food).

Diabetes mellitus,

Insulin resistance

hyperglycemia

• ZDV, d4T, and ddI

• Reported for some PIs (IDV, LPV/r), but not all PIs studied

• ATV +/- RTV not found to alter insulin sensitivity

Hyperlipidemia • d4T > ZDV > ABC:  LDL and TG

• EFV: TG, LDL, HDL

• All RTV-boosted PIs: LDL, TG, HDL

• LPV/r = FPV/r and LPV/r > DRV/r and ATV/r

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Table 4-6

Antiretroviral Therapy-Associated Common and/or 

Severe Adverse Effects

Adverse Effect Antiretroviral Agent(s)

Gastrointestinal • ddI, ZDV > other NRTIs: Nausea and vomiting

• ddI: Pancreatitis

• PIs: Diarrhea, nausea, vomiting

• LPV/r > DRV/r and ATV/r; NFV (common): Diarrhea

• ATV: cholelithiasis

Hepatic toxicity • NRTIs: Reported for most

- ddI: Prolonged exposure linked to noncirrhotic portal 

hypertension, in some cases with esophageal varices

- ZDV, d4T, ddI: Most commonly associated with steatosis

- TDF, 3TC, FTC: When withdrawn, HBV coinfected patients 

may develop severe hepatic flare (also when HBV resistance 

develops)

• NNRTIs: NVP > other NNRTIs

- NVP: Severe hepatic toxicity with NVP is often associated 

with skin rash or symptoms of hypersensitivity. For ARVnaïve patients, risk is greater for women with pre-NVP 

CD4+ cell count >250 cells/mm3. Overall risk is higher for 

women. Risk is greatest during first few months of treatment. 

2-wk dose escalation of NVP reduces risk of rash and may 

reduce hepatotoxicity if related to hypersensitivity. NVP is 

contraindicated in patients with moderate to severe liver 

disease (Child-Pugh classification B or C).

• All PIs: Varying degrees of drug-induced hepatitis and hepatic 

decompensation (and rare cases of fatalities) have been 

reported with all PIs

- TPV/r has a higher frequency of hepatic events than other PIs

- IDV, ATV: Jaundice due to indirect hyperbilirubinemia

- TPV/r: Contraindicated in patients with moderate to severe 

hepatic insufficiency (Child-Pugh classification B or C)

• CCR5 antagonist: MVC

Hypersensitivity 

reaction 

(excluding 

rash alone or 

Stevens–Johnson 

syndrome)

• ABC: Screen for HLA-B*5701 prior to initiation; do not 

start ABC therapy if HLA-B*5701 is positive. Symptoms of 

HSR include (in descending order of frequency): fever, skin 

rash, malaise, nausea, headache, myalgia, chills, diarrhea, 

vomiting, abdominal pain, dyspnea, arthralgia, respiratory 

symptoms. HSR worsens with continuation of ABC. Median 

onset, 9 d; ~90% of reactions occur within first 6 wk. Onset 

of rechallenge reactions is within hours of rechallenge dose. 

Patients, regardless of HLA-B*5701 status, should not be 

rechallenged with ABC if HSR is suspected.

• NVP: Hypersensitivity syndrome of hepatic toxicity and rash 

that may be accompanied by fever, general malaise, fatigue, 

myalgias, arthralgias, blisters, oral lesions, conjunctivitis, facial 

edema, eosinophilia, granulocytopenia, lymphadenopathy, or 

renal dysfunction. For ARV-naïve patients, risk is greater for 

women with pre-NVP CD4+ cell count >250 cells/mm3. Risk is 

higher for women. 2-wk dose escalation of NVP reduces risk.

• RAL: Rash, constitutional findings and sometimes organ dysfunction

• MVC: Reported as part of a syndrome related to hepatotoxicity

continued

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Table 4-6

Antiretroviral Therapy-Associated Common and/or 

Severe Adverse Effects

Adverse Effect Antiretroviral Agent(s)

Lactic acidosis • NRTIs, especially d4T, ZDV, and ddI: Insidious onset with 

GI prodrome, weight loss, and fatigue. May be rapidly 

progressive, with tachycardia, tachypnea, jaundice, muscular 

weakness, mental status changes, respiratory distress, 

pancreatitis, and organ failure. Mortality up to 50% in some 

case series, especially in patients with serum lactate >10 

mmol/L. Increased risk: female sex, obesity.

• Laboratory findings:  lactate (2–5 mmol/L: correlate with symptoms; >5 mmol/L abnormal), anion gap, AST, ALT, PT, 

bilirubin;  amylase and lipase in patients with pancreatitis;  arterial pH, serum bicarbonate, serum albumin

• Upon diagnosis, stop all ARV drugs until recovery

Lipodystrophy 

(fat 

maldistribution 

syndromes)

• Thymidine analogs (d4T > ZDV): Lipoatrophy; may be more 

likely when combined with EFV vs. boosted PI

• EFV-, PI-, and RAL-containing regimens: Lipohypertophy 

(trunk fat increase) has been observed; however, a causal 

relationship has not been established

Myopathy and/

or elevated CPK • ZDV: Myopathy

• RAL:  CPK, muscle weakness, rhabdomyolysis

Nephrotoxicity 

and/or 

urolithiasis

• TDF:  serum creatinine, proteinuria, hypophosphatemia, 

urinary phosphate wasting, glycosuria, hypokalemia, non-anion 

gap metabolic acidosis; concurrent use of PI may increase risk

• IDV:  serum creatinine, pyuria; hydronephrosis or renal 

atrophy

• IDV, ATV: Stone, crystal formation; adequate hydration may 

reduce risk

• EVG (co-formulated with cobicistat): potential for new or 

worsening renal impairment

Osteopenia 

and/or 

osteoporosis

• TDF: Associated with greater loss of bone mineral density 

compared with ZDV, d4T, and ABC

• Decreases in bone mineral density observed in studies of 

regimens containing different NRTIs combined with either 

NNRTIs or PIs

Peripheral 

neuropathy • d4T > ddI, ddC: Peripheral neuropathy (pain and/or 

paresthesias, lower extremities > upper extremities); can be 

irreversible

Rash • All NNRTIs

• ATV, DRV, FPV

• RAL: Uncommon

• MVC

Stevens–Johnson 

syndrome 

and/or toxic 

epidermal 

necrolysis

• ddI, ZDV: Reported cases

• NVP > DLV, EFV, ETR, RPV; females at greater risk than males

• FPV, DRV, IDV, LPV/r, ATV: Reported cases

• RAL: Reported cases

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: Adapted from Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults 

and Adolescents

continued

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Hepatotoxicity: Hepatotoxicity, generally defined as a three- to fivefold 

increase in serum transaminases, may occur with or without clinical hepatitis. 

NVP has the greatest potential for causing hepatotoxicity (up to 12%). 

Approximately two-thirds of NVP-associated cases of clinical hepatitis occur 

within the first 12 weeks of treatment; however, risk continues after this time 

and patients should be monitored closely for the first 18 weeks of treatment.

The initial presentation may include nonspecific gastrointestinal and flu-like 

symptoms. Although liver-enzyme abnormalities may or may not be present 

initially, this syndrome can progress rapidly to fulminant hepatic failure. Risk 

factors for hepatic toxicity include HBV or HCV coinfection, alcohol abuse, 

baseline elevated liver enzymes, and concomitant use of other hepatotoxic 

agents (Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults 

and Adolescents).

Lactic acidosis: Lactic acidosis is usually seen with long-term NRTI exposure. 

Because the initial signs and symptoms are nonspecific, clinicians should have 

a high level of suspicion for this adverse effect. Routine lactate testing is not 

recommended; however,testing should be performed with signs or symptoms 

of possible lactic acidosis. ART should be stopped if clinical and laboratory 

manifestations are consistent with lactic acidosis. A new regimen should 

commence after recovery, which can take months.

Lipodystrophy (fat maldistribution syndromes): Fat accumulation is most 

commonly seen in the abdomen, neck (dorsocervical fat pad), and breasts. 

Lipoatrophy most commonly affects the face, buttocks, and extremities; risk has 

been associated with d4T use in particular. Women seem particularly prone to 

developing truncal obesity (i.e., increased abdominal girth, increased breast 

size). Women who perceive adverse changes in body habitus related to their 

ARV regimens may be at increased risk for nonadherence. It may be useful to 

obtain some standard measurements, such as minimum waist, maximum hip, and 

neck circumference at an early visit, before ART is started, and to question the 

patient at regular intervals about any perceived changes in body shape or 

changes in clothing and brassiere size. Such measurements, while inexact, are 

inexpensive and easier to obtain than anthropomorphic measurements, dualemission X-ray absorptiometry, or computed tomography (CT) scans.

Management of the Treatment-Experienced Patient

In general, a distinction is made between patients with limited prior treatment 

and those with extensive prior treatment because those with more limited ARV 

experience have a greater likelihood of achieving maximal viral suppression 

with an appropriate change in regimen. Assessing and managing a patient 

with extensive prior ARV experience and treatment regimen failure is complex 

and expert advice is critical. Changing therapy sooner rather than later is 

recommended to minimize the continued selection of resistance mutations.

The DHHS Guideline Panel’s overall recommendations for management of 

the patient whose current therapy is failing are as follows: (adapted from 

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and 

Adolescents; http://www.aidsinfo.nih.gov/guidelines/html/1/adult-andadolescent-treatment-guidelines/0/. Accessed 8/25/2012)

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• Evaluate virologic failure (defined as the inability to achieve or 

maintain suppression of viral replication <200 c/mL): Assess the 

severity of the patient’s HIV disease, ART history, use of concomitant 

medications (with consideration of possible adverse drug interactions 

with ARV agents), HIV RNA and CD4+ cell count trends over time, 

and prior drug-resistance testing results.

• Perform drug-resistance testing: Test for drug resistance while the 

patient is taking the failing ARV regimen (or within 4 weeks of 

treatment discontinuation). To avoid false-negative results in patients 

who have discontinued their treatment regimen, it may be helpful to 

have them restart their medications for a week or so and then obtain 

a resistance test.

• Re-establish virologic suppression: The goal of treatment for ARVexperienced patients with drug resistance who are experiencing 

virologic failure is to re-establish virologic suppression (e.g., HIV RNA 

below the current limit of detection).

• Design a new regimen: Use the patient’s treatment history and 

past and current resistance test results to identify at least two, and 

preferably three, fully active agents to combine with an optimized 

background ARV regimen. A fully active agent is one that is likely 

to have ARV activity on the basis of the patient’s treatment history, 

the results of drug-resistance testing, and/or the presence of a novel 

mechanism of action.

• Do not add just one ARV: In general, adding only a single, fully 

active ARV to a new regimen is not recommended because of the 

risk that resistance to this agent will develop rapidly. In patients with 

a high likelihood of clinical progression (e.g. CD4+ cell count <100 

cells/mm3) and limited drug options, however, adding a single drug 

may reduce the risk of immediate clinical progression because even 

transient decreases in HIV RNA and/or transient increases in CD4+ 

cell counts have been associated with clinical benefits.

• Adjust goals: For some highly ART-experienced patients, maximal 

virologic suppression is not possible. In these cases, ART should be 

continued with regimens designed to minimize toxicity, preserve 

CD4+ cell counts, and avoid clinical progression.

• Avoid interruption: Discontinuing or even briefly interrupting therapy 

in a patient with viremia may lead to a rapid increase in HIV 

RNA and a decrease in CD4+ cell count and increases the risk of 

clinical progression (N Engl J Med. 2001;344(7):472; N Engl J Med. 2003;349(9):837). Therefore, this strategy is not recommended.

• In the setting of virologic suppression, no consensus exists on how to 

define or treat immunologic failure.

Other important clinical situations besides overt virologic failure are not 

necessarily linked to the development of resistance, such as

• Incomplete virologic response: defined as two consecutive plasma 

HIV RNA levels >200 c/mL after 24 weeks; the baseline HIV RNA 

level may affect the time course of response and some regimens 

take longer than others to suppress HIV RNA levels

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• Virologic rebound: defined as a confirmed detectable HIV RNA (to 

>200 c/mL) after virologic suppression

Treatment failure may occur for several reasons. It is important to try to 

distinguish among these reasons because approaches to the management of 

treatment failure will vary depending on the reason. In addition to patient 

and regimen characteristics, provider characteristics, such as inexperience in 

treating HIV disease, may also come into play. In some cases, the cause of 

treatment failure may be unknown.

Patient characteristics: ARV regimen characteristics:

• Higher pretreatment or baseline VL

• Lower pretreatment or nadir CD4+ 

cell count

• Prior AIDS diagnosis

• Comorbidities (e.g., active substance 

abuse, depression)

• Presence of drug-resistant virus, either 

transmitted or acquired

• Prior treatment failure

• Incomplete medication adherence and 

missed clinic appointments

• Drug side effects and toxicities

• Suboptimal pharmacokinetics 

(variable absorption, metabolism, 

or [theoretically] penetration into 

reservoirs)

• Food and/or fasting requirements

• Bedtime dosing problems (e.g. falling 

asleep early, sleeping at different 

location from where medications are 

kept)

• Adverse drug-drug interactions with 

concomitant medications

• Suboptimal potency

• Prescription errors 

To assess virologic failure, the clinician should evaluate the following (adapted 

from Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults 

and Adolescents; http://www.aidsinfo.nih.gov/guidelines/html/1/adult-andadolescent-treatment-guidelines/0/. Accessed 8/25/2012):

• ARV treatment history: any changes in VL and CD4+ cell counts 

over time; results of prior resistance testing (if any)

• Occurrence of HIV-related clinical events: thorough interval history 

and physical exam

• Medication-taking behavior: adherence to recommended drug 

doses, dosing frequency, and food/fasting requirements; if problems 

are identified, address the underlying cause(s) (e.g., difficulties 

accessing or tolerating medications, depression, active substance 

abuse)

• Tolerability of medications: severity and duration of side effects; 

even minor side effects can affect adherence

• Concomitant medications and supplements: consider adverse drugdrug interactions

• Comorbidities: e.g., substance abuse

With regard to adherence, some patients do not want to disappoint their 

care providers and will insist that they are adherent even when they are not. 

Avoid putting such patients on the defensive. Refer to the facts provided by 

CD4+ cell count and VL load tests and encourage the patient to participate 

in the process of creating a new regimen or identifying supportive care 

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or behavioral changes that will ensure treatment success. The following 

management strategies may be helpful if problems with adherence are 

suspected or confirmed:

• If possible, simplify the ARV regimen (e.g., decrease pill count or 

dosing frequency)

• Provide symptomatic treatment of side effects, such as antiemetics 

or antidiarrheals; some patients may need scheduled antiemetics 

before each ARV dose until nausea abates

• Exchange one ARV for another within the same drug class (for 

medication intolerance)

• Exchange ARV from one drug class to another if necessary and if no 

prior drug resistance is suspected (for medication intolerance)

• Review recent history of gastrointestinal symptoms, such as vomiting 

or diarrhea, to assess the likelihood of short-term malabsorption

• Review concomitant medications and dietary supplements for 

possible adverse drug-drug interactions (see Chapter 13, 

Pharmacologic Considerations in HIV Infected Pregnant Patients; 

Drug Interactions section, Tables 14–16, Guidelines for the Use of 

Antiretroviral Agents in HIV-1-Infected Adults and Adolescents; http://

www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescenttreatment-guidelines/0/. Accessed 8/25/2012) and make 

appropriate substitutions

• If decreased ARV exposure due to pharmacokinetic drug-drug 

interactions or impaired drug absorption is suspected, therapeutic 

drug monitoring (TDM) may be helpful

Resistance Testing

When a regimen is changed for lack of efficacy, information from resistance 

testing can be of pivotal importance in choosing a new regimen.

Genotypic assays: These assays determine changes in the nucleotide sequences 

in viral genes. Interpretation of test results requires knowledge of the mutations 

for which different ARV drugs select and of the potential conferred by 

certain mutations for cross-resistance to other drugs. The International Antiviral 

Society-USA maintains an updated list of significant resistance-associated 

mutations in the RT, PR, integrase, and envelope genes (see https://www.iasusa.

org/node/128; accessed 8/25/2012). The Stanford University HIV Drug 

Resistance Database (see http://hivdb.stanford.edu; accessed 8/25/2012) 

also provides helpful guidance for interpreting genotypic resistance test results.

Genotypes are reproducible, are less expensive than phenotypes, and provide 

relatively rapid results (1–2 weeks). Results are reported as a three-piece 

string of information for each mutation detected: 1) initial associated with the 

wild-type amino acid (e.g., M for methionine), 2) number of the codon involved 

(e.g., codon 184 in reverse transcriptase), and 3) initial associated with the 

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amino acid coded for by the mutated codon (e.g., V for valine). Thus, the 

common key mutation in the RT gene that confers complete resistance to 3TC 

and FTC is M184V.

Phenotypic assays: These assays directly determine the amount of a 

medication that is required to inhibit the patient’s virus. The median inhibitory 

concentration (IC) 50 (the drug concentration that inhibits viral replication by 

50%) is calculated and the ratio of the IC50 of test and reference viruses is 

reported as the fold increase in IC50 (i.e., fold resistance). Phenotypic assays 

are most useful for finding agents with partial activity in patients with multiple 

drug resistance; this approach is more expensive and time consuming than 

genotypic assays. In addition, although clinically significant fold-increase cutoffs 

are now available for some drugs, information is incomplete regarding the 

specific fold increase in IC50 that is associated with drug failure.

Limitations of resistance testing: Both phenotypic and genotypic assays are 

typically difficult to perform if the viral copy number is <1000 c/mL, although 

some specimens with >500 c/mL but <1000 c/mL can be successfully tested. 

The utility of these assays is also limited by an inability to detect resistant virus 

that makes up less than 10%–20% of the total viral population in a sample, 

termed minority species.

Furthermore, these assays will only reliably detect mutations that confer 

resistance to medications the patient is taking at the time the assay is 

performed; samples from patients who are off therapy are likely to show wildtype (sensitive) virus as the predominant circulating viral strain because it is 

the strain that replicates most successfully. Thus, resistance testing is insensitive 

to mutations secondary to selective pressure that is no longer present after 

a change in regimen. Virus with these mutations likely still exists as a small 

percentage of the circulating virus and may lead to clinical resistance if 

drugs that test “sensitive” are used; however, these drugs are inactive against 

resistant minority species, which can become dominant over time.

If the same ARV agents (or those sharing similar resistance pathways) are 

reinstated, early drug failure usually occurs; the virus present at failure is 

derived from previously archived resistant virus (J Infect Dis 2006;194(9):1309). 

Reversion to predominantly wild-type virus can occur in the first 4–6 weeks 

after drugs are stopped; therefore, resistance testing is of greatest value when 

performed before or within 4 weeks after drugs are discontinued.

Patients with pansensitive virus in the face of virologic failure should be 

questioned carefully but nonjudgmentally about their medication-taking 

behaviors. TDM can also be considered, although no data currently 

demonstrate that TDM improves clinical outcome.

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Treatment Interruptions (Drug Holidays)

Several studies have shown that both HIV-associated and non-HIV-associated 

outcomes (renal, cardiac, hepatic) are worse when treatment is interrupted 

(N Engl J Med 2006;355(22):2283; Lancet 2006;367(9527):1981; HIV Med

2007;8(2):96; AIDS 2004;18(3):439). Therefore, long-term interruption of HIV 

therapy should be avoided if at all possible.

Treatment of Acute and Recent HIV Infection

The benefits of treating acute and recent (with the first 6 months) HIV infection 

are not completely defined. The rationale for early treatment is that it will 

achieve early suppression of viremia with alteration of the initial viral setpoint. 

This can slow disease progression rates, reduce the rate of viral mutation by 

suppressing viral replication, preserve immune function, and reduce the risk 

of viral transmission. The potential risks of initiating therapy include exposure 

to ART without a known clinical benefit, drug toxicities, development of drug 

resistance, creation of an ongoing need for strict adherence to therapy, and 

adverse effects on quality of life. Unanswered questions about the risks and 

benefits of early therapy should be addressed with patients and treatment 

of early HIV infection should be offered. Enrollment in clinical trials and 

observational studies of acute HIV should be considered.

In treating acute HIV, it is always important to use a three- or four-drug 

regimen that would be expected to provide complete viral suppression. 

In addition to considering the source of exposure and local epidemiologic 

information, genotypic resistance testing should be performed. In acute HIV 

infection, a patient’s predominant virus will be the strain that was transmitted, 

without reversion to the wild-type (pansensitive) virus that is seen in chronically 

infected patients who have stopped treatment.

Treatment in Pregnancy

ART is indicated in pregnancy to reduce the risk of perinatal transmission 

and to treat maternal disease. Specific guidelines for optimal therapy are 

addressed in Chapter 8, HIV and Pregnancy, and in the DHHS guideline 

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected 

Women for Maternal Health and Interventions to Reduce Perinatal HIV 

Transmission in the United States, available at http://aidsinfo.nih.gov/

guidelines/html/3/perinatal-guidelines/0/ (accessed 5/16/2013).

Alternative or Complementary Therapy

Some patients may ask questions about alternative or complementary therapy 

or may indicate that they are already taking such therapy. All patients should 

be specifically asked about their use of such therapies because they may 

not consider these remedies to be medications and may not volunteer the 

information to a care provider. Specific complementary therapies change 

rapidly and their use varies widely with geography and patient demographics. 

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For patients who do choose such therapies, it is important to ensure that 

they avoid using agents with toxicities or drug interactions that overlap with 

their prescribed medications and that discussions about complementary or 

alternative therapies occur in a way that does not alienate patients from their 

involvement in medical care.

Presentation and Management of Opportunistic Infections 

and Other Conditions Associated with HIV/AIDS

The risk for various opportunistic processes—so called because they take 

advantage of a weakened immune system—is defined by the total CD4+ 

lymphocyte count. Opportunistic processes include OIs and certain malignancies 

and are similar to the diseases seen in other immunocompromised hosts, such 

as recipients of solid-organ transplants. AIDS was first recognized as a new 

entity by the characteristic pattern of opportunistic diseases—especially PCP 

and Kaposi’s sarcoma (KS)—that were being diagnosed in young, previously 

healthy gay men. The pattern and sequence of OIs that are seen as the total 

CD4+ cell count decreases, described in Table 4-7, is so reliable that in most 

cases the total CD4+ cell count limits the differential diagnosis.

Table 4-7

Correlation of Complications with CD4+ Cell Counts

CD4+ Cell 

Count*

Infectious Complications Noninfectious† Complications

>500 cells/

mm3

• Acute retroviral syndrome

• Candida vaginitis

• PGL

• Guillain-Barré syndrome

• Myopathy

• Aseptic meningitis

200–500 

cells/mm3

• Pneumococcal and other 

bacterial pneumonia

• Pulmonary tuberculosis

• Herpes zoster

• Oropharyngeal candidiasis 

(thrush)

• Cryptosporidiosis, self-limited

• KS

• Oral hairy leukoplakia

• CIN

• Cervical cancer

• B-cell lymphoma

• Anemia

• Mononeuritis multiplex

• ITP

• Hodgkin’s lymphoma

• Lymphocytic interstitial 

pneumonitis

<200 cells/

mm3

• PCP

• Candida esophagitis

• Disseminated histoplasmosis 

and coccidioidomycosis

• Miliary/extrapulmonary TB

• Wasting

• Peripheral neuropathy

• HIV-associated dementia

• Cardiomyopathy

• Vacuolar myelopathy

• Progressive polyradiculopathy

• Non-Hodgkin’s lymphoma

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Table 4-7

Correlation of Complications with CD4+ Cell Counts

CD4+ Cell 

Count*

Infectious Complications Noninfectious† Complications

<100 cells/

mm3

• Disseminated herpes simplex

• Toxoplasmosis

• Cryptococcosis

• Cryptosporidiosis, chronic

• Microsporidiosis

• PML

<50 cells/

mm3

• CMV end-organ disease: 

primarily retinitis (~80–85%), 

GI (~15%)

• Disseminated MAC

• CNS lymphoma

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

* Most complications occur with increasing frequency at lower CD4+ cell counts

† Some conditions listed as “noninfectious” are probably associated with transmissible 

microbes. Examples include lymphoma (Epstein-Barr virus [EBV]) and cervical cancer 

(human papillomavirus [HPV]).

Source: © Adapted with permission from Medical Management of HIV Infection. Baltimore: 

Johns Hopkins University School of Medicine; 2009-2010.

At CD4+ cell counts >500 cells/mm3, illnesses are rarely associated with the 

patient’s HIV serostatus. Non-Hodgkin’s lymphoma and, rarely, mucocutaneous 

KS are occasional exceptions; they can occur at varying CD4+ cell counts but 

are more frequently diagnosed at lower values. Infections that are virulent 

among HIV-seronegative women, such as TB, bacterial pneumonia, and invasive 

cervical cancer, may occur at any CD4+ cell count but are more common and 

more severe as the CD4+ cell count declines.

Between 200 cells/mm3 and 500 cells/mm3, less-serious HIV-associated 

problems begin to manifest themselves, such as oral hairy leukoplakia, various 

skin problems, shingles, and oral or recurrent vaginal candidiasis (thrush). 

According to the 1993 CDC case definition, AIDS may be defined by specified 

OIs or by a decline in the total CD4+ cell count to below 200 cells/mm3. 

This CD4+ cell count criterion acknowledges an important threshold for OI 

risk. PCP, the most common AIDS-defining OI, is usually diagnosed as patients 

approach and drift below this critical number. Other OIs, such as toxoplasmosis, 

cryptococcal meningitis, and disseminated histoplasmosis, tend to occur as the 

CD4+ cell count declines from <200 cells/mm3 to <100 cells/mm3. Typically, 

end-stage illnesses such as CNS lymphoma, CMV end-organ disease, and 

disseminated Mycobacterium avium complex (MAC), tend to occur at very low 

CD4+ cell counts, often less than 25–50 cells/mm3.

continued

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Antimicrobial therapy works in concert with a patient’s immune system to 

clear infection. Before the advent of potent combination ART, HIV-associated 

opportunistic diseases could not be controlled without ongoing suppressive 

therapy because a patient’s immune function was too weak to effect that 

control. Once an OI was diagnosed and treated acutely (induction therapy, 

borrowing from the language of oncology), treatment would be continued 

at a lower maintenance dose or the OI would inevitably recur. “Cure” of OIs 

was not part of the vocabulary of HIV disease management. With potent 

combination ART resulting in dramatic improvement in CD4+ cell counts and 

immune function, however, both prophylactic and chronic suppressive OI 

therapies are being withdrawn successfully in responders. This has opened an 

entirely new era in the care of people with advanced HIV (see Opportunistic 

Disease in the Era of Antiretroviral Therapy, p. 132).

Prophylaxis of Opportunistic Infections

One of the early significant advances in the management of HIV/AIDS was the 

demonstration that chemoprophylaxis could prevent PCP and thereby improve 

survival. Before the development of potent combination ART, an important focus 

of the clinical research effort was to identify effective prophylactic agents for 

other common OIs. The success of this research was in part responsible for the 

slowdown in the death rate from AIDS that first became apparent near the end 

of 1995, just before the era of potent combination ART began.

Recommendations for prophylaxis for specific OIs depend on a number of 

factors (Table 4-8): the CD4+ threshold that defines the greatest risk, overall 

effectiveness of a given approach, risk of developing resistance, pregnancy, 

toxicity, and cost. The U.S. Public Health Service (USPHS)/Infectious Diseases 

Society of America guidelines for OI prophylaxis are updated periodically to 

reflect the most current understanding of disease risk and prevention. Current 

recommendations for initiating primary OI prophylaxis can be found on the 

Clinical Guidelines Portal of the AIDSinfo website (http://www.aidsinfo.nih.gov/

guidelines; accessed 5/17/2013).

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Table 4-8

Prophylaxis to Prevent a First Episode of Opportunistic Disease in Adults and Adolescents Infected With HIVPathogen Indications First Choice Regimen Alternative Regimens

Pneumocystis jirovecii(formerly carinii)

Strong recommendation:• CD4+ cell count <200 cells/mm3 or

• Oropharyngeal candidiasisModerate recommendation:• CD4+ percentage <14% or

• History of AIDS-defining illness or

• CD4+ cell count >200 but <250 cells/mm3

and if CD4+ cell count monitoring every 3 mo is not possible

• TMP-SMX 1 DS or 1 SS po qd • TMP-SMX 1 DS po tiw

• Dapsone 100 mg po qd or 50 mg po bid

• Dapsone 50 mg po qd + pyrimethamine 

50 mg po qw + leucovorin 25 mg po qw

• Dapsone 200 mg po qw + pyrimethamine 

75 mg po qw + leucovorin 25 mg po qw

• Aerosolized pentamidine 300 mg q mo 

via Respirgard II nebulizer

• Atovaquone 1500 mg qd

Tuberculosis Strong recommendation:

• Screen (+) for latent TB infection but no 

evidence of active TB disease and no history of past treatment for active or latent TB

- TST reaction ≥5 mm or- (+) Interferon gamma release assay

• Screen (-) for latent TB infection and no 

evidence of active TB disease but close contact with case of active TB

• Note: Patients with negative screening tests 

for latent TB and with CD4+ cell count <200 cells/mm3 and no indications for initiating 

empiric latent TB treatment should be retested for latent TB once they start ART and attain a CD4+ cell count ≥200 cells/mm3

• Isoniazid 300 mg po qd or isoniazid 900 

mg po biw; both with pyridoxine, 25 mg po qd x 9 mo

• For exposure to resistant TB, consult 

expert

• Rifampin 600 mg po qd x 4 mo or• Rifabutin (dose adjusted based on 

concomitant ART) x 4 mo 

Toxoplasma gondii

Strong recommendation:• IgG antibody to toxoplasma and• CD4+ cell count <100 cells/mm3

or• If toxoplasma seroconversion occurs

• TMP-SMX 1 DS po qd • TMP-SMX 1 DS po tiw

• TMP-SMX 1 SS po qd• Dapsone 50 mg po qd + pyrimethamine 

50 mg po qw + leucovorin 25 mg po qw

• Dapsone 200 mg po qw + pyrimethamine 

75 mg po qw + leucovorin 25 mg po qw 

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Table 4-8

Prophylaxis to Prevent a First Episode of Opportunistic Disease in Adults and Adolescents Infected With HIVPathogen Indications First Choice Regimen Alternative Regimens

Mycobacterium aviumcomplex

Strong recommendation:• CD4+ cell count <50 cells/mm3 after ruling 

out active MAC infection (negative clinical assessment +/-negative MAC blood cultures)

• Azithromycin 1200 mg po qw

• Clarithromycin 500 mg po bid• Azithromycin 600 mg po twice weekly• Both agents are better tolerated if taken 

with food

• Rifabutin 300 mg po qd (dosage 

adjustment based on drug-drug interactions with ART; see Table 13-9, pp. 500–507)

• Rule out active TB before starting rifabutin

Malaria • Travel to disease-endemic area • Recommendations are the same for patients 

with and without HIV infection

• One of the following three drugs is usually 

recommended depending on location: atovaquone/proguanil, doxycycline, or mefloquine

• Refer to the following website for the most 

recent recommendations based on region and drug susceptibility: http://www.cdc. gov/malaria/ (accessed 7/31/2012)

• Prevent exposure with use of DEETcontaining repellants and insecticideimpregnated bed nets, when indicated

Histoplasma capsulatum

Moderate recommendation:• CD4+ cell count ≤150 cells/μL and at high 

risk because of occupational exposure or living in area with high rate of histoplasmosis (>10 cases/100 patient-years)

• Itraconazole 200 mg po qd

Coccidioidomycosis Moderate recommendation:

• New (+) IgM or IgG in patients living in 

disease-endemic area and with CD4+ cell count <250 cells/μL

• Fluconazole 400 mg po qd

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixSource: Adapted from Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

continued

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Regimens, doses, and indications for routine immunizations in HIV infected 

women are outlined in Table 4-9.

Table 4-9

Routine Immunizations for HIV Infected Women*

Vaccine Dose and Regimen Indications and comments

Hepatitis A • 1 mL IM at 0, 6–12 mo 

(Havrix)

• 1 mL IM at 0, 6–18 mo (Vaqta)

• Also available in combination 

with HBV vaccine (Twinrix) 

given in 3–4 doses

• IDU, chronic liver disease, HBV 

or HCV infection, travel to 

endemic areas

• Consider for all HIV infected 

patients who are hepatitis A 

antibody negative

• IgG antibody response should 

be assessed 1 mo after 

vaccination; nonresponders 

should be revaccinated when 

CD4+ cell count >200 cells/μL

Hepatitis B • Engerix B 20 mcg or 

Recombivax HB 10 mcg IM at 

0, 1, and 6 mo

• Available in combination with 

HAV vaccine (Twinrix) given in 

3–4 doses

• Administer to patients without 

evidence of past or current 

HBV infection

• In patients with isolated antiHBc, consider screening for 

HBV DNA before vaccination to rule out occult chronic HBV 

infection

• Test for anti-HBs after dose 

3; repeat series should be 

considered for nonresponders 

(anti-HBs <10 IU/mL 1 mo 

after dose 3) and higher 

dose (40 mcg) booster is 

recommended by some experts

• Some experts may delay 

revaccination until sustained 

increase in CD4+ cell count 

with ART if CD4+ cell count is 

<350 cells/mm3 when patient 

is first vaccinated

HPV • Gardasil 0.5 mL IM at 0, 1–2, 

and 6 mo

or

• Cervarix 0.5 mL IM at 0, 1–2, 

and 6 mo

• Girls and women aged 9–26, 

ideally before onset of sexual 

activity; may consider in other 

groups

• Safety and immunogenicity 

studies in HIV infected patients 

are ongoing

Influenza • 0.5 mL IM annually • All patients

• Do not use live attenuated 

intranasal vaccine (FluMist)

Pneumococcal • 0.5 mL IM of the polyvalent 

polysaccharide vaccine 13 

followed by 0.5 mL IM of the 

polyvalent polysaccharide 

vaccine 23 at least 8 wk later 

(if CD4+ cell count <200 cells/

μL, consider waiting until CD4+ 

cell count >200 cells/μL)

• All patients, regardless of 

CD4+ cell count

• Moderate recommendation for 

re-vaccination with 23-valent 

vaccine ≥5 years after initial 

vaccination

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Table 4-9

Routine Immunizations for HIV Infected Women*

Vaccine Dose and Regimen Indications and comments

Polio • 0.5 mL SC; 3 doses over 6–12 

mo for primary immunization • OPV contraindicated; IPV should be given if vaccine is 

indicated

Tetanus toxoid • Td 0.5 mL IM; Tdap 0.5–0.75 

mL IM as per package insert • Same as for patients who are not HIV infected

• Substitute single dose of Tdap 

at time of next booster, then Td 

every 10 y

Varicella • 0.5 mL IM as two doses given 

3 mo apart • Administer if patient has CD4+ cell count >200 cells/mm3 and 

no evidence of immunity to 

varicella

• Post-exposure prophylaxis:

VZIG, 125 IU per 10 kg 

(maximum of 625 IU) IM, 

administered within 96 h after 

exposure to a person with 

active varicella or herpes 

zoster for patients with no 

evidence of immunity to 

varicella

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

* See Chapter 8, HIV and Pregnancy, for recommendations for pregnant women

Source: © Adapted from Primary Care Guidelines for the Management of Persons Infected 

with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the 

Infectious Diseases Society of America (Clin Infect Dis 2009;49:651)

Common Opportunistic Infections and Other Conditions 

Associated with HIV

Summaries with some key points are presented below (adapted from CDC 

Guidelines for Prevention and Treatment of Opportunistic Infections in HIV 

Infected Adults and Adolescents. 2013). More detailed discussion is beyond 

the scope of this guide; specific treatment agents and alternatives and dosing 

regimens for acute conditions and secondary OI prophylaxis, respectively, can 

be found on the Clinical Guidelines Portal of the AIDSinfo website (http://

www.aidsinfo.nih.gov/guidelines).

Initiation of ART as soon as possible during the course of treatment for an 

acute OI has been associated with longer survival, shorter time to CD4+ 

cell count >50 cells/mm3, and no increase in adverse effects (PLoS One

2009;4(5):e5575). Rapid initiation of ART will also shorten the duration of 

chronic maintenance (suppressive) therapy (i.e., secondary prophylaxis) for 

most patients as they recover immune responsiveness more quickly.

continued

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Pneumocystis jirovicii Pneumonia

Diagnosis: Because the presentation of PCP can be subtle and nonspecific, a 

heightened index of suspicion is warranted in appropriate circumstances. Most 

commonly, symptoms include the subacute onset of fever, exertional dyspnea, 

and nonproductive cough and chest discomfort that worsen over days to weeks.

Physical exam findings are also nonspecific. Auscultation may be entirely 

normal, particularly at rest with mild disease. Fine, dry “cellophane” rales 

may be heard with exertion. In 2%–6% of patients, PCP may present as 

spontaneous pneumothorax. The classic CXR findings are diffuse interstitial or 

perihilar infiltrates, but a wide range of CXR abnormalities is possible and 

radiography is normal in many cases of early disease. PCP is suggested by 

oxygen desaturation with exercise, which is easily measured in the office or 

clinic with a pulse oximeter, with the patient first at rest and then after running 

up a flight of steps, for example. This is particularly useful when symptoms are 

minimal, the patient does not appear acutely ill, and the CXR is unimpressive. 

Severity of illness is indicated by hypoxemia or a widened alveolar-arterial 

oxygen difference (AaDO2) on blood gas analysis.

Other etiologies of pneumonia may have a similar presentation. The 

definitive diagnostic test requires histopathologic or cytologic identification 

of Pneumocystis organisms in bronchoalveolar lavage (generally preferred), 

induced sputum, or transbronchial or open-lung biopsy. Although induced 

sputum is less invasive and less expensive, it should not be attempted in the 

absence of expertise in both obtaining and interpreting the smear.

Treatment: The mainstay of treatment for PCP is TMP-SMX, administered 

intravenously or orally depending on the severity of the episode. PCP should 

be treated for 21 days. Patients with arterial oxygen pressure <70 mm Hg 

or with AaDO2 >35 on room air should receive adjunctive steroids, which 

have been shown to decrease the incidence of ventilatory failure and death. 

A 21-day course of prednisone (40 mg bid x 5 days, then 20 mg bid x 5 

days, followed by 20 mg qd x 11 days) is the most popular and cost-effective 

approach. No additional taper is required.

After completing acute therapy, the patient should begin routine daily PCP 

prophylaxis to prevent recurrence. PCP prophylaxis can be discontinued after 

ART has led to an increase in CD4+ cell count to >200 cells/mm3 for >3 

months. (See Prophylaxis of Opportunistic Infections, p. 115.)

Candidiasis

The appearance of mucosal candidiasis is often the first clinical indication of 

impaired T-cell immunity in HIV infected individuals. Candida esophagitis is the 

second most common OI after PCP, and other mucosal forms of candidiasis (e.g, 

oral thrush, vaginal candidiasis) are common. Candidemia and tissue-invasive 

disease are rare, however.

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Candida esophagitis is a serious infection that may result in significant weight 

loss because of odynophagia and reduced oral intake. Esophagitis should be 

considered when the patient describes midline substernal chest discomfort with 

swallowing instead of pain limited to the throat. It may occur in the absence of 

oropharyngeal thrush and can be diagnosed by endoscopy with visualization 

of lesions and histopathologic demonstration of characteristic Candida yeast 

forms and/or culture confirmation. Empiric treatment may be considered in 

many circumstances. If the patient’s symptoms do not resolve, endoscopy with 

biopsy is recommended for a definitive diagnosis, as HSV and CMV infection 

and giant aphthous ulcers can have the same presentation.

Diagnosis: Oropharyngeal candidiasis is characterized by painless white 

plaques that can be easily scraped from the pharynx or buccal mucosa; 

severe cases will involve the tongue, gums, and lips; significant erythema may 

be present. Less commonly, erythematous patches without white plaques can 

be seen on the upper palate or tongue. Pharyngitis may be asymptomatic 

or may cause dysphagia or burning. Vaginal candidiasis presents similarly in 

HIV infected and uninfected women; however, episodes may be more severe 

or frequent in women with advanced immunosuppression (see Chapter 6, 

Gynecologic Problems). For oropharyngeal or vaginal candidiasis, diagnosis 

usually involves a consistent clinical presentation and demonstration of yeast 

forms on microscopy from scrapings in potassium hydroxide preparation; 

culture is rarely needed but can be helpful in some situations.

Treatment: The treatment of choice for esophagitis is oral fluconazole 100–

400 mg po or intravenously (IV) qd or itraconazole 200 mg po qd for 14–21 

days; topical agents should not be used. Oropharyngeal or vaginal candidiasis 

may be treated with topical or oral antifungals; topical agents are more costeffective and avoid the risk of systemic side effects or drug-drug interactions.

Cryptococcal Meningitis

Cryptococcal meningitis may present as nothing more than the worst headache 

of the patient’s life. Fever is common but meningismus may be minimal or 

absent. Altered mental status is associated with a poorer prognosis. Cranial 

nerve deficits and seizures are seen only in patients who present very late in 

the course of their infection.

When cryptococcosis occurs in the setting of HIV infection, disseminated disease 

is common and virtually any organ can be involved. Skin lesions resembling 

Molluscum contagiosum and isolated pulmonary infection are not infrequent.

Diagnosis: The diagnosis of cryptococcal meningitis is made by detecting 

cryptococcal capsular antigen in the cerebrospinal fluid (CSF). Relying upon 

a positive CSF India ink stain that demonstrates the organism’s thick capsule 

is positive in only about 60%–80% of cases. Serum cryptococcal antigen is 

also almost always positive in cases of CNS disease and in other instances 

of disseminated infection. Cryptococcus neoformans may also be cultured 

from blood and CSF. When performing a diagnostic lumbar puncture, the 

opening pressure may be elevated, with pressures ≥25 cm H2O occurring in 

most patients.

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Treatment: The recommended initial standard treatment is IV amphotericin B 

(liposomal) combined with flucytosine for ≥2 weeks. Renal function should 

be monitored closely and dose adjustments made if indicated. Intracranial 

hypertension can be managed with frequent lumbar punctures to remove large 

volumes of CSF (20–30 mL at a time).

After at least 2 weeks of successful induction therapy (clinical response plus 

negative CSF culture on repeat lumbar puncture), amphotericin B/flucytosine 

may be discontinued and therapy with fluconazole 400 mg po or IV qd may 

be initiated and continued for 8 weeks.

Following the initial 10 weeks of therapy, initiate chronic maintenance therapy 

with fluconazole 200 mg qd for at least 1 year. Maintenance therapy can be 

discontinued in patients who have a sustained increase in CD4+ cell count to 

>100 cells/mm3 for ≥3 months and suppressed HIV VL in response to ART.

Toxoplasmosis

The most common clinical presentation of T. gondii infection among patients with 

AIDS is focal encephalitis with headache, confusion, or motor weakness and 

fever. Physical examination may demonstrate focal neurological abnormalities,

and in the absence of treatment, disease progression results in seizures, stupor, 

and coma.

Diagnosis: CT or magnetic resonance imaging (MRI) classically reveals one 

or more ring-enhancing, space-occupying lesions, although the radiographic 

appearance of the lesions may mimic other processes, such as primary CNS 

lymphoma.

Most HIV infected persons are seropositive for anti-toxoplasma IgG; absence 

of the antibody makes the diagnosis unlikely but not impossible. Definitive 

diagnosis requires a consistent clinical presentation, compatible radiographic 

findings, and a brain biopsy demonstrating T. gondii organisms. Most clinicians, 

however, rely initially on empiric treatment for toxoplasmosis in the absence 

of a likely alternative diagnosis, with confirmation of the diagnosis based on 

objective response (i.e., clinical and radiographic improvement). Brain biopsy is 

generally reserved for patients who fail to respond to specific therapy.

Treatment: The initial therapy of choice for toxoplasma encephalitis (TE) 

is a combination regimen consisting of pyrimethamine, sulfadiazine, and 

leucovorin. Acute therapy for TE should be continued for at least 6 weeks and 

longer if clinical or radiologic disease is extensive or if response is incomplete 

at 6 weeks.

After initial therapy for acute infection, chronic maintenance therapy 

should be administered, with the preferred regimen also a combination of 

pyrimethamine, sulfadiazine, and leucovorin (with slightly altered dosing), 

which also provides protection against PCP. Alternative regimens also provide 

protection against PCP, with the exception of pyrimethamine plus clindamycin. 

Secondary prophylaxis can be discontinued after successful initial therapy, 

when the patient remains without signs or symptoms of TE and her CD4+ cell 

count increases to >200 cells/mm3 for >3 months in response to ART.

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Tuberculosis

TB is one of the most common HIV-related OIs in the world. Because TB is 

virulent enough to cause disease in patients with intact immune systems, it may 

occur in HIV infected individuals who still have high CD4+ cell counts (MMWR 

Recomm Rep 2009;58(RR-4:1). Because rates of progression from latent to 

active TB are significantly increased in the setting of HIV, annual screening of 

all HIV infected patients is critical.

TB in HIV infected patients: In HIV infected patients with CD4+ cell counts 

>350 cells/mm3, TB clinically resembles TB among HIV uninfected people, 

with disease generally limited to the lungs. Common CXR findings include 

upper-lobe infiltrates with or without cavitation. In advanced HIV disease, the 

CXR findings of pulmonary TB are markedly different: lower-lobe, middlelobe, interstitial, and miliary infiltrates are common whereas cavitation is less 

common. Marked mediastinal lymphadenopathy can also be seen.

Extrapulmonary disease is more common in the setting of HIV infection, 

regardless of CD4+ cell count, and is found in most TB patients with CD4+ cell 

counts <200 cells/mm3.

In patients with severe immunodeficiency and a high mycobacterial load, TB 

disease may have few symptoms. With immune reconstitution after initiation of 

ART, however, patients may develop acute signs and symptoms of active TB. 

This type of immune-reconstitution inflammatory syndrome (IRIS) can manifest 

as early as 7 days after starting ART.

Diagnosis: For both the PPD and interferon-gamma release assays, HIVrelated immunosuppression may be associated with false-negative results. 

Approximately 25% of HIV infected patients with pulmonary TB disease have 

false-negative results (Ann Intern Med 2007;146:340).

If active TB Is suspected, a CXR should be obtained; sputum samples for 

acid-fast bacilli smear and culture should be obtained from patients with 

pulmonary symptoms and CXR abnormalities. A normal CXR does not exclude 

the possibility of active pulmonary TB; sputum samples should still be obtained 

if suspicion is high. The sputum smear may be negative, particularly with 

advanced immunosuppression and noncavitary disease, but it is not affected 

by HIV or immunosuppression. Drug-susceptibility testing and adjustment of the 

treatment regimen on the basis of the results of such testing are critical to the 

successful treatment of patients with TB and to preventing transmission of drugresistant Mycobacterium tuberculosis.

Treatment: When active TB is diagnosed or suspected, a multi-drug anti-TB 

treatment regimen should be started immediately. Directly observed therapy 

is recommended for all patients. Until susceptibilities are known, all HIV 

infected patients should be treated initially with at least four drugs expected 

to be active on the basis of local susceptibility patterns. Treatment of drugsusceptible TB disease should include a 6-month regimen with an initial phase 

of INH, RIF (or rifabutin), PZA, and EMB administered for 2 months, followed 

by INH and RIF (or rifabutin) for 4 additional months. More-prolonged therapy 

is recommended for patients with a delayed response to therapy and for 

those with CNS disease or bone and joint TB. All patients receiving INH should 

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also receive pyridoxine supplementation. Expert consultation is recommended 

when treating TB, including when making decisions about the optimal timing of 

the initiation of ART. Treatment should be coordinated through the local public 

health department.

All close contacts of the patient—especially young children—must be 

evaluated for TB so that they may be treated promptly for active disease or 

given prophylaxis as indicated.

Herpes Simplex Virus (see Chapter 6, Gynecologic Problems)

Cytomegalovirus

CMV causes retinitis in 80%–85% of AIDS patients with end-organ CMV 

disease. Gastrointestinal disease, which can occur anywhere from the mouth 

to the anus, is diagnosed in another 12%–15%. Other diagnoses, such as 

encephalitis and pneumonitis, are uncommon (1%).

CMV retinitis can cause visual loss and progresses inexorably to blindness in 

the absence of ART or specific treatment. In two-thirds of patients, CMV retinitis 

occurs as unilateral disease at presentation; however, most patients develop 

bilateral disease in the absence of therapy or immune recovery. Patients may 

be completely asymptomatic or may complain of floaters (due to inflammatory 

debris), diminished acuity, or visual field defects with peripheral lesions.

Diagnosis: Diagnosis is made by visual inspection of the entire retina by an 

experienced ophthalmologist using dilated indirect ophthalmoscopy. Extensive 

disease may lead to retinal detachment, which may require surgical repair. 

Retinitis near critical structures such as the macula or optic nerve may cause 

catastrophic visual loss even when the total infected area is small.

Diagnosis of CMV colitis or esophagitis requires the presence of shallow, often 

large and extensive mucosal ulcerations with histopathologic evidence of 

characteristic intranuclear and intracytoplasmic inclusions. Culturing CMV from 

a biopsy or lesion is not sufficient to establish the diagnosis in the absence of 

histopathologic changes because CMV viremia can be present in the absence 

of clinical disease in persons with low CD4+ cell counts.

Treatment: The ganciclovir intraocular implant coupled with valganciclovir is 

the recommended treatment for CMV retinitis for immediate sight-threatening 

lesions. Systemic therapy has been documented to reduce morbidity in 

the contralateral eye. Decisions about the choice of treatment should be 

individualized on the basis of the location and severity of lesions, level 

of immunosuppression, other medications, and adherence considerations. 

Generally, CMV colitis or esophagitis is treated with IV ganciclovir or foscarnet 

or oral valganciclovir in milder disease and if able to tolerate oral therapy.

Secondary prophylaxis is recommended after CMV retinitis. The choice 

of agent should be made with expert consultation. Prophylaxis can be 

discontinued after an increase in the CD4+ cell count to >100 cells/

mm3 has been sustained for at least 3–6 months in response to ART, after 

ophthalmologic consultation.

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Disseminated Mycobacterium avium Complex

Disseminated MAC presents nonspecifically with fever, weight loss, diarrhea, 

anemia, elevated alkaline phosphatase, and, in some cases, abdominal 

distention or discomfort due to organomegaly and massive intra-abdominal 

lymphadenopathy.

Diagnosis: Mycobacterial culture from blood, lymph-node, bone-marrow, or 

other normally sterile tissue or body fluid provides a definitive diagnosis; 

culture of sputum is not helpful.

Treatment: Combination antimycobacterial therapy is required with two 

or more antimycobacterial drugs to prevent or delay the emergence of 

resistance. Recommended first-line agents are clarithromycin and ethambutol or 

azithromycin and ethambutol; some experts recommend adding a third drug 

for patients with CD4+ cell counts <50 cells/microliter, with high mycobacterial 

load or in absence of effective ART. Generally, initiation of ART in patients with 

disseminated MAC disease who are not already on effective ART should be 

delayed until after the first 2 weeks of antimycobacterial therapy have been 

completed to reduce the risk for drug-drug interactions, adherence problems 

due to pill burden, and potential IRIS.

The same drug regimen should be continued for secondary prophylaxis. This 

regimen can be discontinued after completion of at least a 12-month course of 

treatment if the CD4+ cell count increases to >100 cells/mm3 for >6 months in 

response to ART.

Cryptosporidiosis and Microsporidiosis

These enteric microorganisms can cause debilitating diarrhea and weight 

loss, often associated with severe dehydration in patients with advanced 

HIV disease.

Diagnosis: Cryptosporidiosis and microsporidiosis are generally diagnosed 

with special stool stains.

Treatment: Because no effective specific therapy exists, the mainstay of 

treatment is ART with immune reconstitution and supportive care (volume 

repletion and attempts at slowing the diarrhea). Clinical resolution (and even 

clearing of the organism from stool) have been documented with potent ART.

Attempts at slowing the diarrhea should be made by adding (not substituting) 

additional agents in a stepwise manner as follows:

• Diphenoxylate or loperamide, increased to their maximum dose, 

followed by

• Tincture of opium or paregoric, with the dose titrated gradually until 

the desired effect is achieved

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HIV-Associated Dementia (HAD) and HIV Encephalopathy

In the pre-ART era, frank dementia was the AIDS-defining illness in up to 10% 

of patients. HAD is characterized by symptoms of cognitive, motor, and/or 

behavioral disturbances. The initial manifestations may be subtle and can be 

uncovered by questioning a patient carefully about short-term memory loss 

and difficulty concentrating. Useful questions about the latter include the ability 

to balance a checkbook or make change. In some patients a depressed affect 

may be a prominent finding, whereas unexplained seizures may bring other 

patients to medical attention. Psychomotor retardation—slowing of the impulses 

that match actions to thoughts and intentions—is another hallmark of HAD.

Diagnosis: CT and MRI scans show diffuse cortical loss with prominent sulci 

(“walnut sign”). A good sense of the patient’s level of cognitive functioning 

can often be obtained at the bedside. In subtle or difficult cases, especially 

with a history of depression or subnormal intelligence quotient, the patient 

can be referred for a battery of neuropsychologic tests that demonstrate the 

losses characteristic of HAD. It is important to rule out other possible causes 

of changes in mental function (e.g., cerebrovascular disease, CNS neoplasm 

or other infection, severe depression, substance abuse, or metabolic/systemic 

disorders).

Treatment: Even patients who present with advanced dementia may 

demonstrate a remarkable degree of recovery with ART, so it is valuable to 

attempt treatment of all patients, even those initially referred for hospice or 

nursing home care. Because of indications that potent ART with poorer CNS 

penetration may predispose a patient to neurologic problems despite good 

suppression of HIV VL, it may be particularly useful to include agents that 

achieve good CSF levels.

Wasting Syndrome (aka “Slim Disease”)

Although weight loss is common in HIV disease, especially in its advanced 

stages, the CDC surveillance definition of wasting syndrome specifically refers 

to involuntary weight loss that equals or exceeds 10% of the patient’s baseline 

weight plus either diarrhea (≥2 loose stools per day lasting ≥30 days) or 

chronic weakness with documented fever (intermittent or constant) for ≥30 days 

that is not attributable to a condition other than HIV itself.

Typically, wasting syndrome is accompanied by loss of muscle mass––for 

example, in the temporal areas––and complaints of generalized fatigue and 

weakness. In severe cases, the serum albumin level will be very low.

Wasting can accompany any of the typical end-stage OIs, such as 

disseminated MAC, or may occur by itself in the absence of any evident 

concomitant illness. Loss of weight, and especially loss of lean body mass, 

portends poorer survival.

Treatment: Initiation of effective ART is the best management strategy. 

Appetite stimulants, such as the progestin megestrol acetate or the marijuana 

derivative dronabinol, may be used, although weight gain with these agents 

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typically consists of fat and water rather than an increase in lean body mass. 

The psychological benefit of an improved appetite and some weight gain 

cannot be underestimated, however, even if the gain is primarily fat.

Central Nervous System Lymphoma

CNS lymphoma generally occurs at total CD4+ cell counts under 50 cells/mm3

and is a typical end-stage complication.

Diagnosis: Symptoms include confusion, headache, memory loss, aphasia, 

and possible seizures without fever. Focal or nonfocal signs may be present. 

Definitive diagnosis is made by a brain biopsy or by CSF cytology (and 

possible Epstein-Barr virus [EBV] DNA in CSF) in the presence of one or more 

space-occupying lesions on CT or MRI scan. A presumptive diagnosis may 

sometimes be made by nuclear single-photon emission CT scan. Because a 

brain biopsy may be difficult to obtain, patients who do not respond to a trial 

of therapy for toxoplasmosis are often assumed to have CNS lymphoma.

Treatment: Standard therapy is radiation plus corticosteroids or methotrexate. 

Survival after a diagnosis of CNS lymphoma is usually very limited.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is another end-stage 

complication of HIV disease, usually presenting as cognitive impairment, visual 

field impairment, or other focal neurologic deficit(s).

Diagnosis: PML is caused by the JC virus, which can be detected by PCR 

performed on CSF. An MRI scan of the brain demonstrates involvement of the 

white matter that can be focal or fairly diffuse but is not usually associated 

with either mass effect or surrounding edema. Most commonly, PML affects 

areas adjacent to the cortex, but lesions can be located anywhere in the 

brain. A definitive diagnosis is made by a brain biopsy or positive PCR, which 

is highly specific in the appropriate clinical context. Where these diagnostic 

modalities are unavailable, the typical MRI image usually suffices.

Treatment: Although no specific therapy exists for PML, this is another AIDSassociated condition that responds markedly well to potent ART. Patients can 

recover significant intellectual and physical functioning with ART, although not 

all deficits may resolve completely.

Systemic Lymphoma

HIV infected patients have an increased frequency of Hodgkin’s disease, 

immunoblastic lymphoma, and Burkitt’s lymphoma, as well as less common forms 

of this disease; however, the most common type of lymphoma in HIV infected 

patients is an aggressive non-Hodgkin’s B cell lymphoma. Although lymphomas 

may occur at any CD4+ cell count, the prognosis is worse at lower absolute 

CD4+ cell counts.

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A marked tendency for extranodal presentations has been observed and nonHodgkin’s lymphoma has been described over a range of unusual sites in HIV 

infected patients.

Diagnosis and treatment: AIDS-associated lymphoma is diagnosed and 

staged in the same manner as in HIV uninfected patients and the same types 

of combination chemotherapy are used. HIV infected patients may, however, 

require lower doses of chemotherapy or aggressive support with granulocyte 

colony-stimulating factor because of their baseline bone-marrow fragility. 

Advances in bone marrow transplant techniques offer new opportunities for 

treatment.

Chronic Hepatitis B and Hepatitis C

Many of the same behaviors that put women at risk of acquiring HIV also 

put them at risk for HBV and/or HCV infection. Up to 90% of HIV infected 

individuals have evidence of prior exposure to HBV and up to 10% have 

chronic HBV infection (J Acquir Immune Defic Syndr 1991;4(4):416; J Infect Dis

1991;163(5):1138). A cross-sectional analysis of a large heterogeneous group 

of HIV infected individuals found that 16% had HCV coinfection (Clin Infect Dis

2002;34(6):831), whereas among HIV infected IDUs in the United States, HCV 

infection rates range from 70%–95%.

Diagnosis: Both acute and chronic HBV and HCV infections are often 

asymptomatic or present with minimal or nonspecific symptoms such as fatigue. 

When present, symptoms of acute infection might include right-upper-quadrant 

abdominal pain, nausea, vomiting, fever, anorexia, dark urine, and jaundice. 

All HIV infected women should be serologically screened for HBV and HCV 

with HBsAg, HBsAb, HBcAb and HCV Ab at entry into care. HBV DNA should 

be obtained if HBsAg or HBcAb positive. Chronic HBV is defined as HBsAg 

positive on two occasions at least 6 months apart. Patients with chronic HBV 

infection should be further tested for HBV e antigen (HBeAg), antibody to 

HBeAg (anti-HBe), and HBV DNA. If there is an isolated HBcAb positive test 

and HBsAg is negative, HBV DNA testing should be considered. HCV infection 

is diagnosed if HCV Ab positive with detectable HCV RNA. With abnormal 

LFTs and negative serology, a qualitative HCV RNA PCR test should also be 

considered.Women with detectable HCV should be tested for HCV genotype. 

If acute hepatitis is suspected, screen with HAV IgM Ab, HCV Ab, and HBsAg 

+/- HBc IgM Ab.

HIV infection is associated with an increased risk of developing chronic HBV 

infection (J Infect Dis 1991;163(5):1138) and more rapid progression of 

both HBV- and HCV-related liver disease, including cirrhosis, end-stage liver 

disease, hepatocellular carcinoma (HCC), and fatal hepatic failure (AIDS

2008;22(15):1979; Lancet 2002;360(9349):1921). Periodic screening for 

HCC (every 6–12 months) with serum AFP level and ultrasound of the liver is 

recommended, particularly in patients with documented cirrhosis or other highrisk characteristics (e.g., older age). (Hepatology 2002;36(5 Suppl 1):S84). A 

liver biopsy to evaluate the activity and severity of hepatitis-related disease 

is useful to monitor progression and guide treatment decisions; decisions to 

perform liver biopsy should be individualized, with expert consultation.

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The goals of therapy are to prevent disease progression, reduce viral 

hepatitis-related morbidity and mortality and, in the case of HCV infection, 

eradicate infection. ART may attenuate liver disease progression in persons 

coinfected with HBV and/or HCV by preserving or restoring immune function 

and reducing HIV-related immune activation and inflammation (Hepatology

2009;50(4):1056; BMC Res Notes 2008;1:46; Haemophilia 2009;15(2):552).

High HBV DNA levels predict progression of liver disease, development of 

HCC, and a reduced response to therapy. The decision to treat depends not 

only on the level of HBV viremia and the degree of biochemical and/or 

histologic disease but also on whether the patient is initiating ART.

Treatment of HBV: ART is recommended for all HIV/HBV coinfected patients, 

regardless of CD4+ cell count or HBV treatment status. Regardless of the 

level of HBV DNA, ART must include two drugs active against HBV, preferably 

TDF and FTC, to reduce risk for IRIS, reduce the development of HBV drugresistance mutations, and help to prevent the development of significant liver 

disease by directly suppressing HBV replication (Hepatology 2008;48(4):1062; 

Hepatology 2006;44(5):1110). If HIV/HBV coinfected patients do not 

want or are unable to take ART, treatment of active HBV (elevated alanine 

aminotransferase [ALT] and elevated HBV DNA >2000 IU/mL or significant 

fibrosis) with pegylated interferon (pegIFN) is indicated (Guidelines for 

Prevention and Treatment of Opportunistic Infections in HIV infected Adults and 

Adolescents. 2013).

Hepatitis C (HCV) becomes a chronic infection in about 85% of cases. Six 

distinct HCV genotypes have been described, with genotype 1 infection 

accounting for approximately 75% of all HCV infections in the United States. 

HCV genotyping should be performed in all HIV infected patients who are 

considering HCV treatment, both to guide ribavirin (RBV) dosing and because 

genotyping is the best predictor of response to interferon-based treatment and 

may therefore influence the decision to treat and/or perform a liver biopsy.

Treatment of HCV: Antiviral treatment for HCV infection should be considered 

for all HIV infected patients with acute or chronic HCV infection. Treatment 

of acute infection (<6 months from the time of HCV exposure) may prevent 

the development of chronic HCV infection. (N Engl J Med 2001;345(2):1452; 

Gastroenterology 2006;130:632). In the presence of chronic HCV infection, 

treatment should be considered in the following situations: HCV genotype 

2 or 3 infection, HCV genotype 1 infection with a low HCV RNA level 

(<800,000 IU/mL), significant hepatic fibrosis (bridging fibrosis or cirrhosis), 

stable HIV infection not requiring ART, and cryoglobulinemic vasculitis or 

glomerulonephritis.

PegIFN plus RBV has been the mainstay of treatment for HCV in HIV infected 

patients. In HCV genotype 1–infected patients without HIV, addition of the 

recently FDA-approved drugs boceprevir or telaprevir significantly improves 

the rate of sustained virologic response; clinical trials of these drugs in HIVinfected patients are currently underway. Both boceprevir and telaprevir 

have significant interactions with certain ARV drugs, which may affect dosing 

or the ability to use these agents (see Table 13-8, p. 500). For patients with 

CD4+ counts <200 cells/mm3, it may be preferable to initiate ART and delay 

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HCV therapy until CD4+ counts increase because of better response to HCV 

treatment at higher CD4+ cell counts (Hepatology 2009;49:1335; J Acquir 

Immune Defic Syndr 2009;52:452). Taking into account the rapid pace of HCV 

drug development and evolving information on drug interactions and use in 

the setting of HIV, treatment decisions should be made with expert consultation 

(http://www.aidsinfo.nih.gov/guidelines; accessed 5/17/2013).

IRIS with either HBV or HCV may manifest as dramatic increases in serum 

aminotransferases as CD4+ cell counts rise within the first 6–12 weeks after 

starting ART, with signs and symptoms of hepatitis flares.

HIV-Associated Nephropathy

In HIV infected patients, HIVAN is the most common cause of chronic kidney 

disease leading to end-stage kidney disease (Kidney Int 2004;66(3):1145). 

It is seen almost exclusively in Black patients and can occur at any CD4+ cell 

count. Ongoing viral replication appears to be directly involved in renal injury 

(Nat Med 2002;8(5):522). HIVAN is an uncommon condition in patients with 

suppressed viral loads (Clin Infect Dis 2006;43(3):377).

ART in patients with HIVAN has been associated with preserved renal function 

and better survival (Nephrol Dial Transplant 2006;21(10):2809; J Am Soc 

Nephrol 2005;16(8):2412; AIDS 2008;22(4):481) and therefore should be 

started in these patients.

Cardiovascular Disease

Cardiovascular disease is a major cause of mortality among HIV infected 

patients, accounting for a third of serious non-AIDS conditions and at least 

10% of deaths among HIV infected patients (AIDS 2010;24(10):1537; J 

Acquir Immune Defic Syndr 2010;55(2):262).

In some cross-sectional studies, patients with HIV were found to have 

higher levels of markers of inflammation and endothelial dysfunction than 

HIV uninfected controls (J Acquir Immune Defic Syndr 2008;49(5):499; 

J Acquir Immune Defic Syndr 2009;52(1):25). In addition, several studies 

have found increased markers of inflammation and coagulation, as well 

as increased risk of cardiovascular events, following treatment interruption 

(AIDS 2009;23(8):929; PLoS Med 2008;5(10):e203; N Engl J Med

2006;355(22):2283).

ART has been associated with marked improvements in parameters 

associated with cardiovascular diseases, including markers of inflammation 

(e.g., interleukin 6 [IL-6] and high-sensitivity C-reactive protein [hsCRP]) and 

endothelial dysfunction (J Am Coll Cardiol 2008;52(7):569). Early initiation 

of ART is increasingly being promoted as a strategy to reduce cardiovascular 

disease risk (Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected 

Adults and Adolescents; http://www.aidsinfo.nih.gov/guidelines/html/1/adultand-adolescent-treatment-guidelines/0/. Accessed 8/25/2012).

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Malignancies

Several population-based analyses suggest an increased incidence of nonAIDS-associated malignancies during chronic HIV infection compared with 

that in matched HIV uninfected controls (J Acquir Immune Defic Syndr 2009; 

52:203). Large cohort studies mostly comprising patients receiving ART 

have reported a consistent link between low CD4+ cell counts (<350–500 

cells/mm3) and the risk of AIDS and/or non-AIDS-defining malignancy (J 

Acquir Immune Defic Syndr 2009;52(1):203; AIDS 2009;23(13):1743; 

Lancet Oncol 2009; 10(12):1152; AIDS 2008;22(16):2143; Clin Infect Dis

2009;49(7):1109).

One prospective cohort study found a statistically significant relative risk of 

all cancers evaluated (except for anal carcinoma) in patients with CD4+ 

cell counts <500 cells/mm3 compared with patients with current CD4+ cell 

counts >500 cells/mm3 and a protective effect of ART for HIV-associated 

malignancies (Lancet Oncol 2009; 10(12):1152). The risk is particularly 

prominent in cancers associated with chronic viral infections (e.g., HBV, HCV, 

HPV, EBV, and human herpes virus-8) (AIDS 2009;23(17):2337; Lancet

2007;370(9581):59).

Anemia

Modest anemia (≥9–10 g/dL) is a hallmark of chronic HIV infection and in 

women of childbearing age may be complicated by menstrual blood loss. 

Severe anemia (≤9 g/dL) may occur as part of certain opportunistic diseases, 

especially MAC, disseminated histoplasmosis, and lymphoma, and may also 

result from drug toxicity.

Although severe anemia has been shown to be associated with poorer survival 

in several studies (J Acquir Immune Defic Syndr Hum Retrovirol 1998;19(1):29; 

Semin Hematol 2000;37(4 Suppl 6):18), initiation of ART (J Acquir Immune 

Defic Syndr 2002;29(1):54) and diagnosis and treatment of the opportunistic 

process are often sufficient to improve anemia in these cases.

Patients who are symptomatic with exertional dyspnea and dizziness can be 

transfused acutely. Most HIV infected patients gradually become anemic and 

unconsciously limit their activities to control symptoms. These patients can be 

managed with changes in ART or OI therapies known to have hematologic 

toxicity (e.g., ZDV, TMP-SMX). In patients whose anemia is refractory to 

conservative management, red blood cell production can be stimulated by 

using recombinant erythropoietin along with sufficient iron replacement to 

stimulate production of new red cells.

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Opportunistic Disease in the Era of Antiretroviral Therapy

The impact of ART on the natural history of opportunistic diseases has been 

profound and the clinician must be familiar with at least the broad outline 

of these changes. Immune restoration in a patient on ART may be sufficient 

even for patients with end-stage disease to mount an inflammatory response 

to opportunistic pathogens. Paradoxically, this can result in worsening of an 

OI that has been under active treatment or in an atypical presentation of a 

new acute OI, generally within the first couple of months after initiating potent 

ART, when CD4+ cell counts have begun to improve. For example, a patient 

may acutely develop a tender, focal lymphadenitis due to MAC with negative 

blood cultures, whereas in the pre-ART era MAC would have presented as 

a disseminated disease with diffuse, nontender adenopathy and high-grade 

mycobacteremia. This seemingly paradoxical development of an OI in a 

patient with rising CD4+ cell counts is likely due to an inflammatory response 

to an OI that was subclinical or recently acquired when ART was initiated. 

The development of IRIS during treatment for most of the OIs has been well 

described. Management includes the continuation of ART plus the addition of 

nonsteroidal anti-inflammatory drugs or corticosteroids (especially in TB) to 

alleviate the inflammatory reaction.

Patients who recover pathogen-specific immunity in addition to experiencing 

an overall increase in the CD4+ cell count may be able to discontinue 

chronic suppressive (maintenance) therapy because their immune systems 

are now capable of containing the infection. Thus far, this has been best 

demonstrated for discontinuing chronic suppression of CMV retinitis. Similar 

phenomena have been described for other OIs, such as disseminated MAC, 

and there is no reason to think that other OIs will behave differently. Finally, 

patients with previously untreatable opportunistic processes, such as PML or 

cryptosporidiosis, have had clinical remissions after initiating ART.

Several studies have shown that patients receiving primary prophylaxis for 

PCP and MAC are at very low risk for developing these OIs if prophylaxis 

is withdrawn after total CD4+ cell counts have risen above the threshold 

risk levels for each specific OI and been sustained for at least 3–6 months. 

Most of these studies have been performed among patients with reasonably 

well-controlled HIV VLs, with most having an undetectable VL. At this point, 

it is clear that specific prophylaxis can be safely stopped for any OI when 

CD4+ cell counts have increased above the threshold of risk for ≥3 months. 

The USPHS guidelines on OI prophylaxis describe the data and rationale for 

discontinuing suppressive therapy and prophylaxis in appropriate patients. 

These guidelines are revised periodically (www.aidsinfo.nih.gov).

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Chapter 5:

Adherence to HIV Treatment 

and Retention in Care

Laura Armas-Kolostroubis, MD, AAHIVS

Associate Professor, Co-Medical Director, UF CARES

Center for HIV/AIDS Research, Education and Service

University of Florida

Laura Cheever, MD, ScM

Associate Administrator and Chief Medical Officer

HIV/AIDS Bureau

Health Resources and Services Administration

The authors declare no conflicts of interest

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Chapter 5: Adherence to HIV Treatment and 

Retention in Care

Chapter 5 at a Glance

Adherence to HIV Treatment and Retention in Care..........................................135

Goals of HIV Therapy.....................................................................................................................135

Adherence............................................................................................................................................................136

Factors That Influence Adherence .......................................................................................136

Magnitude of the Adherence Problem..........................................................................138

Retention in HIV Care.............................................................................................................................140

Factors That Influence Linkage to and Retention in Care...........................140

Adherence In Women.............................................................................................................................141

Overview of Study Findings on Adherence in Women.................................142

Pregnancy and Adherence.........................................................................................................142

Special Populations.............................................................................................................................143

Adherence and Retention Assessment...............................................................................143

Methods of Assessing Adherence........................................................................................143

Assessment of Retention in Care...........................................................................................145

Evidence-Based Interventions to Improve Adherence.....................................146

Clinical Approach.................................................................................................................................146

Conclusion...........................................................................................................................................................149

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Adherence to HIV Treatment and Retention in Care

With the availability of accurate HIV identification early in the course of 

infection and the effectiveness of combination antiretroviral (ARV) regimens, 

HIV infection has evolved from a uniformly progressive and fatal condition 

into a chronic disease. With effective antiretroviral therapy (ART), people 

with HIV infection now have the potential to live a near-normal lifespan 

with a decreased risk of transmitting the infection to others. These advances, 

however, have ushered in new challenges. Successful treatment requires 

lifelong ART. Moreover, chronic HIV care and treatment requires a level of 

adherence that exceeds the requirements of treatment for many other chronic 

illnesses because the penalties for nonadherence may be severe (e.g., viral 

resistance, loss of treatment options, potential for transmission of resistant 

virus strains). Additionally, medical and nonmedical circumstances, such as 

stigma, comorbidities, and short- or long-term adverse effects, may interfere 

with optimal adherence and retention in HIV care and treatment. This chapter 

addresses specific challenges to adherence and retention in comprehensive 

care in the setting of chronic HIV infection.

Goals of HIV Therapy

The primary goals of HIV therapy are to decrease the morbidity and 

mortality associated with HIV infection, improve quality of life, restore 

immune function, maximize suppression of viral load (VL), and reduce the risk 

of transmission of HIV to others (HHS Panel on Antiretroviral Guidelines for 

Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV1-Infected Adults and Adolescents; http://www.aidsinfo.nih.gov/ContentFiles/

AdultandAdolescentGL.pdf. Accessed 7/20/2012).

Successful treatment: Successful HIV treatment is generally defined 

virologically, immunologically, and clinically as follows:

• Consistent virologic suppression below the level of detection by a 

sensitive assay (e.g., HIV VL <48 copies/mL)

• Increase of CD4+ cell counts to >350 cells/mm3 or 500 cells/mm3

• Improved clinical status

Treatment failure: Treatment failure is usually defined virologically as the 

inability to achieve or maintain suppression of viral replication to a VL <200 

copies/mL. Suboptimal adherence is a leading cause of virologic failure (J 

Infect Dis 2010;201(5):662). Immunologic failure is more difficult to define; 

some patients have a persistently low CD4+ cell count while maintaining 

maximal VL suppression. Factors associated with poor CD4+ response include 

later initiation of ART, older age, and co-infection (e.g., with hepatitis C virus). 

Early in the course of treatment, and particularly if ART is started in advanced 

immunosuppression, a patient may worsen clinically if she has an underlying 

opportunistic infection that is “unmasked” or worsened after initiation of ART, 

a phenomenon known as immune-reconstitution inflammatory syndrome (see 

Chapter 4, Primary Care). This is not clinical failure; in general, true clinical 

failure occurs after both virologic and immunologic failure.

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Adherence

Adherence is defined as “the extent to which a person’s behavior—taking 

medication, following a diet, and/or executing lifestyle changes—corresponds 

with agreed recommendations from a healthcare provider” (World Health 

Organization (WHO. Adherence to Long Term Therapies: Evidence for Action. 

2003; http://www.who.int/chp/knowledge/publications/adherence_report/

en/. Accessed 7/20/2012). The term adherence is preferred over compliance

because adherence implies that the patient is involved in making decisions 

about her care, whereas compliance suggests that the patient is “bending to 

the will” of her healthcare provider (WHO. Adherence to Long Term Therapies: 

Evidence for Action. 2003).

Factors That Influence Adherence

Adherence has two components: adherence to medication and adherence 

to medical care, including medical visits, which is also known as retention or 

persistence in care. Adherence is a complex behavioral process influenced by 

several factors that can be categorized across five dimensions, as described 

in Table 5-1 (WHO. Adherence to Long Term Therapies: Evidence for Action. 

2003). Given the complexity of adherence, several factors may result in 

low adherence rates. Likewise, interventions to improve adherence are most 

successful if they are multifaceted, addressing problems across multiple 

dimensions, and tailored to overcome individual or clinic-specific barriers.

Table 5-1

Factors That Influence Adherence

Dimension Factors Affecting Adherence

Healthcare 

Team and 

System 

Factors

• Quality of the patient-provider relationship, including provider 

attitudes and healthcare-team communication style

• Reimbursement and medication distribution systems

• Disease management supports, including patient education and 

community supports

• Follow-up and continuity of care

• Evaluation of and interventions to improve adherence

• Amount of time spent with patient

Social and 

Economic 

Factors

• Patients’ competing priorities (e.g., Maslow’s hierarchy of need 

[Perspect Psychol Sci 2010;5(3):292])

• Socioeconomic status

• Availability and quality of social support networks

• Transportation

• Ability to afford healthcare services and/or medications

Table 5-1 continues on the next page

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Table 5-1

Factors That Influence Adherence

Dimension Factors Affecting Adherence

ConditionRelated 

Factors

• Symptom severity (adherence is usually lower when a patient is 

asymptomatic)

• Condition-related disability (physical, psychological, cognitive, 

vocational)

• Rate of progression and prognosis

• Disease severity (patients with more advanced HIV are generally 

more adherent)

• Commonly associated comorbidities (e.g., depression, substance 

abuse, co-infections)

TherapyRelated 

Factors

• Complexity of regimen (e.g., dosing, pill burden, dosing interval)

• Restrictions (e.g., dietary, other drugs, activities)

• Duration (i.e., short-term vs. lifetime; “pill fatigue” has been noted in 

some patients on long-term treatment)

• Immediacy of beneficial effects and relief of symptoms

• Side effects and availability of interventions to manage them

PatientRelated 

Factors

• Ability to follow instructions

• Knowledge of and skill with self-directed health-related behaviors

• Trust in provider and medical system

• Degree of family dysfunction and/or chaotic lifestyle

• Education and literacy

• Age and lifespan factors:

- Children’s dependency on adult

- Adolescents’ capacity to understand risks and consequences

- Adults’ responsibilities for work and care of children, partners, and/or parents

• Personal or cultural beliefs regarding health and disease

• Motivation and perceived need for treatment

• Confidence (self-efficacy)

• Acceptance and understanding of disease vs. negative beliefs 

regarding diagnosis (denial) and treatment efficacy

• Ability to engage in illness-management behaviors

• Perceptions, attitudes, and expectations (e.g., hopelessness, 

acceptance, fear of dependence, frustration, anxiety about regimen, 

disease-associated stigma)

• Neurocognitive function and ability (e.g., forgetfulness, prospective 

memory)

• Psychological status (e.g., stress, depression, influence of substance 

abuse, coping mechanisms)

Source: WHO. Adherence to Long Term Therapies: Evidence for Action. 2003

continued

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Magnitude of the Adherence Problem

Medication adherence among patients suffering from chronic diseases 

averages 50% in developed countries (Adherence to Long Term Therapies: 

Evidence for Action. 2003; http://www.who.int/chp/knowledge/publications/

adherence_report/en/. Accessed 7/20/2012). Among patients with HIV, 

adherence to both medical visits and medication has been associated with 

decreased mortality (Clin Infect Dis 2007;44:1493). For patients with HIV, the 

consequences of medication nonadherence are devastating, which is why so 

much emphasis is placed on adherence to treatment. When medication doses 

are missed, viral resistance can emerge quickly, particularly with medications 

that have lower genetic barriers to resistance, such as the NNRTIs (HIV Clin 

Trials 2007;8(5):282). The early literature suggested that >95% adherence 

was required for success with unboosted protease inhibitors (PIs); more-recent 

studies of boosted PIs, however, have shown that with these more potent 

regimens adherence levels of 80% or greater may be sufficient (Ann Int Med

2000;133:21; Ann Pharmacother 2011;45(3):372).

The level of adherence required for treatment success depends on underlying 

resistance, the pattern of nonadherence, and the treatment regimen. For 

example, resistance is less likely to develop in a patient who is 100% adherent 

to a PI-based regimen, who then stops taking medication altogether for 3 

months and then resumes with 100% adherence, and more likely to develop 

in a patient who regularly takes 60% of her NNRTI-based regimen. NNRTIs 

have a considerably longer half-life than other ARVs; thus, the patient with 

intermittent adherence is essentially taking monotherapy for prolonged periods, 

which increases the likelihood of developing a drug-resistant strain of HIV.

Figure 5-1 illustrates the decrease in virologic failure rates with improved 

adherence. Conversely, the type of ART regimen has an impact on virologic 

failure that correlates with intermediate levels of adherence (56%–95%). At 

high levels of adherence no significant differences are observed in virologic 

failure rates between regimens (HIV Clin Trials 2007;8(5):282).

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Figure 5-1

Self-Reported Adherence and Virologic Failure

0%

50%

45%

40%

35%

30%

25%

20%

15%

10%

5%

Virologic Failure rates %

Total

Single PI

Boosted PI

NNRTI

Self-Reported Adherence

<55% 56-75% 76-95% >95%

Source: © HIV Clin Trials 2007;8(5):282. Reprinted with permission.

Adherence tends to decrease over time and with the initiation of subsequent 

ART regimens, such that adherence duration with the first regimen predicts 

duration with the second and third regimens (AIDS Patient Care STDS

2006;20(9):628). Thus, it is critical to focus on adherence to achieve viral 

suppression; by itself, a change in treatment regimen is not likely to be 

sufficient. Similarly, many patients who have had long periods of high 

adherence may struggle with adherence over time owing to a host of factors 

that may include changes in personal circumstances, such as becoming homeless 

or relapsing into drug abuse; changes in health insurance that make it more 

difficult to access medications; or changes in medical condition, such as 

recurrent hospitalizations, that disrupt medication-taking routines. For all of 

these reasons, clinicians should ask about adherence at each clinic visit.

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Retention in HIV Care

Positive HIV treatment outcomes depend on early diagnosis of HIV infection, 

linkage to care, and retention (persistence) in care. Gaps in access or retention, 

such as failure to keep the first or subsequent appointments, are linked with 

a lack of ART utilization, disease progression, and increased mortality (Clin 

Infect Dis 2007;44:1493; J Acquir Immune Defic Syndr 2009;50:100). In many 

settings, access to HIV care and treatment, defined as no gap between HIVrelated medical appointments of > 6 months within the first year, is achieved in 

only 50% of newly diagnosed patients (AIDS Care 2005;17(6):773). Likewise, 

it is not uncommon for established patients to drop out of HIV care. Fewer 

data exist regarding the numbers of HIV patients lost to follow-up. Table 5-2 

outlines the factors that influence linkage to and retention in care.

Table 5-2

Factors That Influence Linkage to and Retention in Care

Factors Associated with Successful 

and/or Sustained Linkage to and 

Retention in Care

Factors Associated with 

Unsuccessful and/or Poor Linkage to 

and Retention in Care

• Co-location of services (e.g., case 

management, substance abuse, mental 

health services)

• Patient-centered care (e.g., empowered 

patients, shared decision making)

• Transition programs (e.g., from testing 

sites, jails, hospitalizations, adolescentto adult-care programs, which may 

or may not involve the use of patient 

navigators)

• Untreated substance abuse and/or 

mental illness

• Asymptomatic disease; no ART

• Older age (associated with poor 

linkage to care) or younger age 

(associated with decreased retention 

in care)

• Lack of health insurance

• Longer interval between date of 

appointment with healthcare provider 

and patient’s initial call to schedule the 

appointment

• African-American race

• Privacy concerns

• Care-giving responsibilities

• Perceived lower social support

• Perceived stigma from a health care 

professional

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Sources: AIDS Patient Care STDS 2009;23(1):41; Top HIV Med 2008;16(5):156; AIDS 

Patient Care STDs. 2007; 21 Suppl 1:S59; Am J Public Health. 2000; 90 (7): 1138; AIDS 

Care. 1999; 11(3):361; AIDS Patient Care STDs. 2007; 21(8):584

After adjustment for clinical stage and the number of active drugs in a 

patient’s ART regimen, the hazard ratio for developing an AIDS-defining illness 

or death increases as patients’ number of missed clinic appointments increases, 

as illustrated in Figure 5-2.

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Figure 5-2

Risk of Progression by Missed Visit Status

0

10

9

8

7

6

5

4

3

2

1

Risk of Progression (HR compared to no missed visits)

Number of Missed Visits

1 2 >3

2.87

4.37

8.19

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: J Intern Med 2007;261(3):268

Adherence In Women

Gender-specific factors have been noted to influence adherence and retention 

in care. Some studies have found that women have lower rates of adherence 

than men. This is not surprising given the association between family and 

other caretaking responsibilities and lower adherence rates (Pediatrics

2008;121(4):e787; AIDS Patient Care STDS 2009;23(4):289). Many HIV 

infected women are diagnosed during pregnancy and are still dealing with the 

implications of this diagnosis after giving birth, when the new mother becomes 

responsible for managing the care of a newborn, including administering ARV 

prophylaxis, while also managing her own health and medications. Mothers are 

the parents most likely to be responsible for supervising ART for an infected 

child. Childcare and other responsibilities, as well as postpartum physical and 

psychological changes, may increase the likelihood that a woman will miss 

doses of her own medications and may affect the provision of prophylaxis to 

her infant as well (Pediatrics 2002;110(3):e35); J Acquir Immune Defic Syndr

2002;30(3):311; J Acquir Immune Defic Syndr 2008;48(4):408).

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Overview of Study Findings on Adherence in Women

• Women experience higher rates of virologic rebound than men, mostly 

due to nonadherence (J Acquir Immune Defic Syndr 2004;37(4):1470).

• Women are less likely to keep their first HIV healthcare visit 

appointment and to have remained in care after 2 years (J Womens 

Health 2009;18(10):1627; J Assoc Nurses AIDS Care 2007;18(3):33).

• Women have higher rates of mental health problems such as depression, 

which is associated with decreased adherence (Psychosom Med

2008;70(5):531; J Gen Intern Med 2003;18(4):248).

• Women often have a history of intimate-partner violence, which is 

associated with lower adherence (AIDS Educ Prev 2010;22(1):61; J 

Adolesc Health 2003;33(2 Suppl):39).

• Women have less knowledge of healthcare system navigation and 

available ancillary services (South Med J 2004;97(4):342).

• Nonadherence is an independent reason for the discontinuation of ART 

in women (AIDS Behav 2009; 13(1):60; J Acquir Immune Defic Syndr

2009;52(3):336).

• Women have multiple biological differences that influence drug 

tolerability and metabolism, including body weight and composition, 

renal clearance, and protein binding (Pharmacol Res 2008;58(3-4):173).

• Pregnancy may have a significant effect on many other factors that 

influence adherence in women (Clin Pharmacokinet 2004;43(15):1071).

With standardized dosing, gender-based biological differences may result in 

increased side effects; however, more research is needed to better delineate 

sex differences, particularly hormonal/biological differences that affect 

drug tolerability and, by extension, adherence (J Antomicrob Chemother

2007;60(4):724; Gend Med 2007;4(2):106).

Pregnancy and Adherence

Pregnancy may influence adherence to ART, particularly when 

pharmacokinetic interactions influence drug levels, requiring an increase in 

pill burden, or when medication side effects such as nausea overlap with 

symptoms common in pregnancy. Pregnant women, however, may be highly 

motivated to adhere to therapy and are more likely than nonpregnant 

women to be adherent to ART regimens: pregnant women report rates of 

perfect adherence that range from 75% to 91% (J Acquir Immune Defic Syndr

2008;48(4):408; Cell Mol Biol 2003; 49(8):1187). In the postpartum period, 

however, rates of adherence significantly decrease (AIDS Patient Care STDS

2009;23(2):101). This decrease may be due to a number of factors, including 

the inherent chaos of life when caring for a newborn, the additional burden 

of administering ARV prophylaxis during the first 6 weeks of life (which may 

exacerbate feelings of guilt and concerns about disclosure), and for some 

women the effects of postpartum depression.

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Special Populations

As with men, incarceration and homelessness pose special challenges to 

adherence for women. Drug interruptions often occur during short jail stays. 

For example, even in prison systems that have discharge planning, the rate 

of interruption in medication regimens associated with incarceration has been 

reported to be 70% (Public Health Rep 2010;125(Suppl 1):64).

Homeless patients have inherently chaotic lifestyles. Studies have found, 

however, that homeless and marginally housed patients can adhere to 

medication (AIDS 2000;14(4):357). Homeless patients need additional 

supports to ensure access to and adherence with ARVs.

Adherence and Retention Assessment

Accurate assessment of adherence is challenging. Table 5-3 describes the 

advantages and disadvantages of direct and indirect methods of evaluating 

adherence. Figure 5-3 is an example of a visual analog scale for assessing 

adherence.

Table 5-3

Methods of Assessing Adherence

Method Advantages Disadvantages

Behavioral

Self-report • Easy

• Low cost

• Accessible

• Subject to recall bias

• Often not standardized

• Potential for over-reporting 

to garner provider 

approval

Visual analog 

scale • Low cost

• Accessible

• Standardized

• Decreases literacy and 

numeracy barriers

• Subject to recall bias

• Potential for over-reporting 

to garner provider 

approval

Table 5-3 continues on the next page

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Table 5-3

Methods of Assessing Adherence

Method Advantages Disadvantages

Measurement of Medication Utilization

Refill history • Low cost

• Easy to implement in 

closed systems such as 

onsite pharmacy

• May be part of electronic 

medical record

• Challenging if patients use 

multiple pharmacies

• May not reflect actual 

behavior, particularly with 

automatic refills

Pill counts 

during 

healthcare 

visits

• Low cost

• Offers opportunity for 

education and reassurance

• Time consuming

• Depends on patient 

bringing medications to 

visits

• May be inaccurate (i.e., 

pills removed before visit)

Pill counts by 

phone or in 

home

• Low cost if by phone

• Offers opportunity for 

education and reassurance

• Costly if in home

• May be perceived as 

invasive

• Subject to patient 

availability

• Subject to manipulation if 

by phone

Medical 

Electronic 

Monitoring 

System

• More accurate

• Easy to use (medication 

bottle caps)

• Costly

• Does not reflect actual 

ingestion of medications

• Depends on use of pills 

taken directly from 

container each time

Biologic Measurement

Therapeutic 

drug levels • Easy

• Minimally invasive if part 

of routine blood work

• Costly

• Not readily available

• No standardized values

• Does not capture 

adherence between 

measurements if patient 

takes medications only just 

prior to visits

Drug-specific 

surrogate 

markers:

ZDV, AZT: 

Mean 

corpuscular 

volume

ATV: Total 

bilirubin

TDF: Alkaline 

phosphatase

• Part of routine monitoring

• Relatively low cost

• May be influenced by 

effects of other pathologic 

process(es)

• Nonspecific

• Nonquantified

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

continued

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Figure 5-3

Visual Analog Scale for Adherence

Source: © Health Educ Research 2005;20(1):24. Reprinted with permission.

Because of cost and convenience, measuring medication adherence by direct 

report and visual analog scale are most commonly used by healthcare 

providers in clinical settings. Refill history is also very useful for clinics with 

onsite pharmacies, as well as for patients who are not responding as expected 

to HIV treatment and who report 100% adherence. Direct report should be 

time specific and quantified. For example, care providers should ask, “How 

many times in the last _________ (week, month, interval since last visit) have 

you missed a dose of your medicine?” This question should be followed by a 

nonjudgmental exploration of why the medication was missed, particularly if 

the patient routinely misses doses, and by brainstorming with the patient to 

identify ways she might overcome barriers to adherence.

Assessment of Retention in Care

Assessment of retention is important in every clinical setting. Although there 

is no gold standard for measuring retention in care, potential measures may 

include the following:

• The number of 6-month blocks during which the patient attended at 

least one clinic appointment over the 2-year period following an initial 

visit (AIDS Patient Care STDS 2009;23(1):41)

• Number of missed appointments

• Number of kept scheduled appointments per quarter or year

• Percentage of appointments missed

These measures provide different perspectives on appointment adherence 

(AIDS Patient Care STDS 2010;24(10):607). The rate of appointment 

adherence necessary for good clinical outcomes has not been quantified and 

may vary on the basis of stage of HIV disease and other comorbidities.

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Evidence-Based Interventions to Improve Adherence

Because the factors associated with adherence are varied, the most effective 

interventions are multifaceted, individualized, and repeated over time. Asking 

about adherence at each medical visit and discussing barriers and solutions 

may be a key component to individualizing interventions in the context of 

tailoring therapy. Individualized clinic interventions, however, do not address 

broader provider and healthcare system issues or interventions that may 

significantly improve adherence across a wide group of patients. HIV treatment 

response rates have improved significantly in recent years as a result of 

increasingly potent drugs, significantly simpler drug regimens with fewer 

side effects, and less significant resistance among patients who are starting 

second- and third-line therapy (HHS Panel on Antiretroviral Guidelines for 

Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV1-Infected Adults and Adolescents; http://www.aidsinfo.nih.gov/ContentFiles/

AdultandAdolescentGL.pdf. Accessed 7/20/2012). Combined, these factors 

result in lower rates of adherence being necessary to achieve viral suppression.

Even in the face of these advances in HIV care and treatment, HIV medical 

providers must nevertheless maintain a high level of attention to adherence 

and provide ongoing support to patients. The many evidence-based 

interventions to improve adherence have been summarized and made 

available online; see, for example: http://www.cdc.gov/hiv/topics/research/

prs/ma-good-evidence-interventions.htm. These proven interventions can be 

fairly complex. Many providers practicing routine HIV clinical care take a 

multifaceted approach that combines evidence-based interventions, clinical 

experience, and common sense to maximize adherence among their patients.

Clinical Approach

It is critical to consider healthcare system factors that affect a patient’s ability 

to access and stay in HIV care and adhere to an ART regimen. Figure 5-4 

illustrates multiple factors that a healthcare provider should consider when 

determining the right mix of interventions (i.e., clinic/system/care providerbased/patient-based) to improve adherence to HIV care and medications 

(AIDS Patient Care STDS 2009;23(1):41). Table 5-4 describes interventions to 

support adherence and retention in care.

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Figure 5-4

Blueprint for HIV Treatment Success

Retention in Care

Contextual Environment

• Rural vs. urban

• Neighborhood

• Dependent care

Health Care Environment

Clinic Factors

• Clinic distance

• Appointment availability

• Waiting time

System Factors

• Mental health services

• Substance abuse services

• Case management

Provider Factors

• Trust

• Experience

• Concordance

Predisposing Factors

• Age

• Race/ethnicity

• Gender

• Poverty

• Education

• Mental Illness

• Substance abuse

• Stigma

Enabling Factors

• Insurance status

• Transportation

• Housing

• Social support

• Self efficacy

Perceived Need

• Symptoms

• Health beliefs

Linkage 

to Care

Retention in 

Care

ARV Receipt 

& Adherence

HIV Dx Linkage to 

Care ART Receipt ART 

Adherence

Clinical 

Outcomes

A

B

Environment Patient characteristics Health behavior Outcomes

Clinical Outcomes

• Quality of life

• CD4+ cell count

• Plasma HIV RNA

• Opportunistic infections

• Death

A: Blueprint for HIV treatment success: requisite processes from initial diagnosis to 

long-term clinical outcomes. (Adapted from Curr HIV/AIDS Rep 2005;2(4):177; AIDS

2001;15(1):77.)

B: Adaptation of the behavioral model of health services utilization to provide a 

conceptual framework for evaluating the relationships between patient characteristics and 

their contextual and healthcare environmental factors. These relationships contribute to 

the health behaviors outlined in the “blueprint for HIV treatment success” that ultimately 

influence clinical outcomes.

Source: © AIDS Patient Care STDS 2009;23(1):41. Reprinted with permission.

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Table 5-4

Interventions to Support Adherence and Retention in Care PATIENT

Help the patient become ready for therapy

• Promote the development of adaptive coping skills; identify stressors and 

use motivational interviewing to elicit positive coping responses

• Improve attitudes toward and perceptions of treatment

• Address patient concerns about treatment, including conspiracy theories, 

lack of trust in medical system

• Use clear language to discuss short- and long-term goals of therapy, side 

effects, and known positive outcomes; check to ensure patient understands

Minimize the effects of comorbidities

• Treat substance abuse

• Treat depression

• Consider overlapping symptoms and side effects when choosing a 

medication regimen

Assist the patient in taking medication as prescribed

• Tailor the regimen to patient preferences and lifestyle

• Use reminders such as telephone calls or texts and alarms

• Provide education about prescribed regimen (e.g., securing refills 

without gaps in access, developing contingency plans for missed doses 

or disruptions to daily routine, consequences of nonadherence and drug 

resistance)

Enhance patient supports

• Encourage the patient to enlist assistance of friends and family in 

promoting adherence

• Consider use of trained peer outreach workers, pharmacists, nurses, or 

other healthcare personnel such as health educators

• Have pill boxes, alarms, and other adherence aids available in the clinic

CLINIC/SYSTEM

Improve access to care

• Consider expanding clinic hours to include some evenings and weekends

• Develop a refill policy that minimizes interruptions in therapy; educate 

patients about the policy

• Use a multidisciplinary team to provide patient education and adherence 

support (include peers, pharmacists, and system navigators, where 

appropriate)

Structure clinic systems to promote adherence

• Ask about adherence in a nonjudgmental, quantitative manner at each visit

• Inquire about barriers to adherence and retention and work with patient to 

overcome them

• Ensure the entire clinic team is aware of and promotes adherence and 

retention across clinic visits

• Bilingual/bicultural staff on health care team

• Train care providers in motivational interviewing

• Support continuity of care and the building of long-term, trusting 

relationships between the patient and the entire healthcare team

• Develop a continuum of care that includes such support services as case 

management, transportation, mental health and substance abuse services, 

and child care

• Consider developing gender-specific programs that address the special 

needs of women, particularly pregnant women or those who are caring for 

small children

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Table 5-4

Interventions to Support Adherence and Retention in Care REGIMEN

Make the patient’s drug regimen as simple as possible

• Consider and reduce where possible the number of doses per day and pill 

burden

• Account for food restrictions and requirements

• Assess the patient’s willingness to take pills in front of others

Reduce side effects

• Evaluate side effects upon initiation of a medication regimen and 

frequently thereafter

• Educate the patient about potential side effects and proactively train her 

in side-effects management

Sources: AIDS Behav 2007;11(6 Suppl):101; AIDS Behav 2007;11(6 Suppl):149; AIDS 

Care 2002;14 Suppl 1:S15; AIDS Care 2002;14 Suppl 1:S31; AIDS Care 2002;14 

Suppl 1:S109; AIDS Care 2004;16(4):446; AIDS Care 2005;17(8):1022; AIDS Care

2006;18(4):332; AIDS Care 2009;21(4):448; AIDS Care 2009;21(7):874; AIDS Patient 

Care STDS 2000;14(4):189; AIDS Patient Care STDS 2002;16(6):269; AIDS Patient Care 

STDS 2005;19(5):306; AIDS Patient Care STDS 2006;20(4):258; AIDS Patient Care 

STDS 2007;21 Suppl 1:S3; AIDS Patient Care STDS 2007;21 Suppl 1:S59; AIDS Patient 

Care STDS 2007;21 Suppl 1:S85; AIDS Public Policy J 2005;20(3-4):108; Health Psychol

2007;26(4):488; J Acquir Immune Defic Syndr 2008;47(1):62; J Acquir Immune Defic 

Syndr 2009;52 Suppl 2:S104; J Antimicrob Chemother 2008;62(2):246; J Gen Intern Med

1998;13(9):586; J Gen Intern Med 2002;17(5):377; J Gen Intern Med 2003;18(4):248; 

J Urban Health 2008;85(5):717; Med Decis Making 2001;21(1):17; Qual Health Res

2008;18(4):458

Conclusion

Treatment success with ART depends on high rates of adherence and retention 

in HIV care. Assessment of facilitators and barriers to adherence and retention 

is important for every woman in HIV care. Interventions to address adherence 

and retention should be tailored to the specific needs and circumstances of 

each patient. Although system- and policy-related interventions are important 

and necessary long-term goals, patient-specific and healthcare-related 

interventions are suitable for everyday clinical practice.

continued

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Chapter 6:

Gynecologic Problems

Jean R. Anderson, MD

Director, The Johns Hopkins HIV Women’s Health Program

Professor, Gynecology and Obstetrics

The Johns Hopkins Medical Institutions

The author declares no conflict of interest

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Chapter 6: Gynecologic Problems

Chapter 6 at a Glance

A Problem-Oriented Approach to Common Gynecologic Complaints......155

Abnormal Uterine Bleeding and Amenorrhea..................................................................................155

History, Physical Exam, Evaluation, Differential Diagnosis, and 

Management of Abnormal Bleeding........................................................................................................157

Abnormal Pap Smear...................................................................................................................................160

HIV and Human Papillomavirus.....................................................................................................................160

Effect of Antiretroviral Therapy on Human Papillomavirus–related Disease.........163

Screening Tests.............................................................................................................................................................164

Management of Cervical and Other Lower-Genital-Tract Dysplasia..........................169

Prevention of Human Papillomavirus Infection..................................................................................172

Genital Ulcers.......................................................................................................................................................172

History, Physical Exam, Evaluation, and Differential Diagnosis..........................................172

Herpes Simplex Virus.............................................................................................................................................173

Syphilis............................................................................................................................................................................... 175

Chancroid.........................................................................................................................................................................177

Cytomegalovirus.........................................................................................................................................................178

Other Infectious Causes of Genital Ulcers...........................................................................................178

Noninfectious Causes of Genital Ulcers.................................................................................................179

Vaginal Discharge...........................................................................................................................................180

History, Physical Exam, Evaluation, and Differential Diagnosis..........................................180

Bacterial Vaginosis...................................................................................................................................................181

Vulvovaginal Candidiasis....................................................................................................................................182

Trichomoniasis...............................................................................................................................................................185

Gonorrhea.......................................................................................................................................................................187

Chlamydia........................................................................................................................................................................188

Other Causes of Abnormal Vaginal Discharge...............................................................................189

Pelvic and/or Lower Abdominal Pain.........................................................................................189

History, Physical Exam, Evaluation, and Differential Diagnosis..........................................190

Pregnancy.......................................................................................................................................................................191

Pelvic Inflammatory Disease.............................................................................................................................191

Other Causes of Pelvic and/or Lower Abdominal Pain............................................................194

Pelvic Mass.............................................................................................................................................................195

History, Physical Exam, Evaluation, and Differential Diagnosis..........................................195

Urinary Symptoms ..........................................................................................................................................196

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management......................................................................................................................................................196

Genital Warts........................................................................................................................................................198

History, Physical Exam, and Evaluation...................................................................................................199

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Genital Masses and/or Nodules.......................................................................................................201

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management......................................................................................................................................................201

Bartholin’s Abscess or Cyst................................................................................................................................201

Molluscum contagiosum.........................................................................................................................................202

Cysts and Folliculitis.................................................................................................................................................202

Tumors and Other Masses..................................................................................................................................202

Genital Itching and/or Irritation........................................................................................................202

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management......................................................................................................................................................203

Fungal Infection...........................................................................................................................................................203

Allergic and/or Irritative Reaction..............................................................................................................204

Scabies............................................................................................................................................................................... 204

Pediculosis Pubis..........................................................................................................................................................205

Other: Vaginitis or Cervicitis, Vulvar Atrophic Changes, Vulvar Dystrophy.............205

Breast Lump...........................................................................................................................................................206

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management......................................................................................................................................................206

Fibrocystic Changes.................................................................................................................................................207

Fat Maldistribution Syndrome.........................................................................................................................207

Breast Abscess and/or Mastitis.....................................................................................................................207

Benign Breast Tumor................................................................................................................................................207

Breast Cancer...............................................................................................................................................................208

Sexual Dysfunction.........................................................................................................................................208

Menopause.............................................................................................................................................................209

History, Physical Exam, and Evaluation...................................................................................................209

Management .................................................................................................................................................................210

Health Maintenance Issues ....................................................................................................................211

Gynecologic Evaluation........................................................................................................................................211

Pap Smears.....................................................................................................................................................................212

Screening for Sexually Transmitted Infections...................................................................................212

Mammography............................................................................................................................................................212

Colorectal Cancer Screening...........................................................................................................................212

Osteoporosis Prevention ......................................................................................................................................213

Lipid Screening............................................................................................................................................................213

Guidelines for Gynecologic Referral............................................................................................214

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A Problem-Oriented Approach to Common Gynecologic 

Complaints

Gynecologic problems are common among HIV infected women and are 

frequently present at the time of initial presentation for evaluation and care. 

Minkoff and colleagues found, with prospective assessment over 1 year, 

that 47% of 262 HIV infected women had at least one incident gynecologic 

condition (Am J Obstet Gynecol 1999;180:824). A study of women admitted 

to an inpatient AIDS service revealed that although only 9% were admitted 

with a primary gynecologic problem, 83% had coexisting gynecologic disease 

when evaluated (Clin Infect Dis 1997;25:706). Some gynecologic issues are 

unrelated to a patient’s serologic status, whereas others are directly related 

to HIV disease and associated immunosuppression. Still others are associated 

epidemiologically with HIV because of common risk factors such as sexual 

behavior or substance abuse.

Because HIV infection primarily affects women during their reproductive 

years, gynecologic and reproductive healthcare play an important role in the 

overall care of HIV infected women. With improved longevity and quality 

of life, gynecologic problems may be encountered more commonly or may 

be more prominent. With these issues in mind, the goal of this chapter is to 

use a problem-oriented approach in reviewing the most common gynecologic 

complaints together with their differential diagnosis, evaluation, management, 

and relationship to HIV.

Abnormal Uterine Bleeding and Amenorrhea

What is considered “abnormal” bleeding? A normal menstrual period 

should occur every 21–35 days and last from 2–6 days. The average 

blood loss during menses is 20–60 mL, but up to 14% of healthy women 

have blood loss >80 mL and, as a result, are more likely to be anemic 

(Comprehensive Gynecology. 6th ed. St. Louis: Mosby; 2012). Abnormal 

bleeding may be of several types, described below along with the most 

common causes of each type.

• Menorrhagia: excessive or prolonged menstrual bleeding, defined as 

blood loss >80 mL and/or periods lasting for >7 days. Menorrhagia is 

most commonly caused by fibroids or by a hemostatic disorder.

• Metrorrhagia: light bleeding from the uterus at irregular intervals, often 

caused by hormonal contraception or continuous hormone replacement 

therapy (HRT) in the first few months after initiation. Megestrol can 

cause metrorrhagia. Pregnancy should be ruled out.

• Menometrorrhagia: heavy bleeding from the uterus at irregular 

intervals, commonly caused by anovulation, fibroids, or uterine or 

cervical neoplasm

• Intermenstrual bleeding: bleeding that occurs between menses or during 

expected times of hormonal withdrawal in women using hormonal 

contraception. Intermenstrual bleeding is commonly caused by polyp(s) 

or is breakthrough bleeding with hormonal contraception.

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• Oligomenorrhea: bleeding that occurs at intervals >35 days. 

Oligomenorrhea is generally caused by ovulatory dysfunction, but may 

be normal with newer extended-phase oral contraceptives.

• Polymenorrhea: bleeding that occurs at intervals <24 days. It may 

indicate ovulatory dysfunction.

• Postcoital bleeding: vaginal bleeding noted within 24 hours of vaginal 

intercourse when not at the expected time of menses. This type of 

bleeding may indicate cervicitis. Cervical neoplasm must be ruled out.

• Postmenopausal bleeding: any vaginal bleeding or spotting after total 

cessation of menses. If a woman is on HRT, this is any bleeding that 

occurs at times other than expected withdrawal. Neoplasm must be 

ruled out.

• Dysfunctional uterine bleeding: excessive, noncyclic uterine bleeding 

that is not caused by an anatomic lesion or systemic disease. Most often, 

it is caused by anovulation.

• Amenorrhea: absence of menstrual bleeding. Primary amenorrhea 

is the absence of menses by age 16. Secondary amenorrhea is 

the absence of menses for a variable period of time—at least 3 

months, but generally 6 months or longer—in a woman who has 

previously menstruated.

Relationship to HIV disease: Menstrual disorders are reported by 20%–

30% of HIV infected women (J Obstet Gynaecol Res 2010;36(5):1053; J 

Womens Health 2006;15(5):591; AIDS Patient Care STDS 2009;23(6):463). 

Older controlled studies yielded conflicting evidence regarding a clinically 

significant direct effect of HIV or HIV-related immunosuppression on menstrual 

function (J Acquir Immune Defic Syndr Hum Retrovirol 1996;12:489; Obstet 

Gynecol 1996;87:1030; Obstet Gynecol 1994;83:397). Several more 

recent large cross-sectional and cohort studies, however, suggest that, when 

compared with uninfected women, HIV infected women are more likely to 

have amenorrhea, oligomenorrhea, and irregular periods (J Obstet Gynaecol 

Res 2010;36(5):1053; Obstet Gynecol 2006;108(6):1423; Obstet Gynecol

2006;108(6):1423) and/or that menstrual abnormalities may be more 

common with lower CD4+ cell counts (J Obstet Gynaecol Res 2010;36(5):1053; 

J Acquir Immune Defic Syndr 2000;24:68; J Womens Health 2006;15(5):591).

Some studies also suggest that taking antiretroviral therapy (ART) and/or 

having suppressed HIV RNA levels may reduce the prevalence or incidence 

of menstrual disorders (J Obstet Gynaecol Res 2010;36(5):1053; J Womens 

Health 2006;15(5):591; AIDS Patient Care STDS 2009;23(6):463). Analysis 

of data collected at 6-month intervals from women in the WIHS prospective 

cohort indicated no difference in the prevalence or incidence of menstrual 

disorders by HIV serostatus; amenorrhea and oligomenorrhea were less likely, 

however, in women with CD4+ cell counts >200 cells/mm3. Both effective ART 

and higher CD4+ cell counts were associated with lower rates of incident 

menstrual abnormalities (J Womens Health 2006;15(5):591). In a recent crosssectional study from Spain, approximately 75% of HIV infected women with 

menstrual disorders attributed the disorders to the use of ART; two-thirds of 

those women were <95% adherent to their antiretroviral (ARV) regimens (AIDS 

Patient Care STDS 2009;23(6):463).

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Most studies of menstrual function in HIV infected women have relied on 

patient self-report of menstrual function; accurate determination of the cause 

of abnormal function, however, requires hormonal levels and potentially 

endometrial biopsy. In a study of HIV infected women with prolonged 

amenorrhea (>1 year), follicle-stimulating hormone (FSH) levels were assessed 

and levels >25 mIU/mL were used to define the presence of ovarian failure. 

More than 50% of the HIV infected women with prolonged amenorrhea, 

including 75% of women aged ≥45, did not have ovarian failure. After 

adjusting for age, HIV infected women were about threefold more likely than 

uninfected women to have prolonged amenorrhea without ovarian failure 

(Obstet Gynecol 2006;108(6):1423). Independent predictors of prolonged 

amenorrhea without ovarian failure included opiate use, low serum albumin 

(reflecting poor nutritional status or liver disease), and a history of AIDSdefining illness. These findings highlight the fact that amenorrhea may be 

incorrectly interpreted as menopause, with significant implications for patients 

who discontinue contraception on the basis of that presumption.

Some of the variability in previous study results may represent failure to take 

into account potential confounding variables. In the setting of HIV infection, 

those variables include age, weight loss, body mass index (BMI), chronic 

disease or opportunistic infections (including hepatitis), drug and alcohol 

abuse (Menopause 2007;14(5):859; Obstet Gynecol 2006;108(6):1423), and 

use of psychotherapeutic medications (Am J Obstet Gynecol 2003;188:881). 

Progestational agents used for appetite stimulation or contraception also may 

be related to menstrual dysfunction. Menorrhagia, or excessive menstrual 

blood loss, has been reported with ritonavir (Lancet 1999;353:811) and more 

recently with atazanavir (Int J STD AIDS 2007;18(9):651).

History, Physical Exam, Evaluation, Differential Diagnosis, and 

Management of Abnormal Bleeding

History

• Characteristics of bleeding:

- Date of last normal menstrual period

- Duration and frequency of menses

- Amount of bleeding (i.e., number of pads/tampons used per day)

- Presence of clots or associated pain/cramping

- Duration and pattern of menstrual irregularities or amenorrhea

- Presence of intermenstrual or postcoital bleeding

• History of other abnormal bleeding:

- Gastrointestinal bleeding or bleeding from the urinary tract (vs. from a 

gynecologic source)

- Easy bruising

- Nose or gum bleed

• History of gynecologic problems and/or other symptoms:

- Abnormal Pap smears

- Uterine fibroids or polyps

- Prior ectopic pregnancy

- Abnormal vaginal discharge

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• Medical history:

- Timing of diagnosis of HIV/AIDS

- Comorbid conditions, including hepatitis

- Clinical symptoms of HIV

- CD4+ cell count and viral load (VL)

- Platelet disorders; thrombocytopenia is frequently diagnosed in patients 

with HIV infection, particularly those with more advanced stages of 

disease (Eur J Haematol 1992;48:168)

- Substance abuse

- Medications

• Sexual history: Last sexual intercourse and use of contraception and condoms

Physical Exam

• Abdominal exam: Presence of abdominal tenderness or mass

• External genitalia, vagina, and cervix: Inflammation and actively bleeding lesions 

(e.g., lacerations, condylomata, polyps)

• Bimanual and rectovaginal exam:

- Pelvic tenderness

- Enlarged uterus

- Other pelvic mass

Evaluation

Further evaluation or referral is indicated based on results of the tests outlined 

below, severity of the problem, and response to basic management.

• Pregnancy test (urine or serum): All women within reproductive age range

• Blood tests:

- Complete blood count (CBC)

- Platelet count

- Coagulation profile: with evidence of systemic bleeding, rule out coagulopathy

- Thyroid-stimulating hormone (TSH), prolactin levels: consider with any irregular bleeding/amenorrhea without apparent cause

- FSH, estradiol: with oligomenorrhea/amenorrhea and/or signs/symptoms 

of decreased estrogen production (hot flashes, vaginal atrophic changes); 

particularly helpful in distinguishing ovarian failure (low estradiol, high FSH) from 

hypothalamic amenorrhea, as with wasting (low estradiol, low/normal FSH)

• Cervical testing: Gonorrhea, chlamydia

• Pelvic ultrasound:

- With finding of uterine enlargement, adnexal mass, significant tenderness, or 

positive pregnancy test

- Transvaginal approach commonly used in evaluation of abnormal bleeding to 

assess endometrial thickness, especially in peri- and postmenopausal women or to 

look for other possible abnormalities (e.g., polyps, fibroids)

• Endometrial biopsy:

- Postmenopausal bleeding

- Prolonged amenorrhea followed by onset of irregular or heavy bleeding

- Persistently irregular bleeding

- Used liberally with any form of abnormal bleeding if no other cause is found and 

bleeding does not respond to conservative management with progestins or oral 

contraceptives

- Helpful in diagnosing endometritis, endometrial hyperplasia, and uterine cancer

- Necessary for diagnosis of cytomegalovirus (CMV) or tuberculous endometritis; 

alert pathologist if these are considerations

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• Pap smear:

- May be inadequate with active bleeding

- Biopsy required if cervical lesion is seen

Differential Diagnosis

• Pregnancy:

- Must be considered in any woman of reproductive age with irregular bleeding or 

amenorrhea

- May be intrauterine or ectopic (usually tubal)

- Bleeding with intrauterine pregnancy may indicate threatened or incomplete 

abortion or miscarriage

- If later in pregnancy, may indicate serious obstetric complication

• Anovulation:

- Most common cause of abnormal uterine bleeding among women of reproductive 

age. Women with anovulation typically have a history of menstrual irregularity.

- Onset of heavy and prolonged bleeding may follow several months of no 

bleeding. Anovulatory bleeding is a diagnosis of exclusion; organic, systemic, and 

iatrogenic causes must be ruled out.

- More common among perimenopausal women and adolescents soon after 

menarche, along with oligo-ovulation

• Perimenopause/menopause: Declining estrogen levels may cause irregular menses; 

menopause is associated with cessation of menses

• Uterine fibroids: Common benign uterine tumors; usually asymptomatic, but may cause heavy and/or prolonged periods

• Adenomyosis:

- Migration of endometrial glands and stroma into uterine muscle (myometrium)

- Uterus often somewhat enlarged and boggy to palpation

- Benign condition

• Cancer:

- Malignant processes in vulva, vagina, cervix, uterus, fallopian tubes, and ovaries 

may present with abnormal bleeding

- Most common in postmenopausal women

- Non-Hodgkin’s lymphoma of endometrium has been reported in the setting of HIV 

(Obstet Gynecol 1997;90(4 Pt 2):697)

• Genital tract infections:

- Cervicitis, endometritis, vaginitis, and vulvitis may present with abnormal vaginal 

bleeding or spotting

- Aids to diagnosis include pain and/or tenderness, discharge, fever, and other 

signs and symptoms of infection

- In the setting of severe immunosuppression, consider opportunistic processes, 

including tuberculous or CMV endometritis

• Medical conditions:

- Thyroid disorders: hypothyroidism or hyperthyroidism

- Coagulopathy, including platelet disorders

- Cirrhosis

- Chronic illness

- Wasting

• Substance abuse: Drug use, including methadone, can lead to disturbances of the 

hypothalamic-pituitary axis, with resulting irregular bleeding or amenorrhea

• Medications: Hormonal agents: Progestational agents, such as those used for 

contraception (e.g., depot medroxyprogesterone acetate [DMPA], etonogestrel 

implant) or for appetite stimulation (e.g., megestrol acetate), frequently cause 

irregular vaginal bleeding. Combined estrogen-progestin contraceptive methods 

generally result in regular menstrual periods, although some breakthrough bleeding 

may occur early after initiation; inconsistent use can cause bleeding and increase 

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risk for pregnancy. Consider antiretroviral agents as a potential cause of abnormal 

bleeding. Medications that can affect prolactin concentrations and possibly result 

in amenorrhea include psychotropic drugs (tricyclic antidepressants, phenothiazines, 

opiates) and metoclopramide. Thalidomide has also been associated with the 

development of secondary amenorrhea (Eur J Dermatol 2002;12:63).

Management of Abnormal Bleeding

Management depends on the diagnosis and on the results of testing.

• Positive pregnancy test: Refer to specialist. If suspect ectopic pregnancy (based on 

pain, HCG levels and ultrasound findings) requires urgent evaluation and treatment.

• Suspected anovulatory bleeding: Medical management with oral contraceptive 

pills or cyclic progestins: DMPA 10 mg po qd for 10–14 days each month

- May restore regular menstruation, reduce the possibility of anemia, and protect 

endometrium from prolonged estrogenic stimulation, which can cause hyperplasia 

or neoplasia

- Oral contraceptives also provide effective contraception but are contraindicated 

in heavy smokers aged >35 years and with hypertension or other cardiovascular 

disease, diabetes, or markedly abnormal liver function

• Refer to specialist for:

- Severe bleeding and anemia

- Pelvic mass

- Suspected malignancy

- Bleeding not resolved with conservative measures

Abnormal Pap Smear

In the setting of HIV infection 30%–60% of Pap smears exhibit cytologic 

abnormalities and 15%–40% have evidence of dysplasia; these rates are 

10–11 times greater than those observed among women who are not HIV 

infected (J Natl Cancer Inst Monogr 1998;23:43).

HIV and Human Papillomavirus

The spectrum of human papillomavirus (HPV) disease includes subclinical 

disease, classic genital warts and other HPV-related skin lesions, lower 

anogenital-tract intraepithelial neoplasia, and invasive cancers of the lower 

genital tract and anal canal. There are >100 HPV subtypes, categorized as 

low, intermediate, or high risk on the basis of their oncogenic potential, though 

the categories are not exclusive; low-risk HPV types have been described in 

cervical carcinomas.

HPV is an extremely common infection. Studies suggest that more than 50% of 

sexually active adults have been infected with one or more genital HPV types, 

but most HPV infections are transient (J Infect Dis 1995;171:1026; N Engl J 

Med 1998;338:423). HPV VL is independently associated with HPV persistence 

(J Infect Dis 2001;184:682).

Compared with women who are not HIV infected, women with HIV have

• higher prevalence and incidence of HPV (Int J STD AIDS 2003;14:417; 

J Infect Dis 2001;184:682),

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• higher HPV VL (Am J Obstet Gynecol 2002;186:21),

• longer persistence of HPV infection (Am J Epidemiol 2000;151:1148; 

N Engl J Med 1997;337(19):1343),

• a higher likelihood of infection with multiple HPV subtypes (Am J 

Obstet Gynecol 2002;186:21; Acta Cytol 2009;53:10, Br J Cancer

2007;96(9):1480; Arch Virol 2007;152:75), and

• greater prevalence of oncogenic subtypes (Am J Obstet Gynecol

1998;178(5):982; J Med Virol 1998;56:133; Acta Cytol 2009;53:10).

Among HIV infected women with normal cervical cytology, the rate of cervical 

HPV infection has been found to vary from >30% in Asia, North America, 

and Europe to >55% in South America, Central America, and Africa (AIDS

2006;20:2337).

In HIV infected women the prevalence and persistence of HPV infection 

increase as CD4+ cell counts decrease and HIV VL increases (J Natl Cancer 

Inst 1999;91:226; Obstet Gynecol 2008;111:1380). Higher HPV VLs are also 

associated with lower CD4+ cell counts (Obstet Gynecol 2000;96(3):403). 

Some studies have found that oncogenic HPV types may be more common with 

lower CD4+ cell counts and/or higher HIV VL (J Infect Dis 1999;179:1405; 

Am J Obstet Gynecol 1998;178(5):982; Br J Cancer 2007;96:1480). 

Immunosuppression also may increase the risk of clinically expressed (versus 

latent) HPV infection by approximately twofold in HIV infected women with 

CD4+ cell counts >500 cells/mm3 to as much as 10-fold in women with CD4+ 

cell counts <200 cells/mm3 (Obstet Gynecol 1995;85(5 Pt 1):680).

HIV and cervical dysplasia: Both the prevalence and incidence of abnormal 

Pap smears are greater among HIV infected women than among uninfected 

women. Abnormal cervical cytology is associated with the presence of HPV 

infection and the degree of immunosuppression. The frequency and severity 

of abnormal Pap smears, as well as histologically documented dysplasia, 

increase with declining CD4+ cell counts and have also been associated 

with higher HIV RNA levels (Gynecol Obstet Invest 1995;40:52; Gynecol 

Oncol 2001;80(3):350; JAMA 2000;282:1031; AIDS Care 2007;19:1052; 

Obstet Gynecol 2008;111:1388; J Acquir Immune Defic Syndr 2001;27:432). 

Increased HPV VL, seen in women with more-advanced HIV, is associated with 

increased frequency, severity, and incidence of cervical dysplasia (Obstet 

Gynecol 2000;96(3):403; J Clin Microbiol 2003;41:2763; Am J Obstet Gynecol

2001;184:322). HIV is also associated with more extensive and/or a larger 

volume of cervical involvement (Gynecol Oncol 1990;38:377).

Progression and regression of Pap smear abnormalities have been associated 

with level of immunosuppression and plasma viremia, as reflected in the CD4+ 

cell count and HIV VL (J Acquir Immune Defic Syndr 2001;27:432; J Infect Dis

2003;188(1):128). The incidence of invasive cervical cancer, however, is not 

higher among HIV infected women who are screened regularly and receive 

recommended treatment than among women who are not HIV infected (Obstet 

Gynecol 2004;104:1077; Cancer 2009;115:524).

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Invasive cervical cancer in HIV disease: In 1993, the U.S. Centers for Disease 

Control and Prevention (CDC) expanded the case definition of AIDS to include 

invasive cervical cancer (ICC). Oncogenic HPV types play a central role in the 

relationship between HIV and cervical cancer. Recent data from Africa indicate 

that in the absence of high-risk HPV, there was no increased risk for cervical 

cancer among HIV infected women (J Infect Dis 2003;188:555). In a study of 

ICC in both HIV infected and uninfected Kenyan women, HPV types 16 and 18 

were the most common and were detected in 65% of ICCs in the HIV infected 

patients, with potential implications for prevention with HPV vaccines. Almost 

half of the cancers associated with HPV type 16 or 18 involved multiple HPV 

types (Int J Cancer 2008;122:244).

Analysis of matching data from AIDS and cancer registries in 15 regions in 

the United States indicates an increased risk of ICC among women with AIDS 

relative to HIV uninfected women (J Natl Cancer Inst 2009;101(16):1120); 

however, among women diagnosed with AIDS between 1996 (when ARVs were 

introduced) and 2004, ICC was not significantly increased in women with low 

CD4+ cell counts, a finding that may reflect the effects of active screening 

(Natl Cancer Inst 2009;101(16):1120). Other studies have found no evidence 

of an increased incidence of ICC among women who are screened regularly 

and who receive appropriate evaluation and treatment of abnormal Pap 

smears (Obstet Gynecol 2004;104:1077; Cancer 2009;115:524).

Cervical cancer affects HIV infected women at younger ages than it 

does uninfected women (about a decade earlier). Compared with other 

opportunistic infections (OIs), cervical cancer affects HIV infected women with 

more intact immune systems (Gynecol Oncol 2000;77:460).

HIV infected women with ICC may present at more advanced stages 

(especially with CD4+ cell counts <200 cells/mm3). ICC may also behave 

differently in HIV infected women: it may metastasize to unusual locations (e.g., 

psoas muscle, clitoris, meninges), respond more poorly to standard therapy, 

recur more frequently and at shorter intervals, cause death more often, or 

progress to death more rapidly than it does in uninfected women with ICC at a 

similar stage (Obstet Gynecol 1996;88:269; Gynecol Oncol 1990;38:377).

HIV- and HPV-related dysplasia outside of the cervix: The association of HPV 

with disease outside of the cervix is also linked to persistent infection with 

oncogenic HPV subtypes and to the level of immunosuppression.

Compared with high-risk uninfected women, HIV infected women have about 

a 10-fold increase in the prevalence and incidence of vulvar (VIN), vaginal 

(VAIN), and perianal (PAIN) dysplasia or intraepithelial neoplasia (Obstet 

Gynecol 2006;107:1023; AIDS 1996;10:1641; Gynecol Oncol 1995;61:384; 

Gynecol Oncol 1990;38:377; Gynecol Oncol 1996;60:30; Obstet Gynecol

1994;83:205). In the WIHS cohort, VIN incidence was greater among HIV 

infected women and was associated with abnormal Pap smears and high- or 

medium-risk HPV. ART was associated with reduced VIN (Am J Obstet Gynecol

2004;190:1241).

Genital warts: See p. 198.

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Anal HPV and/or dysplasia: Anal HPV has been reported in up to 90% of 

HIV infected women and is more common with lower CD4+ cell counts and in 

the presence of cervical HPV and/or cervical dysplasia (Eur J Obstet Gynecol 

Reprod Biol 2008;140(1):103; J Infect Dis 2001;183:383; Sex Transm Dis

2011;38(4):253). Multiple HPV types and oncogenic types are common (Sex 

Transm Infect 1999;75:172).

Abnormal anal cytology or anal squamous intraepithelial lesions (ASIL) have 

been reported in up to 26% of HIV infected women. Risk factors include a 

lower CD4+ cell count, increased HIV VL, high HPV VL, history of receptive 

anal intercourse, and concurrent abnormal cervical cytology (J Natl Cancer Inst

2001;93:843; AIDS 1993;7:43). Even with the use of ART, high-grade anal 

intraepithelial neoplasia was found in 9% of HIV infected women in a large 

prospective study (AIDS 2009;23:59).

The sensitivity of anal Pap smears appears to be similar to that of cervical 

cytology, although the grade of anal dysplasia may not correlate well with 

histology (Int J STD AIDS 2007;18:77).

The incidence of invasive anal cancer is seven- to 20-fold greater among 

women with HIV/AIDS than among women in the general population, with 

the highest incidence observed among women with AIDS (J Natl Cancer Inst

2000;92(18):1500; J Natl Cancer Inst 2009;101(16):1120).

Oral disease: Oral HPV infection is more common among HIV infected than 

uninfected women, although both the prevalence and incidence of oral HPV 

infection are substantially lower than cervical HPV infection (Int J Cancer

2007;121:143). A meta-analysis of cancer incidence in HIV infected patients 

indicated that cancers of the oral cavity or pharynx are 2.32 times as likely 

to develop in patients with HIV infection as in uninfected patients (Lancet

2007;370:59).

Effect of Antiretroviral Therapy on Human Papillomavirus–

related Disease

Conflicting findings: The role of ART and immune reconstitution in reducing the 

incidence and progression of and promoting the regression of HPV infection 

and cervical or other abnormalities remains unclear. Conflicting findings 

may be related to any of a number of factors: differences in study design, 

screening and diagnostic protocols, virologic and immunologic parameters, 

duration and type of ART, length of follow-up, recruitment and referral 

strategies, and definitions of screening test and disease positivity.

In some studies, ART has been associated with increased regression and 

decreased risk of progression of cervical cytologic abnormalities and with 

increased regression of cervical dysplasia (AIDS 2002;16:1799; AIDS

2001;15:2157). Among women with pre-existing abnormal cervical cytology 

in the HERS cohort, ART was associated with enhanced HPV clearance but not 

with regression of abnormal Pap results (Obstet Gynecol 2009;113(1):26). 

In a study of women initiating ART, a high prevalence of cervical HPV DNA 

found at baseline declined over 8 months of ART (J Acquir Immune Defic Syndr

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2009;51(3):274). In another study, with 15 months of follow-up, persistence 

of high-risk HPV and progression of squamous intraepithelial lesions (SIL) 

were comparable among three groups: women not on ART, women treated 

with nucleoside analogues only, and women on effective ART (J Infect Dis

2001;184:547).

In a more recent analysis from WIHS, the prevalence, incidence, and clearance 

of HPV infection and/or SILs were compared among women before and 

after they initiated ART. Use of effective ART and good adherence (≥95% 

of medications taken) were associated with a significant reduction in the 

prevalence and incident detection of oncogenic HPV infection and with 

decreased prevalence and more-rapid clearance of oncogenic HPV-positive 

SILs (J Infect Dis 2010;201(5):681). Six months of ART had no effect on anal 

HPV or ASIL (J Acquir Immune Defic Syndr 2001;28(5):422). Another analysis 

indicated that anal cancer was the only cancer found to be increasing in 

incidence among HIV infected people in the United States in the ART era (Ann 

Intern Med 2008;148(10):728). The incidence of high-grade vulvar neoplasia 

was not reduced with ART use (Am J Obstet Gynecol 2004;190:1241), even 

though rates of low-grade vulvar lesions and anal or genital warts did 

decrease with ART (Am J Obstet Gynecol 2004;190:1241).

Why don’t HPV-related lesions respond to ART as other opportunistic illnesses 

do? Although there is partial restoration of immune competence with ART, 

this may be counteracted by increasing longevity, with increased cumulative 

exposure to oncogenic HPV infections and the accumulation of somatic 

mutations and epigenetic changes that contribute to cervical carcinogenesis. 

It is likely that women with higher nadir CD4+ cell counts and/or earlier 

intraepithelial lesions may respond best to effective ART (J Transl Med

2009;7:108). HIV infected women should continue to be followed closely for 

evidence of neoplasia in the lower genital tract, regardless of ART or VL.

Screening Tests

Cervical cytology: Cervical cytology screening programs have been associated 

with marked reductions in cervical cancer incidence (Prev Med 1986;15:582; 

Ann Intern Med 1990;113:214). It is estimated that 60% of women diagnosed 

with ICC have never had cervical cytology testing or have not been screened 

within the 5 years prior to diagnosis (NIH Consensus Statement Online 

1996;43(1):1; http://consensus.nih.gov/1996/1996CervicalCancer102html.

htm. Accessed 7/12/12). Because of errors in sampling or interpretation, falsenegative Pap smears are associated with 30% of new cases of cervical cancer 

each year (NIH Consensus Statement Online 1996;43(1):1; CA Cancer J Clin

1995;45:305). A single Pap smear is associated with false-negative rates of 

10%–25%; accuracy is significantly improved with regular periodic screening.

The accuracy of standard cervical cytology appears to be similar in both HIV 

infected and uninfected women (Obstet Gynecol 1993;81:372; Gynecol Oncol

1998;69:109). In the HERS cohort, HIV infected women were more likely than 

high-risk HIV uninfected women to have abnormal biopsy results with normal 

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Pap smears. Most of the HIV infected women, however, developed abnormal 

Paps within 1 year of the abnormal biopsy results, suggesting that current Pap 

smear screening guidelines are appropriate (Clin Infect Dis 2006;42(4):562).

If available, liquid-based Pap smears are preferred because they appear to 

decrease the number of inadequate smears and to reduce, but not eliminate, 

false-negative results; they also offer the possibility of direct HPV testing on 

collected specimens. Liquid-based Paps, however, are more expensive than 

conventional Pap tests. A review of more than 400 conventional and liquidbased cytologic screening tests in HIV infected women found that liquidbased preparations reduced the proportion of smears diagnosed as atypical 

squamous cells of undetermined significance (ASCUS)/atypical glandular 

cells of undetermined significance (AGCUS) (Acta Cytol 2004;48(2):165). 

It is believed that liquid-based cytology helped to resolve findings of 

“undetermined significance” into either normal or clearly abnormal results, 

potentially reducing the need for further evaluation.

HPV testing: HPV testing can identify both oncogenic and nononcogenic viral 

types. In HIV uninfected women, HPV testing for cancer-associated types is 

used as a triage test to stratify risk in women with a cytology diagnosis of 

ASCUS, in postmenopausal women with a cytology diagnosis of low-grade 

squamous intraepithelial lesion (LSIL), and as an adjunct to cytology for 

primary screening in women aged >30 years (ACOG Practice Bulletin 109; 

Obstet Gynecol 2009;114(6):1409).

The role of HPV DNA testing in HIV infected women, however, is unclear. In a 

WIHS substudy of HIV infected and uninfected women with normal baseline 

cytology, incidence of SIL was examined by baseline HPV DNA results and 

stratified by CD4+ cell count. Over 3 years of follow-up, incidence of any 

SIL was similar in both HIV uninfected women and HIV infected women with 

CD4+ cell counts >500 cells/mm3 who had negative results for oncogenic HPV 

or all HPV, suggesting that similar cervical cancer screening practices may be 

applicable to both groups. On the other hand, after just 2 years of follow-up, 

incidence of any SIL in HIV infected women with CD4+ cell counts <500 cells/

mm3 was increased, even among women with negative results for any HPV, 

suggesting that a closer screening strategy may be needed for women with 

lower CD4+ cell counts (JAMA 2005;293(12):1471).

The 2006 American Society for Colposcopy and Cervical Pathology (ASCCP) 

Consensus Guidelines endorse the option of reflex high-risk HPV testing 

for triage of ASCUS on Pap smear irrespective of HIV status (Am J Obstet 

Gynecol 2007;197(4):346). CDC guidelines, however, although based on 

limited and conflicting data, recommend routine colposcopy or repeat cytology 

in 6–12 months for HIV infected women with ASCUS and colposcopy for a 

higher-grade abnormality (Guidelines for the Prevention and Treatment of 

Opportunistic Infections in HIV-Infected Adults and Adolescents (http://aidsinfo.

nih.gov/guidelines/html/4/adult-and-adolescent-oi-prevention-and-treatmentguidelines/343/hpv; accessed 5/17/2013). In two prospective studies of 

HIV infected women with ASCUS, approximately 30% of participants had 

evidence of oncogenic HPV, a finding that would support the use of HPV 

testing in this population if HPV testing remained highly sensitive (J Womens 

Health 2004;13:147; J Low Genit Tract Dis 2004;8:298). One of these studies, 

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however, reported a sensitivity of HPV testing of 100% for the detection 

of cervical intraepithelial neoplasia (CIN) 2 or higher (J Low Genit Tract Dis

2004;8:298); the other study reported a sensitivity of only 50% for detecting 

high-grade CIN (J Womens Health 2004;13:147).

Currently, CDC and the American Congress of Obstetricians and Gynecologists 

(ACOG) do not recommend HPV testing for triage of HIV infected women 

with abnormal cytology results, for follow-up after treatment for CIN, or to 

lengthen screening intervals (Guidelines for the Prevention and Treatment of 

Opportunistic Infections in HIV-Infected Adults and Adolescents (http://aidsinfo.

nih.gov/guidelines/html/4/adult-and-adolescent-oi-prevention-and-treatmentguidelines/343/hpv; accessed 5/17/2013); ACOG Practice Bulletin 117; 

Obstet Gynecol 2010;116(6):1492).

A study examining HPV DNA testing as a primary screening method for 

cervical dysplasia in 94 HIV infected women found that HPV DNA testing 

identified high-grade cervical dysplasia more accurately than Pap smear 

(Gynecol Oncol 1999;75(3):427). Further study is needed regarding a 

potential role for HPV DNA testing for primary screening in the setting of HIV, 

especially given the high rates of HPV infection in HIV infected women.

Recommendations for cytologic and other screening and colposcopy:

Pap smear results are reported according to the Bethesda System (JAMA

2002;287(16):2114), outlined in Table 6-1.

Table 6-1

Pap Smear Results: Bethesda System

Specimen 

adequacy • Satisfactory for evaluation: note presence/absence of 

endocervical transformation zone component

• Unsatisfactory for evaluation: specify reason

General 

categorization • Negative for intraepithelial lesion or malignancy

• Epithelial cell abnormality

• Other

Interpretation

and/or result

• Negative for intraepithelial lesion or malignancy

- Infections

- Reactive changes (inflammation, radiation)

- Atrophy

• Epithelial cell abnormalities

- ASC

- ASCUS

- ASC-H

- LSIL, including HPV changes and mild dysplasia, CIN 1

- HSIL, including moderate and severe dysplasia, CIN 2, CIN 3

- Squamous cell carcinoma

- Glandular cell abnormalities

• Other

- Endometrial cells in a woman aged ≥40 years 

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

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Suggested frequency of Pap smears:

• Normal Pap: once yearly

• ASC/LSIL, evaluated and followed without treatment: every 6 months

• Following treatment of preinvasive lesions: every 3–4 months for first 

year, then every 6 months

Evaluation of abnormal results: Women with HIV infection should be screened 

with cervical cytology twice in the first year after diagnosis of HIV and, if 

results are normal, annually thereafter (Guidelines for the Prevention and 

Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents 

(http://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-oiprevention-and-treatment-guidelines/343/hpv; accessed 5/17/2013); ACOG 

Practice Bulletin 109; Obstet Gynecol 2009;114:1409). More-frequent Pap 

smears should be considered with an abnormal Pap smear that is followed 

conservatively (after colposcopic evaluation to rule out HSIL), with HPV 

infection, and after treatment for cervical dysplasia.

Although adolescents with HIV have a higher incidence of cervical dysplasia 

than uninfected adolescents, the incidence of high-grade abnormalities appears 

to be low (J Low Genit Tract Dis 2008;12:199; J Infect Dis 2004;190:1413; Am 

J Obstet Gynecol 2009;200:149.e1). Cytologic surveillance in adolescents with 

HIV should be the same as that recommended for adults.

Pap smear results are reported according to the Bethesda System (see Table 

6-1). Abnormal Pap smears (ASCUS or worse) require further evaluation with 

colposcopy and biopsy of abnormal areas for histologic confirmation and to 

confirm or exclude a high-grade cervical lesion. The 2006 ASCCP Consensus 

Guidelines recommend that ASCUS on Pap trigger the use of reflex high-risk 

HPV testing for triage to colposcopy (HPV positive) vs. short-term cytologic 

follow-up (HPV negative) for both HIV infected and uninfected women (Am 

J Obstet Gynecol 2007;197(4):346). Current CDC guidelines recommend 

colposcopy or repeat cytology in 6–12 months for all HIV infected women with 

ASCUS (Guidelines for the Prevention and Treatment of Opportunistic Infections 

in HIV-Infected Adults and Adolescents (http://aidsinfo.nih.gov/guidelines/

html/4/adult-and-adolescent-oi-prevention-and-treatment-guidelines/343/

hpv; accessed 5/17/2013), irrespective of CD4+ cell count, HIV VL, or 

ART. Currently, ACOG states that HIV infected women with ASCUS may be 

monitored with repeat cytology alone or referred for colposcopy (ACOG 

Practice Bulletin 117; Obstet Gynecol 2010;116(6):1492).

Indications for colposcopy of the cervix include

• cytologic abnormality: atypia or greater, including ASC and 

atypical glandular cells (AGC);

• history of untreated abnormal Pap smear;

• repeat colposcopy in women with AGC not otherwise specified 

(AGC-NOS) if the initial evaluation is negative and follow-up 

cytology is abnormal; and

• evidence of HPV infection (consider).

Consider periodic colposcopy

• after treatment of cervical dysplasia, particularly with recurrence or 

persistence of cytologic abnormalities;

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• with ASCUS or LSIL after ruling out a high-grade lesion; and

• with cytologic progression of ASCUS or LSIL that is being followed 

conservatively.

The finding of ASC represents the mildest Pap smear abnormality. ASC is 

stratified into two categories: ASCUS and ASC-H. In the general population, 

5%–17% of women with ASC have underlying CIN 2–3 and approximately 

0.1% have invasive cancer (J Natl Cancer Inst 2001;93:293), whereas 

24%–92% of women with ASC-H have CIN 2–3 confirmed with biopsy (JAMA

2002;287(16):2120). HIV infected women with ASCUS are approximately 

twice as likely to have underlying dysplasia as are uninfected women (Obstet 

Gynecol 1996;87:515). Immunosuppression does not appear to increase 

the frequency of dysplasia associated with ASCUS on Pap (Gynecol Oncol

1999;75(1):118).

It remains unclear whether HIV infected women with mild cytologic 

abnormalities are at a similar or increased risk for clinically significant disease 

(i.e., HSIL or worse) compared with uninfected women. In a cross-sectional study 

of HIV infected and uninfected women with ASCUS and LSIL, HIV infected 

women were no more likely to have CIN 2 or higher on biopsy than were 

uninfected women (Obstet Gynecol 2008;112:238). Other studies have shown 

that with ASCUS or LSIL on Pap and no histologic evidence of high-grade CIN, 

the absolute risk of progression to CIN 2 or higher is approximately 12% 

(Obstet Gynecol 2005;106(3):525) and that CIN 1 infrequently progresses to 

more advanced disease (AIDS 2004;18:109).

The risk of underlying pathology with a diagnosis of AGC is significant. The 

2001 Bethesda System stratifies AGC into three categories: AGC, either 

endocervical, endometrial, or NOS; AGC, favor neoplasia; and endocervical 

adenocarcinoma in situ (AIS). Various studies have found that 9%–54% of 

women with AGC have CIN on biopsy, 0%–8% have AIS on biopsy, and up to 

9% have invasive cancer (JAMA 2002;287(16):2120). The risk of a significant 

abnormality increases with the severity of the AGC reading. Colposcopy, as 

well as endocervical sampling, is indicated with any AGC on Pap. Endometrial 

sampling is indicated in women aged >35 years and in younger women with 

AGC who have unexplained vaginal bleeding (JAMA 2002;287(16):2120). 

Women who have AGC, favor neoplasia, or endocervical AIS should undergo 

a diagnostic excisional procedure (e.g., cervical conization) if the initial 

evaluation is negative for invasive cancer (JAMA 2002;287(16):2120).

Even in high-resource areas, screening for cervical dysplasia in the setting 

of HIV can be challenging. Women receiving gynecologic and primary HIV 

care at the same location are more likely to have had Pap-smear screening 

within the previous year (J Acquir Immune Defic Syndr 2001;27:463); however, 

despite high rates of HPV and CIN, many women with HIV do not engage in 

the recommended annual Pap testing (J Womens Health 2008;17(10):1609; J 

Acquir Immune Defic Syndr 2009;51(4):430).

Vaginal and vulvar screening: Careful visual inspection of the vagina and 

vulva should be performed at least annually; look for evidence of HPV 

infection (e.g., warts, hyperpigmented or hyperkeratotic lesions). Consider 

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vaginal cytology and careful examination and/or colposcopy of the entire 

lower genital tract (vagina, vulva, and perianal region) with any of the 

following: visible evidence of cervical, vaginal, or vulvar HPV infection; current 

CIN or history of CIN; or cervical, vaginal, or vulvar cancer.

Continued vaginal cytologic surveillance is warranted in HIV infected women 

who have a history of CIN 2 or greater who undergo hysterectomy (ACOG 

Practice Bulletin 117; Obstet Gynecol 2010;116(6):1492). Abnormal vaginal 

cytology should be evaluated with colposcopy +/– Lugol’s iodine, with biopsy 

of abnormal areas. Persistent ulcer or mass of concern for possible cancer 

should be biopsied.

Anal screening: Question patients at least annually about such symptoms as 

rectal bleeding and/or pain and perform an annual digital rectal exam to 

detect mass on palpation.

The role of anal cytology remains unclear pending further screening and 

treatment studies; recommendations for routine anal Pap smear screening 

are not currently part of national guidelines. If anal cytology is performed, 

it is critical to refer for further evaluation of abnormal screening (e.g., highresolution anoscopy, biopsy) and treatment.

At a minimum, consider anal cytology in women with a history of abnormal 

cervical cytology and/or genital warts.

The approach suggested by experts in this field is similar to recommendations 

for cervical Pap-smear screening: perform an anal Pap as part of the initial 

evaluation; if results are normal, repeat in 6 months and annually thereafter. 

More-frequent anal Pap smears should be considered with a previous 

abnormal anal Pap smear and after treatment for anal dysplasia. Anal Pap 

smears with ASCUS or SIL should be evaluated with high-resolution anoscopy 

and biopsy.

Anal Pap smears are performed by inserting a moistened Dacron swab 1–1.5 

inches into the anal canal and rotating it while slowly withdrawing it over 

15–20 seconds and maintaining contact with the mucosa. Both rectal columnar 

and anal squamous cells must be obtained to have an adequate specimen. The 

swab should then be vigorously shaken in liquid-based cytology media.

Management of Cervical and Other Lower-Genital-Tract Dysplasia

Management of abnormal Pap smears is outlined in Table 6-2. The purpose of 

colposcopy is to identify abnormal areas and their extent for targeted biopsy. 

The results of Pap smear plus colposcopy and/or biopsy are used to determine 

the need for treatment, follow-up, or further evaluation.

Treatment is recommended with documentation of a high-grade cervical 

lesion on biopsy; standard excisional or ablative treatment is recommended. 

Cryotherapy has had the highest rate of recurrence and should be avoided 

if other treatment methods are available. Close observation should be 

considered for management of CIN 1 and CIN 2 in HIV-infected adolescents. 

Hysterectomy should be used as treatment for high-grade cervical dysplasia 

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only after excluding invasive cancer with an excisional treatment and in 

general should not be used as a primary treatment. It is generally reserved 

for persistent or recurrent high-grade disease. Hysterectomy as treatment 

for recurrent or persistent cervical dysplasia has also been associated with 

significant rates of vaginal recurrence (Am J Obstet Gynecol 2002;186:880).

HIV infected women have an increased incidence (>50%) of recurrence of 

cervical lesions after treatment (Int J STD AIDS 2006;17(8):507), particularly 

with any of the following:

• Positive surgical margins with a loop electrosurgical excision 

procedure or cervical conization (present in >40% of HIV infected 

women) (Am J Obstet Gynecol 1999;181(6):1395; Gynecol Oncol

2005;96(1):112; Int J Gynaecol Obstet 2009;104:100)

• Glandular involvement (Int J Gynaecol Obstet 2009;104:100)

• Greater level of immunosuppression (Gynecol Oncol 1999;74:428; 

J Obstet Gynaecol 2008;28(3):327)

• Absence of suppressive ART (Am J Obstet Gynecol 2001;184(4):538)

Most recurrences appear to be low-grade disease, which may be associated 

with new HPV infections (J Low Genit Tract Dis 2007;11:90), but re-excision 

may be necessary in some cases (Gynecol Oncol 1999;74:428; Anticancer 

Res 2007;27:1795). Follow-up with cervical cytology alone or cytology and 

colposcopy together at 6-month intervals during the first year after treatment 

is recommended (Am J Obstet Gynecol 2007;197(4):346).

After treatment for cervical dysplasia, abstinence should be emphasized 

until complete healing has occurred because treatment has been shown to 

dramatically increase genital-tract HIV shedding, which may increase risk for 

sexual transmission of HIV (Am J Obstet Gynecol 2001;184(3):279).

Table 6-2

Recommended Management for Abnormal Pap Smear*

Pap Smear Result Management

Unsatisfactory • Repeat Pap smear

Partially obscuring 

(inflammation) • Evaluate for infection

• Consider repeat Pap smear

Epithelial Cell Abnormalities

Atypical glandular 

cells • Colposcopy, endocervical sampling

• Endometrial sampling if aged >35 y or with abnormal 

bleeding

• If AGC, favor neoplasia: cervical conization if initial 

evaluation is negative

• If AGC-NOS:

- Consider cervical conization

- If observation is elected, repeat Pap smear and/or 

colposcopy in 6 mo

- If persistent reading of AGC, proceed to diagnostic 

excision

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Table 6-2

Recommended Management for Abnormal Pap Smear*

Pap Smear Result Management

Atypical squamous 

cells (ASCUS and 

ASCUS-H)

• Colposcopy (repeat cytology alone in 6–12 mo can be 

considered for ASCUS)

• Biopsy if indicated

• Endocervical sampling if unsatisfactory colposcopy

• Follow with Pap smear every 6 mo

• Consider repeat colposcopy annually if Pap smear is 

unchanged

• May resume annual Pap smears after two successive 

negative results

Low-grade squamous 

intraepithelial lesion 

(LSIL, CIN 1)

• Colposcopy

• Biopsy if indicated

• Endocervical sampling if unsatisfactory colposcopy

• Follow with Pap smear every 6 mo

• Consider annual repeat colposcopy if Pap smear 

is unchanged

High-grade 

squamous 

intraepithelial lesion 

(HSIL, CIN 2–3,

carcinoma in situ)

• Colposcopy

• Biopsy

• Endocervical sampling

• Treat with loop excision or conization

• If evaluation is negative, consider diagnostic excision

• If close follow-up is elected, repeat Pap smear and 

colposcopy in 6 mo

• Proceed to excisional procedure with repeat reading 

of HSIL

Invasive carcinoma • Colposcopy with biopsy or conization for diagnosis

• Treat confirmed invasive disease with surgery or radiation

• Referral to gynecologic oncologist

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

*Management should be based on histologic findings when biopsy is performed

Management of other lower-anogenital-tract dysplasia: Women with 

documented vaginal, vulvar, or anal dysplasia should be managed in 

consultation with a specialist. Treatment options include observation, excision, 

cavitational ultrasonic surgical aspiration, or laser vaporization; 5-FU has been 

used successfully to treat vulvar and vaginal lesions and small studies suggest a 

possible role for topical 1% cidofovir gel with lower-genital-tract HPV-related 

lesions (J Med Virol 2001;64:195; Clin Infect Dis 2001;33:597). Regardless 

of the type of treatment, recurrence rates are higher in HIV infected women 

than in uninfected women and close follow-up is needed (Dis Colon Rectum

2002;45:453).

continued

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Prevention of Human Papillomavirus Infection

HPV vaccine: Use of the HPV vaccine is an issue of concern in HIV infected 

adolescents, a significant percentage of whom were infected perinatally. 

Although the safety of the HPV quadrivalent vaccine has been demonstrated 

in HIV infected children, the efficacy of currently available HPV vaccines in 

HIV infected women or girls has not yet been established (J Acquir Immune 

Defic Syndr 2010;55(2):197). Given existing evidence that the vaccine is safe 

and immunogenic, and because of the potential benefit in preventing HPVassociated disease and cancer in HIV-infected women, either the bivalent or 

quadrivalent HPV vaccine is recommended for HIV-infected females aged 13 

through 26 years. (MMWR Recomm Rep 2007;56(RR-2):1; Obstet Gynecol

2010;116;800; Guidelines for the Prevention and Treatment of Opportunistic 

Infections in HIV-Infected Adults and Adolescents (http://aidsinfo.nih.gov/

guidelines/html/4/adult-and-adolescent-oi-prevention-and-treatmentguidelines/343/hpv; accessed 5/17/2013)).

Condoms: Consistent and correct use of condoms has been associated with 

a reduced risk of acquiring genital HPV infection (including genital warts), 

CIN, and cervical cancer (N Engl J Med 2006;354:2645; Cancer Epidemiol 

Biomarkers Prev 2006;15:326; Sex Transm Dis 2002;29:725), although data 

are limited in the HIV setting.

Genital Ulcers

The presence of genital ulcers in HIV infected patients increases HIV 

shedding, which may increase the risk of HIV transmission to partners 

and also increases vulnerability to HIV acquisition (Curr Infect Dis Rep

2008;10:505). History, physical examination, and evaluation for patients 

with HIV ulcers are outlined below.

History, Physical Exam, Evaluation, and Differential Diagnosis

History

• Duration and location of lesion(s)

• Previous history of genital ulcers, syphilis, or genital herpes

• Associated symptoms, e.g., pain, pruritus, fever

• Medications and timing of ulcers relative to initiation of new medication

• Sexual history (including condom use)

• CD4+ cell count

• HIV VL

Physical Examination

• Dimensions and location of lesion(s)

• Presence of pigmentation, edema, erythema, or induration

• Presence of associated exudate or tenderness

• Presence of oral lesions

• Associated lymphadenopathy or rash

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Evaluation

• Syphilis serology or darkfield examination

• Culture or PCR from lesion for herpes simplex virus (HSV); in some circumstances 

(e.g., genital ulcers and negative evaluation), consider type-specific HSV 

antibody test

• Biopsy with unclear diagnosis, lack of response to treatment: consider special stains 

(e.g., CMV acid-fast bacillus)

• Culture for Haemophilus ducreyi: not widely available commercially; diagnosis of 

chancroid generally made with typical clinical presentation, after excluding syphilis 

and HSV

Differential Diagnosis

• Infectious causes

- HSV

- Syphilis

- Chancroid

- CMV

- Other (lymphogranuloma venereum, granuloma inguinale, TB)

• Noninfectious causes

- Inflammatory conditions (Crohn’s disease, Behçet’s syndrome, hidradenitis 

suppurativa)

- Neoplasia

- Drug reaction

- Trauma

- Aphthous genital ulcerations

Herpes Simplex Virus

HSV is the most prevalent infectious cause of genital ulcers in the United States. 

Two distinct serotypes exist: HSV-1 and HSV-2; most cases of recurrent genital 

herpes (60%–95%) are caused by HSV-2, but HSV-1 is causing an increasing 

proportion of first episodes of anogenital herpes in some populations, 

including young women (Sex Transm Infect 2009;85:416). Since the late 1970s, 

the seroprevalence of HSV-2 infection has increased by 30%; infection is 

detectable in 21.9% of people aged ≥12 years nationwide (N Engl J Med

1997;337(16):1105). Most people with HSV-2 do not know they are infected 

because they have mild or unrecognized symptoms; they may, however, shed 

virus intermittently in the genital tract and transmit infection to their sexual 

partners. Age-adjusted HSV-2 prevalence is significantly higher among 

women than men (J Infect Dis 2002;185(8):1019). Viral shedding and sexual 

transmission can occur during asymptomatic periods.

HSV in HIV infected patients: Approximately 70% of HIV infected patients 

are co-infected with HSV-2 (JAMA 2006;296:964). More-frequent, prolonged, 

and/or severe episodes are common with progressive immunosuppression and 

lesions may be atypical in appearance or location.

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HSV viral shedding, which increases with declining CD4+ cell counts (Ann Intern 

Med 1995;123:845) and higher plasma HIV VL (Clin Infect Dis 2003;36:207), 

may be more common in women who use oral contraceptives or DMPA and in 

women with severe vitamin A deficiency (J Infect Dis 2000;181:58). Most viral 

shedding is asymptomatic.

Although ART reduces the severity and frequency of symptomatic genital 

herpes, HIV infected women have comparatively more genital ulcers, and 

frequent subclinical shedding still occurs among women on ART (J Infect Dis

2004;190:693; AIDS 2006;20:1051). HSV is associated with increased 

risk for HIV transmission and/or acquisition (Lancet 1994;343:255) and HIV 

disease progression is increased by HSV-2 infection (PLoS One 2010;5:e9973). 

Higher levels of cervical HSV have been associated with increased HIV 

shedding in the genital tract (AIDS 2002;16:2425) and plasma HIV VL is 

increased during HSV reactivation (J Infect Dis 2002;186:1718)

Diagnosis: Lesions typically present as painful vesicles that ulcerate and heal 

without scarring. Primary infection is often associated with systemic symptoms 

(fever, photophobia, headache); duration of lesions and viral shedding are 

more prolonged with primary infection. After the primary episode, latency 

is established in sacral dorsal root ganglia. Recurrent episodes occur with 

variable frequency and are associated with more localized lesions and shorter 

duration than primary or nonprimary first episodes.

Nonprimary first-episode herpes, which is often milder and shorter in duration, 

is diagnosed with antibodies to HSV-2 or HSV-1 in patients who present with 

symptoms but have no previous clinical symptoms of HSV.

Treatment: Recommended HSV treatment regimens are outlined in Table 6-3. 

HIV infected women often need higher doses and longer courses of treatment, 

particularly with more advanced immunosuppression, and they may benefit 

from suppressive therapy. Daily suppressive therapy reduces the frequency 

of recurrences by ≥75% among patients who suffer from six or more HSV 

recurrences per year. Suppressive therapy reduces but does not eliminate viral 

shedding. Suppressive or episodic therapy with oral antiviral agents is effective 

in decreasing genital ulcers and genital HSV-2 shedding as well as genital HIV 

shedding and plasma HIV VL among co-infected women (AIDS 2009;23:461; 

J Acquir Immune Defic Syndr 2008;49:77; N Engl J Med 2007;356:790; AIDS

2006;20:2305; Int J STD AIDS 2002;13(1):12; J Infect Dis 2003;188:1009). 

Daily HSV suppressive therapy in HSV-2/HIV co-infected persons was not 

associated with reduced HIV transmission to HIV uninfected sexual partners, 

despite a reduction in HIV VL and occurrence of genital ulcers due to HSV-2 

(N Engl J Med 2010;362(5):427). Clinical manifestations of genital herpes 

might worsen during immune reconstitution after initiation of ART.

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Table 6-3

Recommended Treatment for Herpes Simplex Virus

Indication Treatment Options

First clinical 

episode • Acyclovir 400 mg po tid x 7–10 d or 200 mg po 5x/d x 7–10 d

• Famciclovir 250 mg po tid x 7–10 d

• Valacyclovir 1 g po bid x 7–10 d

Recurrent 

episodes • Acyclovir 400 mg po tid x 5–10 d

• Famciclovir 500 mg po bid x 5–10 d

• Valacyclovir 1 g po bid x 5–10 d 

Daily 

suppressive 

therapy

• Acyclovir 400–800 mg po bid–tid

• Famciclovir 500 mg po bid

• Valacyclovir 500 mg po bid

Severe 

disease • Acyclovir 5–10 mg/kg body weight IV q8h x 2–7 d or until 

clinical improvement is observed

• Follow with oral antiviral therapy to complete at least 10 d total 

therapy

Acyclovirresistant HSV • Intravenous foscarnet: 40 mg/kg IV q8h or 60 mg/kg IV q12h 

until clinical resolution

• Intravenous cidofovir: 5 mg/kg q wk

• Topical cidofovir gel 1%: apply to lesions qd x 5 consecutive 

days

• Topical imiquimod: apply to lesions qd x 5 consecutive days

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: MMWR Recomm Rep 2010;59(RR-12):1

Acyclovir resistance: Suspect acyclovir resistance if lesions persist or recur in a 

patient on antiviral treatment; obtain a viral isolate for sensitivity testing (Arch 

Intern Med 2003;163:76). Acyclovir-resistant HSV strains are cross-resistant 

to valacyclovir and usually to famciclovir. The prevalence of resistant HSV in 

immunocompromised patients has remained stable at approximately 4%–7% 

(Clin Microbiol Rev 2003;16:114). Most of these isolates are susceptible to 

intravenous (IV) foscarnet or topical cidofovir. Factors associated with acyclovir 

resistance are low CD4+ cell counts and long-term exposure to acyclovir. 

Results of a study of immunocompromised but HIV uninfected patients showed 

that daily suppressive antiviral therapy was less likely than episodic therapy 

during outbreaks to be associated with the development of acyclovir-resistant 

HSV (J Infect Dis 2007;196:266).

Syphilis

Syphilis is a systemic disease caused by infection with Treponema pallidum.

Syphilis in HIV infected patients: HIV infected patients may have abnormal 

serologic test results (unusually high titers, false negatives, delayed 

seroreactivity). Generally, however, serologic tests can be interpreted in the 

usual manner. If clinical findings suggest syphilis but serology is nonreactive, then 

biopsy, darkfield examination, or PCR of lesion material should be considered.

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The clinical presentation of syphilis is very variable at all stages; atypical 

manifestations may be seen in the setting of HIV disease. HIV infected patients 

with primary syphilis are more likely than HIV uninfected patients to have 

multiple ulcers and those with secondary syphilis are more likely to have 

concomitant genital ulcers (Sex Transm Dis 2001;28:158; MMWR Recomm Rep

2010;59(RR-12):1).

The CDC recommends annual screening for syphilis among sexually active HIV 

infected women, with more-frequent screening if indicated by symptoms or 

risk behaviors (MMWR Recomm Rep 2010;59(RR-12):1). Although some study 

results indicate no influence of HIV serostatus on rates of successful syphilis 

treatment (Sex Transm Dis 2006;33:151), others indicate significantly more 

treatment failures or a longer median time to successful serologic response 

in HIV infected patients (Sex Transm Infect 2007;83(2):97; Int J STD AIDS

2007;18:814). Close follow-up after treatment is essential.

Neurosyphilis should be considered in the differential diagnosis of neurologic 

signs or symptoms in HIV infected patients, who may be at increased risk for 

neurologic complications in early syphilis (MMWR Morb Mortal Wkly Rep

2007;56:625). Clinical and cerebrospinal fluid (CSF) abnormalities consistent 

with neurosyphilis are most likely in HIV infected patients who have been 

diagnosed with syphilis and have a CD4+ cell count of ≤350 cells/mm3 and/

or a rapid plasma reagin (RPR) titer of ≥1:32 (J Infect Dis 2004;189:369; Sex 

Transm Dis 2007;34:141; Clin Infect Dis 2009;49:162).

Diagnosis: Definitive methods for diagnosing early syphilis are darkfield 

examination and PCR (not commercially available) of lesion exudate or 

tissue. Presumptive diagnosis is possible using two types of serologic tests: 

nontreponemal (venereal disease reaction level or RPR) and a confirmatory 

treponemal test (fluorescent treponemal antibody absorption test, 

microhemagglutination-T. pallidum, various enzyme immunoassays [EIAs], and 

chemiluminescence immunoassays). Nontreponemal antibody titers usually 

correlate with disease activity and are used to assess treatment response. 

Serial assessment during follow-up after treatment should use the same type of 

nontreponemal test.

Treatment: Recommended management strategies are outlined in Table 

6-4. ART may improve clinical outcomes in patients co-infected with HIV and 

syphilis (Clin Infect Dis 2008;47:893; AIDS 2008;22:1145; Clin Infect Dis

2008;47:258).

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Table 6-4 

Recommended Treatment of Syphilis

Syphilis 

Stage

Treatment

Primary, 

secondary, 

and early 

latent

• Benzathine penicillin G, 2.4 million units IM (single dose)

• CSF examination indicated with neurologic signs/symptoms

• Routine CSF exam not associated with improved clinical outcomes

• If penicillin-allergic: consider skin testing and PCN desensitization 

if positive

Late latent, 

unknown 

duration, and 

tertiary

• Benzathine penicillin G, 7.2 million units IM; administer as 2.4 

million units q wk x 3 wk

• CSF examination indicated with neurologic signs/symptoms

• Routine CSF exam not associated with improved clinical outcomes

Neurosyphilis • Aqueous crystalline penicillin G, 18–24 million units qd; administer 

as 3–4 million units IV q4h or by continuous infusion x 10–14 d

• Some recommend benzathine penicillin 2.4 million units IM q wk x 

1–3 wk after completion of IV regimen

Recommended Follow-up for Management of Syphilis

Syphilis 

Stage

Treatment

Primary, 

secondary • HIV infected patients: clinical and serologic evaluation for 

treatment failure at 3, 6, 9, 12, and 24 mo after treatment

• Treatment failure (with signs or symptoms that persist or recur 

or sustained fourfold increase in nontreponemal test titer): CSF 

examination; if CSF exam is negative, retreat with benzathine 

penicillin G, 2.4 million units IM q wk x 3 wk; consider same for 

patients whose titers do not decrease fourfold within 6–12 mo

Latent • HIV infected patients: clinical and serologic evaluation at 6, 12, 

18, and 24 mo after treatment

• With development of clinical symptoms, fourfold rise in titers, or 

titers that do not decrease fourfold between 12 and 24 mo after 

evaluation, perform CSF examination and follow with appropriate 

treatment

Neurosyphilis • Repeat CSF examination q 6 mo until cell count is normal

• Consider retreatment if cell count has not decreased after 6 mo 

or if CSF is not entirely normal after 2 y

• Limited data suggest that changes in CSF parameters might occur 

more slowly in HIV infected patients, especially those with more 

advanced immunosuppression (AIDS 2008;22:1145)

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: MMWR Recomm Rep 2010;59(RR-12):1

Chancroid

Chancroid is caused by infection with Haemophilus ducreyi, which is endemic 

in some areas of the United States and also occurs in discrete outbreaks. Ten 

percent of patients with chancroid are co-infected with T. pallidum or HSV.

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Chancroid in HIV infected patients: Response to treatment may be diminished 

in HIV infected patients, who may require longer or repeated courses of 

therapy and may be at increased risk for treatment failure.

Diagnosis: The initial presentation typically consists of a tender papule that 

becomes pustular and then ulcerative; the ulcer is usually well demarcated, with 

ragged, undermined edges. Definitive diagnosis requires the identification of 

H. ducreyi on special culture media (not widely available; sensitivity <80%). 

No U.S. Food and Drug Administration (FDA)-cleared PCR test for H. ducreyi

is available in the United States. A probable diagnosis can be made if the 

patient has one or more painful ulcers, no evidence of T. pallidum or HSV 

infection is apparent, and the clinical presentation (appearance of ulcers and 

regional lymphadenopathy) is typical for chancroid.

Treatment: In HIV infected patients, single-dose therapies should be used only 

if follow-up can be ensured. Recommended regimens include the following 

(MMWR Recomm Rep 2010;59(RR-12):1):

• Azithromycin 1 g po (single dose), or

• Ceftriaxone 250 mg intramuscularly (IM) (single dose), or

• Ciprofloxacin 500 mg po bid x 3 days, or

• Erythromycin base 500 mg po 4x/day x 7 days

Cytomegalovirus

CMV should be suspected with genital ulcers in severely immunocompromised 

patients. Cervical shedding of CMV is associated with low CD4+ cell counts 

(J Acquir Immune Defic Syndr Hum Retrovirol 1997;15:341).

Diagnosis: Biopsy of lesion with immunohistochemical stains is required.

Treatment: Ganciclovir 5 mg/kg IV bid x 3–4 weeks or foscarnet 60 mg/kg 

IV q8h or 90 mg/kg q12h for 3–4 weeks.

Other Infectious Causes of Genital Ulcers

Lymphogranuloma venereum: Infection is rare in the United States and is 

associated with tender, usually unilateral inguinal or femoral lymphadenopathy, 

proctocolitis, or rectal fistulas/strictures. Diagnosis is made with serology and 

exclusion of other causes. Treatment is a 3-week course of doxycycline or 

erythromycin. HIV infected patients may require more-prolonged treatment 

and resolution of symptoms may be delayed.

Granuloma inguinale (donovanosis): Infection is rare in the United States. 

It is associated with painless, progressive ulcers that bleed easily on contact, 

without regional lymphadenopathy. Diagnosis is made with biopsy or 

tissue-crush preparation. Treatment options are doxycycline, azithromycin, 

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ciprofloxacin, erythromycin, or trimethoprim-sulfamethoxazole, taken for 3 

weeks or until all lesions are healed. The CDC recommends considering the 

addition of aminoglycoside to the treatment regimen in HIV infected patients.

Tuberculosis: Genital TB is generally a secondary manifestation of primary 

disease, usually pulmonary. In the United States, the incidence of genital 

disease is <1%. Diagnosis is made with biopsy. Genital TB should be treated 

in the same manner as extrapulmonary disease; expert consultation is 

necessary (Eur J Obstet Gynecol Reprod Biol 1998;80(2):227).

Noninfectious Causes of Genital Ulcers

Crohn’s disease: This disease is easy to misdiagnose because its principal 

clinical features (fever, abdominal pain, diarrhea, fatigability, weight loss) are 

often found in patients with HIV infection. Crohn’s disease may also present 

with genital ulcers, rectal fissures, perirectal abscesses, or intestinal fistulas. 

Sigmoidoscopy or barium enema is essential in making this diagnosis. Manage 

with expert consultation.

Behçet’s syndrome: This is a multisystem disorder that presents with recurrent 

oral and genital ulcerations as well as uveitis, arthritis, and vasculitis. Vaginal 

ulcers are usually painless, whereas lesions on the external genitalia are 

generally painful. Ulcers range between 2 mm and 10 mm in diameter and 

can be shallow or deep, with a central yellowish necrotic base. A single lesion 

or crops of lesions may be evident. Diagnosis is established on the basis of 

the clinical presentation and biopsy. Treatment consists of topical or systemic 

corticosteroids.

Hidradenitis suppurativa: This is a chronic, refractory condition involving the 

skin, subcutaneous tissues, and apocrine glands. Lesions are painful and are 

associated with a foul-smelling discharge. Eventually a deep-seated chronic 

infection of the apocrine glands develops, with multiple draining abscesses and 

sinuses. A biopsy is necessary to establish the diagnosis. In the early stages of 

disease, treatment options include antibiotics, anti-androgens, and retinoids. 

Treatment of advanced disease requires surgical intervention (Dermatol Clin

2010;28:779).

Neoplasia: Any nonhealing genital ulcer must be biopsied to rule out a 

neoplastic process, including squamous cell carcinoma, basal cell carcinoma, 

adenocarcinoma, melanoma, lymphoma, and Kaposi’s sarcoma. Refer to an 

oncologist for management.

Drug reaction: Genital ulcers have been described as a rare side effect of 

treatment with zalcitabine and foscarnet.

Trauma: Consider with a history of traumatic injury and the possibility of 

sexual violence.

Aphthous genital ulcerations: Aphthous genital ulcers have no identifiable 

specific etiology (typical or opportunistic organism) and are similar to 

aphthous ulcers seen in the gastrointestinal tract (J Acquir Immune Defic Syndr 

Hum Retrovirol 1996;13(4):343). Most patients with these types of ulcers 

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are significantly immunosuppressed (median CD4+ cell count 50 cells/mm3). 

Oro-esophageal ulcers coexist in about one-third of cases, and one-fifth are 

associated with genital fistula formation.

The lesions can be painful, multiple, deep, and extensive (1–6 cm). Associated 

morbidity includes immobility, bleeding, and superinfection. Most have been 

reported to be chronic and/or recurrent or relapsing.

Treatment: After standard evaluation for other causes, consider empiric 

therapy for HSV. If empiric therapy fails, systemic steroids (prednisone 40–60 

mg/day for 1–2 weeks, then taper) have been moderately successful. There 

has been one report of successful treatment of oral aphthous ulcers with ART 

(Int J Infect Dis 2007;11(3):278).

Thalidomide: Thalidomide 200 mg qd x 2–4 weeks has been used to treat 

similar ulcers in the oropharynx or esophagus, with complete healing in 55%–

73% of cases (N Engl J Med 1997;336:1487; J Infect Dis 1999;180:61). 

There are anecdotal reports of similar success in treating genital aphthous 

ulcers. WARNING: Thalidomide is a powerful teratogen and should be used by 

women of reproductive age only after appropriate counseling and pregnancy 

testing and in the setting of reliable contraception or abstinence.

Vaginal Discharge

Abnormal vaginal discharge is a common gynecologic complaint among 

women, including HIV infected women.

History, Physical Exam, Evaluation, and Differential Diagnosis

History

• Duration and characteristics of discharge

• Associated symptoms (e.g., pruritus, malodor, burning, pelvic pain)

• Associations with menstrual cycle

• Sexual history, including condom and other contraceptive use

• History of sexually transmitted diseases

• History of douching

• Recent antibiotic use

• CD4+ cell count

• HIV VL

• Medications

Physical Exam

• Complete genital inspection and bimanual pelvic examination

• Document characteristics and amount of discharge as well as presence of erythema, 

edema, and tenderness

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Evaluation

• Saline wet mount

• 10% potassium hydroxide (KOH) preparation

• Vaginal pH determination

• Test for gonorrhea and chlamydia

• Perform fungal culture if indicated (signs/symptoms of yeast infection with negative findings on microscopy; chronic/recurrent yeast infections)

Differential Diagnosis

• Bacterial vaginosis (BV)

• Vulvovaginal candidiasis

• Trichomoniasis

• Gonorrhea

• Chlamydia

• Other causes of abnormal vaginal discharge

Bacterial Vaginosis

BV is the most prevalent cause of vaginal discharge or malodor. It results 

from the replacement of normal Lactobacillus-dominant vaginal flora with 

mixed flora, including anaerobic bacteria, Gardnerella vaginalis, and 

Mycoplasma hominis. It is associated with increased rates of several obstetric 

and gynecologic complications, including pelvic inflammatory disease (PID), 

postabortion and posthysterectomy infections, and preterm labor. BV increases 

the risk of HIV-1 acquisition in women (AIDS 2008;22(12):1493; J Infect Dis

2005;192(8):1372) and increases HIV-1 shedding in the genital tract (J Infect 

Dis 2005;191(1):25).

Bacterial vaginosis in HIV infected patients: Data conflict on whether HIV 

infection is associated with increased BV prevalence compared with high-risk 

uninfected women (Obstet Gynecol 2001;98(4):656; J Acquir Immune Defic 

Syndr 2006;43:161). One study found both increased prevalence of BV and 

increased bacterial persistence in HIV infected women; increased persistence 

could result in higher prevalence, but not necessarily more frequent infections 

(Obstet Gynecol 2001;98(4):656). Prevalence, persistence, and severity all 

increase as CD4+ cell counts decrease (Obstet Gynecol 2001;98(4):656; Clin 

Infect Dis 1999;29:1145; Sex Transm Dis 1999;26:143). Use of ARVs has been 

associated with lower BV prevalence (Infect Dis Obstet Gynecol 2001;9:133).

Diagnosis: Standard diagnosis is made by clinical criteria and requires the 

presence of three of the following: 1) homogeneous grayish or yellowish 

discharge that may coat vaginal walls; 2) clue cells on microscopic 

examination; 3) vaginal pH >4.5; and/or 4) a positive whiff test (i.e., fishy 

odor of discharge before or after addition of 10% KOH).

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Treatment: Treatment is indicated for women who have symptoms of BV. No 

current data suggest that screening and treatment of asymptomatic women 

reduces obstetric or gynecologic complications. A Pap smear report of 

“bacterial flora shift suggestive of BV” does not indicate treatment, but does 

indicate the need to question the patient about signs or symptoms.

Recommended regimens include the following (MMWR Recomm Rep

2010;59(RR-12):1):

• Metronidazole 500 mg po bid x 7 days (avoid alcohol during treatment 

and for 24 hours after completion), or

• Clindamycin cream 2%, 5 g intravaginally qhs x 7 days (oil based and 

may weaken latex condoms and diaphragms), or

• Metronidazole gel 0.75%, 5 g intravaginally qd x 5 days

Alternative regimens include the following (MMWR Recomm Rep

2010;59(RR-12):1):

• Tinidazole 2 g qd x 2 days, or

• Tinidazole 1 g qd x 5 days, or

• Clindamycin 300 mg po bid x 7 days, or

• Clindamycin ovules 100 g intravaginally qhs x 3 days

Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is most commonly caused by infection with 

Candida albicans; however, the prevalence of infections due to non-albicans

species is increasing. Up to 75% of all women will have at least one episode 

of candidiasis and 40%–45% will have two or more episodes; fewer than 5% 

of women experience recurrent episodes of candidiasis.

Typical symptoms are a thick, white discharge and pruritus; other symptoms 

include vulvar burning, vaginal soreness, dyspareunia, and external dysuria.

Vulvovaginal candidiasis in HIV infected patients: VVC is associated with 

increased HIV seroconversion in women who are not HIV infected and 

with increased genital tract HIV in HIV infected women (Sex Transm Dis

2008;35(11):946; J Acquir Immune Defic Syndr 2008;48(2):203).

Prevalence among HIV-infected women is 3%–15%; most studies suggest 

no significant difference in the prevalence of infection between relatively 

immunocompetent HIV infected women and uninfected controls. Analysis of 

longitudinal data from HERS indicated that VVC occurred with higher incidence 

and greater persistence, but not greater severity, among HIV infected women 

compared with uninfected women. A lower CD4+ cell count and higher VL 

were associated with VVC (Clin Infect Dis 1999;29:1145; Obstet Gynecol

2003;101:548). More-frequent use of antibiotics is a possible confounding 

factor for HIV infected women and pregnancy is a predisposing factor for 

candidiasis irrespective of HIV status.

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Most studies show increased rates of vaginal, rectal, and oral colonization 

in HIV infected women, particularly with declining immune function (J Acquir 

Immune Defic Syndr 2006;43:161; J Infect Dis 2003;188:118; Obstet 

Gynecol 1997;90(2):252; Obstet Gynecol 2003;101:548). In HIV infected 

women, 26%–27% of vaginal isolates are non-albicans strains (Clin Infect 

Dis 1998;27:1161); although the most common strain is C. glabrata, data 

conflict on the proportion of non-albicans strains in HIV infected women 

compared with uninfected women. No association has been found between 

strain diversity and HIV progression.

Diagnosis: Diagnosis is made by identifying budding yeast or pseudohyphae 

on a wet mount, KOH preparation, or Gram stain of vaginal discharge. Positive 

identification can also be accomplished with culture. In general, wet mount 

and KOH are used as point-of-care tests if microscopy is available. Culture is 

usually reserved for cases of unclear diagnosis or for species identification in 

recurrent and/or persistent cases.

Treatment: Table 6-5 details recommended treatment regimens. In general, 

conventional antifungal therapies are less effective with non-albicans species; 

10–14 days of therapy with a non-fluconazole azole drug is recommended as 

first-line therapy.

Table 6-5

Management of Vulvovaginal Candidiasis

Agent Dosing and Notes

Topical Azoles 

Butoconazole • 2% cream* 5 g vaginally x 3 d

• 2% single-dose bioadhesive 5 g: one vaginal application

Clotrimazole • 1% cream* 5 g vaginally x 7–14 d

• 2% cream* 5 g vaginally x 3 d

Miconazole • 2% cream* 5 g vaginally x 7 d

• 4% cream* 5 g vaginally x 3 d

• 200 mg vaginal suppository* qd x 3 d

• 100 mg vaginal suppository* qd x 7 d

• 1200 mg vaginal suppository* (one application)

Tioconazole • 6.5% ointment* 5 g vaginally (one application)

Terconazole • 0.4% cream* 5 g vaginally x 7 d

• 0.8% cream* 5 g vaginally x 3 d

• 80 mg vaginal suppository qd x 3 d

Oral Agent

Fluconazole • 150 mg single dose po; avoid concomitant use with terfenadine, 

astemizole, and cisapride secondary to cardiotoxicity

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Table 6-5

Management of Vulvovaginal Candidiasis

Agent Dosing and Notes

Other Agents

Nystatin • 100,000-unit vaginal tablet qd x 14 d; less effective than other treatments

Gentian violet • 1% for vaginal application q7d x 4; messy; may be useful in 

chronic or recurrent cases; causes mucosal exfoliation; encourage 

abstinence during treatment; reinforce condom use

Boric acid • 600 mg intravaginal capsules qd x 14 d; may be useful in chronic 

or recurrent cases; encourage abstinence during treatment; 

reinforce condom use

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

*Available over the counter

Source: MMWR Recomm Rep 2010;59(RR-12):1

Special treatment considerations for HIV infected women

• Topical therapies may be more effective when given for at least 7 

days; fluconazole may be more effective when given in two sequential 

150-mg doses 3 days apart (Adv Stud Med 2005;5:403)

• Consider prophylactic use of topical antifungals when antibiotics are given

• Long-term prophylactic therapy with fluconazole at a dose of 200 

mg weekly has been found effective in reducing colonization with 

C. albicans and symptomatic vulvovaginal candidiasis in HIV infected 

women, but this regimen is not recommended for routine primary 

prophylaxis in HIV infected women (Clin Infect Dis 2001;33:1069; 

MMWR Recomm Rep 2010;59(RR-12):1). Consider in selected cases with 

recurrent vaginal candidiasis.

Azole resistance: There is some concern that extensive use of oral azoles 

may promote azole resistance and possibly limit the use of these agents for 

other HIV-related indications. Information about reduced azole susceptibility is 

limited but suggests that it is relatively uncommon with C. albicans isolates, with 

no evidence of a progressive reduction in susceptibility over time. Among nonalbicans isolates, reduced susceptibility occurs frequently and is more common 

among HIV-seropositive women (J Infect Dis 2001;183(2):286; Rev Iberoam 

Micol 2004;21(4):177; Ann Intern Med 1997;126:689). No current data 

suggest that intermittent therapy with a single dose of fluconazole increases 

the development of azole resistance. Weekly prophylaxis with fluconazole has 

been associated with the infrequent development of resistance (Ann Intern Med

1997;126:689). Nevertheless, long-term treatment with fluconazole may select 

for more resistant and difficult-to-treat non-albicans species and should be 

used with caution.

continued

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Recurrent Candidiasis

Four or more symptomatic episodes of candidiasis per year are considered 

recurrent candidiasis. Evaluation includes identification and/or elimination 

(if possible) of predisposing factors that may include uncontrolled diabetes, 

corticosteroid use, topical or systemic antibiotics, spermicides (conflicting data), 

tight-fitting synthetic underwear, douching, pregnancy, and immunosuppression.

Diagnosis: Fungal culture may be needed if the diagnosis is unclear, symptoms 

are recurrent or persistent, and wet mount and/or KOH or Gram stain are 

negative. Speciation and/or susceptibility testing may be required.

Treatment: Management options include the following:

• Longer duration of standard treatment regimen (e.g., 7–14 days of 

topical therapy; fluconazole 100 mg, 150 mg, or 200 mg every third 

day for total of three doses)

• Chronic intermittent therapy (e.g., with perimenstrual episodes)

• Restriction of orogenital and/or anogenital sexual contact (anecdotal 

evidence only; double-blind, placebo-controlled trials of topical therapy 

for male sexual partners showed no benefit [Sexually Transmitted 

Diseases. 4th ed. New York: McGraw Hill; 2008])

• Possible role for boric acid vaginal capsules and gentian violet 

(Gynecol Obstet Invest 2010;70:306)

• Maintenance therapy, comprising an initial intensive regimen followed 

by one of the following maintenance regimens for at least 6 months: 

fluconazole 100, 150, or 200 mg po weekly (avoid concomitant use 

with terfenadine, astemizole, cisapride secondary to cardiotoxicity) or clotrimazole 500 mg vaginal suppository weekly

• Immune reconstitution: ART initiation has potential benefit if indicated 

(J Infect Dis 1999;180:448)

Trichomoniasis

Trichomoniasis is caused by infection with Trichomonas vaginalis. Clinical 

features include profuse, malodorous, often frothy, yellow-green discharge 

and vulvar irritation, which may be accompanied by urinary symptoms or 

dyspareunia and signs of inflammation (i.e., vaginal erythema, “strawberry” 

vagina, cervix with punctate hemorrhages). In chronic cases, infection may 

be asymptomatic.

Trichomoniasis in HIV infected patients: In HIV infected women T. vaginalis

infection increases genital HIV shedding and possibly sexual and perinatal 

transmission. Treatment of T. vaginalis has been shown to reduce HIV 

shedding (J Infect Dis 2003;187:375; J Infect Dis 2001;183:1017; Sex 

Transm Dis 2009;36:11; J Perinatol 2010;30(11):717). Trichomoniasis has 

also been associated with an increased risk of HIV acquisition (J Infect Dis

2008;197:548; J Infect Dis 2007;195:698).

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In HIV infected women, trichomoniasis prevalence is 5%–23% and incidence 

is 10%–17% (Am J Obstet Gynecol 1999;180:824; Am J Trop Med Hyg

1998;58:495); however, studies have not shown increased prevalence, 

incidence, persistence, or recurrence in HIV infected women compared with 

either uninfected women or HIV infected women with lower CD4+ cell counts 

(Clin Infect Dis 2002;34:1406; J Acquir Immune Defic Syndr 2006;43(2):161).

Results of a study from South Africa indicated that trichomoniasis was 

associated with a significantly higher risk of PID, specifically in women with HIV 

(Clin Infect Dis 2002;34(4):519).

Diagnosis: Diagnosis is made with a variety of methods: saline wet mount 

(motile trichomonads seen in 50%–70% of culture-positive cases), Pap smear 

(60%–70% sensitivity; false positives not uncommon), culture (95% sensitivity), 

PCR, DNA probes, and monoclonal antibodies. Point-of-care testing with wet 

mount is the preferred method if microscopy is available. Other methods are 

useful in the absence of microscopy or with consistent symptoms and a negative 

wet mount result.

Treatment: Recommended regimens are outlined in Table 6-6. If sex partners 

are treated simultaneously, cure rates of >90% can be expected. Topical 

metronidazole has been found to be less effective than the oral preparation 

(MMWR Recomm Rep 2010;59(RR-12):1).

Table 6-6

Treatment of Trichomoniasis

Drug Dosage Comments

Metronidazole 500 mg po 

bid x 7 d • More effective than single-dose metronidazole 

regimen in setting of HIV (J Acquir Immune Defic 

Syndr 2010;55:565)

• Avoid alcohol during treatment and for 24 h 

after completion of therapy

• Treat sex partners with same regimen; avoid 

intercourse until therapy is complete and patient 

and partner are asymptomatic

Metronidazole 2 g po 

(single dose) • Avoid alcohol during treatment and for 24 h 

after completion of therapy

• Treat sex partners with same regimen; avoid 

intercourse until therapy is complete and patient 

and partner are asymptomatic

Tinidazole 2 g po 

(single dose) • No studies have evaluated tinidazole treatment 

in women co-infected with HIV and T. vaginalis

• Avoid alcohol during treatment and for 72 h 

after completion of therapy

• Treat sex partners with same regimen; avoid 

intercourse until therapy is complete and patient 

and partner are asymptomatic

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: MMWR Recomm Rep 2010;59(RR-12):1

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Three months after completion of treatment, consider rescreening HIV infected 

women, regardless of symptoms, given the high proportion of recurrent or 

persistent infection and the association between HIV and T. vaginalis infection 

(Sex Transm Dis 2000;27:284; Clin Infect Dis 2008;46:994; Ann Intern Med

2006;145:564).

Resistance: Low-level metronidazole resistance has been identified in 

2%–5% of cases of vaginal trichomoniasis (Antimicrob Agents Chemother

2006;50:4209), but high-level resistance occurs only rarely. Organisms with 

decreased susceptibility usually respond to tinidazole or to higher doses 

of metronidazole. If treatment failure occurs with either regimen, re-treat 

with metronidazole 500 mg po twice a day for 7 days. If treatment failure 

occurs repeatedly, treat with metronidazole or tinidazole 2 g po once 

a day for 5 days. Patients with documented infection (with re-infection 

excluded) who have not responded to these measures should be managed in 

consultation with an expert.

Gonorrhea

Gonorrhea is caused by infection with Neisseria gonorrhoeae. Infection is 

commonly asymptomatic but vaginal discharge may be present. If untreated, 

10%–20% of infected women develop PID. The urethra is the primary site of 

colonization after hysterectomy. Gonorrhea may also cause rectal infection, 

pharyngitis, and (rarely) disseminated infection.

Gonorrhea in HIV infected patients: There are no differences in prevalence, 

clinical presentation, diagnosis, or treatment between HIV infected and 

uninfected patients.

Diagnosis: Diagnosis is made by nucleic acid amplification tests (NAATs) of 

endocervical, vaginal, or urine specimens; by nucleic acid hybridization tests of 

endocervical or urethral (after hysterectomy) specimens; or through culture of 

the endocervix or urethra (after hysterectomy). The sensitivity of NAATs for the 

detection of N. gonorrhoeae in genital and nongenital anatomic sites is superior 

to culture but varies by NAAT type. The NAAT may detect gonorrhea and 

chlamydia simultaneously. Because nonculture tests cannot provide antimicrobial 

susceptibility results, in cases of suspected or documented treatment failure, 

clinicians should perform both culture and antimicrobial susceptibility testing 

(MMWR Recomm Rep 2010;59(RR-12):1).

Treatment: N. gonorrhoeae has the ability to develop antibiotic resistance, 

which makes it a moving target for treatment. In the United States, as of 

April 2007, quinolones are no longer recommended for the treatment 

of gonorrhea and associated conditions; cephalosporins are the only 

antimicrobial class currently recommended and available (MMWR Recomm 

Rep 2010;59(RR-12):1). In the United States, minimum inhibitory concentrations 

of N. gonorrhoeae to cephalosporins have been increasing—particularly 

for cefixime—though no resistant cases have been seen yet. The CDC is 

now recommending treatment of gonorrhea with single-dose ceftriaxone 

250 mg IM and the preferential co-treatment of chlamydia with single-dose 

azithromycin 1 g po, instead of 1 week of doxycycline, because azithromycin 

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offers coverage of both gonorrhea and chlamydia (MMWR Morb Mortal 

Wkly Rep 2011;60(26):873). The CDC’s website (http://www.cdc.gov/std/

gisp) and state health departments can provide the most current information on 

gonorrhea treatment.

For uncomplicated gonococcal infections of the cervix, urethra, and rectum, 

the following regimens are recommended (MMWR Recomm Rep 2010;59(RR12):1), with rescreening 3 months after treatment:

• Single-dose ceftriaxone 250 mg IM; or, if not an option,

• Single-dose cefixime 400 mg po (less effective for pharyngeal 

infection); or

• Single-dose injectable cephalosporin regimen plus, for presumptive 

chlamydia treatment, single-dose azithromycin 1 g po (preferred) or, if 

azithromycin is not an option, doxycycline 100 mg po bid for 7 days; or

• Alternative single-dose injectable cephalosporin regimens: ceftizoxime 

500 mg IM, cefoxitin 2 g IM with probenecid 1 g po, and cefotaxime 

500 mg IM (efficacy for pharyngeal infection is less certain)

It is recommended that women be treated for chlamydia presumptively, 

particularly in areas with high rates of co-infection, or where there is no 

chlamydia testing, and/or when a patient may not return for test results. Avoid 

the use of doxycycline or quinolones in pregnancy.

Treatment of sex partners: Sex partners should be treated for both gonorrhea 

and chlamydia if their last sexual contact with the patient was within 60 days 

before the diagnosis or onset of symptoms. If a patient’s most recent sexual 

contact occurred more than 60 days before the onset of symptoms, her most 

recent partner should be treated. Intercourse should be avoided until treatment 

is completed and symptoms have resolved.

Culture and susceptibility testing are recommended after apparent treatment 

failure with the standard regimen; persistent positive test results with or without 

persistent symptoms indicate treatment failure.

Chlamydia

Chlamydia is caused by infection with Chlamydia trachomatis. Asymptomatic 

infection is common, but clinical presentation may include abnormal discharge 

and/or symptoms of urethritis. If untreated, 10%–40% of infected women 

develop PID.

Chlamydia in HIV infected patients: There are no differences in prevalence, 

clinical presentation, diagnosis, or treatment between HIV infected and 

uninfected women.

Diagnosis: NAATs, cell culture, direct immunofluorescence, EIA, and nucleic 

acid hybridization tests are available for the detection of C. trachomatis

on endocervical specimens. NAATs have the highest sensitivity and can also 

be used with urine. Some NAATs are cleared for use with vaginal swab 

specimens, which can be collected by the provider or self-collected by the 

patient. Self-collected vaginal swab specimens perform well compared with 

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other approved specimens using NAATs (Sex Transm Dis 2005;32:725; Int J 

STD AIDS 2008;19:507) and are well accepted by women. NAATs may also 

be used to detect C. trachomatis at rectal and oropharyngeal sites and have 

demonstrated improved sensitivity and specificity compared with culture at 

these sites (Sex Transm Dis 2008;35:637; J Clin Microbiol 2010;48:1827; 

J Clin Microbiol 2009;47:902).

Treatment: Recommended regimens include the following (MMWR Recomm Rep

2010;59(RR-12):1), with rescreening 3 months after completion of treatment:

• Single-dose azithromycin 1 g po, or

• Doxycycline 100 mg po bid x 7 days (avoid in pregnancy)

Alternative regimens include the following:

• Erythromycin base 500 mg po 4x/day x 7 days, or

• Erythromycin ethylsuccinate 800 mg po 4x/day x 7 days, or

• Ofloxacin 300 mg po bid x 7 days (avoid in pregnancy), or

• Levofloxacin 500 mg po x 7 days (avoid in pregnancy)

Recommendations for the management of chlamydia in sex partners are the 

same as for gonorrhea (see above).

Other Causes of Abnormal Vaginal Discharge

Abnormal vaginal discharge may have several other potential causes.

Atrophic vaginitis: This condition, which is related to estrogen deficiency, is 

characterized by irritative symptoms, vaginal dryness, and dyspareunia. The 

vaginal epithelium appears thin and a watery discharge may be present. Treat 

with either topical or oral estrogen.

Foreign body: If suspected, a careful speculum exam should be performed to 

identify retained tampons, toilet paper, etc.

Local irritants: Remove possible offending agents, including spermicides, 

vaginal medications, toilet-paper dye, hygiene sprays, soap, detergent, 

douches, etc.

Pelvic and/or Lower Abdominal Pain

Abdominopelvic pain can be classified as acute, chronic, or cyclic. Acute pain 

is typically sudden in onset and short in duration, whereas chronic pain is of at 

least 6 months’ duration. Cyclic pain is associated with the menstrual cycle.

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History, Physical Exam, Evaluation, and Differential Diagnosis

History

• Characteristics of pain:

- onset rapid or gradual

- character crampy, colicky, sharp, or dull

- location generalized or localized

- duration

- severity

- radiation of pain

- constant or intermittent

• Associated symptoms:

- abnormal vaginal bleeding or discharge

- gastrointestinal symptoms (e.g., nausea/vomiting, anorexia, constipation, diarrhea)

- urinary symptoms (e.g., dysuria, frequency, urgency, hematuria)

- fever or chills

• History of other medical conditions

• Surgical history

• Gynecologic history:

- date of last menstrual period

- use of contraception and condoms

- history of sexually transmitted infections (STIs)

• Medications

• CD4+ cell counts

• HIV VL

Physical Exam

• Obtain complete set of vital signs

• Focus on abdominal and pelvic findings

• Abdominal exam should evaluate

- presence and character of bowel sounds

- presence of distention

- suprapubic or costovertebral angle tenderness

- other abdominal tenderness, including location, presence of rebound, 

and guarding

- presence of mass or organomegaly

• Pelvic exam should determine

- presence of abnormal bleeding or discharge

- reproducibility and location of tenderness (e.g., uterine, adnexal, or cervical 

motion tenderness)

• Presence of a palpable abdominal or pelvic mass

Evaluation

• Pregnancy test

• Laboratory tests

- CBC with differential

- sedimentation rate or C-reactive protein

- chemistry panel

- others as indicated

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• Wet mount and/or STI testing

• Urinalysis and urine culture

• Stool studies (cultures, evaluation for ova and parasites, Clostridium difficile toxin 

assay), if indicated by gastrointestinal (GI) symptomatology

• Pelvic ultrasound, computed tomography (CT) scans, if indicated

• Blood cultures for bacteria and/or Mycobacterium avium, if indicated

Differential Diagnosis

Differential diagnosis includes but is not limited to

• Pregnancy

• PID

• Ruptured/hemorrhagic ovarian cyst

• Ovarian torsion

• Uterine leiomyomas (fibroids)

• Endometriosis

• Dysmenorrhea

• Mittelschmerz

• Gastrointestinal pathology

• Urinary tract pathology

• Medication-related pathology

Pregnancy (see Chapter 8)

Refer as indicated. With pain and a positive pregnancy test with or without 

bleeding, suspect ectopic pregnancy; urgent evaluation is indicated.

Pelvic Inflammatory Disease

PID is an upper-genital-tract infection, usually polymicrobial in nature. 

Sexually transmitted organisms, including N. gonorrhea and C. trachomatis, 

are implicated in most cases of PID; BV-associated organisms are also 

commonly present. CMV, M. hominis, Ureaplasma urealyticum, and M. 

genitalium may be associated with some cases of PID (Sex Transm Infect

2005;81:463; Sex Transm Infect 2007;83:319; Clin Infect Dis 2009;48:417). 

Symptoms may be virtually absent or mild and nonspecific (e.g., abnormal 

bleeding, dyspareunia, vaginal discharge; less commonly, right-upperquadrant pleuritic pain secondary to perihepatitis).

PID in HIV infected patients: Several studies have found an increased 

seroprevalence of HIV in patients hospitalized with PID (Am J Obstet Gynecol

1990;163:1135; J Reprod Med 1991;36:122). An analysis of hysterectomy 

specimens from HIV infected and uninfected women, matched for surgical 

indication, found chronic endometritis twice as commonly in the specimens 

from HIV infected women as in those from uninfected women; some degree of 

abnormal uterine bleeding had occurred in all cases (Infect Dis Obstet Gynecol

1998;6:186). The clinical presentation of PID in HIV infected women may be 

more severe or otherwise altered (e.g., lower white blood cell counts) (Obstet 

Gynecol 1997;89:65; J Infect Dis 1998;178:1352; Am J Obstet Gynecol

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severe illness, including tubo-ovarian abscess, and longer hospital stays were 

found in women with significant immunosuppression (Am J Obstet Gynecol

1995;172:919; J Infect Dis 1998;178:1352).

HIV infected and uninfected women respond equally well to standard 

parenteral and oral antibiotic regimens (Obstet Gynecol 2006;107:807; 

Am J Obstet Gynecol 1999;181:1374). The microbiology of infection and 

the response to standard antibiotic regimens are similar in HIV infected 

and uninfected women, although one study found that mycoplasmas and 

streptococci were more likely to be isolated from HIV infected women (Obstet 

Gynecol 2000;95:525). Some studies have reported a greater need for 

surgical intervention in HIV infected women (Obstet Gynecol 1993;82:765).

CMV, cryptococcosis, and tuberculosis may cause upper-genital-tract infection 

in rare cases and should be considered in appropriate clinical situations (Infect 

Dis Obstet Gynecol 2009;2009:745060; Int J Gynecol Pathol 2008;27(1):37).

Diagnosis: The current minimum CDC-recommended criteria for diagnosis 

of PID are cervical motion tenderness or uterine tenderness or adnexal 

tenderness (MMWR Recomm Rep 2010;59(RR-12):1). Because PID is difficult 

to diagnose and has the potential to cause long-term complications, empiric 

therapy should be initiated if these criteria are present and no other cause 

for symptoms is identified.

Criteria that enhance diagnostic specificity include

• oral temperature >101oF (>38.3oC),

• abnormal mucopurulent cervical or vaginal discharge,

• elevated erythrocyte sedimentation rate,

• elevated C-reactive protein,

• documented cervical gonorrhea or chlamydia infection, and

• elevated white blood cells on saline wet mount of vaginal secretions.

In patients who are severely ill and/or when diagnosis is uncertain, the most 

specific criteria for diagnosis of PID are

• endometritis on endometrial biopsy;

• tubo-ovarian complex, or thickened, fluid-filled tubes on transvaginal 

ultrasound or magnetic resonance imaging (MRI), or Doppler studies 

suggesting pelvic infection (e.g., tubal hyperemia); and

• laparoscopic abnormalities consistent with PID.

Treatment: The decision to treat with oral vs. parenteral antibiotics (Table 6-7) 

should be individualized, as should the decision to hospitalize an HIV infected 

patient with PID for treatment. Indications for hospitalization include

• inadequate response to outpatient therapy;

• uncertain diagnosis (surgical emergency cannot be excluded);

• pregnancy;

• inability to tolerate or follow outpatient regimen;

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• tubo-ovarian abscess or other evidence of severe illness, nausea and 

vomiting, or high fever; and

• consider with immunosuppression or other significant comorbidity: low 

CD4+ cell count, clinical AIDS, on immunosuppressive drugs.

Table 6-7

Parenteral Regimens for Treatment of Pelvic Inflammatory Disease

Regimen A Cefotetan 2 g IV q 

12 h + doxycycline 

100 mg po or IV 

q 12 h

or

Cefoxitin 2 g IV q 

6 h + doxycycline 

100 mg po or IV 

q 12 h

• Parenteral therapy may be discontinued 24 h 

after evidence of clinical improvement

• Oral therapy with doxycycline 100 mg bid 

should continue through completion of 14 

days of therapy

• When tubo-ovarian abscess is present, clindamycin 450 mg orally 4x/d or metronidazole 500 mg bid + doxycycline 

can be used for continued therapy rather 

than doxycycline alone; this regimen provides 

more effective anaerobic coverage

Regimen B Clindamycin 900 

mg IV q 8 h + 

gentamicin loading 

dose IV or IM (2 

mg/kg of body 

weight), followed 

by maintenance 

dose (1.5 mg/kg) 

q 8 h

(Single daily dosing 

of gentamicin 3–5 

mg/kg may be 

substituted)

• Parenteral therapy may be discontinued 24 h 

after evidence of clinical improvement

• Oral therapy with doxycycline 100 mg bid or clindamycin 450 mg po 4x/d should 

continue through completion of a total of 14 

d of therapy

• When tubo-ovarian abscess is present, 

clindamycin should be continued, rather 

than doxycycline, to provide more effective 

anaerobic coverage

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: MMWR Recomm Rep 2010;59(RR-12):1; see same for alternative oral and 

parenteral regimens

Oral Regimens

• Ceftriaxone 250 mg IM in a single dose + doxycycline 100 mg po bid 

x 14 days +/- metronidazole 500 mg po bid x 14 days, or

• Cefoxitin 2 g IM in a single dose + probenecid 1 g po administered 

concurrently in a single dose + doxycycline 100 mg po bid x 14 days 

+/- metronidazole 500 mg po bid x 14 days, or

• Other parenteral third-generation cephalosporin (e.g., ceftizoxime 

or cefotaxime) + doxycycline 100 mg po bid x 14 days +/- 

metronidazole 500 mg po bid x 14 days

Sexual partners of women diagnosed with PID should be evaluated and 

treated presumptively for gonorrhea and chlamydia if the couple have had 

sexual contact within the 60 days preceding the onset of symptoms.

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Other Causes of Pelvic and/or Lower Abdominal Pain

Ruptured/hemorrhagic ovarian cyst: A ruptured cyst can cause acute pelvic/

abdominal pain. Bleeding associated with rupture is usually self-limited but 

may require surgical intervention.

Ovarian torsion: Torsion can cause acute, severe, unilateral lower-abdominal/

pelvic pain, often with a history of previous similar episodes. A palpable 

adnexal mass is often present. Surgical intervention is required.

Uterine leiomyomas (fibroids): Fibroids may cause pain with rapid 

enlargement, degeneration, or torsion. Referral to a gynecologic specialist is 

indicated for management.

Endometriosis: This condition can cause acute or chronic pain and usually 

includes secondary dysmenorrhea and/or dyspareunia. Referral to a 

gynecologic specialist is indicated if endometriosis is suspected.

Dysmenorrhea: This cyclic pain with menses affects about 50% of all 

menstruating women. Primary dysmenorrhea is menstrual pain in the absence 

of pelvic pathology; secondary dysmenorrhea is associated with underlying 

pathology, such as endometriosis. Treatment of primary dysmenorrhea consists 

of nonsteroidal anti-inflammatory drugs (NSAIDs), which are 80% effective, 

or oral contraceptive pills, which are 90% effective. Treatment of secondary 

dysmenorrhea is directed at the specific underlying problem.

Mittelschmerz: This pain with ovulation is generally self-limited and is managed 

with NSAIDs.

Gastrointestinal pathology: Opportunistic infections, including cryptosporidia, 

CMV, and M. avium may cause chronic diarrhea in patients with AIDS; clinical 

features usually include abdominal pain. Other types of GI pathology include

• appendicitis;

• diverticulitis, with pain generally localized to the left lower quadrant 

(usually seen at older ages);

• irritable bowel syndrome, in which pain is usually intermittent, cramplike, more common in the left lower quadrant, and exacerbated by 

certain foods;

• inflammatory bowel disease;

• infectious enterocolitis, with pain, cramping, and diarrhea; and

• obstruction, with colicky pain, distention, vomiting, and obstipation.

Urinary tract pathology: Pathology of the urinary tract may include renal 

and/or ureteral stones, cystitis, and pyelonephritis. Urinalysis and urine 

culture should identify the presence of infection, which should be treated 

on the basis of microbial sensitivities. Renal or ureteral stones are generally 

associated with severe, often colicky pain and hematuria; ultrasound or 

other imaging of the urinary tract may show partial obstruction. The patient 

generally needs IV fluids, pain control, and possibly lithotripsy. Referral to a 

urologic specialist is indicated.

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Medication-related pathology: Indinavir may cause renal stones; didanosine 

may cause pancreatitis.

Pelvic Mass

A pelvic mass may be detected by the patient or may be felt on abdominal or 

pelvic exam. Symptoms vary; a mass often may occur without any symptoms.

History, Physical Exam, Evaluation, and Differential Diagnosis

History

• Presence and duration of associated symptoms

• Pain

• Abnormal vaginal bleeding or discharge

• Urinary symptoms (e.g., frequency, urinary retention)

• Gastrointestinal symptoms (e.g., nausea, vomiting, constipation, diarrhea, bloating)

• Constitutional symptoms (e.g., fever, chills, sweats, weight loss or gain)

Physical Exam

• Vital signs

• Constitutional signs

• Complete abdominal and pelvic examination, with particular attention given to

- Size, location, mobility, and characteristics of the mass if palpable

o With functional ovarian cysts, a normal ovary may be up to 5 cm–6 cm in size 

for a woman in the reproductive age range

o A palpable ovary in a postmenopausal woman may be abnormal and requires 

further evaluation

• Signs of ascites

• Lymph node survey

Evaluation

• Pregnancy test if premenopausal

• Laboratory tests

- CBC with differential

- chemistry panel

- tumor markers if indicated (e.g., carcino-embryonic antigen, Ca-125; tests for 

these markers produce frequent false positives and false negatives and should be 

used only in conjunction with other diagnostic procedures)

• Radiologic studies as indicated

- pelvic ultrasound (transabdominal and/or transvaginal): generally the first 

diagnostic modality employed in evaluating pelvic anatomy; concerning 

characteristics include a complex or solid mass and the presence of ascites

- CT and/or MRI: if indicated; CT and/or MRI are better than ultrasound at 

imaging the GI tract, retroperitoneal lymphadenopathy, and liver

• Additional evaluation (e.g., laparoscopy, colonoscopy): refer to appropriate specialists

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Differential Diagnosis

• Ectopic pregnancy: primary consideration in the setting of an adnexal mass and a 

positive pregnancy test; urgent evaluation is indicated

• Ovarian functional cysts: most-common ovarian masses found among women 

of reproductive age; usually less than 5 cm–6 cm in size; resolution occurs 

spontaneously in 1–3 months

• Uterine leiomyomas (fibroids): often asymptomatic, but may be associated with heavy and/or prolonged menses, urinary frequency, or sensation of pelvic pressure

• Endometrioma: consider in women with a documented or suspected history of 

endometriosis

• Hydrosalpinx/pyosalpinx and tubo-ovarian abscess: consider in women with a 

history and exam suggestive of PID; initial management is with broad-spectrum 

antibiotics, even if the patient is asymptomatic

• Benign or malignant ovarian neoplasm: surgical intervention required

- no evidence of increased prevalence in HIV infected women, although anecdotal 

reports suggest ovarian cancer may present at a more advanced stage, with a 

poorer response to cytoreductive surgery and chemotherapy (Obstet Gynecol Surv

1996;51:679)

- non-Hodgkin’s lymphoma of the ovary in an HIV infected woman has been 

described (Obstet Gynecol 1996;88:706)

• Retroperitoneal lymphadenopathy: may present as a pelvic mass; possible causes 

include tuberculosis, lymphoma

• Gastrointestinal masses: includes diverticular abscess and bowel malignancy

Note: In general, the presence of a pelvic or abdominal mass requires expert 

consultation and referral to an appropriate specialist.

Urinary Symptoms

Urinary symptoms are common complaints in both HIV infected and uninfected 

women. Causes of symptoms include both lower and upper urinary tract disease.

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management

History

• Duration and severity of urinary symptoms:

- dysuria

- pain with urination

- frequency

- urgency

- hematuria

- nocturia

- incontinence

• Associated symptoms:

- pain, suprapubic or flank

- fever

- chills

- weight loss

• Other medical conditions (e.g., diabetes, sickle-cell disease)

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• Surgical history

• Medications (increased risk of renal toxicity with TDF, IDV, ATV)

• CD4+ cell count and VL

Physical Exam

• Vital signs

• Abdominal exam: document presence of suprapubic, flank, or costovertebral 

angle tenderness

• Pelvic exam: document presence of vulvar sores/ulcers, vaginal atrophic changes 

or discharge, palpable pelvic mass or tenderness

Evaluation

• Microscopic exam of urine (midstream, clean-catch urinalysis) or catheterized 

specimen (contamination from vaginal discharge or bleeding may occur if a simple 

voided specimen is collected)

• Urine culture and sensitivity

• Gonorrhea and chlamydia testing, if indicated

• Urine cytology: consider in women aged >50 y who present with irritative symptoms 

or hematuria and negative culture

• Urine for acid-fast bacillus (AFB) culture; purified protein derivative (PPD) or 

interferon gamma release assay, if urinary TB is suspected

• Urinary tract imaging (if indicated; consider if stones, urinary tract anomalies, or 

urinary TB is suspected)

- CT

- ultrasound

- intravenous pyelogram

• Other tests: cystoscopy, urodynamics—refer to appropriate specialist

Differential Diagnosis and Management

• Bacterial urinary tract infection: lower tract (cystitis) or upper tract (pyelonephritis); may be asymptomatic; clinical signs and symptoms cannot reliably distinguish 

between upper- and lower-tract infection

- Cystitis is classically characterized by the presence of dull, suprapubic pain. 

Typical associated symptoms include dysuria, urinary frequency and urgency, and 

occasionally hematuria.

o Vulvar dysuria is the sensation of burning when urine flows over the vulva and 

can be misdiagnosed as a urinary tract infection; it is often caused by active 

herpetic or other vulvar lesions

- Pyelonephritis is associated with flank or costovertebral pain and tenderness 

to percussion. Typical systemic signs and symptoms include fever, chills, 

nausea, vomiting, and tachycardia. Treat with appropriate antibiotics; severe 

pyelonephritis requires hospitalization for IV antibiotics and hydration.

• Urethral syndrome: dysuria, frequency with negative urine culture

- Rule out urethritis due to gonorrheal or chlamydial infection

• Renal and/or ureteral stones: characterized by severe, colicky pain

- Stones are usually associated with urinary stasis or chronic infection, although 

they may be related to metabolic abnormalities such as gout or to problems with 

calcium homeostasis

- Atazanavir and indinavir therapy increase the risk for stones

- IV hydration and pain control are often required; surgical intervention is 

sometimes needed

• Interstitial cystitis: symptoms include severe urinary frequency and urgency 

(urinating as often as every 15 minutes daytime and nighttime) as well as 

suprapubic or perineal discomfort before, during, and after urination

- Refer to a urologic specialist for definitive evaluation

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• Urinary tuberculosis: one of the most common sites of extrapulmonary TB

- Consider with gross or microscopic hematuria and pyuria with negative bacterial 

culture; manage with expert consultation

• Tumors: most common presenting complaint is gross or microscopic hematuria; 

hematuria without identifiable etiology (e.g., infection) requires referral to a 

urologist

• Urinary incontinence: can be caused by many factors, including anatomic 

displacements related to aging and childbearing; bladder muscle (detrusor) 

instability; neurologic disease; infection; fistulas secondary to surgical injury, 

radiation, or cancer; and some medications

- Review medication list

- Rule out infection with culture and “overflow” incontinence secondary to 

an overdistended bladder with postvoid catheterization for residual urine 

determination

- Further evaluation requires referral to a urogynecologist or urologist

- Management depends on etiology and is beyond the scope of this manual; expert 

consultation is recommended

• Urinary retention: may be caused by obstruction, neurologic disorders, or 

certain medications (e.g., antihistamines, antidepressants, antipsychotics, opiates, 

antispasmodics, terbutaline, over-the-counter cold remedies)

• HIV-associated nephropathy: presents with nephrotic syndrome and progressive 

renal failure; may have symptoms of increased urination, excessive thirst, and 

fatigue

- If untreated, may lead to end-stage renal disease

- Risk is increased in African Americans and injection drug users

- Usually occurs with advanced disease and, generally, CD4+ cell count 

<200 cells/mm3

Genital Warts

Genital warts are a common manifestation of HPV infection. HPV types 6 and 

11 are usually the cause of visible genital warts. Oncogenic types (i.e., 16, 

18, 31, 33, and 35) are occasionally found in visible warts and have been 

associated with squamous intraepithelial neoplasia of the external genitalia 

(see Abnormal Pap Smear, p. 160).

HIV infected women are more likely to have HPV co-infection, and both 

the prevalence and incidence of genital warts are greater in infected 

than uninfected women. Increased immunosuppression is associated with an 

increased prevalence and incidence of warts, larger or more numerous warts, 

poorer response to therapy for genital warts, and more frequent recurrences 

after treatment (Sex Transm Dis 2002;29:427; Sex Transm Dis 2002;29:121; 

Lancet 2002;359(9301):108; AIDS 2008;22:1213). ART and immune 

reconstitution have been associated with a decreased incidence of warts after 

treatment (Am J Obstet Gynecol 2004;190:1241). Squamous cell carcinomas 

that arise in or resemble genital warts may occur more commonly in the setting 

of immunosuppression, making confirmation of the diagnosis with biopsy more 

often necessary.

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History, Physical Exam, and Evaluation

History

• Location of warts

• Duration

• Presence of associated symptoms (e.g., itching, irritation, pain, bleeding)

• History of prior occurrences of similar lesions and their treatment

• History of abnormal Pap smear results

Physical Exam

• Perform a complete examination of the external genitalia, vagina, cervix, and 

perianal region. Increasingly, HPV disease is found in the oral cavity, which should 

be examined as well.

• Document the location, size, and characteristics of warts

- Genital warts can present as cauliflower-shaped growths (condyloma acuminata); 

smooth, dome-shaped, skin-colored papules; keratotic warts with a thick horny 

layer; or flat or slightly raised flat-topped papules

Evaluation

• Biopsy: Biopsy of the lesion and histopathologic confirmation of the diagnosis are 

always indicated in the following situations:

- Diagnosis is uncertain

- Warts do not respond to therapy

- Lesions worsen during therapy

- Warts are pigmented, indurated, fixed, or ulcerated

• Typical condyloma acuminata are diagnosed by inspection and do not require 

biopsy, although current CDC guidelines suggest biopsy when the patient is 

immunocompromised

• Colposcopy: Colposcopy and directed biopsies of the entire lower genital tract 

should be considered in HIV infected women with evidence of HPV infection

- Perform colposcopy and biopsy to rule out the presence of HSIL before initiating 

treatment of cervical warts

Treatment: The primary goal of treatment is the removal of symptomatic 

lesions. When left untreated, visible warts may resolve spontaneously, may 

remain unchanged, or may increase in number or size. There is no evidence 

that currently available therapies eradicate HPV, affect the natural history of 

infection, or affect the subsequent development of cervical cancer. Infectivity 

may or may not be decreased by the removal of visible warts.

The choice of treatment modality depends on the number, size, and location of 

warts. When the lesions are few in number and fairly small in size, a topical 

agent may be employed. Table 6-8 presents provider-applied and patientadministered regimens recommended by the CDC (MMWR Recomm Rep

2010;59(RR-12):1). Intralesional interferon is an alternative to the therapies 

listed below, but it is expensive and associated with a high frequency of 

systemic side effects. Efficacy data are limited for the two other alternatives, 

photodynamic therapy and topical cidofovir.

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Most treatment modalities are associated with mild to moderate discomfort 

and local irritation. Persistent hypo- or hyperpigmentation is common after 

ablative therapies and can occur with imiquimod. Rarely, scarring or chronic 

pain can occur at the treatment site. Warts located on moist surfaces respond 

best to topical treatment.

Most genital warts respond within 3 months of therapy. The treatment method 

should be changed if a patient has not improved substantially after a 

complete course of treatment or if side effects are severe. Data are limited 

on combining modalities, which does not necessarily increase efficacy but may 

increase complications.

Recurrence rates are significant with all modalities; frequent follow-up will 

allow retreatment when new warts are small and few in number. When the 

number of warts is large or the lesions are very extensive, consider referral for 

possible laser or excisional surgery.

Table 6-8

Recommended Management of Genital Warts

Provider-applied Patient-applied

TCA or BCA:

• Weekly application if necessary

• Remove excess acid with talc powder, 

baking soda, or liquid soap

Podofilox 0.5% solution or gel:

• Apply bid x 3 d, then 4 d of no 

therapy

• May repeat application for up to four 

cycles

• Should be limited to 0.5 mL/d and 

<10 cm2 area of warts

• Avoid during pregnancy

Cryotherapy with liquid nitrogen or 

cryoprobe:

• Repeat every 1–2 wk

Imiquimod 5% cream:

• Apply 3x/wk for up to 16 wk

• Treated area should be washed with 

mild soap and water 6–10 h after 

application

• Avoid during pregnancy

Podophyllin resin 10%–25%:

• Weekly application if necessary

• Limit application to <0.5 mL of 

podophyllin or <10 cm2 of warts 

per session

• Preparation should be thoroughly 

washed off 1–4 h after application to 

reduce local irritation

• Avoid use on mucosal surfaces or with 

any open wounds or lesions because 

of concern about potential systemic 

absorption and toxicity

• Avoid during pregnancy

Sinecatechins 15% ointment:

• Apply tid (0.5 cm strand of ointment to 

each wart)

• Do not continue past 16 wk

• Do not wash off after use

• Avoid sexual contact while ointment is 

on skin

• Not currently recommended for HIV 

infected women because of lack of 

safety/efficacy data in HIV setting

• Avoid during pregnancy

Surgical removal: Laser or excision

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: MMWR Recomm Rep 2010;59(RR-12):1

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Genital Masses and/or Nodules

Genital masses or nodules are relatively common complaints among women in 

general and may be associated with pain or discomfort or with no symptoms 

at all. All genital masses or nodules, however, require careful evaluation for 

appropriate diagnosis and management.

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management

History

• Duration

• Changes in size or appearance

• Associated symptoms (e.g., pain, tenderness, itching, edema)

• History of similar nodules and their treatment

• Sexual history, including the presence of similar lesions on partner’s genitals

• Medications

• CD4+ cell count and VL

Physical Exam

• Document anatomic location, number, and size of nodules

• Presence of associated edema, erythema, induration, fluctuance, tenderness, 

discharge, or bleeding

Evaluation

• Biopsy indicated if etiology is unclear

• Culture abscess contents

Differential Diagnosis and Management (JAMA 2003;290:1001)

• Bartholin’s abscess or cyst

• Genital warts (see p. 198)

• Molluscum contagiosum

• Subepithelial cysts, folliculitis

• Tumors, other masses

Bartholin’s Abscess or Cyst

Bartholin’s glands are normally nonpalpable and located deep in the 

perineum at the 5 o’clock and 7 o’clock positions in the entrance to the 

vagina. Obstruction of a Bartholin’s duct by nonspecific inflammation, infection 

(e.g., gonorrhea or chlamydia), or trauma can lead to the formation of an 

exquisitely tender abscess. Treatment consists of incision and drainage. Often 

a residual Bartholin cyst is present after the resolution of infection. This does 

not require treatment unless it becomes repeatedly infected, is growing, or is 

otherwise symptomatic. The differential diagnosis of a new-onset mass in the 

Bartholin’s region in women aged >40 years must include malignancy.

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Molluscum contagiosum

Molluscum contagiosum is an asymptomatic viral disease that primarily affects 

the skin of the vulva, although in immunosuppressed patients it can present as 

a generalized skin disease. It is spread through sexual and nonsexual close 

contact. Clinical presentation is small nodules or domed papules, usually 1 

mm–5 mm in diameter; more mature nodules appear to have an umbilicated 

center. This disease tends to be self-limited; however, the disease course may 

be complicated by repeat infection and autoinoculation of the virus.

Molluscum contagiosum in HIV infected patients: This disease affects 5%–10% 

of HIV infected patients. Extensive, severe lesions that respond poorly to 

therapy are common, particularly with more advanced immunosuppression. 

Unresponsive lesions have been found to regress with ART (Indian J Dermatol

2009;54(2):180; Eur J Dermatol 1999;9:211), but they have also been 

reported as a manifestation of immune reconstitution syndrome (Dermatol 

Online J 2007;13(2):6).

Treatment: Treatment consists of serial applications of liquid nitrogen or 

removal of nodules with a dermal curet and chemical cauterization of the 

base with 85% trichloroacetic acid or ferric subsulfate. Successful eradication 

with systemic interferon has been reported in an immunocompromised patient 

(Dermatology 2008;217(3):196).

Cysts and Folliculitis

Several benign processes in the genital area may present as a mass or nodule 

and are self-limited, requiring no or limited specific treatment. These are 

generally small and minimally symptomatic and can usually be diagnosed on 

the basis of typical appearance.

Tumors and Other Masses

A biopsy is required for suspected tumors and other masses; expert 

consultation is indicated.

Genital Itching and/or Irritation

Genital itching and irritation are among the most common gynecologic 

complaints in both HIV infected and uninfected women.

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History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management

History

• Duration, location, and severity of pruritus/irritation

• Associated symptoms (e.g., erythema, edema, vulvar burning, dysuria, dyspareunia, 

vaginal discharge)

• Prior episodes of similar symptoms and treatment

• Exposure to particular agents coincident with onset of symptoms (see Allergic and/

or Irritative Reaction, p. 204)

• Presence of similar symptoms or a recent diagnosis of genital tract infection in 

close contacts

• Medications, including antibiotics

• CD4+ cell count

• HIV VL

Physical Exam

• Physical appearance and distribution of any lesions on irritated area (e.g., diffuse 

rash, papular or vesicular lesions, skin burrows)

• Associated findings, including erythema, edema, tenderness, or vaginal discharge

• More thorough inspection of the skin over the whole body may be indicated if a 

more generalized process is suspected (e.g., scabies, allergic reaction to detergent)

Evaluation

• Fungal culture and/or KOH preparation is indicated if fungal infection is suspected

• HSV culture: herpes may appear atypically and should be ruled out in the presence 

of vesicular lesions, unexplained abrasions, fissuring, or if warranted by history

• Other cultures/saline wet mount, if indicated by exam findings

• Skin scrapings: the skin papule is scraped with a needle and the crust is 

placed under a drop of mineral oil on a slide; eggs, parasites, or fecal pellets 

microscopically visualized by this technique are diagnostic of scabies or pubic lice. 

A biopsy should be considered if other diagnostic tests are negative or with lack of 

response to treatment.

Differential Diagnosis and Management (JAMA 2003;290:1001)

• Fungal infection

• Allergic and/or irritative reaction

• Scabies

• Pediculosis pubis

• Other: vaginitis or cervicitis, vulvar atrophic changes, vulvar dystrophy

Fungal Infection

Although the primary symptom associated with fungal infections is itching, 

women also complain of vulvar burning, dysuria, and dyspareunia, particularly 

with the involvement of vulvar skin. Examination often reveals edema, 

erythema, and excoriation; when extensive skin involvement is present, pustular 

lesions may be found to extend beyond the line of erythema.

Diagnosis: Fungal infection is diagnosed through KOH preparation or 

fungal culture.

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Treatment: The infection is treated with the topical application of an antifungal 

preparation (see Vulvovaginal Candidiasis, p. 182).

Allergic and/or Irritative Reaction

Contact dermatitis frequently affects the vulvar skin, particularly the 

intertriginous areas. Etiologic agents include urine or feces, latex, semen, and 

cosmetic or therapeutic agents, including vaginal contraceptives, lubricants, 

sprays, perfumes, douches, fabric dyes, fabric softeners, synthetic fibers, 

bleaches, soaps, chlorine, dyes in toilet tissues, and local anesthetic creams. 

Severe cases of dermatitis may be due to poison ivy or poison oak. Typical 

symptoms are itching, vulvar burning, and tenderness.

Diagnosis: Examination of the skin reveals erythema, edema, and 

inflammation; the skin may be weeping and eczematoid. Secondary infection 

may occur.

Treatment: Remove the offending agent. Severe lesions may be treated with 

wet compresses of Burow’s solution diluted 1:20 for 30 minutes several times 

a day. If possible, the vulva should be dried with cool air from a hair dryer 

following application of the compresses. Lubricating agents such as Eucerin 

cream or petroleum jelly can help reduce the itching. Nonmedicated baby 

powders can be used to facilitate vulvar dryness. Symptomatic relief can 

be achieved with hydrocortisone (0.5%–1%) or fluorinated corticosteroid 

(Valisone 0.1% or Synalar 0.01%) lotions or creams applied to the skin two to 

three times a day for a few days. Dermatitis due to poison ivy or poison oak 

may require treatment with systemic corticosteroids. The use of white cotton 

undergarments is advisable, and tight-fitting clothing should be avoided.

Scabies

Scabies is a parasitic infection produced by the itch mite Sarcoptes scabiei. It is 

sexually acquired in adults. The main reported symptom is severe, intermittent 

itching that tends to be more intense at night.

Diagnosis: Lesions can present as vesicles, papules, or burrows; although any 

area of skin may be affected, hands, wrists, breasts, vulva, and buttocks are 

most often affected. HIV infected and other immunosuppressed patients are at 

increased risk for crusted or Norwegian scabies, a disseminated dermatologic 

infection, which can appear classically as hyperkeratotic, nonpruritic lesions; as 

crusting with pruritus; as a pruritic, papular dermatitis; or as lesions resembling 

psoriasis (South Med J 1994;87:352).

Treatment: The CDC-recommended treatment for scabies is permethrin cream 

(5%) applied to all areas of the body from the neck down and washed off 

after 8–14 hours or ivermectin 200 mcg/kg po, repeated in 2 weeks (MMWR 

Recomm Rep 2010;59(RR-12):1). An alternative regimen is lindane (1%) 1 oz 

of lotion or 30 g of cream applied to all areas of the body from the neck 

down and washed off thoroughly after 8 hours. Lindane should not be used by 

pregnant or lactating women and should not be used after a bath.

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Itching may persist for days following treatment; antihistamine therapy 

should be considered for symptomatic relief. Bedding and clothing should be 

decontaminated (machine washed or dry cleaned) or removed from body 

contact for at least 72 hours. Norwegian scabies should be managed in 

consultation with an expert.

Pediculosis Pubis

Pediculosis pubis is caused by infestation with the crab louse Phthirus pubis, or 

pubic louse. Transmission is by close contact, but the louse can also be acquired 

from bedding or towels. This infection is usually confined to the hairy areas of 

the vulva, although eyelids are occasionally infested. The presenting symptom 

is constant itching in the pubic area.

Diagnosis: Eggs, adult lice, and fecal material can be seen upon close 

examination, without magnification. The diagnosis can be definitively 

established by microscopic visualization, as described above.

Treatment: The CDC-recommended treatment is permethrin 1% cream rinse 

or pyrethrins with piperonyl butoxide applied to affected areas and washed 

off after 10 minutes (MMWR Recomm Rep 2010;59(RR-12):1). Alternative 

regimens include malathion 0.5% lotion applied for 8–12 hours and then 

washed off or ivermectin 250 mcg/kg orally, repeated in 2 weeks if symptoms 

do not resolve.

Patients should be reexamined in 1 week; re-treat if lice or eggs are seen at 

the hair–skin junction. All clothing and bedding must be decontaminated (i.e., 

either dry cleaned or machine washed and dried using the hot setting) or 

removed from body contact for at least 72 hours. Close household contacts and 

recent sexual contacts (i.e., within the previous month) should be treated.

Other: Vaginitis or Cervicitis, Vulvar Atrophic Changes, Vulvar 

Dystrophy

Diagnosis: based on exam findings and the results of cultures and/or saline 

wet mount when indicated. A biopsy may be needed if lesions are seen (scaly, 

hypertrophic, fissures).

Treatment: indicated if another infectious process is identified; topical estrogen 

for atrophic vaginitis and/or vulvitis; topical steroid therapy empirically for 

suspected vulvar dystrophy or other dermatosis, with biopsy if symptoms or 

lesions do not resolve.

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Breast Lump

A clinical breast exam should be part of the routine physical examination for 

all HIV infected women and should be performed on an at least an annual 

basis. The presence of a breast lump always requires further evaluation, 

depending on the factors listed below.

History, Physical Exam, Evaluation, and Differential Diagnosis 

and Management

History

• Palpable by the patient?

• Duration of lump

• Any associated symptoms (e.g., tenderness, nipple discharge or bleeding, 

cyclic pain)

• Changes in characteristics of the lump (e.g., increase in size)

• Menstrual phase or menopausal status

• History of previous breast lumps

• Family history of breast disease, cancer, or history of genetic screening showing 

BRCA-1 or BRCA-2 mutation

• Mammogram history

Physical Exam

• Examination of both breasts: symmetry, contour, and general appearance of the 

breasts; presence of edema, erythema, skin dimpling, or nipple retraction

• Presence and size of dominant masses; nodularity, tenderness, mobility

• Nipple discharge, including color; evidence of blood

• Lymph node survey: lymphadenopathy, axillary and supraclavicular

Evaluation

• Mammogram should be performed with any persistent palpable mass or other 

suspicious changes in the breast (e.g., bloody nipple discharge, skin retraction)

- Negative mammogram alone is not sufficient to rule out malignant pathology 

in a patient with a palpable breast mass or bloody nipple discharge; further 

evaluation and a possible biopsy are indicated

• Ultrasound is most helpful to distinguish cystic and solid masses

- Useful initial test in younger women when a simple cyst is suspected

• Needle aspiration for cystic lesion

- Fluid can be discarded if clear and if mass disappears

- Otherwise, send fluid for cytology; biopsy may be needed

• Biopsy is indicated in cases of a dominant mass, even with normal mammographic 

findings, or suspicious nonpalpable mammographic findings

Differential Diagnosis and Management

• Fibrocystic changes

• Fat maldistribution syndrome

• Breast abscess and/or mastitis

• Benign breast tumor

• Breast cancer

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Fibrocystic Changes

Fibrocystic changes are typically found among women aged 30–50 years.

Diagnosis: Fibrocystic changes usually present as breast nodularity associated 

with cyclic bilateral pain or tenderness that is worse premenstrually. Breast 

engorgement, increased density, and cyst formation are common and vary with 

the menstrual-cycle phase.

Treatment: The pain/discomfort associated with this condition can be relieved 

by wearing a brassiere that gives adequate support. Analgesics can aid in 

symptomatic relief. Some women have reported improvement of symptoms 

with vitamin E (400 IU per day) and a decrease in caffeine consumption. Oral 

contraceptives are known to decrease benign breast disease. The appearance 

of a persistent dominant mass requires a biopsy.

Fat Maldistribution Syndrome

HIV or antiretroviral treatment may affect breast tissue, resulting in 

gynecomastia or increased fatty deposition (Breast J 2002;8:234).

Breast Abscess and/or Mastitis

This condition usually presents with tender breasts with evidence of 

inflammation (redness, swelling). If an abscess is present, a fluctuant mass 

may be palpated; fever may be present. The etiology is generally bacterial, 

but tuberculous mastitis and/or abscess should be considered in appropriate 

circumstances. This condition is most commonly, but not exclusively, seen in 

lactating women.

Treatment: Antibiotics, incision and drainage of abscess. Consider a biopsy 

and/or other diagnostic tests with nonresponse to treatment.

Benign Breast Tumor

The most frequently diagnosed benign tumors of the breast are 

fibroadenomas, which are usually found in women aged 20–35 years. 

Typically, masses are about 2 cm–3 cm in diameter, although they can 

become much larger. Examination reveals a firm, smooth, rubbery mass 

that is freely mobile. Inflammation, skin dimpling, and nipple retraction are 

absent. On mammographic examination, the mass appears smooth with welldefined margins.

Diagnosis: Definitive diagnosis is established by means of a biopsy.

Treatment: A fibroadenoma may simply be observed; however, a large, 

growing, or otherwise suspicious mass should be surgically excised.

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Breast Cancer

The incidence of breast cancer increases with age. Risk factors include a 

positive family history, early menarche, late menopause, and nulliparity or late 

childbearing. If a palpable mass is present, it is usually firm and nontender, 

with irregular margins; it may be fixed to skin or underlying tissue.

Diagnosis: Definitive diagnosis is established by means of a needle or open 

biopsy; referral to a surgeon is indicated.

Breast cancer in HIV infected patients: There is no apparent increase in the 

incidence of breast cancer among HIV infected women; however, breast cancer 

in the setting of HIV infection may occur at a relatively early age, may be 

more likely to be bilateral and to have unusual histology, and may be more 

aggressive, with early metastatic spread and poor outcome. Most cases occur 

in women with CD4+ cell counts above 200 cells/mm3. Kaposi’s sarcoma and 

non-Hodgkin’s lymphoma may also be localized to the breast in women with 

AIDS (Breast J 2002;8:234; Cancer Invest 2002;20:452).

Sexual Dysfunction

When the validated Female Sexual Function Index (FSFI) was administered 

to women in the WIHS cohort, HIV infected women reported more sexual 

problems than uninfected women. Lower sexual function was also associated 

with menopause, symptoms of depression, or not being in a relationship. 

Women with CD4+ cell counts <200 cells/mm3 also reported lower sexual 

functioning than did women with higher CD4+ cell counts (J Acquir Immune 

Defic Syndr 2010;54(4):360). In another study of the responses of clinically 

stable women with HIV to the FSFI, one-third reported sexual dysfunction. The 

major determinant was self-perceived body changes; there were no significant 

associations with sex hormones, CDC stage, CD4+ cell count, HIV RNA level, or 

cumulative exposure to ARV drugs (Antivir Ther 2009;14(1):85).

Clinicians should proactively address issues related to sexual function and 

related concerns. Signs and symptoms of menopause (see below) and 

depression should be assessed and, when indicated, appropriate interventions 

implemented. Treatment of depression with selective serotonin reuptake 

inhibitors (SSRIs) is also a common cause of decreased libido or inability to 

reach orgasm. Because of the possible association with body image and a 

potential relationship with medication adherence, concerns about changes in 

body appearance should be addressed when a patient is starting ART and at 

regular intervals during the course of therapy.

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Menopause

Menopause is defined as the permanent cessation of menstruation caused 

by the loss of ovarian function. The mean age at which women undergo 

menopause is genetically predetermined; in the United States, the average 

age of menopause onset is 51–52. As HIV infected women live longer, 

and as greater numbers of women who are nearing menopause or are 

postmenopausal become infected, it is increasingly important to consider and 

address issues related to menopause.

History, Physical Exam, and Evaluation

History

• Last menstrual period

• Recent menstrual pattern (i.e., cycle length, duration, amount of flow)

• Any irregular or intermenstrual bleeding or spotting

• Hot flashes

• Genitourinary dryness/atrophy

• Decreased libido

• Anxiety

• Irritability

• Sleep disturbances

• Depression

• Difficulty with memory

• Urinary symptoms

Physical Exam

• Vagina appears smoother in contour, “drier”

• May be more easily traumatized and more vulnerable to infection

Evaluation

• If indicated, confirmation of menopause can be provided by an elevated serum FSH 

level and a low estradiol level

Menopause in patients with HIV infection: Although data regarding the effect 

of HIV on the age at menopause are not conclusive, studies suggest that the 

mean age at menopause for HIV infected women is 3–4 years younger than 

that for uninfected women (J Womens Health 2007;16:1402). Several factors 

associated with earlier menopause are common among women with HIV, 

including smoking, substance abuse, African-American race, lower socioeconomic 

level, and low relative body weight, and may factor into the earlier onset of 

menopause (Menopause Int 2008;14:163). CD4+ cell count<200 cells/mm3

has also been associated with an earlier onset of menopause (Clin Infect Dis

2005;41:1517; Int J STD AIDS 2011;22(2):67).

Among women in the WIHS cohort, age at menopause was not affected by 

HIV status, but amenorrhea lasting longer than 12 months was more common 

among HIV infected women than among uninfected women. Predictors of 

ovarian failure included lower BMI and lower serum albumin (Obstet Gynecol

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2006;108:1423). In a cross-sectional analysis of 429 HIV infected and 

uninfected women (median age 45 years), HIV infected women on ART had 

approximately a twofold increase in estradiol levels across the menopause 

transition, with a potential increased likelihood of abnormal perimenopausal 

bleeding (Menopause 2007;14(5):859).

Women are at increased risk for osteoporosis compared with men, and this 

risk increases after menopause. Recent studies suggest a potential association 

between HIV infection, ART, and loss of bone density (J Acquir Immune Defic 

Syndr 2003;33:281). Low bone mineral density has been found to be more 

prevalent among women with HIV approaching menopause than among 

uninfected women (Menopause 2009;16:199). Results of a population-based 

case-control study indicated that, even among women with normal bone 

mineral density, HIV infected women reported significantly more history 

of fragility fractures than did women in the control group (Osteoporos Int

2007;18:1345).

Studies have also found that more than 60% of HIV infected patients are 

vitamin D insufficient or deficient; in addition to known risk factors, the 

association of renal insufficiency with the use of some ARV agents is consistent 

with both HIV-related and treatment-mediated alterations in vitamin D 

metabolism (Clin Infect Dis 2011;52(3):396). Data regarding osteoporosis 

treatment in HIV infected women are lacking. Nonetheless, standard 

suggestions can be made for treatment and prevention: increase physical 

activity, stop smoking, and take calcium and vitamin D supplements. Small 

studies confirm the benefits and safety of alendronate therapy in HIV infected 

patients (AIDS 2007;21:657).

Management

Hormone replacement therapy (combined estrogen-progestin replacement 

therapy): Currently, the recommendation is to use HRT to treat menopausal 

symptoms at the lowest effective dose for the shortest duration needed, with 

periodic evaluation of the need for continued use.

A variety of estrogen and progestin formulations are available. Estrogen can 

be given orally, transdermally, or topically; progesterone and/or progestin 

is generally administered orally or by transdermal patch. These agents can 

be given on a continuous (daily) basis or cyclically (estrogen given daily and 

progestin 12–14 days per month). Combined oral and transdermal regimens 

are available and improve adherence.

The benefits and risks associated with HRT have been studied extensively 

among HIV uninfected women. HRT is known to ameliorate symptoms of 

vasomotor instability (e.g., hot flashes, sleep disturbances, irritability) and 

urogenital atrophy (e.g., vaginal dryness, dyspareunia); it is also associated 

with a decreased risk of colon cancer, osteoporosis, and osteoporosis-related 

fractures (JAMA 2002;288:321). A recent position paper from the United 

Kingdom National Osteoporosis Society concluded that HRT has a role to play 

in the management of osteoporosis in postmenopausal women aged <60 years 

(Menopause Int 2011;17(2):63).

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The results of a large, randomized, placebo-controlled study of combined 

estrogen-progestin therapy (at higher doses than are generally used today 

and in women with a mean age of 63 years) found a small but statistically 

significant increase in the incidence of breast cancer, dementia, stroke, 

pulmonary embolism, and cardiovascular disease (JAMA 2002;288:321; 

JAMA 2003;289:2717; JAMA 2003;289:3243). An increased risk of 

endometrial cancer was seen in women treated with estrogen only, which is not 

recommended for women who still have a uterus.

Because of the higher prevalence of active liver disease in patients co-infected 

with HIV and hepatitis B or C and a potential increased risk for cardiovascular 

disease associated with the metabolic changes that occur with long-term ART, 

HRT may be associated with increased risk in the setting of HIV infection and 

should be used only if the benefit is felt to outweigh the risk.

Alternatives to Hormone Replacement Therapy

• Progestin-only regimens (medroxyprogesterone acetate 10–30 mg qd 

or norethindrone 1–5 mg qd) may help relieve hot flashes; the health 

effects of long-term therapy are unknown

• SSRIs may help relieve hot flashes

• Nonhormonal lubricants and/or moisturizers or local/topical estrogen 

formulations may be used to manage urogenital atrophy

• Bisphosphonates (e.g., alendronate, ibandronate) may be used for the 

prevention or treatment of osteoporosis

• Selective estrogen receptor modulators (raloxifene 60 mg po daily) 

offer bone benefit without evidence of breast or endometrial 

stimulation. They are also FDA indicated for breast cancer prophylaxis 

in high-risk postmenopausal women. These drugs have no effect on hot 

flashes, pose a small increased risk of venous thromboembolism (VTE), 

and are contraindicated in women with a history of VTE.

Health Maintenance Issues

Regardless of coexisting medical problems and even in the absence 

of gynecologic symptoms, regular gynecologic evaluation and other 

recommended health screening tests are important to identify potential 

problems that require further evaluation and treatment.

Gynecologic Evaluation

Perform annually and as indicated by the presence of symptoms, need for 

follow-up of ongoing problems, exposure to STIs, development of abnormal 

Pap smear, or other need for referral based on primary care evaluation.

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Pap Smears

Perform twice within the first year of HIV diagnosis and then annually. Morefrequent screening may be indicated with a history of abnormal Pap smear, 

HPV infection, and/or after treatment for cervical dysplasia.

Screening for Sexually Transmitted Infections

• Screen annually for syphilis and if neurologic signs and symptoms develop

• Screen annually for gonorrhea, chlamydia, and trichomoniasis in 

sexually active women. Screen as indicated by the presence of relevant 

symptoms or exam findings and with a recent change in sexual partners 

and/or a history of STI in the sexual partner. Screen periodically as 

indicated by sexual practices (e.g., commercial sex work, multiple sex 

partners, inconsistent use of condoms) or on patient request.

Mammography

ACOG recommends baseline mammography beginning at age 40 and then 

every 1–2 years until age 50, with annual screening thereafter (ACOG 

Committee Opinion No. 483; Obstet Gynecol 2011;117(4):1008); women 

at increased risk (e.g., first-degree relative(s) with breast cancer, BRCA-1 

or BRCA-2 mutation) may benefit from earlier initiation of screening or the 

addition of screening modalities other than mammography, such as ultrasound 

or MRI. Mammogram should also be performed with the presence of a 

persistent, palpable mass or other suspicious findings on exam.

Colorectal Cancer Screening

Begin screening at age 50, followed by colonoscopy every 10 years 

thereafter (preferred). Other screening methods include: 1) annual fecal 

occult blood testing or fecal immunochemical test (patient-collected; requires 

2–3 stool samples collected at home and returned for analysis); 2) flexible 

sigmoidoscopy every 5 years; 3) double contrast barium enema every 5 

years; 4) CT colonography every 5 years; or 5) stool DNA (ACOG Committee 

Opinion No. 483; Obstet Gynecol 2011;117(4):1008).

Begin screening colonoscopy earlier and continue at shorter intervals in women 

with a family history of colorectal cancer or adenomatous polyps (i.e., in any 

first-degree relative aged <60 years, or in two or more first-degree relatives 

at any age), family history of familial polyposis or hereditary nonpolyposis 

colon cancer, personal history of colorectal cancer, inflammatory bowel 

disease, or adenomatous polyps. The American College of Gastroenterology 

recommends that screening in African Americans begin at age 45 with 

colonoscopy because of increased incidence and earlier age at onset of 

colorectal cancer (Am J Gastroenterol 2005;100:515).

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Osteoporosis Prevention

The recommended dietary reference intake for calcium is 1000–2000 mg/

day; for vitamin D, 600–800 IU/day (Dietary Reference Intakes for Calcium and 

Vitamin D–Consensus Report. Institute of Medicine. November 2010; http://

www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-andVitamin-D.aspx. Accessed 7/6/2012). Regular weight-bearing exercise is also 

recommended. Baseline bone-density screening should be performed at age 

65 and periodically thereafter, with the screening interval determined by the 

presence of bone loss or risk factors for premature bone loss. Earlier screening 

should be considered in younger postmenopausal women with one or more 

risk factors for premature bone loss (Clin Infect Dis 2009;49(5):651; ACOG 

Committee Opinion No. 483; Obstet Gynecol 2011;117(4):1008).

Risk factors for premature bone loss include

• caucasian or Asian race/ethnicity,

• alcohol abuse,

• smoking,

• low BMI,

• sedentary lifestyle,

• chronic steroid use,

• phenytoin therapy,

• hyperparathyroidism,

• vitamin D deficiency,

• thyroid disease,

• history of prior fracture as an adult,

• dementia,

• family history of osteoporosis,

• premature menopause (<45 years),

• prolonged (>1 year) premenopausal amenorrhea, and

• history of falls.

Vitamin D deficiency is common and is more severe in darker-skinned women; 

a baseline 25-OH vitamin D level will detect this. Minimal deficiency and levels 

near the lower limit of normal can be corrected by an over-the-counter vitamin 

D supplement of 1000 IU daily; more-severe deficiency requires prescription 

high-dose (50,000 IU) repletion followed by chronic maintenance dosing of 

1000 IU/day.

Lipid Screening

Assess and address risk factors for hyperlipidemia at the initial visit and 

periodically thereafter. Risk factors include a history of cardiovascular, 

peripheral vascular, or cerebrovascular disease; age >55 years; family history; 

smoking; diabetes; hypertension; obesity; and physical inactivity. Perform a 

fasting lipid profile every 6–12 months in all patients and consider performing 

it 1–3 months after starting or modifying ART (Clin Infect Dis 2009;49(5):651).

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Guidelines for Gynecologic Referral

In general, referral to an obstetric-gynecologic specialist should be considered 

under the following circumstances:

• Uncertain diagnosis, with a gynecologic condition as part 

of the differential diagnosis

• Diagnosis of pregnancy

• Inadequate response to standard treatment regimens for 

gynecologic conditions

• Possible need for surgical intervention

• Suspected premalignant or malignant condition

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Color Plates

Plate 1.

Trichomonas vaginalis protozoa in a saline wet mount (high power) 

(CDC, 1986)

Plate 2.

Clue cells of bacterial vaginosis in saline wet mount (high power) 

(Seattle STD/HIV Prevention Training Center at the University of Washington)

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Plate 3.

Candida albicans in a saline wet mount (high power) (CDC/

Dr. Stuart Brown, 1976)

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Color Plate 4.

Vaginal candidiasis: thrush patches on the vaginal wall of a patient 

with candidiasis (© courtesy J. Anderson, MD).

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Color Plate 5.

Bartholin’s abscess (CDC, Division of STD Prevention)

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Color Plate 6.

Chancre in a woman with primary syphilis (CDC, Division of STD Prevention)

Color Plate 7.

Secondary syphilis (CDC, Division of STD Prevention)

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Color Plate 8.

Extensive vulvar condylomata acuminata (human papillomavirus) (CDC)

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Color Plate 9.

Granuloma inguinale (CDC, Division of STD Prevention)

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Color Plate 10.

Herpes simplex cervicitis (CDC, Division of STD Prevention)

Color Plate 11.

Lice in pubic area (CDC, Division of STD Prevention)

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Color Plate 12.

Molluscum contagiosum (CDC, Division of STD Prevention)

Color Plate 13.

Condylomata late in secondary syphilis (CDC, Division of STD Prevention)

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Color Plate 14.

Lesion of herpes simplex (© courtesy J. Anderson, MD).

Color Plate 15.

Herpes simplex in woman with AIDS, CD4<50 

(© courtesy J. Anderson, MD).

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Color Plate 16.

Aphthous genital ulceration (© courtesy J. Anderson, MD).

Color Plate 17.

Aphthous oral ulceration (© courtesy J. Anderson, MD).

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Chapter 7:

Preconception Care and Contraception

Erika Aaron, RN, CRNP, MSN

Director of Women’s Services

Division of Infectious Diseases and HIV Medicine

Drexel University College of Medicine

Jean R. Anderson, MD

Director, The Johns Hopkins HIV Women’s Health Program

Professor, Gynecology and Obstetrics

The Johns Hopkins Medical Institutions

The authors declare no conflicts of interest

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Chapter 7: Preconception Care and Contraception

Chapter 7 at a Glance

Preconception Care and Contraception.............................................................................229

Preconception Care............................................................................................................................229

When to Discuss Pregnancy.......................................................................................................230

Evaluation......................................................................................................................................................233

Preconception Counseling............................................................................................................235

Preconception Interventions........................................................................................................235

Safe Conception............................................................................................................................................236

Serodiscordant Couples.................................................................................................................237

HIV and Fertility............................................................................................................................................239

Potential Causes of Infertility...................................................................................................239

Unintended Pregnancy in HIV Infected Women......................................................240

Contraception...................................................................................................................................................242

Considerations in the Choice of a Contraceptive Method........................242

Condoms.........................................................................................................................................................253

Spermicides.................................................................................................................................................253

Hormonal Contraception...............................................................................................................253

Intrauterine Devices............................................................................................................................258

Emergency Contraception............................................................................................................259

Conclusions........................................................................................................................................................261

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Preconception Care and Contraception

Studies of pregnancy in the HAART era indicate that pregnancy is common 

after a diagnosis of HIV and live birth rates are significantly increased when 

compared with the pre-HAART period; abortion is less common; and HIV 

infected women often desire more children, influenced by advances in HIV care 

(Am J Public Health 2000;90:1074; AIDS 2000;14:2171; AIDS 2004;18:281; 

Am J Obstet Gynecol 2007;196:541.e1; AIDS Care 2011;23:1093). Many HIV 

infected women, 80% of whom are of childbearing age, now feel that they 

can have more normal lives that include bearing children with the realistic hope 

of raising them to adulthood. Viewed through this lens, pregnancies among 

women with HIV can be seen as part of the success story of HIV—a chapter in 

the evolution of HIV infection from a progressive and uniformly fatal condition 

to a chronic disease that is serious but survivable.

The U.S. Centers for Disease Control and Prevention (CDC), the American 

Congress of Obstetrics and Gynecology (ACOG), and other national 

organizations recommend offering all women of childbearing age 

comprehensive family planning, including effective contraceptive counseling, 

and the opportunity to receive preconception counseling and care as 

an integral component of routine primary medical care (Obstet Gynecol

2007;110:1473; Obstet Gynecol 2009;452:1444; MMWR Recomm Rep

2006;55(RR-6):1).

This chapter reviews issues related to reproductive decision-making, including 

preconception care and counseling and use of contraception to reduce 

unintended pregnancy.

Preconception Care

The CDC defines preconception care as a series of “interventions that aim 

to identify and modify biomedical, behavioral, and social risks to a woman’s 

health or pregnancy outcome through prevention and management” (MMWR 

Recomm Rep 2006;55(RR-6):1).

Goals of preconception care include

• prevent unintended pregnancy,

• optimize maternal health prior to pregnancy,

• improve maternal and fetal outcomes in pregnancy,

• prevent mother-to-child transmission of HIV, and

• prevent transmission of HIV to an uninfected sexual partner 

while trying to conceive.

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When to Discuss Pregnancy

Several studies have documented predictors of the desire to conceive (AIDS 

Behav 2010;14:1106; PLoS One 2009;4:e7925; AIDS Behav 2009;13:949; 

Fam Plann Perspect 2001;33:144). Commonly, the women who most want to 

conceive are younger, have no children, and have a husband/partner/other 

family member who wants them to get pregnant. Nonetheless, the desire to 

have a child and decisions regarding whether and when to do so are complex, 

multifaceted, changeable over time, and not necessarily related to health 

status. Therefore, all women of childbearing capacity should be assessed 

for childbearing desires or intentions at their initial evaluation with an HIV 

care provider and at regular intervals throughout the course of care. This is 

particularly important if a woman

• has expressed an interest in conceiving,

• is not using effective contraception or is not using it regularly 

or appropriately,

• has changed sexual partners or experienced a change in 

personal circumstances (e.g., is postpartum),

• is taking medications with potential reproductive toxicity or 

interactions with hormonal contraception,

• is at risk for unintended pregnancy,

• may benefit from or be otherwise affected by new 

developments in the field of pregnancy and HIV, and/or

• plans to enroll in clinical trials.

Primary HIV care providers should be proactive in addressing reproductive 

needs and desires, as many women may not feel comfortable in raising these 

issues for fear of being judged harshly or discouraged (AIDS Patient Care 

STDS 2010;24:317). Patient-provider tools such as those shown in Figure 7-1 

may facilitate this discussion by helping to identify patient needs.

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Figure 7-1

HIV and Pregnancy: Decision Aids for the Patient and Provider

1. Patient Decision Aid

With effective HIV treatment, women and men with HIV infection can now enjoy a 

long and healthy life and can look forward to a future that may include planning 

a family. When taken during pregnancy, HIV medications can decrease the risk 

of transmitting HIV to the baby to 1%–2% or less. It is also important to prevent 

pregnancy when you are not yet ready to become a mother. As a woman with 

HIV, it is important to plan carefully so that you can get the treatment you need 

to have a safer pregnancy, prevent transmission of HIV to your baby, and prevent 

pregnancy until you are ready. This survey is designed to help you and your 

healthcare provider take the first steps in that planning.

Name: Date: 

1. Your current age is 

2. Have you ever been pregnant?  YES  NO

3. If YES, how many times? How many children do you 

have? 

4. Are you interested in getting pregnant?  YES  NO

5. If YES, when do you wish to conceive?

 Trying to conceive now  6 months – 1 year from now

 1 – 2 years from now  More than 2 years from now

6. Have you had sex with a man in the last 6 months?  YES  NO

7. Are you currently using condoms?  YES  NO

8. Are you currently using birth control other than condoms?

A. What type?

 None  Birth control pill  IUD  Injection (Depo-Provera)

 Patch/vaginal ring  Implant under the skin (Implanon)

 Sterilization (tubes tied)  Unsure

 Other: 

B. Are you trying to get pregnant?  YES  NO

9. Would you or your partner like to talk to someone about planning a 

safer pregnancy that may reduce the risk of HIV transmission to your 

baby?  YES  NO

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Figure 7-1 continued

HIV and Pregnancy: Decision Aids for the Patient and Provider

2. Provider Decision Aid

This tool is designed to help you, the health care provider, better address fertility 

issues (desire to conceive and desire to prevent pregnancy) with your patients.

1. Patient is postmenopausal or post-hysterectomy.

A. Yes – End of tool

B. No – Go to question 2

2. Does patient wish to have more children?

A. Yes – Go to question 3

B. No – Go to question 5

3. Does patient wish to conceive within the next year?

A. Yes – Go to question 4

B. No – Go to question 5

4. Patient would like to conceive within the next year.

A. Review medication list with patient for drugs that are contraindicated in 

women trying to conceive (e.g., efavirenz, statins, ribavarin, tetracycline/ 

doxycycline). Other drugs should be used unless no alternate agents are 

available that are both effective and safer in women who are trying to 

conceive.

AND

B. Offer and encourage referral for preconception counseling and evaluation.

5. Patient wishes to prevent pregnancy.

A. Patient has completed childbearing: Refer to a gynecologist to discuss longterm or permanent options for contraception.

OR

B. Patient wants more children, but not within the next year: Review 

nonpermanent options for contraception and strongly recommend referral 

for preconception counseling.

Key Considerations:

1. Patient has a problem with irregular menses or amenorrhea: If yes, perform a 

pregnancy test and refer for a gynecologic evaluation.

2. Menopause: Can be difficult to diagnose

– If the woman is >50 y with no vaginal bleeding for >1 y, she is 

postmenopausal.

– If uncertain, refer for a gynecologic evaluation.

3. Formal preconception counseling and evaluation is strongly recommended if the 

patient

A. Is in a serodiscordant relationship

B. Has significant medical co-morbidities

C. Has problems with substance abuse

D. Is taking a medication that is contraindicated in women trying to conceive

E. Reports a desire to conceive and a history of infertility or difficulty getting 

pregnant

While primary HIV care providers may feel comfortable discussing 

contraception and prevention of mother-to-child-transmission (MTCT) of HIV, 

they may not feel fully able to address preconception counseling and care 

needs, in which case consultation and referral are appropriate.

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Evaluation

Table 7-1 outlines the comprehensive preconception evaluation designed to 

identify factors that may affect a woman’s ability to get pregnant or may 

increase the risk of adverse pregnancy outcomes for the mother or her fetus.

Table 7-1

Comprehensive Preconception Evaluation

History Comments

HIV • Date of diagnosis

• History of OIs or other HIV-related illnesses

• ART history, including use in prior pregnancies and/or 

reasons for change(s) in ART regimens (e.g., adverse effects, 

resistance, tolerability)

• Adherence history and challenges

• Results of resistance tests

• Nadir and current CD4+ cell count

• Current HIV VL

Pregnancy • Number of previous pregnancies and their outcomes (e.g., 

miscarriages, abortions, ectopic pregnancy, preterm births)

• Number of living children and ages

• Number of HIV infected children

• Pregnancy complications (e.g., preterm labor, preeclampsia, 

birth defects)

• Modes of delivery

Gynecologic • Prior and current contraception use

• Satisfaction with current contraception method and/or 

adverse effects

• Current condom use and consistency of use (100% vs 

<100%)

• Prior STIs or genital tract infections

• Past difficulties in conceiving

• Abnormal Pap smears and treatment

• Other gynecologic problems and treatment (e.g., fibroids, 

endometriosis)

General Medical 

and Surgical • Other medical conditions (e.g., DM, HTN, renal or cardiac 

disease, depression or other psychiatric illness)

• All prior surgery

• Blood type and history of transfusions

• Allergies

Immunizations • HBV, HAV, influenza, pneumococcus, HPV, tetanus

Medications • All prescribed medications

• All OTC medications

• All complementary medications

Nutrition • History of anemia or nutritional deficiencies

• Special diet (e.g., vegetarian, vegan, gluten-free)

• Use of nutritional supplements and vitamins

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Table 7-1

Comprehensive Preconception Evaluation

History Comments

Social History • Relationship status

• Use of illicit drugs, tobacco, alcohol

• Employment status

• Social support and disclosure to partner and others

• Economic support

• History and nature of domestic violence (i.e., physical, 

sexual, psychological)

Family History 

of Heritable 

Diseases

• Birth defects

• Chromosomal abnormalities

• Muscular dystrophy

• Sickle cell disease

• Mental retardation

• Others

Male Partner • HIV status and knowledge of partner’s status

• If HIV infected:

- Disclosure status

- History of OIs and other HIV-related conditions

- ART history and history of adverse effects, resistance, 

adherence problems

- Nadir and current CD4+ cell count

- Current HIV VL

• Medical and reproductive history

• Medications

• Use of illicit drugs, tobacco, alcohol

• Employment status

Physical Exam • Comprehensive, with focus on genital tract

Laboratory

(Emphasis is on lab 

tests that will affect 

counseling and/or 

result in changes 

in care prior to 

pregnancy)

• Tests

• STI screening: GC/chlamydia; syphilis; HSV culture or HSV-2 

antibody, if indicated

• CBC

• Current CD4+ cell count

• HIV RNA

• Resistance testing, if indicated

• Rubella

• HBV: HBsAb, HBsAg

• HCV antibody and HCV RNA, if indicated

• Pap smear

• Other, as indicated by medical history and medications

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

continued

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Preconception Counseling

Preconception counseling of the HIV infected woman should address the 

following issues:

• Effect of pregnancy on HIV course (see Chapter 8, HIV and Pregnancy)

• Effect of HIV on pregnancy course and outcome (see Chapter 8, HIV 

and Pregnancy)

• MTCT and prevention, including the role of antiretroviral drugs (ARVs), 

cesarean section, etc.

• Use of HIV-related medications, including maternal and fetal safety 

and toxicity

• Long-term care plans, including advance directives, care for children 

should mother and/or father die or become disabled

• Non-HIV-related factors, including age, drug use, other medical conditions, 

and their potential effects on pregnancy course or outcome

• Safe conception if the patient is in a serodiscordant relationship

• Safe sexual practices

• Healthy living and health maintenance, including smoking cessation, 

elimination of alcohol and illicit drug use, etc.

Preconception Interventions

Preconception interventions for the HIV infected woman may include the 

following:

• Contraception to reduce unintended pregnancy (see below)

• Initiation or modification of antiretroviral therapy (ART) regimen. ART 

should be initiated prior to attempts to conceive if the woman meets 

criteria for starting ART, in which case maximal suppression of HIV viral 

load (VL) should be achieved prior to pregnancy and the patient’s 

regimen should be well tolerated without significant adverse effects.

• If a woman does not meet current CD4+ cell count criteria, initiation of 

ART prior to conception may still be considered. Maximal suppression 

of HIV VL potentially reduces, though it does not eliminate, the risk of 

perinatal transmission (AIDS 2008;22:973; Clin Infect Dis 2010;50:585). 

Also to be considered, however, are the potential adverse effects of 

ART on certain pregnancy outcomes, the patient’s readiness for lifelong 

therapy, and the risks versus benefits of stopping ART postpartum (see 

Chapter 8, HIV and Pregnancy).

• If a patient’s current ART regimen is not effective (i.e., suboptimal 

suppression of VL), not well tolerated, associated with significant 

adverse effects, or contains EFV, it should be modified prior to 

attempts to conceive.

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Optimal treatment of other medical conditions: Also recommended is optimal 

therapeutic control of hypertension, diabetes, and other medical conditions. 

Care providers should review all of a woman’s current medications (not just 

HIV-related medications) and, if indicated, substitute medications that may 

be safer in pregnancy. The risk-benefit profile of any medication is important 

to consider. A drug classified as U.S. Food and Drug Administration (FDA) 

category D signifies positive evidence of human fetal risk, but potential 

maternal benefits may make the risk acceptable. FDA category X is assigned 

to drugs for which the risk to a pregnant woman clearly outweighs any 

possible benefit. If a woman is taking an FDA category D or X drug, the 

feasibility of safely stopping or substituting for the medication must be 

determined, and expert consultation is advised (see Table 13-1, p. 448). 

(Note: At the time of publication of this guide, the FDA was preparing a 

revision of drug categories for pregnancy and lactation that will likely do 

away with the current letter categories.)

Other preconception interventions should include the following when indicated:

• Opportunistic infection (OI) treatment or prophylaxis

• Screening for and treatment of existing genital tract infections in both 

partners (genital tract inflammation is associated with increased HIV 

shedding in the genital tract, even when plasma VL is fully suppressed; 

if untreated, genital tract infections may increase the risk of adverse 

pregnancy outcomes and potential MTCT)

• Treatment of anemia and/or other nutritional interventions

• Treatment of drug and/or alcohol abuse

• Assistance with smoking cessation

• Treatment of depression and other mental illnesses

• Immunizations

• Provision of prenatal vitamins, including folic acid supplementation 

for prevention of neural tube defects

• Assistance with advance directives

Safe Conception

If both partners are HIV infected, condom use should be encouraged. 

Unprotected intercourse should be timed to coincide with the most fertile 

period of a woman’s menstrual cycle. Fertile periods may be determined 

with ovulation predictors, basal body temperature measurement, or the use 

of an ovulation calculator (see, for example: http://www.marchofdimes.

com/ovulation_calendar.html. Accessed 7/9/2012). Semen analysis should 

be considered because HIV is associated with a higher prevalence of semen 

abnormalities (see below).

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Serodiscordant Couples

There are an estimated 140,000 HIV-serodiscordant heterosexual couples 

in the United States, about half of whom want more children (Am J Obstet 

Gynecol 2011;204:488.e1). Expert consultation is recommended to address the 

individual needs of serodiscordant couples attempting to conceive.

Female HIV infected and male uninfected: The uninfected partner of an 

HIV infected woman should be encouraged to use condoms with each act of 

intercourse. Intravaginal insemination for conception using the partner’s semen 

can be performed at home or by the healthcare provider and is effective 

with normal fertility. Timed insemination during the most fertile period may 

be considered to maximize the chance of conception. She should be on ART 

and attain maximal viral suppression prior to attempting conception. PrEp 

(see below) can also be considered for an uninfected male partner who wants 

additional protection if the couple opt for timed unprotected intercourse when 

trying to conceive.

Male HIV infected and female uninfected: The risk of HIV transmission to 

an uninfected woman with an HIV infected partner can be minimized but not 

entirely eliminated, unless donor sperm is used. Observational studies and 

a meta-analysis have demonstrated a decreased rate of HIV transmission 

among heterosexual serodiscordant couples on ART, particularly when HIV VL 

is fully suppressed in the infected partner (AIDS 2009;23:1397). Recent data 

from HPTN 052, a randomized clinical trial designed to evaluate ART for the 

prevention of sexual transmission among serodiscordant couples, indicates that 

earlier initiation of ART (at CD4+ cell counts 350–550 cells/mm3) reduced HIV 

transmission to the uninfected partner by 96% (N Engl J Med 2011; 365(6):493).

• ART for the infected male: He should be on ART and attain maximal viral 

suppression prior to attempting conception. 

• Treatment of an infected partner does not fully protect against HIV 

transmission, even in the setting of maximal plasma VL suppression. 

Although effective ART decreases virus in genital secretions, discordance 

between plasma and genital VLs has been reported, and individuals may 

have isolated semen HIV shedding even when plasma VL is undetectable 

(AIDS 2008;22:1677; AIDS 2010;24(16):2489) and independent 

of semen drug levels and ART regimen (AIDS 2009;23(15):2050). 

Additionally, ARV penetration of the genital tract varies among agents 

(Curr Opin HIV AIDS 2010;5(4):335).

Screen for and treat genital tract infections: Genital tract infections, both 

sexually transmitted and nonsexually transmitted (e.g., bacterial vaginosis, 

yeast), may increase the HIV uninfected woman’s vulnerability to HIV 

acquisition. In the HIV infected man, genital tract infections may increase 

his infectiousness.

Semen analysis: Semen abnormalities are more common in the setting of HIV. 

Abnormalities are correlated with lower CD4+ cell counts and may include 

lower sperm volume, concentration, and motility, and higher rates of abnormal 

forms (Hum Reprod 2004;19:2289; Arch Gynecol Obstet 2011; 284(1):229). 

Some data suggest that ART may have an adverse effect on semen quality. 

A longitudinal study of 34 men with serial semen analyses prior to ART and 

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up to 48 weeks post-ART found that the proportion of progressively motile 

spermatozoa was low at all time points, but decreased significantly over the 

course of follow-up (AIDS 2008;22:637). Therefore, when there is little or 

no likelihood of natural conception, an uninfected female partner may be at 

increased risk for infection through repetitive exposure over time.

Assisted reproductive technology: The method with the lowest risk of 

transmission is semen washing, with negative PCR testing after preparation, 

coupled with intrauterine insemination (IUI), in vitro fertilization (IVF), or 

intracytoplasmic sperm injection (ICSI). The results of studies that, combined, 

included more than 6500 cycles of sperm washing plus IUI, IVF, or ICSI 

indicate no female seroconversions (Reprod Biomed Online 2005;10:135; 

AIDS 2007;21:1909; Fertil Steril 2009;91:2455). A more recent systematic 

analysis of safety and effectiveness of ART in serodiscordant couples found no 

seroconversions in 3900 IUI cycles (50% cumulative pregnancy rate) and 738 

ICSI/IVF cycles (53% cumulative pregnancy rate (Fertil Steril 2011;95:1684).

Most insurance plans, however, (including Medicare/Medicaid) do not cover 

these services and the cost is usually prohibitive. The National Perinatal 

HIV Hotline (1-888-448-8765) can provide a list of institutions offering 

reproductive services for HIV serodiscordant couples.

Timed unprotected intercourse and condom use at all other times: For 

serodiscordant couples who cannot afford assisted reproduction and who, 

after comprehensive counseling, still wish to conceive, this is the best approach. 

The most fertile time in a woman’s menstrual cycle can be determined with 

ovulation predictors (available over the counter at pharmacies), basal 

body temperature measurement, or ovulation calculators (e.g., http://www.

marchofdimes.com/ovulation_calendar.html).

Pre-exposure prophylaxis (PrEP): Providing ARVs topically or orally to an 

uninfected female partner may offer some additional protection against HIV 

transmission from an infected male partner during attempts to conceive, but 

study results to date have been mixed. A Phase IIb randomized placebocontrolled trial (CAPRISA 004) of a 1% intravaginal TDF gel used before 

and after sex reduced HIV acquisition by 39% and by up to 54% with 

greater adherence (Science 2010;329(5996):1168); however, in the VOICE 

study, a multi-country, multi-arm Phase IIb study of vaginal and oral PrEP in 

women at high risk of acquiring HIV, 1% TDF gel used daily was no better 

than placebo. A Phase III study of daily oral TDF/FTC in uninfected male 

couples (iPrEX) reported a 44% overall reduction in HIV acquisition compared 

with placebo; effectiveness was significantly affected by adherence (N 

Engl J Med 2010;363(27):2587; N Engl J Med 2010;363(27):2663). In 

the Partners PrEP study conducted in Kenya and Uganda among more than 

1400 HIV-serodiscordant couples, the use of daily TDF or daily TDF/FTC 

by the uninfected partner was found to have efficacy of 66% and 73%, 

respectively, compared with placebo, in reducing HIV transmission (reported 

97% adherence by returned pill count, but only 81% of those assigned to the 

active-treatment arm had detectable blood levels of the study drug) (N Engl 

J Med 2012;367(5):399). Within a subgroup of those who received TDF/FTC 

and whose plasma drug levels were tested, measurable concentrations of TDF

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were associated with a 90% reduction in risk compared with placebo. In 

another trial in Botswana, TDF/FTC given to 1200 HIV uninfected heterosexual 

men and women reduced transmission by 66% compared with placebo with 

84% adherence by returned pill count (Curr Opin Infect Dis 2012;25(1):51; 

N Engl J Med 2012;367(5):423). The FEM-PrEP clinical trial and the VOICE 

study, however, both conducted in high-risk uninfected African women, found no 

efficacy with either daily oral TDF/FTC or TDF, but adherence was quite low 

with detectable drug levels found in less than one-third of those tested and 

randomized to active drug. (Curr Opin Infect Dis 2012 Feb;25(1):51; N Engl 

J Med 2012;367(5):411; 20th Conference on Retroviruses and opportunistic 

Infections, Atlanta, GA, Abstract 26LB, 2013). Therefore, it is likely that 

adherence is a key factor in the discrepant results of these studies.

In studies of PrEP to date, safety and tolerability were excellent and limited 

resistance was observed in seroconverters. Twice-weekly and coital dosing of 

TDF/FTC, as well as longer-acting formulations, intravaginal rings, and new 

candidate ARVs, are being evaluated for PrEP.

Use of this approach will require individual counseling that addresses a 

number of considerations: 1) effectiveness of periodic (e.g., use for a certain 

period of days, currently undefined, around ovulation) versus daily use; 2) 

effectiveness in the presence of resistance to agents used for prophylaxis in 

the infected partner; 3) risk of resistance should transmission occur despite the 

use of prophylaxis; 4) potential risk of adverse effects in pregnancy or to the 

developing fetus; and 5) potential decrease in other risk-reduction behaviors, 

such as condom use. Providers should counsel patients that the efficacy of 

PrEP is highly dependent on adherence. In August 2012 the CDC issued the 

following interim guidance for clinicians considering the use of PrEP for HIV 

prevention in heterosexually active adults, particularly those with known HIVinfected partners (MMWR 2012; 61(31):586) (see Chapter 3). It is not known 

if the use of PrEP adds additional benefit when the infected partner has 

maximal viral suppression.

HIV and Fertility

HIV appears to have an adverse effect on fertility in both symptomatic and 

asymptomatic women (AIDS 1999;13:517; J Acquir Immune Defic Syndr

2000;25(4):345; Lancet 1998;351:98; Am J Epidemiol 2000;151:1020; Int 

J STD AIDS 2006;17(12):842). This includes increased risk of infertility and 

pregnancy loss. Recent data from low-resource settings suggest that fertility 

improves after treatment with ART (AIDS Res Treat 2011;2011:519492; PLoS 

Med 2010;7(2):e1000229).

Potential Causes of Infertility

In the setting of HIV infection there are several potential causes of infertility, 

some of which are confounding factors that may independently reduce fertility.

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• HIV infected women frequently have a history of other sexually 

transmitted infections (STIs), such as gonorrhea, chlamydia, and syphilis, 

which reduce fertility. In a cross-sectional study of fertility assessment in 

130 HIV infected women, 27.8% had tubal occlusion, generally indicative 

of past tubal damage with gonorrhea or chlamydia (Reprod Biomed 

Online 2007;14:488).

• HIV infected women may be at increased risk for amenorrhea and/or 

ovulatory dysfunction due to chronic drug use (especially use of opiates) 

and/or poor nutrition and weight loss.

• Menstrual dysfunction and/or amenorrhea are common in the setting 

of HIV; however, controlled studies have produced conflicting results 

regarding a direct effect of HIV or HIV-related immunosuppression on 

menstrual function.

• Sexual dysfunction is reported in 53%–71% of HIV infected men. It 

may be associated with the presence and/or treatment of depression or 

anxiety. Semen abnormalities are also more common in the setting of HIV 

(see above).

• Higher VLs have been associated with decreased fertility (Int J STD AIDS

2006;17:842).

Legal right to care: In a 1998 U.S. Supreme Court decision, Bragdon v. Abbott, 

the Court ruled that a person with HIV is considered to be ‘‘disabled’’ and 

therefore protected under the Americans with Disabilities Act. “Unless health 

care workers can show that they lack the skill and facilities to treat HIV 

infected patients safely or that the patient refused reasonable testing and 

treatment, they may be legally, as well as ethically, obligated to provide 

requested reproductive assistance” (Fertil Steril 2010;94:11). To date, there 

have been no reported cases of occupational transmission to personnel 

providing assisted reproductive care or contamination of gametes or embryos 

in the provision of this care that would support the denial of services to HIV 

infected individuals or couples.

Unintended Pregnancy in HIV Infected Women

Many pregnancies among HIV infected women are unintended or unplanned. 

In the United States, approximately 50% of all pregnancies are unintended, 

a rate that has not changed in 15 years. Approximately 50% of unintended 

pregnancies occur in women using contraception, and more than 50% are 

aborted (Fam Plan Perspect 1998;30:24; Contraception 2007;75(3):168; 

Perspect Sex Reprod Health 2006;38(2):90). A 2006 study from Italy indicated 

that the rate of unintended pregnancy among HIV infected women on ART was 

57.6% (Antivir Ther 2006;11(7):941). A 2007 study of more than 1000 HIV 

infected pregnant adolescents in the United States found that 83.3% of those 

pregnancies were unplanned (Am J Obstet Gynecol 2007;197(3 Suppl):S123). 

The majority of pregnancies reported by HIV infected women in the WIHS 

from 1994 to 2005 occurred in women who were not seeking to conceive 

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(AIDS 2004;18:281). Recent studies have also suggested that ART increases or 

restores fertility, particularly in those with higher CD4+ cell counts and a good 

immunologic response to therapy (AIDS Res Treat 2011:2011:519492).

Because of advances in HIV treatment, many perinatally infected adolescents 

are now reaching sexual maturity and may be at particular risk for unplanned 

or unintended pregnancy. A report on 174 perinatally HIV infected and 

sexually active girls older than 13 years found that by age 19, 24.2% had 

been pregnant at least once and some more than once (Am J Public Health

2007;97:1047).

Reasons for unintended pregnancy: Women who are not using contraception 

of any type do not necessarily intend to become pregnant. Other reasons for 

unintended pregnancy include the following:

• Power imbalance in a sexual relationship

• Pressure from partner and/or family to have children

• Fear of abandonment that results in lack of disclosure and, 

often, nonuse of condoms or other contraception

• Belief that one cannot become pregnant

• Lack of awareness of contraception options

• Disorganized lifestyle that precludes consistent use of 

condoms and/or contraception

• Decision to take one’s chances

Increased risk for unintended pregnancy: Women who are in any of the 

groups listed below are at increased risk for unintended pregnancy (Fam Plann 

Perspect 1998;30:24; Perspect Sex Reprod Health 2006;38(2):90):

• Adolescents

• Aged >40 years

• Poor and less educated

• Unmarried but cohabiting

• Mentally ill or mentally retarded

• Victims of domestic violence

• Abusers of drugs or alcohol

• Those with HIV-associated cognitive impairment

Unplanned does not mean unwanted: An unplanned pregnancy is not 

necessarily an unwanted pregnancy. In the WIHS cohort, abortion was 

significantly less likely in the era of effective ART than it was in the pre-ART 

era. Further, abortion rates among HIV infected women were not significantly 

different from abortion rates among high-risk uninfected women in the ART era 

(AIDS 2004;18(2):281-6). Unintended pregnancy is a predictor, however, for 

pregnancy termination among women with HIV (AIDS Care 2010;22(1):50).

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Contraception

The goals of contraception are to prevent unintended pregnancy or to delay 

pregnancy until it is desired. Women with HIV infection should have access to 

effective contraception and can use all available methods. Decisions regarding 

contraceptive options in HIV infected women require thoughtful discussions with 

the patient and with her partner if appropriate; however, the high proportion 

of HIV infected women who report unintended pregnancy or who conceive 

while using contraception suggests that this counseling is not taking place or 

is not sufficient. A number of barriers to contraceptive counseling have been 

identified. For example, women may have more immediate and pressing 

needs that consume the time allocated for clinic visits or preclude an in-depth 

discussion of contraception. Care providers may not be trained to provide 

contraceptive counseling.

Additional challenges to contraception use occur when women experience side 

effects from contraception that they were not prepared for and don’t know 

how to manage or when they do not have enough power to control the use of 

contraception in an intimate relationship.

Between 1994 and 2005, 2784 women enrolled in WIHS were asked every 

6 months about their use of contraception. About one-third of women reported 

using barrier methods; approximately one-quarter reported using sterilization; 

and <10% reported using hormonal methods. Use of dual protection—barrier 

method plus a more effective method of contraception—was low but did 

increase somewhat over time. Use of no method of contraception was reported 

in >30% of visits, even though 40% of these women reported sexual activity 

during the previous 6 months.. Use of all forms of contraception decreased 

with age and behavior change was minimal over time despite long-term study 

participation and study participant exposure to a variety of health messages 

(J Women’s Health 2007;16(5):657). Other studies have found that condom 

use among women rises substantially after a diagnosis of HIV (J Acquir Immune 

Defic Syndr 2005;39(4):446)

Considerations in the Choice of a Contraceptive Method

When choosing the most appropriate contraceptive method for themselves 

and their partners, women should be encouraged to consider several 

factors, described below. Voluntary informed choice and respectful 

contraceptive counseling are important to the successful choice and use of 

contraceptive methods. One effective approach is motivational interviewing 

(Table 7-2), a client-centered and goal-directed style of counseling that 

incorporates sensitivity to the patient’s current stage of change (Addict Behav

1985;10(4):407; J Consult Clin Psychol 1988;56(4):520). When appropriate, 

it is desirable to include the partner in the conversation about contraceptive 

choice because partner involvement may increase successful and sustainable 

use of the method.

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Table 7-2

Motivational Interviewing for Contraception Counseling

Stage of Change Counseling and Goal 

Setting for Condom 

Use

Counseling and Goal Setting 

for Prevention of Unwanted 

Pregnancy

Pre-Contemplation:

Patient sees no need to 

engage in the target 

behavior (“No way...”) 

Review information 

about condom use and 

consequences of not 

using condoms.

Review information about 

contraception and the 

consequences of not using 

contraception; prescribe EC.

Contemplation: Patient 

sees the need to 

engage in the target 

behavior, but barriers 

preclude readiness for 

action (Yes, but...”)

Discuss pros and cons 

of condom use and ask 

patient to plan to use 

them during 3 of the 

next 5 sexual acts she 

engages in.

Discuss barriers to contraception 

use and ways to overcome 

them and plan initiation of 

contraception use.

Review contraception choices; 

plan to review again at next 

visit; elicit patient’s agreement 

to choose a method at next visit 

and reinforce use of EC.

Ready for Action:

Patient is ready to 

engage in the target 

behavior and may 

already be trying the 

new behavior (“Let’s 

do it...”)

Ask patient to use 

condoms during 4 of 

next 5 sexual acts, and 

help patient practice 

negotiating use of 

condoms.

Discuss the importance of 

consistent use of contraception; 

prescribe the patient’s method 

of choice and prescribe EC.

Action: Patient has 

been engaging in the 

target behavior for 3 

to 6 mo (“Doing it...”)

Ask patient to plan to 

use condoms during 

all 5 of next 5 sexual 

acts and discuss results 

of negotiations about 

condom use.

Discuss patient’s experience with 

contraception use; plan ways to 

solve future problems, such as 

the need to obtain refills, how 

to use EC if doses are missed, 

and how to handle missed 

appointments.

Maintenance: Patient 

has been engaging in 

the target behavior 

for more than 6 mo 

(“Living it...”)

Provide positive 

reinforcement for 

consistent condom use 

and discuss relapse 

prevention.

Provide positive reinforcement 

for consistent contraception 

use, and discuss prevention of 

imperfect use.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

An ideal strategy for HIV infected women is simultaneous protection against 

both unintended pregnancy and HIV transmission or STI acquisition or 

transmission, often called “dual protection.” Dual protection can be accomplished 

through avoidance of penetrative sex, condom use alone, or use of condoms in 

combination with another more effective method of contraception.

In general, HIV infected women can use all available contraceptive methods. 

Condom use, while less effective at preventing pregnancy than other 

contraceptive methods, is the only method that reduces the risk of HIV/

STI transmission or acquisition. Dual protection may be optimal, particularly 

for serodiscordant couples, although this approach does have both pros 

and cons that should be considered and discussed with a patient during 

contraceptive counseling.

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Advantages of Dual Protection Disadvantages of Dual Protection

• Condoms alone have a higher failure 

rate in prevention of pregnancy than 

most other methods of birth control.

• Hormonal methods may have significant 

noncontraceptive benefits, such as a 

decrease in iron deficiency anemia, 

decreased risk of PID, and decreased 

risk of some cancers.

• HIV infected women may be taking 

medications that have teratogenic potential 

(e.g., EFV, warfarin, tetracyclines, statins) 

and need more reliable contraception than 

is provided by condoms alone.

• Seroconcordant couples may be less likely 

to use condoms consistently, while also 

wishing to prevent pregnancy.

• Drug interactions between hormonal 

contraceptives and ART may decrease 

contraceptive effectiveness, creating a 

greater need for use of a back-up method.

• Possible reduction in consistent 

condom use

• Potential negative effect on ART 

adherence (less of a concern with 

non-oral hormonal delivery systems)

• Adverse effects and/or safety 

considerations or contraindications 

with hormonal methods

Factors to consider when helping a woman choose the best method of 

contraception for herself and her partner include the following:

• Age

• Childbearing plans (i.e., does she need contraception that is 

temporary or permanent, short-term or long-term?)

• Cost

• Convenience and ease of use

• Side effects and toxicity

• Efficacy

• Effect on HIV transmission

• Effect on HIV progression

• Noncontraceptive benefits

• Protection against STIs

• Other medical conditions

• Acceptability and accessibility

• Drug interactions

Contraception works best if a woman likes it and if it makes practical sense for 

her. When choosing the best method, a patient’s patterns of adherence to ART 

and other medications as well as her adherence with clinic visits may serve as 

predictors of her success with particular contraceptive methods.

Contraceptive decision making should take into consideration current 

medications, including ART, as well as fetal safety should contraception fail. 

EFV is the only current ARV agent that is a proven teratogen. Anencephaly, 

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anophthalmia, microphthalmia, and cleft palate were seen in primates at 

exposures comparable to those in humans, and there are retrospective case 

reports and one prospective report of CNS defects in infants of women who 

received EFV at conception and during the first trimester (Sustiva drug label. 

http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020972s03

5,021360s023lbl.pdf. Accessed 4/9/12; Antiretroviral Pregnancy Registry. 

Interim Report. December 2011. http://www.apregistry.com/forms/interim_

report.pdf. Accessed 4/9/12)

EFV is the only ARV agent labeled as FDA pregnancy category D (“positive 

evidence of human fetal risk based on adverse reaction data from 

investigational and marketing experiences, but the potential benefits from 

the use of the drug among pregnant women might be acceptable despite 

its potential risks”). The absolute risk after early exposure to EFV may be 

low, however; a recent meta-analysis found no increased risk of overall birth 

defects among women exposed to EFV compared with other ARVs during the 

first trimester (AIDS 2011;25(18):2301). Nevertheless, EFV should be avoided 

in women who are trying to become pregnant or who do not or cannot use 

effective contraception consistently (Recommendations for Use of Antiretroviral 

Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions 

to Reduce Perinatal HIV Transmission in the United States. September 14, 2011. 

http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf. Accessed 4/4/2012). 

Long-acting contraceptive methods may be more desirable for women on EFVcontaining regimens (Curr HIV/AIDS Rep 2007;4:135).

Medications taken for treatment of other medical conditions must be 

considered as well. In some cases, these medications are FDA category D or 

category X (“risk for pregnant women clearly outweighs any possible benefit”).

In 2010, the CDC released U.S. Medical Eligibility Criteria for Contraceptive Use

as evidence-based guidelines for the use of different contraceptive methods 

in the setting of different medical conditions, including HIV. The four categories 

identified by the CDC are used in the discussion of contraceptive choice in this 

chapter (MMWR Recomm Rep 2010;59(RR-4);1).

• Category 1: a condition for which there is no restriction on the use 

of the contraceptive method

• Category 2: a condition for which the advantages of using the 

method generally outweigh the theoretical or proven risks

• Category 3: a condition for which the theoretical or proven risks 

usually outweigh the advantages of using the method

• Category 4: a condition that represents an unacceptable 

health risk if the contraceptive method is used

Contraceptive effectiveness depends on both the inherent effectiveness of a 

method and the need for independent action by the user. Methods that require 

remembering to take a pill every day will have lower efficacy with typical use 

than methods with theoretically similar effectiveness that require keeping an 

appointment for an injection once every 3 months. The relative effectiveness of 

various contraceptives is outlined in Table 7-3.

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

COMBINED ORAL CONTRACEPTIVE PILLUse is independent of sexual intercourse

• Typical: 8 • Perfect: 0.3 • History of DVT, stroke, ischemic heart disease

• HTN• Hyperlipidemia 

(depending on type, severity, other risk factors)

• Aged >35 y and smoker • Multiple risk factors for 

arterial cardiovascular disease (e.g., older age, smoking, DM, HTN)

• Complicated valvular 

heart disease

• Migraine, especially with 

aura or in women >35 y

• Severe liver cirrhosis, 

acute hepatitis

• Hepatocellular adenoma• DM with nephropathy, 

retinopathy, neuropathy, or vascular disease

• Breast cancer• Major surgery with 

immobilization

• Current gallbladder 

disease

• Postpartum <3 wk

• Nausea• Headache• Weight gain • Dizziness• Breast tenderness • Vaginal spotting • Chloasma• Depression

• Decreased 

menstrual pain, PMS, and blood loss

• May reduce acne • Decreased benign 

breast disease • Decreased functional ovarian 

cysts

• Decreased ovarian 

and endometrial cancers

• Decreased PID

• No STD protection • May increase 

susceptibility to some STDs

• Must remember to take 

pill daily

• Some ARV agents may 

decrease or increase bioavailability of ethinyl estradiol and/or progestin component

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

COMBINED ESTROGEN/PROGESTIN VAGINAL RING (Nuva Ring)Use is independent of sexual intercourse. Vaginal ring is inserted for 3 wk out of every mo. Precise placement is not required.

• Typical: 8 • Perfect: 0.3 • Same as for OCs • Similar to OCs

• Possible increased 

vaginal discharge

• Same as for OCs • Confers no STD 

protection, and may increase susceptibility to some STDs

COMBINED ESTROGEN/PROGESTIN PATCH (Ortho Evra)Use is independent of sexual intercourse. Patch is applied weekly for 3 of 4 wk.

• Typical: 8 • Perfect: 0.3 • Same as for OCs • Similar to OCs

• Skin irritation • Same as for OCs • Improved user 

compliance

• No STD protection • May increase 

susceptibility to some STDs

DMPAOften causes amenorrhea. Requires only 4 injections per year. Requires no ongoing action by user. Use is independent of sexual intercourse.

• Typical: 3 • Perfect: 0.3 • Breast cancer

• Unexplained vaginal 

bleeding

• Multiple risk factors for 

arterial cardiovascular disease (e.g., older age, smoking, DM, HTN)

• Ischemic heart disease, 

stroke

• Menstrual changes 

(spotting, irregular bleeding, amenorrhea)

• Decreased bone 

density with longterm use

• Weight gain • Breast tenderness • Headache• Adverse effect on 

lipids

• Depression

• May have protective effects 

against PID, ovarian and endometrial cancer

• Decreased blood 

loss, anemia • Amenorrhea

• No interaction with 

ART established, but data are limited

• No STD protection

continued

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

Etonogestrel IMPLANT (Implanon®)

Lasts 3 y. Removal is easier than earlier implant (Norplant). Requires no ongoing action by user. Use is independent of sexual intercourse.

• Typical: 0.5 • Perfect: 0.5 • Unexplained vaginal bleeding

• Breast cancer• Severe liver disease, 

tumors

• Ischemic heart disease, 

stroke

• Tenderness or 

infection at site

• Menstrual changes 

(spotting, irregular bleeding, amenorrhea

• 1/3 of women have amenorrhea 

after 1 y

• Weight gain • Breast tenderness • Depression

• Same as above • No STD protection • Requires office insertion • Costs $400–$800

PROGESTIN-ONLY PILLUse is independent of sexual intercourse

• Typical: 1.1–13.8 • Perfect: 0.5 • Unexplained vaginal bleeding

• Breast cancer• Severe liver disease, 

tumors

• Ischemic heart disease, 

stroke

• Menstrual changes 

(spotting, irregular bleeding, amenorrhea)

• Breast tenderness • Depression• Weight gain

• Same as above • No STD protection • Ectopic pregnancy more 

likely with progestinonly pills than with other forms of hormonal contraception

• Must remember to take 

pill daily

• Potential drug interactions 

with certain seizure medications, rifampin/ rifabutin, RTV-boosted PIs

CONDOM, MALE (LATEX, POLYURETHANE, NATURAL MEMBRANE)Inexpensive and readily available. Use does not require 

i

ti

• Typical: 15 • Perfect: 2 • Allergy to latex condom material • Allergy or sensitivity to latex 

material

• Decreased 

sensitivity

• Protects against 

STDs, including HIV (except for natural membrane)

• Delays premature 

ejaculation

• Requires partner 

cooperation

• Possible loss of 

spontaneity during sex

continued

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

CONDOM, FEMALEWoman controlled. Less likelihood of breakage. Can be inserted up to 8 h before intercourse. Use does not require a prescription.

• Typical: 21 • Perfect: 5 • Data are limited

• Polyurethane allergy 

(rare) • Allergy or sensitivity to 

polyurethane

• Possible 

decreased sensitivity

• Protects against 

STDs, including HIV • May be awkward to use • Aesthetically unappealing 

to some

CERVICAL CAP — PAROUS/NONPAROUSWoman controlled. Can be inserted ahead of time.

• Typical:• 36 (parous)/ 18 (nonparous) • Perfect: 26/9

• Latex allergy • Abnormal cervical/ vaginal anatomy• History of TSS or 

recurrent UTIs

• Known or suspected cervical/uterine malignancy• Abnormal Pap smear • Vaginal or cervical infection• Recent delivery or 

spontaneous or induced abortion

• Pelvic pressure • Vaginal irritation • Allergy or 

sensitivity to latex

• Vaginal or urinary tract infections

• Limited STD 

protection • Efficacy based on high motivation

• Spermicide re-application 

required with each act of coitus

• Should not be used 

during menses

• Spermicide may increase 

HIV acquisition and transmission

DIAPHRAGMWoman controlled. Can be inserted up to 6 h before intercourse.

• Typical: 16 • Perfect: 6 • Latex allergy • Abnormal vaginal 

anatomy

• History of TSS or 

recurrent UTIs

• Same as above • Limited STD 

protection • Reduces risk of PID

• No protection against HIV 

transmission

continued

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

SPERMICIDESWoman controlled. Use does not require a prescription. Easily available and inexpensive.

• Typical: 29 • Perfect: 18 • Allergy to nonoxynol-9 • HIV/AIDS (CDC category 3)

• Vaginal irritation • Allergy• Vaginal and 

urinary tract infection

• Protection against 

some STDs, with significant protection against gonorrhea and chlamydia.

• In vitro activity 

against HIV

• Efficacy reduced when 

used without a barrier method

• Increased susceptibility to HIV with frequent sexual 

activity

• No protection against HIV

IUD (copper-Paragard®)

Provides contraception for 10 y. Requires no ongoing user action.

• Typical: 0.8 • Perfect: 0.6 • Unexplained vaginal bleeding

• Recent (within 3 mo), 

recurrent, or active pelvic infection

• Postpartum, postabortion 

endometritis

• Active STD • Women at increased risk 

for STDs

• Severely distorted 

uterine cavity

• Menstrual cramping • Increased bleeding

• Risk of PID and 

uterine perforation following insertion

• Anemia

• No increase in 

pelvic infection with HIV

• No STD protection • Increased risk of PID

LEVONORGESTREL INTRAUTERINE SYSTEM (Mirena)Provides contraception for 5 y. Requires no ongoing 

user action.

• Typical: 0.2 • Perfect: 0.2 • Unexplained vaginal bleeding

• Breast cancer• Active pelvic infection/ STDs• Severe liver disease/

tumor

• Distorted uterine cavity

• Increased 

incidence ofirregular bleeding in first 6 mo compared with copper IUD

• Risk of PID 

and uterine perforation following insertion

• Overall reduction 

in menstrual blood loss (20% amenorrhea after 1 y) and cramping

• Possible decreased 

rates of anemia, PID

• No increase in 

pelvic infection 

ith HIV

• No STD protection

continued

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

FEMALE SURGICAL STERILIZATIONProvides permanent contraception. Requires no ongoing user action.

• Typical: 0.5• Perfect: 0.5

• Desire for future fertility• Active pelvic infection

• Pain at surgical 

site

• Subsequent regret• Increased risk of 

ectopic pregnancy if sterilization not achieved

• Possible decreased 

risk of ovarian cancer

• Decreased risk of 

salpingitis

• Permanent• No STD protection• Requires anesthesia• Surgical procedure in OR

TRANSCERVICAL FEMALE STERILIZATION(Essure®, Adiana®; data more 

limited for Adiana but suggest somewhat higher failure rate)Provides permanent contraception. Requires no ongoing user action. Lower cost; does not require incision or general anesthesia; may be performed in physician’s office. Decreased risk of intraabdominal injury.

• Typical: 0.2–0.4• Perfect: 0.2–0.4

• Desire for future fertility• Active pelvic infection

• Subsequent regret• Increased risk of 

ectopic pregnancy if sterilization not achieved

• Cramping, 

nausea, vomiting with placement

• Expulsion 

or uterine perforation (<3%)

• Probably similar 

to surgical sterilization (experience limited)

• Permanent

• No STD protection• Requires use of alternate contraception for 3 mo• For Adiana, requires confirmation of 

tubal occlusion by hysterosalpingography (Essure can be visualized radiographically)

MALE STERILIZATIONProvides permanent sterilization for the man

• Typical: 0.15

• Perfect: 0.10

• Desire for future fertility • Pain at surgical 

site

• Subsequent regret

• None • Same as above, except 

sterility not immediate

continued

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Table 7-3

Contraceptive MethodsMethod and Convenience Pregnancies in Year 

1 of Typical Use and Perfect Use, %

Contraindications (CDC Category 3 or 4)

Potential Side Effects

Benefits Disadvantages

EMERGENCY CONTRACEPTIONLevonorgestrel 0.75mg (Plan B); levonorgestrel 0.25mg/ethinyl estradiol 50 mcg (Preven); ulipristal acetate 30 mg single dose (marketed for EC as Ella®)

Can be used after unprotected intercourse or with other contraceptive failure (e.g., condom breakage). Treatment should be initiated as soon as possible to maximize effectiveness and is generally recommended within 72 h after intercourse. Ulipristal given as single dose for EC is effective up to 120 h (5 d) after unprotected intercourse.

• Typical: 3.2 (57% of expected 

pregnancies prevented)

• Perfect: 1.1 (85% of expected 

pregnancies prevented)

• Effectiveness 

of ulipristal is similar to that of 

levonorgestrel in first 72 h and superior 72–120 h after unprotected sex

• Established pregnancy N/A N/A • No STD protection

• Nausea and vomiting 

common with levonorgesterl/ethinyl estradiol combination (30–60%); prophylactic antiemetics may be beneficial

• Failure rate higher with intercourse during fertile phase of cycle• Ulipristal more expensive 

than other EC options

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixSource: MMWR Recomm Rep 2010;59(RR-4);1; Contraceptive Technology, 19th ed, 2007

continued

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Condoms

The consistent use of male or female condoms protects against HIV and 

other STD transmission and acquisition and provides contraception. It is the 

only contraceptive method that provides dual protection against both HIV 

infection and pregnancy. Therefore, these two issues should be separately 

discussed when counseling patients. Condom use also should be reinforced 

for HIV infected women when prevention of pregnancy is not an issue (i.e., 

postmenopause, during pregnancy, after sterilization, when a woman is 

infertile, or for use with a more effective contraceptive method).

The female condom is less likely than the male condom to break or leak during 

sex; however, intrusion of the outer vaginal ring that covers the introitus into 

the vagina occurs in 2% of cases, allowing potential insertion of the penis 

between the condom and vaginal wall (Sex Transm Infect 2004;80:167). Some 

couples also complain about noise during sex; however, women who receive 

instruction about use of the female condom and are given the opportunity to 

practice its use in the clinical setting have an increased likelihood of using the 

device correctly and viewing it favorably (Am J Public Health 2002;92:109). 

Counseling during the early adoption phase and an increased sense of power 

in negotiating for safe sex have been linked to increased acceptability and 

adoption of the female condom (AIDS Behav 2006;10(4 Suppl):S67).

Spermicides

Standard spermicidal doses of nonoxynol-9 (N-9) have been associated with 

an increase in irritation, colposcopic and histologic evidence of inflammation, 

and decreased numbers of vaginal lactobacilli as compared with placebo 

recipients (J Acquir Immune Defic Syndr Hum Retrovirol 1998;17:327). A 

randomized placebo-controlled clinical trial of an N-9 vaginal gel conducted 

in four countries among commercial sex workers with high rates of sexual 

activity did not demonstrate protection against HIV; instead, HIV transmission 

was increased among those who used the N-9–containing gel more frequently 

(Lancet 2002;360:971). A meta-analysis of randomized controlled trials of 

N-9 use found no evidence of protection against HIV acquisition (Cochrane 

Database Syst Rev 2002;(4):CD003936). N-9 also appears to offer no 

protection against STDs such as gonorrhea or chlamydia (Reprod Health Matters

2002;10(20):175). Newer spermicides that cause less inflammation are being 

tested for their potential to decrease the risk of HIV transmission. In the setting 

of HIV/AIDS, spermicides that may disrupt vaginal or cervical mucosa and 

potentially increase viral shedding and risk to uninfected partners are assigned 

to CDC category 3 (risk generally outweighs advantages).

Hormonal Contraception

Combined estrogen/progestin contraceptives: Studies of oral combined 

estrogen/progestin contraceptives and several ARVs have found drug 

interactions (primarily through the cytochrome p450 [CYP] 3A4 system) that 

resulted in an increase or decrease in levels of estrogen and/or progestin 

(Table 7-4). One study demonstrated a decrease in ARV blood level 

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(Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and 

Adolescents. January 10, 2011. Available at http://www.aidsinfo.nih.gov/

ContentFiles/AdultandAdolescentGL.pdf. Accessed 4/4/12). To date, data on 

these interactions are primarily pharmacokinetic and the true clinical effect is 

not clear. The concern is that effectiveness may be decreased, breakthrough 

bleeding may occur (with decreased hormonal levels), or rates of adverse 

effects may increase (with increased hormonal levels), although these outcomes 

have not been confirmed. Only with FPV, which is metabolized to APV, does 

the drug-drug interaction also reduce the concentration of the ARV. Unboosted 

FPV should not be co-administered with hormonal contraceptives (HCs). There is 

minimal information about drug interactions with the use of alternative delivery 

methods for estrogen/progestin contraceptives (i.e., transdermal patch, 

intravaginal ring), although a recent study suggests that these delivery methods 

may also be vulnerable to drug interactions and that different progestins (e.g., 

norethindrone vs norelgestromin) may be affected differently in interaction with 

specific ARV agents (J Acquir Immune Defic Syndr 2010;55(4):473). Although 

data are lacking on the safety and efficacy of altering hormonal dosages in 

an effort to circumvent these interactions, a preparation containing a minimum 

of 30 mcg ethinyl estradiol is suggested.

Table 7-4

Drug Interactions Between Antiretroviral Therapy and Hormonal 

Contraception

Effect on Antiretroviral 

or Hormonal Drug 

Concentrations

Dosing Recommendations for 

Hormonal Contraceptives and 

Clinical Comments

NRTIs No effect on hormonal levels No dosage adjustment is necessary

RTV-Boosted PIs

ATV/r Ethinyl estradiol  19%

Norgestimate  85%

Use alternative or additional method

DRV/r Ethinyl estradiol AUC  44%

Norethindrone AUC  14%

Use alternative or additional method

FPV/r Ethinyl estradiol AUC  37%

Norethindrone AUC  34%

Use alternative or additional method

LPV/r Ethinyl estradiol AUC  42%

Norethindrone AUC  17%

Norelgestromin (transdermal 

patch) AUC  83%

Use alternative or additional method

SQV/r  Ethinyl estradiol Use alternative or additional method

TPV/r Ethinyl estradiol AUC  48%

Norethindrone: no significant 

change

Use alternative or additional method

Unboosted PIs

Indinavir 

(IDV)

Ethinyl estradiol AUC  25%

Norethindrone AUC  26%

No additional contraceptive 

protection needed

Nelfinavir 

(NFV)

Ethinyl estradiol AUC  47%

Norethindrone AUC  18%

Use alternative or additional method

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Table 7-4

Drug Interactions Between Antiretroviral Therapy and Hormonal 

Contraception

Effect on Antiretroviral 

or Hormonal Drug 

Concentrations

Dosing Recommendations for 

Hormonal Contraceptives and 

Clinical Comments

ATV Ethinyl estradiol AUC  48%

Norethindrone AUC  110%

No additional contraceptive 

protection needed

Oral contraceptive should contain 

no more than 30 mcg of ethinyl 

estradiol, or use alternative method. 

Oral contraceptives containing <25 

mcg of ethinyl estradiol or progestins 

other than norethindrone or 

norgestimate have not been studied.

FPV With APV:  ethinyl estradiol 

and  norethindrone;  APV 

20%

Use alternative method

NNRTIs

EFV Ethinyl estradiol no change

Levonorgestrel AUC  83%

Norelgestromin AUC  64%

With levonorgestrel alone (not 

as part of combined estrogen/

progestin contraceptive, 

levonorgestrel AUC  58%

Implant:  etonogestrel

Use alternative or additional 

methods

Norelgestromin and levonorgestrel 

are active metabolites of 

norgestimate

Effectiveness of emergency 

postcoital contraception may be 

diminished

ETR Ethinyl estradiol AUC  22%

Norethindrone: no significant 

effect 

No additional contraceptive 

protection needed

NVP Ethinyl estradiol AUC  20%

Norethindrone AUC  19%

May consider alternative or 

additional methods

DMPA: no significant change No additional contraceptive 

protection needed

RPV Ethinyl estradiol AUC  14%

Norethindrone: no significant 

change

No additional contraceptive 

protection needed

CCR5 Antagonist

MVC No significant effect on ethinyl 

estradiol or levonorgestrel

No additional contraceptive 

protection needed

Integrase Inhibitor

RAL No clinically significant 

effect on ethinyl estradiol or 

levonorgestrel

No additional contraceptive 

protection needed

Elvitegravir/

Cobicistat

Norgestimate AUC  2.26

Ethinyl estradiol AUC  0.75

No additional contraceptive 

protection needed

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use 

of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. January 10, 2011; Tables 

15a, 15b, and 15d

continued

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Concerns about drug interactions should not cause providers to avoid 

prescribing combined estrogen/progestin HC, but should prompt close 

follow-up and thorough counseling about additional or alternative 

contraceptive methods. The consistent use of condoms is recommended to 

prevent HIV transmission or other STI acquisition and to compensate for any 

possible reduction in the effectiveness of the HC.

Other medications are also known to interact with combined estrogen/progestin 

HCs (and in some cases with progestin-only contraceptives) and may require 

consideration of alternative and/or additional contraceptive methods and/

or dose adjustment for the interacting agent, when appropriate (Contraceptive 

Technology,19th ed, 2007).

Drugs that alter estrogen and/or progestin levels and may reduce the 

effectiveness of HC:

• Anticonvulsant agents (i.e., phenytoin, carbamazepine, barbiturates, 

primidone, topiramate, oxcarbazepine) used with combined 

estrogen/progestin methods or progestin-only pills

• Lamotrigine (if used as single agent) used with combined 

estrogen/progestin methods

• Rifampin or rifabutin used with combined estrogen/progestin 

methods, progestin-only pills, or progestin implants

• St. Johns wort used with combined estrogen/progestin 

methods or progestin-only pills

Recommendation: Use an alternative or additional method. If a combined oral 

estrogen/progestin method is used, use a formulation containing a minimum of 

30 mcg ethinyl estradiol.

Drugs that may require dose adjustment and/or monitoring of drug effect 

when used with combined estrogen/progestin HC:

• Fluoroquinolones, some anticonvulsants (reduced drug levels)

• Theophylline, diazepam, chlordiazepoxide, tricyclic 

antidepressants (increased drug levels)

Recommendation: Monitor drug levels when available; dose may need 

to be increased.

Among HIV infected women, the use of combined estrogen/progestin 

contraceptives may be contraindicated because of comorbidities such as 

smoking or hypertension, common in this population. Because chronic viral 

hepatitis is a frequent comorbidity in the setting of HIV, the concomitant use of 

combined HCs is of special interest. Data suggest that in women with chronic 

hepatitis, combined hormone use does not increase the rate or severity of 

cirrhotic fibrosis, nor does it increase risk for hepatocellular carcinoma. In 

general, though, these methods should not be used in women with severe liver 

cirrhosis, acute hepatitis, or liver tumors.

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Progestin-only contraceptives: Although data are limited, there is no evidence 

of significant drug interactions between depot medroxyprogesterone acetate 

(DMPA) and ARVs. The clinical profile associated with DMPA administration was 

examined in women on regimens containing NFV, EFV, or NVP and appeared 

similar to that observed in HIV uninfected women. DMPA prevented ovulation 

and did not affect CD4+ cell counts or HIV RNA levels in HIV infected 

women when compared with women on NRTIs only or no ARVs (Contraception

2008;77:84). Another study found no DMPA pharmacokinetic differences 

between 15 women on ZDV, 3TC, and EFV and 15 women on no ART (Fertil 

Steril 2008;90(4):965). The U.S. Medical Eligibility Criteria classify DMPA with 

HIV/AIDS as Category 1 (MMWR Recomm Rep 2010;59(RR-4);1). There are 

few data on drug interactions of progestin implants or progestin-only pills 

with ARVs and recommendations by experts are generally the same as for 

combined hormonal contraceptives.

Long-term use of DMPA has been associated with diminished bone mineral 

density (BMD), although recent studies indicate that the rate of bone loss is 

greatest in the first 24 months of use and decreases thereafter; furthermore, 

current evidence suggests that partial or full recovery of bone mass occurs 

after discontinuation of DMPA (Fertil Steril 2006;86:1466; Contraception

2006;74:90). There have been no randomized controlled trials of DMPA and 

fracture risk. Decreased BMD is more common among people with HIV infection 

and has been associated with the use of a variety of ARVs, in particular 

d4T and TDF. Although no studies have examined BMD and DMPA use in the 

setting of HIV infection, the efficacy of DMPA—particularly in adolescents or 

others who may have difficulty adhering to a contraceptive method—must be 

balanced against possible adverse effects on bone density. ACOG has stated 

that “concerns regarding the effect of DMPA on BMD should neither prevent 

practitioners from prescribing DMPA nor limit its use to 2 consecutive years.” 

(ACOG Committee Opinion #415. September 2008. Available at http://www.

acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_

Adolescent_Health_Care/Depot_Medroxyprogesterone_Acetate_and_Bone_

Effects. Accessed 7/9/12). Daily exercise and appropriate calcium and vitamin 

D intake should be encouraged.

Hormonal contraception and HIV progression: Data from prospective and 

cohort studies conflict on the effect of HC (combined estrogen/progestin or 

DMPA) on HIV progression, defined as progression to AIDS or death (Clin 

Infect Dis 2008;47:945; J Acquir Immune Defic Syndr 2011;56(2):125; AIDS

2010;24(12):1937; AIDS 2009; 23 Suppl 1:S69; AIDS 2007;21:749). 

Members of a cohort of Kenyan women who were taking DMPA at the time 

of HIV acquisition were found to have higher viral set points and a greater 

likelihood of multiple viral variants being detected shortly after infection (Clin 

Infect Dis 2006;42(9):1333); however, the use of hormonal contraception prior 

to seroconversion was not associated with higher viral set points in a Ugandan 

cohort (J Acquir Immune Defic Syndr 2011;56(2):125). Most of these studies 

did not have VL measurements for comparison. In both a longitudinal U.S. 

cohort and a prospective cohort in Kenya, however, HC was not associated 

with a change in VL over time as compared with women who were not using 

contraception (AIDS 2003;17(11):1702; AIDS 2007;21(6):749). In general, 

these studies did not include women on ART, but there is no reason to believe 

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that women on ART with suppressed HIV RNA levels would be at increased risk 

for HIV progression related to the use of HC. Given the availability of ARVs 

and the fact that most studies show no effect of HC on HIV progression, which 

would be expected to supersede a potential effect on untreated women, the 

full range of HC methods should continue to be available to women with HIV.

Hormonal contraception and HIV transmission and/or acquisition: Data 

on the role of HC in HIV susceptibility or infectiousness also conflict. Two 

large prospective studies have demonstrated a modestly increased risk of 

HIV acquisition associated with the use of combined oral estrogen/progestin 

and/or DMPA (AIDS 2004;18(16):2179; AIDS 2007;21(13):1771; AIDS

2010;24(11):1777). A recent secondary analysis of data from a large 

prevention trial among more than 3700 serodiscordant African couples 

demonstrated an increased risk of HIV seroconversion (both transmission and 

acquisition) associated with HC (primarily DMPA). Moreover, HIV infected 

women who transmitted to their uninfected male sex partners also had higher 

genital HIV VL, which has the potential to increase transmission (Lancet Infect 

Dis 2012;12(1):19). Other mechanisms with the potential for altering risk 

of transmission or acquisition include increased cervical ectopy with HC use, 

possible thinning of vaginal mucosa, alterations in vaginal flora or heightened 

susceptibility to other STIs, or other changes in local or systemic immunity (Am J 

Reprod Immunol 2011;65(3):302).

There are, however, also significant methodologic issues with most studies, 

including potential selection bias and confounding factors such as changes 

in HC use over time, presence of STIs (including HSV-2 serostatus), and 

dependence on self-report regarding actual use of HC, sexual behavior, and/

or condom use (Am J Reprod Immunol 2011;65(3):302).

Although some data suggest that HC may increase HIV susceptibility or 

infectiousness, there is a critical need for safe and effective contraceptive 

methods for women who are at risk for or infected with HIV. Rather than 

discouraging the use of effective HC methods, these studies highlight the 

importance of dual protection with condoms to prevent both acquisition and 

transmission of HIV in women. Moreover, now that ART has been confirmed 

to effectively reduce sexual transmission among serodiscordant couples by 

96% (N Engl J Med 2011;365(6):493), this intervention will be increasingly 

important to circumvent transmission of HIV, regardless of HC use. A recent 

update to the CDC’s U.S. Medical Eligibility Criteria for Contraceptive 

Use 2010 reaffirmed the safety of hormonal contraceptives for women 

at high risk for HIV, but added a clarification for women using progestinonly injectables highlighting the inconclusive nature of the evidence around 

hormonal contraceptive use and risk for HIV acquisition among women, and 

strongly encouraging condom use and other measures to prevent HIV (MMWR

2012:61(24):449).

Intrauterine Devices

No association between the copper IUD (Cu-IUD) and risk of HIV acquisition or 

progression has been demonstrated (Am J Obstet Gynecol 2007;197(2):144; 

Best Pract Res Clin Obstet Gynaecol 2009; 23(2):263). Although data are 

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limited, there is also no evidence of higher risk from Cu-IUDs for overall 

complications or for pelvic infections in HIV infected women in general 

or when stratified by CD4+ cell count (BJOG 2001;108(8):784; Lancet

1998;351:1238; Am J Obstet Gynecol 2007;197(2):144). Cu-IUD use also 

was not associated with an increased rate of cervical HIV shedding (AIDS

1999;13(15):2091).

In U.S. practice today, the Cu-IUD has largely been eclipsed by the 

levonorgestrel-releasing intrauterine system (LNG-IUD). The LNG-IUD is both 

highly effective as a contraceptive method and associated with reduced 

menstrual blood loss. It is an increasingly popular treatment for menorrhagia, 

dysmenorrhea, uterine fibroids, endometriosis, and adenomyosis, and also 

provides endometrial protection in women with or at risk for endometrial 

hyperplasia. Fewer data are available regarding the use of the LNG-IUD in 

women with HIV infection; however, a recent study comparing 15 women using 

the LNG-IUD with 25 age- and CD4+ cell count–matched controls followed 

for 5 years found no unplanned pregnancies or pelvic infections among the 

IUD users and no difference in CD4+ cell counts over the follow-up period 

compared with controls. LNG-IUD use was associated with an increase in 

hemoglobin levels, which remained higher over time than those of controls (Am 

J Obstet Gynecol 2011;204(2):126.e1). In another study, genital shedding of 

HIV RNA was not affected by LNG-IUD use and estradiol levels remained in 

the follicular range in all women (Hum Reprod 2006;21(11):2857). Although 

no data address the issue of drug interactions with ARV agents in the setting 

of LNG-IUD use, interactions would be expected to be minimal, given the low 

levels of systemic absorption of LNG.

Emergency Contraception

Emergency contraception (EC) is the use of a drug or device to prevent 

pregnancy after unprotected intercourse or contraceptive failure (e.g., condom 

breakage). EC works by inhibiting or delaying ovulation. It also may interfere 

with sperm transport, impair corpus luteum function, or inhibit implantation. 

Since EC does not act after implantation and establishment of pregnancy, it 

is not considered an abortion method (NEJM 1997;337(15):1058). While 

EC should be initiated as soon as possible after unprotected intercourse 

to maximize efficacy, it should be made available for up to 5 days after 

unprotected intercourse to patients who request it. No clinician examination or 

pregnancy testing is necessary before provision of EC (ACOG Practice Bulletin 

No. 112; Obstet Gynecol 2010;115(5):1100). No data specifically on EC in 

the context of HIV or ARV treatment are available, but EC does not protect 

against STI acquisition or HIV transmission.

There are currently four EC options:

• Progestin only: Levonorgestrel (marketed for EC as Plan B, Plan B 

One-Step). The levonorgestrel-only regimens are more effective, 

with prevention of up to 85% vs 57% of expected pregnancies 

when compared with combined estrogen/progestin regimens (Lancet

1998;352:428). They also are associated with significantly less nausea 

and vomiting than the combined estrogen/progestin regimens. In the 

United States, both progestin-only regimens are available over the 

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counter (OTC) to women aged ≥17 years. Available pharmacokinetic 

data indicate that, compared with combined estrogen/progestin regimens, 

progestin-only regimens should cause fewer drug interactions with ARVs.

- Two-dose regimen: levonorgestrel 0.75 mg po, to be repeated 

12–24 hours after the first dose

- One-dose regimen: 1.5 mg levonorgestrel

• Combined estrogen–progestin regimens: Nineteen combined estrogen/

progestin oral contraceptives have been declared safe and effective 

for use as EC by the FDA (The Emergency Contraception Website. 

http://ec.princeton.edu/questions/dose.html. Accessed 4/9/12). All 

of the combined hormonal regimens require two doses taken 12 hours 

apart. Each dose contains two to six active hormonal (not placebo) 

pills, depending on the pill formulation, and includes ethinyl estradiol 

(total of 100–120 mcg) and levonorgestrel (total of 0.50–0.60 mg). As 

noted above, these regimens are less effective and more likely to cause 

nausea and vomiting than progestin-only regimens. If given, prophylactic 

antiemetics may be useful. The EC dose should be repeated if vomiting 

occurs within 2 hours of ingestion. If severe vomiting occurs, pills may 

be administered vaginally with effective absorption (Contraception

1987;36(4):471).

• Progesterone agonist/antagonist: Ulipristal acetate 30 mg single dose 

(marketed for EC as Ella®) was approved by the FDA in August 2010 

for EC up to 120 hours (5 days) after unprotected intercourse (Obstet 

Gynecol 2010;115(2 Pt 1):257).

• Copper IUD: Although not currently FDA-approved specifically for EC, 

the Cu-IUD can be used for EC in women who meet the standard criteria 

for IUD insertion. It is most effective if inserted within 5 days after 

unprotected intercourse. The pregnancy rate with this method is 0% to 

0.09% (Hum Reprod 2012;27:1994). This method has the advantage of 

providing long-term contraception in addition to EC. The LNG-IUD is not 

effective as EC (J Fam Plann Reprod Health Care 2004;30:99).

EC use should not be encouraged as a regular contraceptive method. 

Randomized controlled trials have not demonstrated a reduction in unintended 

pregnancy or abortion associated with access to EC (Contraception

2008;78(5):351). Condom use should be encouraged immediately after EC 

use; other short- or long-term hormonal methods may be initiated following 

the woman’s next menstrual period, when it is clear that she is not pregnant. If 

menses are delayed by a week or more after the expected time or if lower 

abdominal pain or persistent irregular bleeding develops, clinical evaluation is 

indicated to evaluate for intrauterine or ectopic pregnancy.

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Conclusions

HIV clinics are experienced in providing systems of care that address the 

multiplicity of concerns relevant to people with HIV infection. Integration of 

family planning services within primary HIV care is an additional strategy 

that can improve the lives of women with HIV. Establishing relationships with 

local family planning agencies can help to improve linkages to those services 

and improve access to safe and effective contraception. Integration of HIV 

services into family planning clinics should be considered as well. “Every 

woman [at] every visit” should be engaged in discussions concerning her 

intentions regarding pregnancy and her use of contraception. Integration of 

preconception counseling and contraceptive options must be an integral part 

of HIV primary care.

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Chapter 8:

HIV and Pregnancy

Jean R. Anderson, MD

Director, The Johns Hopkins HIV Women’s Health Program

Professor, Gynecology and Obstetrics

The Johns Hopkins Medical Institutions

The author declares no conflict of interest

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Chapter 8: HIV and Pregnancy

Chapter 8 at a Glance

HIV and Pregnancy...................................................................................................................................265

Pregnancy Testing................................................................................................................................265

Effects of Pregnancy on HIV Infection............................................................................266

Effect of HIV on Pregnancy Course and Outcome...........................................267

Effect of HIV and Pregnancy on Other Infections ................................................268

Vulvovaginal Candidiasis.............................................................................................................268

Bacterial Vaginosis..............................................................................................................................269

Genital Herpes Simplex................................................................................................................269

Human Papillomavirus......................................................................................................................270

Syphilis.............................................................................................................................................................271

Cytomegalovirus....................................................................................................................................272

Toxoplasmosis............................................................................................................................................274

Hepatitis B....................................................................................................................................................275

Hepatitis C...................................................................................................................................................276

Perinatal Transmission..........................................................................................................................276

Rate.....................................................................................................................................................................276

Timing................................................................................................................................................................277

Risk Factors..................................................................................................................................................277

Antiretroviral Drug Use In Pregnancy.................................................................................280

General Principles for Treatment.........................................................................................280

Recommendations for Use of Specific ARV Agents In Pregnancy.....284

Special Considerations....................................................................................................................299

Adverse Pregnancy Outcomes................................................................................................300

Guidelines for Antepartum Care...............................................................................................303

History and Physical Examination .......................................................................................303

Laboratory Examination................................................................................................................304

Antepartum Fetal Surveillance and Testing..............................................................308

Prevention for Positives...................................................................................................................311

Antepartum Scenarios for Antiretroviral Drug Use...........................................311

Stopping ART During Pregnancy..........................................................................................314

Special Situations..................................................................................................................................316

Opportunistic Infections..................................................................................................................320

Immunizations............................................................................................................................................321

Frequency of Visits..............................................................................................................................324

Consultations to Consider During Pregnancy ..........................................................324

Counseling and Support................................................................................................................324

Guidelines For Intrapartum Care ..............................................................................................325

Universal Precautions........................................................................................................................325

Intrapartum ART and Prophylaxis (http://aidsinfo.nih.gov).......................326

Mode of Delivery.................................................................................................................................327

Other Intrapartum Considerations......................................................................................329

Postnatal Care for the HIV-Exposed Infant....................................................................329

Antiretroviral prophylaxis............................................................................................................329

Neonatal Evaluation..........................................................................................................................332

Diagnosis of HIV....................................................................................................................................333

Pneumocystis jirovecii Pneumonia Prophylaxis........................................................333

Guidelines for Postpartum Care.................................................................................................333

Antiretroviral Treatment.................................................................................................................335

Stopping ARV Drugs Postpartum.........................................................................................336

Contraception and Condom Use..........................................................................................337

Dolutegravir (Tivicay, DLG)........................................................................................................337

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HIV and Pregnancy

With increasing numbers of HIV infected women, 80% of whom are of 

childbearing age, and concerns about perinatal transmission of HIV, pregnancy 

in the setting of HIV infection has been a focus of much interest, research, 

and, often, discrimination. The number of HIV infected women who become 

pregnant may grow with therapeutic advances in care and the prevention of 

vertical transmission and because new diagnoses of HIV are still often made 

in pregnancy. This chapter reviews issues related to pregnancy and discusses 

guidelines for care during pregnancy to optimize the health of both the mother 

and her baby.

Pregnancy Testing

Indications: For currently or recently sexually active women, pregnancy testing 

is indicated in the following circumstances:

• Missed menses, unless on etonogestrel (ETG)-releasing 

contraceptive implant, levonorgestrel (LNG) intrauterine device 

(IUD), or depot medroxyprogesterone acetate (DMPA)

• Irregular bleeding (unless on ETG-releasing implant, 

LNG-IUD or DMPA)

• New onset of irregular bleeding after prolonged 

amenorrhea on ETG-releasing implant, LNG-IUD, or DMPA

• New onset of pelvic pain

• Enlarged uterus or adnexal mass on exam

• Before instituting new therapies (consider)

Pregnancy tests are performed on blood or urine and may be qualitative 

(positive/negative) or quantitative. Quantitative tests are useful in early 

pregnancy when ectopic pregnancy or abnormal intrauterine pregnancy (e.g., 

missed abortion) is suspected. Several qualitative urine pregnancy tests are 

available over the counter. Most pregnancy tests in current use are positive 

before the first missed menses with normal intrauterine pregnancy. Table 8-1 

lists types of available pregnancy tests and their sensitivity.

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Table 8-1

Pregnancy Tests

Type Source Sensitivity Comments

Radioimmunoassay Blood Positive within 7 d 

of fertilization

Quantitative or qualitative; 

used to follow women with 

possible ectopic pregnancy

Enzyme 

immunoassay 

Blood, 

urine

Positive 

approximately 

10 d after 

fertilization

Available for home urine 

testing; positive results require 

confirmation

Antibody 

agglutination 

inhibition

Urine Positive 

approximately 

18–21 d after 

fertilization

False positives may occur 

with hypothyroidism, renal 

failure, immunologic disorders, 

increased luteinizing hormone

Effects of Pregnancy on HIV Infection

CD4+ cell count and HIV RNA levels: The CD4+ cell count response to 

pregnancy is variable in all women, whether HIV infected or not (Obstet 

Gynecol 1997;89:967). Many studies have suggested that a decline in 

absolute CD4+ cell count occurs in pregnancy; the count returns to baseline at 

the end of pregnancy or during the postpartum period. The decline is thought 

to be secondary to hemodilution because the percentage of CD4+ cells 

remains relatively stable. Therefore, percentage, rather than absolute number 

of CD4+ cells, may be a more accurate measure of immune function for HIV 

infected pregnant women (AIDS Res Hum Retroviruses 2007;23:1469; AIDS

1997;11:1859; AIDS 1995;9:1177).

HIV RNA levels (viral load [VL]) remain relatively stable throughout pregnancy 

in the absence of treatment (Am J Obstet Gynecol 1998;178:355). Recent data 

suggest, however, that HIV RNA levels increase during the postpartum period 

regardless of antiretroviral (ARV) treatment (although use of antiretroviral 

therapy [ART] appears to blunt the effect), possibly as a result of immune 

activation associated with hormonal changes or labor-induced cytokines (Clin 

Vaccine Immunol 2010;17:2024). The implications of increased VL on the risk 

of transmission and on treatment recommendations in the early postpartum 

period are unclear (Clin Vaccine Immunol 2010;17:2024). The increase in 

postpartum VL does not appear to reflect a long-lasting effect of pregnancy 

on VL (Am J Obstet Gynecol 2003;189:552).

Clinical Course of HIV: To date, most studies of the effects of pregnancy 

on HIV disease have not demonstrated significant differences in HIV 

progression or survival in HIV infected pregnant women. A meta-analysis of 7 

prospective cohort studies found no significant differences between cases and 

controls in death, HIV disease progression, progression to an AIDS-defining 

illness, or decline in CD4+ cell count to <200/mm3 (Br J Obstet Gynaecol

1998;105:827). In a subsequently reported prospective study, 331 women 

with known dates of seroconversion were followed for a median of 5.5 

years, during which time, 69 of the women were pregnant. No differences 

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in progression were found between those who were and were not pregnant 

during follow-up (Arch Intern Med 1997;157:2585). In addition, a long-term 

observational study showed no difference in VL, CD4+ cell count, or clinical 

disease progression in women with repeat pregnancies compared with women 

with one pregnancy (Am J Obstet Gynecol 2003;189:552).

Effect of HIV on Pregnancy Course and Outcome

Adverse outcomes: Adverse pregnancy outcomes may occur secondary to 

underlying disease processes or their treatment or for reasons that cannot be 

determined. In the United States, approximately 10% of pregnancies end 

prematurely and preterm birth is the leading cause of perinatal morbidity and 

mortality. No evidence supports a significant direct effect of HIV on pregnancy 

outcome; however, the effects of advanced disease, including anemia, 

malnutrition, and other HIV-related infections, may increase the risk of some 

adverse outcomes (Br J Obstet Gynaecol 1998;105:836; AIDS 1998;12:1087; 

J Acquir Immune Defic Syndr 2003;33:393; Am J Clin Nutr 2003;77:1337; 

BJOG 2001;108:1125; J Acquir Immune Defic Syndr Hum Retrovirol

1998;18:293; J Coll Physicians Surg Pak 2011;21:356; BJOG 2008;115:616; 

Am J Obstet Gynecol 2002;186:903; Lancet 1998;351:98; Eur J Obstet 

Gynecol Reprod Biol 2010;150:34). Moreover, HIV infected women may be 

at risk of adverse pregnancy outcomes as a result of an increased likelihood 

of other risks, such as use of tobacco, alcohol, and illicit drugs; presence of 

sexually transmitted infections (STIs); and poor perinatal care. If these other 

risk factors are controlled for, however, HIV infection has no independent effect 

on adverse outcomes (AIDS 2000;14:1389).

A study of 497 HIV infected pregnant women enrolled in a perinatal clinical 

trial found that risk factors for adverse pregnancy outcomes (preterm birth, 

low birthweight, and intrauterine growth retardation) in ARV-treated women 

were similar to those reported for uninfected women (AIDS 2000;14:1389). 

Although concerns have been raised that ARV use may increase some 

adverse outcomes in pregnancy (see Adverse Pregnancy Outcomes, p. 300), 

the benefits of this therapy in reducing the risk of perinatal transmission 

far outweigh the risks. Results of a study comparing hospitalization among 

HIV infected pregnant women in the United States prior to and during the 

era of HAART indicate that rates of conditions responsible for increased 

hospitalization among HIV infected women decreased or remained stable after 

the introduction of ART (J Acquir Immune Defic Syndr 2006;43:186). Those 

conditions included major puerperal sepsis, genitourinary infections, influenza, 

bacterial infections, preterm labor/delivery, and liver disorders. Table 8-2 

summarizes the relationship between common pregnancy-related complications 

and untreated HIV.

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Table 8-2

Relationship of Adverse Pregnancy Outcomes to Untreated HIV 

Infection

Adverse Outcome Relationship to Untreated HIV Infection 

• Perinatal/infant mortality

• Stillbirth

Evidence of increased risk in developing countries

• Chorioamnionitis Most studies do not suggest an increased risk in 

clinical or histologic chorioamnionitis; however, 

evidence of possible increased risk in developing 

countries

• Group B strep infection

• Intrauterine growth 

restriction

• Spontaneous abortion

Evidence of possible increased risk

• Low birthweight (<2500 g)

• Preterm delivery

Evidence of possible increased risk, especially 

with more advanced disease

• Fetal malformation

• Gestational diabetes

• Placental abruption

• Placenta previa

• Preeclampsia

• Oligohydramnios

No evidence of increased risk

Effect of HIV and Pregnancy on Other Infections

Both HIV infection and pregnancy may affect the natural history, presentation, 

treatment, or significance of a number of infections, thereby causing 

complications in pregnancy or perinatal infection.

Vulvovaginal Candidiasis

Pregnancy is associated with both increased rates of colonization and 

increased symptomatic infections with species of Candida. HIV infection is also 

associated with increased rates of colonization and may be associated with 

increased infection rates, especially with declining immune function (J Infect Dis

2003;188:118; Clin Infect Dis 1997;24:201; Obstet Gynecol 1997;90:252; 

Clin Infect Dis 1998;27:1161). Therefore, HIV infected pregnant women may 

be particularly susceptible to yeast infections.

Treatment: Only topical azole agents should be used during pregnancy, and 

they should be given for at least 7 days. Prophylactic topical therapy should 

be considered during courses of systemic antibiotics.

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Bacterial Vaginosis

Bacterial vaginosis (BV) has been associated with several adverse pregnancy 

outcomes, including preterm labor and birth, premature rupture of membranes, 

low-birthweight infants, chorioamnionitis and amniotic fluid infection, 

postpartum and postabortal endometritis, and perinatal HIV transmission. HIV 

infection has been associated with increased prevalence and persistence of BV, 

the prevalence, persistence, and severity of which increase as CD4+ cell counts 

decline (Obstet Gynecol 2001;98:656).

Screening: Because BV is more common in the setting of HIV, and because 

both BV and HIV have been linked to an increased risk of preterm birth, 

pregnant women with HIV should be asked regularly about signs or symptoms 

of vaginal infection. If such signs or symptoms are present, evaluation for 

possible BV should follow. Infection should be treated if identified. Currently, 

data are insufficient to suggest that routine screening for and treatment 

of BV during pregnancy reduces the rate of preterm birth in the general 

population (Am J Prev Med 2001;20 suppl 3:59); no data are available in 

the setting of HIV infection. Multiple studies and meta-analyses have found no 

relationship between birth defects and metronidazole exposure during the first 

trimester of pregnancy (Am J Obstet Gynecol 1995;172:525; Obstet Gynecol

1993;82:348; Br J Clin Pharmacol 1997;44:179).

Treatment: If BV is diagnosed during pregnancy, preferred therapies are oral 

metronidazole 500 mg twice daily or 250 mg 3 times daily for 7 days, or oral 

clindamycin 300 mg twice daily for 7 days.

Genital Herpes Simplex

Primary herpes simplex virus (HSV) infection during early pregnancy has been 

associated with prematurity, neonatal chorioretinitis, microcephaly, and, in rare 

cases, skin lesions (J Pediatr 1987;110:97). Although congenital or intrauterine 

infection is uncommon, maternal HSV shedding at delivery is associated with 

neonatal HSV infection, which is almost always symptomatic (including skin, 

eye, and central nervous system [CNS] involvement or disseminated infection 

involving multiple organ systems). Although the mortality associated with 

neonatal herpes has declined significantly over the past 2 decades, it remains 

at 30% for disseminated disease and 4% for CNS disease. Approximately 

20% of survivors of neonatal herpes have long-term neurologic sequelae 

(Antiviral Res 2009;83:207)

The risk of neonatal herpes is greatest with primary HSV, especially when 

acquired close to delivery (30%–60%), whereas only 3% of neonates become 

infected with recurrent maternal disease at delivery when the mother has 

recurrent HSV. Because recurrent HSV is more common than primary disease, 

however, most neonatal infections are associated with recurrent HSV. Twothirds or more of mothers with HSV infected infants are asymptomatic during 

pregnancy; in only one-third of cases does either the mother or her sexual 

partner have a history of HSV infection. Because most neonatal infection 

occurs during vaginal delivery, if genital lesions or prodromal symptoms are 

present at the time of labor or membrane rupture, cesarean section (CS) 

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should be performed. CS is not indicated for recurrent HSV distant from 

the genital tract, such as on the thighs or buttocks (ACOG Practice Bulletin

No. 82; Obstet Gynecol 2007;109:1489; reaffirmed 2009). HIV infection, 

particularly with evolving immune compromise and higher plasma HIV VL (Clin 

Infect Dis 2003;36:207), is associated with increased HSV shedding and more 

frequent, severe, and prolonged episodes of genital or perianal herpes (Ann 

Intern Med 1995;123:845). Approximately 70% of HIV infected individuals 

are co-infected with HSV-2 (JAMA 2006;296:964); co-infection with HSV-2 

is common among pregnant HIV infected women, and reactivation of HSV 

in labor occurs more frequently in the setting of HIV infection (Am J Obstet 

Gynecol 1997;177:450).

Screening: Prevention of neonatal herpes should also emphasize prevention 

of herpes acquisition in susceptible pregnant women. If a pregnant woman’s 

sexual partner has a history of oral or genital HSV infection or serologic 

evidence of HSV infection, or if the partner’s infection status is unknown, 

the woman should be counseled to avoid unprotected genital and oral 

sexual contact during pregnancy. Type-specific HSV serology may be useful 

to identify the pregnant woman at risk for HSV and to guide counseling, 

especially if her sexual partner has HSV infection. At the onset of labor, 

all women should be questioned carefully about HSV symptoms, including 

prodromal symptoms, and all women should be examined carefully for herpetic 

lesions, so that judicious decisions can be made about the use of CS.

Treatment: Treatment of symptomatic HSV infections and suppressive therapy 

for frequent recurrences should be offered to HIV infected women during 

pregnancy (Guidelines for Prevention and Treatment of Opportunistic Infections 

in HIV infected Adults and Adolescents. 2012 [in press];. http://www.aidsinfo.nih.

gov) Visceral HSV disease is more likely to occur during pregnancy and can be 

fatal in rare cases. Either acyclovir or valacyclovir can be used for treatment 

or suppression (Guidelines for Prevention and Treatment of Opportunistic 

Infections in HIV infected Adults and Adolescents. 2012 [in press]; http://www.

aidsinfo.nih.gov); JAMA 2010;304:859). During pregnancy, documented HSV 

infections that do not respond to these agents should be managed with expert 

consultation.

For pregnant women with recurrences of genital herpes, suppressive therapy 

with either acyclovir or valacyclovir is recommended starting at 36 weeks’ 

gestation to reduce the need for CS delivery (ACOG Practice Bulletin No. 82; 

Obstet Gynecol 2007;109:1489; reaffirmed 2009). No known benefit of 

suppressive therapy exists for women who are only seropositive for HSV-2 

without a history of genital lesions. Maternal genital herpes was a risk 

factor for perinatal HIV transmission in the pre-HAART era (Obstet Gynecol

2005;106:1341); it is not known whether HSV suppression reduces the risk of 

mother-to-child transmission (MTCT) among women on HAART.

Human Papillomavirus

Correlated with level of immunosuppression, both human papillomavirus 

(HPV) infection in general and genital warts in particular are more common 

in HIV infected individuals. Genital warts may be seen more frequently in 

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pregnancy, when they often enlarge and become friable; in some cases, 

they cause mechanical obstruction of the vaginal canal during labor. In rare 

cases perinatal exposure can result in laryngeal papillomatosis in infants and 

children (Am J Obstet Gynecol 1998;178:365).

Screening: Pregnant women with abnormal Pap smears should undergo 

colposcopy and cervical biopsy if lesions suspicious for high-grade HPV 

disease or cervical cancer are present. Increased bleeding may occur with 

biopsy during pregnancy. Endocervical curettage should not be performed 

during pregnancy. Colposcopy can be deferred until 6 weeks postpartum if 

Pap results indicate atypical squamous cells of unknown significance (ASCUS). 

Treatment of cervical intraepithelial neoplasia (CIN) is not recommended 

during pregnancy unless invasive disease is suspected, in which case 

diagnostic excision is indicated. Reevaluation with cytology and colposcopy is 

recommended 6 weeks postpartum. Women with preinvasive cervical lesions 

can deliver vaginally, if otherwise appropriate. Women with suspected invasive 

cervical cancer should be referred to a gynecologic oncologist.

Treatment: Podophyllin and podofilox should not be used in pregnancy 

because of increased risk for fetal death in several animal models and case 

reports in humans. At present, evidence is insufficient to recommend imiquimod 

use during pregnancy (Guidelines for Prevention and Treatment of Opportunistic 

Infections in HIV infected Adults and Adolescents. 2012 [in press]; http://www.

aidsinfo.nih.gov). Other topical treatments (e.g., bichloroacetic and trichloroacetic acid) and ablative therapies (i.e., laser, cryotherapy, and excision) can 

be used during pregnancy, although treatment is likely to be less effective in 

pregnant women than in women who are not pregnant.

CS is not currently recommended to prevent neonatal exposure to HPV, 

although, in rare instances, CS may be indicated when extensive HPV lesions 

obstruct the vagina.

Syphilis

HIV may affect clinical manifestations, serologic response, or response 

to treatment for syphilis. Although pregnancy does not alter the clinical 

manifestations of syphilis, untreated primary or secondary syphilis during 

pregnancy affects essentially all fetuses, with a 50% rate of prematurity, 

stillbirth, or neonatal death (Sexually Transmitted Diseases. 3rd ed. New York: 

McGraw-Hill; 1999). Even with later stages of syphilis, there is a significant 

increase in adverse pregnancy outcomes, although the frequency and severity 

of fetal disease decrease with longer duration of untreated maternal infection. 

Manifestations of congenital syphilis in the newborn include mucocutaneous 

lesions, hepatosplenomegaly, osteochondritis/periostitis, jaundice, petechiae/

purpura, and meningitis.

Screening: Congenital syphilis can generally be prevented by identification 

and appropriate treatment of syphilis during pregnancy. All pregnant women 

should have serologic testing for syphilis at the beginning of prenatal care; 

testing should be repeated at 28 weeks’ gestation and at delivery, particularly 

in women who remain at risk for infection or who live in areas with high syphilis 

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prevalence. Any woman with stillbirth after 20 weeks’ gestation should be 

tested for syphilis. Development of neurologic symptoms mandates evaluation 

for possible neurosyphilis. Concurrent syphilis infection in the mother has 

been associated with increased risk for perinatal transmission of HIV (AIDS

2006;20:1869; BJOG 2004;111:579).

Treatment: Syphilis during pregnancy should be treated with the penicillin 

regimen appropriate for the stage of disease. Because of concerns about 

the effectiveness of standard therapy in pregnant women and in the setting 

of HIV infection, however, a second injection 1 week after the first should be 

considered in cases of primary, secondary, or early latent syphilis (Guidelines for 

Prevention and Treatment of Opportunistic Infections in HIV infected Adults and 

Adolescents. 2012 [in press]; http://www.aidsinfo.nih.gov). Ultrasound evidence 

of hydrops fetalis or hepatosplenomegaly suggesting fetal syphilis increases risk 

for treatment failure and should be managed with expert consultation.

Treatment of syphilis during the second half of pregnancy is associated 

with the Jarisch-Herxheimer reaction in up to 40% of cases, with resulting 

premature labor and/or fetal distress (Obstet Gynecol 1998;92:859). Fetal 

and contraction monitoring for 24 hours should be considered, especially in 

the setting of abnormal ultrasound findings; alternatively, patients should be 

advised to seek immediate medical attention after treatment if contractions 

or a decrease in fetal movements occur after syphilis treatment (Guidelines for 

Prevention and Treatment of Opportunistic Infections in HIV infected Adults and 

Adolescents. 2012 (in press); http://www.aidsinfo.nih.gov).

Pregnant women with a history of penicillin allergy should be skin tested and, 

if necessary, desensitized and treated with penicillin because there are no 

proven effective alternatives to penicillin for the treatment and prevention of 

congenital syphilis (MMWR Recomm Rep 2010;59 RR-12:1).

Even with appropriate treatment of the pregnant woman with syphilis, fetal 

infection may still occur; therefore, neonates should be carefully evaluated for 

evidence of congenital infection. Clinical and serologic follow-up should be 

performed in the third trimester, at delivery, and at 3, 6, 9, 12, and 24 months 

following treatment. Treatment failure should be managed with cerebrospinal 

fluid examination and retreatment. Serologic titers can be checked monthly 

in women at high risk for reinfection or in geographic areas in which the 

prevalence of syphilis is high.

Cytomegalovirus

Cytomegalovirus (CMV) is the most common cause of congenital viral 

infection in the United States: 0.2% to 2.2% of liveborn infants acquire this 

infection perinatally and it is the leading cause of congenital hearing loss 

(Int J Gynaecol Obstet 2002;76(1):95 [reaffirmed 2011]). Most maternal 

CMV infections are asymptomatic but may cause a mononucleosis-like illness. 

Because CMV has been recovered from virtually all body fluids, transmission 

can occur sexually or with injection drug use. Transmission can also occur with 

oral contact with infected secretions (e.g., from children). Primary infection, 

reactivation, and reinfection with different CMV strains during pregnancy all 

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can lead to in utero transmission and congenital CMV (Am J Obstet Gynecol

2010;202:297). Although about one-third of newborns acquire congenital 

CMV infection after primary infection, only 1%–2% of newborns acquire CMV 

after a recurrent infection in women who are not HIV infected. Because in most 

studies >90% of HIV infected pregnant women are CMV antibody positive, 

the risk for symptomatic infection in the fetus is expected to be low (JAMA

1986;256:1904; JAMA 1987;257:2617; J Pediatr 1998;132:285; N Engl J 

Med 1999;341:77); however, recent studies of HIV-exposed infants suggest 

that rates of congenital CMV may be increased, ranging from 2%–7%, with 

higher rates in babies born to mothers with CD4+ cell counts <200/mm3

and in HIV infected infants (Pediatr Infect Dis J 2010;29:915; Clin Infect Dis

2009;48:1516).

Ninety percent of CMV infected infants are asymptomatic at birth. 

Symptomatic infection is more likely with maternal infection acquired early in 

pregnancy. Severe clinical manifestations of congenital CMV include symmetric 

growth restriction, hepatosplenomegaly, chorioretinitis, microphthalmia, 

hydrocephaly, microcephaly, and cerebral calcifications. Up to 90% of infected 

infants who are symptomatic at birth will have serious long-term problems, 

including hearing loss, visual impairment, mental retardation, and/or cognitive 

impairment. Among asymptomatic newborns, however, only 5%–15% are at 

risk for serious long-term impairment, notably late-onset hearing loss in non-HIV 

infected children (J Clin Virol 2006;35:226).

Treatment: Indications for treatment of CMV infection during pregnancy are 

the same as for treatment of nonpregnant HIV infected adults. Treatment 

of asymptomatic maternal CMV infection to prevent infant infection is not 

indicated. For retinal disease, use of intraocular implants or intravitreous 

injections for local therapy should be considered in the first trimester, if possible, 

to limit fetal exposure to systemically administered antiviral drugs. Systemic 

antiviral therapy should then be started after the first trimester. Valganciclovir 

is recognized as the treatment of choice for CMV during pregnancy (Guidelines 

for Prevention and Treatment of Opportunistic Infections in HIV infected Adults 

and Adolescents. 2012 (in press); http://www.aidsinfo.nih.gov).

Fetal monitoring: The fetus should be monitored in the third trimester by fetalmovement counting and after 20 weeks’ gestation by periodic ultrasound 

monitoring to look for evidence of hydrops fetalis indicating substantial 

anemia. Any ultrasound findings suspicious for congenital CMV infection 

(e.g., cerebral calcifications, abdominal and liver calcifications, hydrops, 

microcephaly, ventriculomegaly, ascites, echogenic fetal bowel) should prompt 

consideration of amniocentesis for definitive diagnosis.

Although invasive fetal testing was associated with increased rates of perinatal 

HIV transmission in early studies (Am J Obstet Gynecol 1996;175:661), more 

recent data suggest that the risk may be minimal in women who are on 

effective ART and have undetectable HIV RNA levels (Am J Obstet Gynecol

2009;200:160.e1; Eur J Obstet Gynecol Reprod Biol 2008;140:212; Eur J 

Obstet Gynecol Reprod Biol 2003;108:137).

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Referral to a maternal-fetal medicine specialist for evaluation, counseling, and 

potential further testing is recommended. Because infants who are co-infected 

with HIV and CMV have more rapid progression of HIV infection and develop 

AIDS more frequently (J Pediatr 1998; 132:285; N Engl J Med 1999;341:77), 

they should be a priority to receive ART. Methods to reduce the risk of 

exposure to CMV include safe sexual practices, careful handwashing, and 

transfusion of only CMV antibody–negative blood products.

Toxoplasmosis

Approximately one-third of women in the United States have toxoplasma 

antibodies, reflecting prior infection. Primary infection occurs in approximately 

0.1%–0.5% of pregnancies and places the fetus at risk for congenital 

toxoplasmosis. Congenital infection is more common when infection in the 

mother occurs during the third trimester (>60% in the third trimester vs. 

10%–15% in the first trimester) but is generally more severe when occurring in 

the first trimester. Although the majority of infected infants are asymptomatic 

at birth, most will develop some sequelae of congenital toxoplasmosis. Twothirds of infants infected after maternal first-trimester infection have severe 

manifestations; 5% are stillborn or die in the perinatal period (ACOG Technical 

Bulletin No. 177, February 1993).

Congenital toxoplasmosis may affect all systems, but the most common findings 

are chorioretinitis, microcephaly, hydrocephaly, and cerebral calcifications. 

Transmission of toxoplasmosis from a mother with antibody evidence of 

prior infection can occur in the setting of HIV infection (as opposed to in HIV 

uninfected women) but seems to be uncommon (0%–3.7% in two studies); there 

are case reports of transmission with reactivation of chronic infection in HIV 

infected women with severe immunosuppression (Eur J Obstet Gynecol Reprod 

Biol 1996;68:93; Am J Obstet Gynecol 1997;176:555).

Testing for IgG antibodies to toxoplasma is recommended for all HIV infected 

patients soon after the diagnosis of HIV is made and should be considered as 

part of prenatal testing in HIV infected pregnant women. Pregnant women with 

symptoms that may include fever, chills, malaise, lymphadenopathy, myalgias, 

and headache should be evaluated serologically for possible primary 

toxoplasmic infection. Primary Toxoplasma gondii infection can typically be 

distinguished from chronic infection with the use of multiple serologic assays, 

including IgG, IgM, IgA, and IgE antibodies; IgG avidity; and the differential 

agglutination (AC/HS) tests (Guidelines for Prevention and Treatment of 

Opportunistic Infections in HIV infected Adults and Adolescents. 2012 [in press]; 

http://www.aidsinfo.nih.gov).

Screening: Detailed ultrasound examination of the fetus to evaluate specifically 

for hydrocephalus, cerebral calcifications, and growth restriction should be 

performed in cases of suspected primary or symptomatic reactivation of T. 

gondii during pregnancy (Clin Infect Dis 2008;47:554). Polymerase chain 

reaction (PCR) testing of amniotic fluid may be considered for pregnant 

women on ART who have serologic evidence of acquired infection during 

the immediate preconception period or during pregnancy and among 

those women with ultrasound findings suggestive of fetal T. gondii infection 

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(Clin Infect Dis 2008;47:554). Infants born to HIV infected women who 

are seropositive for toxoplasma also should be evaluated for evidence of 

congenital toxoplasmosis if suspected by the infant’s clinical presentation.

To prevent T. gondii exposure, pregnant women should be counseled to avoid 

raw or undercooked meat, to wash hands after contact with raw meat or 

with soil, and to thoroughly wash fruits and vegetables before eating them 

raw. Cats should preferably be kept inside and fed only canned or dried 

commercial food, and their litter boxes should be changed daily, preferably 

by someone who is not HIV infected or pregnant.

Treatment: Treatment of the pregnant woman with toxoplasmic encephalitis 

should be the same as treatment for nonpregnant adults: pyrimethamine 

plus sulfadiazine plus leucovorin. This regimen is thought to also prevent 

transmission of T. gondii to the fetus and may treat affected fetuses (Clin Infect 

Dis 2008;47:554). Pregnant HIV infected women with suspected or confirmed 

primary T. gondii infection during pregnancy should be managed with expert 

consultation. (Primary prophylaxis and prophylaxis against recurrent disease in 

pregnancy are discussed below; see Opportunistic Infections, p. 320.)

Hepatitis B

Hepatitis B virus (HBV) is the leading cause of chronic liver disease worldwide 

(N Engl J Med 1997;337:1733). Most patients who become infected with HBV 

have complete resolution of infection and develop protective levels of antibody 

(anti-HBs). Of those infected as adults, 6%–10% develop chronic infection (i.e., 

they are chronically HBsAg+), which puts them at risk for chronic liver disease, 

including cirrhosis and hepatocellular carcinoma (CDC. The ABCs of Hepatitis 

Fact Sheet. http://www.cdc.gov/hepatitis/HAV/ProfResourcesA.htm. Accessed 

6/27/12).

The presence of HBeAg indicates active viral replication and increased 

infectivity. HBV is transmitted parenterally, sexually, perinatally, and 

through household or institutional contact. Approximately 25% of regular 

sexual contacts of infected individuals will become seropositive, and sexual 

transmission accounts for 30%–60% of new infections. Without preventive 

measures, perinatal transmission, usually through intrapartum contact with 

maternal blood and genital secretions, occurs in 10%–20% of women who 

are HBsAg+. If the mother is also HBeAg+, the perinatal transmission rate 

increases to approximately 90%. Chronic HBV infection develops in about 

90% of infected newborns, putting them at high risk for chronic liver disease 

(ACOG Practice Bulletin No. 86; Obstet Gynecol 2007;110:941). Rates of 

perinatal transmission of HBV are reduced to under 5% when hepatitis B 

immune globulin (HBIG) and hepatitis B vaccine are provided at birth to infants 

born to mothers who are HBsAg+.

Approximately 10% of HIV infected individuals have evidence of 

chronic hepatitis B (J Acquir Immune Defic Syndr 1991;4:416; J Infect Dis

1991;163:1138). Impaired cellular immunity is associated with higher levels 

of hepatitis B viremia and lower viral clearance rates following acute HBV 

infection. HIV patients with chronic HBV infection may be more likely to have 

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detectable HBeAg (Hepatology 1999;29:1306; AIDS 1997;11:597), lower 

rates of seroconversion, and an increased risk for liver-related mortality and 

morbidity (Lancet 2002;360:1921).

Hepatitis C

Hepatitis C virus (HCV) infection is the most common chronic bloodborne 

infection in the United States (Ann Intern Med 2006;144:705). HCV infection is 

transmitted primarily through injection drug use, but may also be transmitted 

sexually. Chronic HCV infection develops in 70%–85% of HCV infected 

people; 60%–70% of people with chronic HCV infection develop evidence 

of active liver disease and are at risk for hepatocellular carcinoma (CDC. The 

ABCs of Hepatitis Fact Sheet. www.cdc.gov/hepatitis/HAV/ProfResourcesA.htm. 

Accessed 6/27/12). Most people remain unaware of their infection because 

they are not clinically ill.

Among HIV infected pregnant women, the HCV seroprevalence rate ranges 

from 17%–54% (Int J Epidemiol 1998;27(1):108). Co-infection with HIV 

increases risk for and accelerates the rate of development of progressive 

liver disease (Clin Infect Dis 2001;33:562; J Hepatol 1997;26:1). Cofactors 

influencing disease progression include age, low CD4+ cell count, and 

history of alcoholism. Evidence suggests that HCV infection may also hasten 

progression of HIV infection (J Viral Hepat 2000;7:302). In most studies, the 

incidence of HCV transmission from mother to infant increases if the mother 

is co-infected with HIV, with transmission rates between 10% and 20% 

(Clin Infect Dis 1997;25:1121; Lancet 2000;356(9233):904; J Infect Dis

2005;192(11):1880; J Hepatol 2006;44 suppl 1:S6; BJOG 2001;108:371). 

This is likely related to an increase in HCV viremia and/or other HIVrelated effects on HCV disease activity (Clin Infect Dis 2007;44(8):1123). 

Furthermore, maternal co-infection with HIV and HCV may also increase risk 

for perinatal HIV transmission (J Infect Dis 1997;176(2):414). Pregnancy does 

not appear to influence the course of HCV infection; women with chronic viral 

hepatitis generally do well during pregnancy unless they have progressed to 

decompensated cirrhosis (Ann Hepatol 2006;5(3):190).

Perinatal Transmission

Rate

The baseline rate of perinatal HIV transmission without prophylactic therapy 

is approximately 25%; however, with the use of combination ART and 

suppression of HIV RNA (VL) to undetectable levels, along with avoidance 

of breast feeding and the use of CS delivery when appropriate, the rate of 

perinatal transmission may be reduced to 1%–2% or less (J Acquir Immune 

Defic Syndr 2002;29:484; AIDS 2008;22:973; J Public Health Manag Pract

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2010;16:481). Nevertheless, approximately 100–200 infants are infected 

annually in the United States (Am J Obstet Gynecol 2007;197(3 Suppl):S10), 

most commonly because the mother did not receive HIV testing or other 

recommended prevention interventions during pregnancy; these infections 

therefore represent missed opportunities (Women Health 2010;50(5):414). 

Lack of prenatal care and active substance abuse, which frequently coexist, 

have also been linked to a potentially avoidable increased risk for perinatal 

transmission (N J Med 2001;98:23). Acute HIV infection in pregnancy or during 

breastfeeding is associated with an increased risk of perinatal HIV transmission 

and may represent a significant proportion of residual mother-to-child HIV 

transmission (MTCT) in the United States (Obstet Gynecol 2010;115(6):1247).

Timing

The timing of transmission is a critical factor in prevention. Although transmission 

can occur throughout the course of pregnancy, around the time of labor 

and delivery, or postpartum through breastfeeding, most transmissions 

appear to occur during or close to the intrapartum period, particularly in 

non-breastfeeding populations (JAMA 2000;283:1175). Table 8-3 outlines 

the estimated timing and risk of MTCT; Table 8-4 identifies key clinical and 

potentially modifiable factors associated with the risk of perinatal transmission.

Risk Factors

Table 8-3

Estimated Timing and Risk of Mother-to-Child HIV Transmission 

(Absolute Rate) in the Absence of Antiretroviral Use

No 

Breastfeeding

Breastfeeding 

through 6 mo

Breastfeeding through 

18–24 mo

Intrauterine 5–10% 5–10% 5–10%

Intrapartum 10–20% 10–20% 10–20%

Postpartum

Early (2 mo) 5–10% 5–10%

Late (>2 mo) 1–5% 5–10%

Overall 15–30% 25– 35% 30–45%

Source: JAMA 2000;283(9):1175

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Table 8-4

Clinical Factors Associated with Risk of Perinatal Transmission

HIV Related Clinical Factors

Maternal plasma 

HIV-1 RNA level • Risk increases with higher maternal serum HIV-1 RNA levels 

(N Engl J Med 1999;341:394; J Acquir Immune Defic Syndr 2002;29:484; N Engl J Med 1999;341:385)

• No absolute threshold exists below which transmission does 

not occur or above which transmission always occurs

CD4+ cell count • Risk of transmission is higher with lower CD4+ counts

Genital tract VL • Independently associated with perinatal transmission 

(J Infect Dis 2000;181:99), genital tract VL usually 

correlates with plasma VL, but discordance may occur, 

especially with genital tract infections

Clinical HIV stage • Both acute infection and late-stage disease are associated 

with increased risk of perinatal transmission (AIDS

2010;24(4):573; Obstet Gynecol 2010; 115(6): 1247)

Maternal Related Clinical Factors

Co-infection • Genitally transmitted infections have been shown to 

increase both genital tract HIV shedding and plasma 

viremia (AIDS Res Hum Retroviruses 1998;14 suppl 1:S5), 

both of which may increase risk for perinatal transmission

• Syphilis, HSV, and vaginal infections (BV, yeast, 

trichomoniasis) (AIDS 2008;22:1169; Int J Gynaecol Obstet

1998;63:247; J Perinatol 2010;30(11):717) have been 

associated with increased risk of perinatal transmission

• HCV infection, TB, and placental malaria have also been 

associated with increased risk for vertical transmission 

(J Hepatol 2006; 44 suppl 1:S6; Int J Epidemiol

1998;27:296; J Infect Dis 2011;203:358)

Substance abuse • Illicit drug use has been associated with increased risk for 

perinatal transmission (AIDS 1996;10:273)

Cigarette smoking • Smoking is associated with increased risk for perinatal 

transmission (J Acquir Immune Defic Syndr Hum Retrovirol

1997;14:327)

Sexual behavior • Unprotected intercourse during pregnancy associated with 

increased risk for perinatal transmission (J Acquir Immune 

Defic Syndr Hum Retrovirol 1997;15:76)

ARV use • ARV use is consistently associated with decreased risk 

for perinatal transmission; the greatest reductions are 

associated with longer and more complex regimens 

(J Acquir Immune Defic Syndr 2002;29:484; AIDS

2008;22:973)

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Table 8-4

Clinical Factors Associated with Risk of Perinatal Transmission

Obstetrical Related Clinical Factors

Preterm delivery • Delivery at preterm gestational age has been associated 

with increased risk for perinatal transmission (J Infect Dis

1999;179:52)

Mode of delivery • CS delivery prior to onset of labor or membrane rupture 

is associated with decreased risk of perinatal transmission 

with HIV-1 RNA level >1000 copies/mL near time of 

delivery or with AZT only (studies done before routine use 

of VL testing/use of HAART) (Lancet 1999;353:1035; N 

Engl J Med 1999;340:977)

• Data are insufficient to evaluate the potential benefit of 

CS delivery for prevention of perinatal transmission in 

pregnant women receiving combination ARV drugs with 

plasma HIV RNA levels <1000 copies/mL near the time of 

delivery

Invasive intrapartum 

monitoring • Fetal scalp sampling and use of fetal scalp electrodes are 

associated with increased risk for perinatal transmission 

in some studies (Eur J Obstet Gynecol Reprod Biol

1999;87:63; JAMA 1994;271:1925)

Chorioamnionitis/ 

Placental abruption • Placental barrier disruption and/or inflammation are 

associated with increased risk for perinatal transmission 

(J Acquir Immune Defic Syndr 2002;29:262)

Duration of rupture 

of membranes • Longer duration of membrane rupture is associated 

with increased risk for perinatal transmission (AIDS

2001;15:357)

Forceps/vacuum/

episiotomy • A potentially increased risk of transmission exists due to 

increased exposure to maternal blood/genital secretions 

with trauma to maternal or neonatal tissue (Obstet Gynecol

1999;94:897)

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Breastfeeding: Globally, breastfeeding is estimated to have accounted for 

up to 40%–50% of newly infected children (JAMA 1999;282:781). Factors 

associated with an increased risk of breast-milk transmission are summarized in 

Table 8-5.

continued

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Table 8-5

Factors Associated with Increased Risk of Transmission of HIV via 

Breast Milk

Maternal • Acute HIV infection (Lancet 1992;340:585)

• Advanced HIV infection with low CD4+ cell counts

• High VL in plasma or breast milk

• Breast conditions (e.g., clinical or subclinical mastitis, breast 

abscess, cracked nipples)

Newborn • Preterm birth or low birthweight

• Loss of mucosal integrity resulting from trauma, nutritional 

deficiency, or infection (e.g., oral thrush)

• Maternal-infant HLA incompatibility; possible protective effect 

(J Infect Dis 2008;197(8):1156)

Breastfeeding • Timing and duration; although transmission rates are possibly 

higher in early breastfeeding, duration is a major determinant of 

transmission (PLoS One 2009;4(10):e7397)

• Pattern of breastfeeding; mixed feeding (addition of other 

solids or liquids to breast milk) is associated with increased risk 

compared with exclusive breastfeeding (AIDS 2005;19:699)

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Antiretroviral Drug Use In Pregnancy

The administration of ARV drugs to the mother during pregnancy and 

labor and to the neonate are the interventions associated with the greatest 

decreases in perinatal transmission. ARV drugs reduce perinatal transmission 

by several mechanisms, among them, by lowering maternal VL and by 

providing pre- and post-exposure prophylaxis for the infant through placental 

transfer. Therefore, at least 1 nucleoside/nucleotide agent with high placental 

transfer should be included in ARV regimens in pregnancy (J Infect Dis

2004;190(12):2167; J Clin Pharmacol 2001;41(7):732; Clin Pharmacol Ther

2009;85(2):182; Antimicrob Agents Chemother 2009;53(3):1067).

General Principles for Treatment

ARV prophylaxis is recommended for all HIV infected pregnant women, 

regardless of CD4+ cell count and/or VL. Although rates of perinatal 

transmission are low in women with undetectable or low HIV RNA levels, no 

threshold exists below which lack of transmission can be assured.

Decisions regarding use of ART or prophylaxis during pregnancy should be 

made by the woman after detailed and noncoercive discussion of the benefits 

and potential risks of therapy.

Regimen: Combination ARV regimens containing at least 3 drugs for 

prevention of perinatal HIV transmission are associated with the lowest risk 

of transmission and should be discussed and offered to all pregnant women 

with HIV infection. Although the initial study (PACTG 076) documenting the 

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effectiveness of ARVs in reducing perinatal transmission rates involved the use 

of AZT alone, subsequent studies and clinical experience have shown that the 

lowest rates of transmission are associated with more complex regimens that 

lower maternal VL to undetectable levels (AIDS 2008;22(8):973).

Choice of ARV regimens in pregnancy should follow the same principles 

applied when choosing ARV regimens for patients who are not pregnant: 

1) optimize efficacy and durability of response; 2) maximize safety and 

tolerability; 3) simplify regimens to improve the likelihood of adherence 

and reduce the chance of resistance; and 4) for pregnant women, address 

special considerations such as maternal and fetal safety. To preserve future 

maternal options, the durability, tolerability, and simplicity of the ARV 

regimen is of particular importance. Table 8-6 summarizes maternal and 

fetal/neonatal factors to be considered when formulating an ARV regimen 

for a pregnant woman.

Table 8-6

Considerations in Choosing and Individualizing an Antiretroviral 

Regimen in Pregnancy

Mother:

• Efficacy and durability of response

• Safety and tolerability

• Comorbidities

• Potential for adherence

• Convenience

• Potential adverse drug effects

• Potential interactions with other 

medications

• Results of genotypic resistance testing

• Pharmacokinetic changes in pregnancy

Fetus/Neonate:

• Potential teratogenic effects

• Potential carcinogenicity or 

mutagenicity

• Side effects or toxicity from 

transplacentally transferred drugs

Potential for adverse effects may be related to several factors: the drug itself, 

dose, gestational age at exposure, duration of exposure, interactions with other 

drugs or agents to which the fetus is exposed, and genetic make-up of the 

mother and fetus. Potential ARV toxicity with perinatal exposure applies both 

to the infected and uninfected fetus/infant.

Duration: Longer duration and/or earlier initiation of ARVs are associated 

with lower rates of transmission. In a French study evaluating risk factors 

for perinatal transmission in women with VL <500 copies/mL at the time of 

delivery, the overall transmission rate was 0.5%; the highest transmission rates 

occurred among women who were not taking ARVs at the time of conception 

and who did not have VL <500 copies/mL at 14, 28, and 32 weeks’ gestation 

(Clin Infect Dis 2010;50(4):585). When ARVs were started during pregnancy, 

gestational age at initiation of therapy did not differ between groups (30 

weeks), but VL decreased earlier in the nontransmitters. The ability to reach 

maximal viral suppression is affected by the VL at the beginning of pregnancy; 

in a study from the United Kingdom, with initial VL >10,000 copies/mL (c/mL), 

deferring ARV initiation past 20 weeks’ gestation reduced the likelihood of 

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VL <50 c/mL at delivery, whereas only 37% of those with initial VL >100,000 

c/mL reached maximal VL suppression by the end of pregnancy and this was 

dependent on the duration of the ARV regimen (AIDS 2012;26(9):1095)

Resistance: The development of ARV resistance is a major factor in treatment 

failure. The most common causes of resistance are the prescription of 

ineffective regimens and lack of adherence. ARV regimens are ineffective 

when they include drugs to which there is existing resistance or when they are 

composed of just one or two drugs or drugs from just one ARV class. Viral 

replication of HIV is inherently mutation-prone and resistant viral variants 

emerge under selective pressure, especially with incompletely suppressive 

regimens. Resistant viral variants are believed to be archived permanently 

in latent HIV reservoirs, and resistance to one drug may be associated 

with resistance to other drugs within the same class; therefore, if ineffective 

regimens are used or if ARV regimens are taken incorrectly, patients’ future 

treatment options may be significantly limited.

When developed during pregnancy, drug resistance may compromise the 

prevention of perinatal transmission or may result in transmission of a resistant 

virus to the fetus, which would limit the infant’s future treatment options. It could 

also limit the mother’s future treatment options or decrease the effectiveness 

of prophylactic regimens in future pregnancies. Although perinatal transmission 

of resistant virus has been reported, it appears to be unusual, and little 

evidence exists that the presence of resistance mutations increases the risk of 

transmission when current recommendations for ARV management in pregnancy 

are followed.

Several factors unique to pregnancy may increase risk for the development 

of resistance:

• If prophylactic regimens include drugs with significant halflife differences, such as NVP or EFV combined with two 

nucleoside analogue drugs, then postpartum discontinuation 

of all regimen components simultaneously may result in 

persistent subtherapeutic drug levels and increase risk for 

the development of NNRTI resistance.

• Problems such as nausea and vomiting in early pregnancy 

may compromise adherence or absorption.

• Pharmacokinetic changes during pregnancy, such as 

increased plasma volume and renal clearance, may lead to 

subtherapeutic drug levels that increase risk for resistance.

Current recommendations for HIV drug-resistance testing in pregnant women 

are as follows (resistance testing requires VL >500–1000 copies/mL for 

accurate detection of resistance mutations):

• Before starting treatment or prophylaxis, test for resistance 

in all pregnant women not currently taking ARVs (unless 

previously tested and patient ARV-naïve).

• Test for resistance in all pregnant women entering 

pregnancy on ART with detectable VL.

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• Test for resistance in all pregnant women who have 

suboptimal viral suppression after initiation of ARV drugs 

in pregnancy (Recommendations for Use of Antiretroviral 

Drugs in Pregnant HIV-1-Infected Women for Maternal Health 

and Interventions to Reduce Perinatal HIV Transmission in the 

United States. 2013. http://www.aidsinfo.nih.gov).

For optimal prevention of perinatal transmission, empiric initiation of ARV drugs 

before obtaining the results of resistance testing is warranted for women who 

present late in pregnancy, with adjustment as needed after the test results are 

available.

Women who have documented ZDV resistance should still receive intravenous 

ZDV during labor if VL >400 c/mL near delivery, along with their established 

ARV regimens, and their infants should receive oral ZDV.

Recommendations for preventing ARV resistance include the following:

• Use of an effective combination ARV regimen

• Emphasis on and reinforcement of the importance of good 

adherence at each patient visit

• Not recommended: Addition of single-dose NVP (sdNVP) 

to a combination ARV regimen; sdNVP does not increase 

efficacy of MTCT prevention and may lead to maternal or 

infant NVP resistance (J Infect Dis 2002;186:181)

• For pregnant women receiving an NNRTI-based combination 

regimen that is discontinued after delivery:

- Continue the NRTI components after stopping the 

NNRTI (J Infect Dis 2006;193(4):482; PLoS Med

2009;6(10):e1000172)

- An alternative strategy is to substitute a PI for the NNRTI 

prior to the interruption and continue the PI with dual NRTIs 

(AIDS 2008;22(17):2279)

The optimal interval between stopping an NNRTI and discontinuing the 

other ARVs is not known, but current recommendations suggest an interval 

of 7–30 days. Because NNRTI concentrations may remain detectable for 

more than 3 weeks in patients receiving EFV-based therapy, some experts 

recommend continuing other ARV agents or substituting a PI plus two other 

agents for up to 30 days (J Acquir Immune Defic Syndr 2005;38(3):283; AIDS

2005;19(15):1716). A recent study of 412 women who received single-dose 

nevirapine and were randomized to receive zidovudine/lamivudine, tenofovir/

emtricitabine, or lopinavir/ritonavir for either 7 or 21 days found an overall 

new nevirapine resistance mutation rate of 1.2% when assessed by population 

genotype at 2 and 6 weeks following completion of treatment, with no 

difference by length of treatment. However, low-frequency nevirapine-resistant 

mutations at codons 103, 181, and 184 detected using allele-specific PCR 

emerged significantly more often in the 7-day arms (13/74 [18%]) than in the 

21-day arms (3/66 [5%], P = .019). (Clin Infect Dis 2013;56(7):1044).

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All cases of ARV drug exposure during pregnancy should be reported to the 

Antiretroviral Pregnancy Registry (see details at http://www.APRegistry.com. 

Accessed 6/26/12). The registry is a collaborative project of pharmaceutical 

manufacturers, with an advisory committee of obstetric and pediatric 

practitioners, that collects observational data regarding ARV exposure during 

pregnancy for the purpose of assessing the potential teratogenicity of these 

drugs. The registry does not use patient names; registry staff members obtain 

birth outcome follow-up information from the reporting provider.

Limited data are available on both the long-term maternal consequences of 

ARV drug use during pregnancy solely for transmission prophylaxis and on the 

long-term consequences for the infant of in utero ARV exposure.

Expert consultations: Expert consultation on care of the HIV infected pregnant 

woman is recommended and/or should be considered in the following 

situations:

• When use of ZDV alone is being considered

• If maximal virologic suppression is not achieved with the 

prescribed ARV regimen

• When choosing an ARV regimen for a woman with extensive 

ART experience and/or multiple resistance mutations

• Prior to discontinuation of ARVs when they were being taken 

only for prophylaxis

• If a patient has significant toxicity that is related to, or 

potentially related to, use of ARVs

• If a patient has significant medical comorbidities that may 

affect drug choice (e.g., HBV)

• If premature membrane rupture occurs

• When maternal ARV resistance is known or suspected, with 

high maternal VL at or near delivery, or when the mother 

has received no ARVs prior to and/or during labor (to 

determine potential for use of additional drugs in the infant; 

consult with a pediatric HIV specialist)

Recommendations for Use of Specific ARV Agents In Pregnancy

Table 8-7 provides information about all currently Food and Drug 

Administration (FDA)-approved ARV agents, with information and 

recommendations specific to pregnancy. These recommendations specifically 

relate to agents used to construct initial ARV regimens in antiretroviral naïve 

pregnant women and are predicated on ARV sensitivity by resistance testing. 

If a woman enters pregnancy on a stable ARV regimen with viral suppression, 

the regimen should be continued. Antiretroviral drugs or drug combinations 

are divided into several categories for use in pregnancy, based on efficacy 

and durability; safety for mother, fetus and newborn; ease of use; available 

pregnancy-specific pharmacokinetic data; medical comorbidities limiting drug 

choice; and experience in pregnancy.

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

NRTIs/NtRTIs: Nucleoside/nucleotide reverse transcriptase inhibitors are recommended for use as part of combination regimens that usually include 2 NRTIs and/or NtRTIs plus either an NNRTI or 1 or more PIs. Use of single or dual NRTIs/NtRTIs alone is not recommended for treatment of HIV infection. Long-term use is associated with potential maternal and infant mitochondrial toxicity.PREFERREDLAMIVUDINE(Epivir®, 3TC)

Dose: 150 mg po bid or 300 mg po qdFood requirements: Take without regard to meals.Available as:• Tabs: 150 mg; 300 mg• Oral sol: 10 mg/mL• Combivir: ZDV 300 mg/3TC 150 mg 

(1 tab po bid)

• Trizivir: ZDV 300 mg/3TC 150 mg/ABC 

300 mg (1 tab po bid)

• Epzicom: 3TC 300 mg/ABC 600 mg 

(1 tab po qd)

Generally very well toleratedOccasional headache, nausea, diarrhea, abdominal pain, and insomniaLactic acidosis/hepatic steatosis not generally associated with 3TCSevere acute exacerbation of hepatitis may occur in HBV-coinfected patients who d/c 3TC

Placental transfer: HighPK: Not significantly altered in pregnancy; use standard doses

Because of extensive experience with 3TC in pregnancy in combination with ZDV, 3TC + ZDV is a recommended dual NRTI/NtRTI backbone for pregnant womenActive against HBVResistance profile is identical to FTCNo evidence of human teratogenicity

ZIDOVUDINE(Retrovir®, AZT, 

ZDV)

Dose: 300 mg po bid or 200 mg po tidFood requirements: Take without regard to meals.Intrapartum: 2 mg/kg IV for first hour then 1 mg/kg IV until birthAvailable as:• Caps: 100 mg• Tabs: 300 mg• IV sol: 10 mg/mL• Oral sol: 10 mg/mL

• Combivir: ZDV 300 mg/3TC 150 mg 

(1 tab po bid)

• Trizivir: ZDV 300 mg/3TC 150 mg/ABC 

300 mg (1 tab po bid)

GI intolerance, malaise; headache (in 5%–10%); bone marrow suppression (anemia and neutropenia), myopathy/myalgia; transaminase elevation; fingernail discolorationRare cases of lactic acidosis and severe hepatomegaly with steatosis have been reported

Placental transfer: HighPK: Not significantly altered in pregnancy; use standard doses

Because of extensive experience with ZDV in pregnancy in combination with 3TC, ZDV + 3TC is a recommended dual NRTI/NtRTI backbone for pregnant womenZDV should not be included in prenatal regimen if there is severe toxicity, d4T use, documented resistance, or if already on effective and well-tolerated regimen that does not include ZDVNo evidence of human teratogenicityShort-term safety for mother and infant has been demonstrated

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

PREFERRED

ABACAVIR(Ziagen®, ABC)

Dose: 300 mg po bid or 600 mg po qdFood requirements: Take without regard to mealsAvailable as:• Tabs: 300 mg• Oral sol: 20 mg/mL• Trizivir: ZDV 300 mg/3TC 150 mg/ ABC 

300 mg (1 tab po bid)

• Epzicom: 3TC 300 mg/ABC 600 mg 

(1 tab po qd)

Hypersensitivity reaction: fever, rash, fatigue, malaise, GI symptoms, and arthralgias~4% before HLA B5701 testing in nonpregnant patients (rate in pregnancy unknown)Deaths reported upon rechallenge

Placental transfer: HighPK: Not significantly altered in pregnancy; use standard dose

Must screen for HLA-B5701 before starting ABC and results documented as negative before initiating ABC. Mandatory and permanent d/c with hypersensitivity reactionPatients should be educated regarding symptoms of hypersensitivity reactionNo evidence of human teratogenicity

EMTRICITABINE(Emtriva®, FTC)

Dose: 200 mg po qd or240 mg (24 mL) oral solution once dailyFood requirements: Take without regard to mealsAvailable as:• Caps: 200 mg hard gel• Oral sol: 10mg/mL• Truvada: FTC 200 mg/ TDF 300 mg 

(1 tab po qd)

• Atripla: FTC 200 mg/EFV 600 mg/TDF 

300 mg (1 tab po hs; take on empty stomach to reduce side effects)

Generally well toleratedOccasional headache, diarrhea, nausea, rash; hyperpigmentation/skin discolorationLactic acidosis/hepatic steatosis not generally associated with FTCSevere acute exacerbation of hepatitis may occur in HBV-coinfected patients who d/c FTC

Placental transfer: HighPK: Slightly lower concentrations in 3rd trimester compared with postpartum; no clear need to increase dose

Active against HBVResistance profile is identical to 3TCNo evidence of human teratogenicity

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

TENOFOVIR DF(Viread®, TDF)

Dose: 300 mg po qdFood requirements: Take without regard to mealsAvailable as:• Tabs: 300 mg• Truvada: TDF 300 mg/FTC 200 mg 

(1 tab po qd)

• Atripla: FTC 200 mg/EFV 600 mg/TDF 

300 mg (1 tab po hs; take on empty stomach to reduce side effects)

Generally well toleratedHeadache, diarrhea, nausea and vomiting reported; renal insufficiency, Fanconi’s syndrome; potential decrease in bone mineral densityLactic acidosis with hepatic steatosis not generally associated with TDFSevere acute exacerbation of hepatitis may occur in HBV–co-infected patients who d/c TDF

Placental transfer: HighPK: Lower AUC in the 3rd trimester compared with postpartum, but adequate trough levels

Considered a preferred NtRTI in combination with 3TC or FTC in women with chronic HBV infection; monitor renal function. Possible HBV flare if drug is d/c’ed postpartum.No evidence of human teratogenicityClinical studies in humans (particularly children) show bone demineralization with chronic use. Recent study found no difference in growth patterns, bone health or markers of bone metabolism in infants with and without in utero TDF exposure (Antivir Ther 2011;16:1259).

NOT RECOMMENDEDDIDANOSINE(Videx® EC, 

generic didanosine enteric coated (EC), ddI)

Dose:Wt ≥ 60 kg: 400 mg po qd; with TDF, 250 mg po qdWt <60 kg: 250 mg po qd; with TDF, 200 mg po qdPreferred dosing with oral solution is bid (i.e., total daily dose divided into 2 doses)Food requirements: Take 1/2 h before or 2 h after meals

Available as:• Caps (enteric coated): 125 mg, 200 mg, 

250 mg, or 400 mg

• Oral sol: 10 mg/mL

GI intolerance (diarrhea, mouth sores); peripheral neuropathy (in 5%–12% of patients); pancreatitis (in 1%–9% of patients with 6% of cases fatal); transaminase elevation; rare cases of lactic acidosis and severe hepatomegaly with steatosis; noncirrhotic portal hypertension resulting in esophageal variceal bleed, liver failure, and death have been reported; optic neuritis

Placental transfer:ModeratePK: Not significantly altered in pregnancy; use standard dose

Not recommended due to toxicityCases of lactic acidosis, some fatal, have been reported in pregnant women receiving ddI and d4T together.In the Antiretroviral Pregnancy Registry, an increased rate of birth defects with ddI compared with general population was noted after both 1st trimester (4.6%) and later exposure (4.3%). No specific pattern of defects was noted and clinical relevance is uncertain.

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

STAVUDINE(Zerit®, d4T)

Dose:Wt ≥ 60 kg: 40 mg po bidWt <60 kg: 30 mg po bidWHO recommends 30 mg po bid for all patientsFood requirements: Take without regard to mealsAvailable as:• Caps: 15 mg, 20 mg, 30 mg, 40 mg• Oral sol: 1mg/mL

Peripheral neuropathy (in 5%–15% of patients); transaminase elevation (in 8% of patients); rare cases of lactic acidosis and severe hepatomegaly with steatosis; lipoatrophy; pancreatitis; rare cases of rapidly progressive ascending neuromuscular weakness

Placental transfer: HighPK: Not significantly altered in pregnancy; use standard doses

Not recommended due to toxicityCases of lactic acidosis, some fatal, have been reported in pregnant women receiving combination of d4T and ddI as component of ARV therapy.Due to antagonism, ZDV and d4T should never be used together as a part of a combination ARV regimenNo evidence of human teratogenicity

NNRTIs: Non-nucleoside reverse transcriptase inhibitors are recommended for use in combination regimens that include 2 NRTI/NtRTI drugs. Hypersensitivity reactions, including hepatic toxicity and rash, are more common in women; unclear if risk is increased in pregnancy.

PREFERREDEFAVIRENZ(Sustiva®, EFV)

May be initiated after first 8 wks of pregnancy.

Dose: 600 mg po qhsFood requirements: Take on empty stomach to decrease side effectsAvailable as:• Caps: 50 mg, 200 mg• Tabs: 600 mg• Atripla: EFV 600 mg/FTC 200 mg/TDF 

300 mg (1 tab po hs; take on empty stomach to reduce side effects)

Morbilliform rash in 15%–27% of patients, with 1%–2% requiring d/c; 1 case of Stevens-Johnson syndrome reported; CNS effects (confusion, depersonalization, abnormal dreams) seen in up to 52% of patients (generally resolves in 2–4 wk); transaminase elevation in 2%–3% of patients, hyperlipidemia

Placental transfer:ModeratePK: AUC decreased during the 3rd trimester compared with postpartum, but generally exceeded target exposure; no change in dose needed

Significant malformations (anencephaly, anophthalmia, cleft palate) observed in 3 (15%) of 20 infants born to cynomolgus monkeys receiving EFV during 1st trimester at a dose that produced plasma levels comparable to systemic human therapeutic exposure. Human retrospective reports and 1 prospective case report of NTDs with 1st-trimester exposure and 1 prospective case of anophthalmia with facial clefts. However, meta-analysis of >1300 1st-trimester EFV exposures found no increased risk of birth defects and only 1 NTD (incidence 0.07%) (AIDS2011;25:2301). More data are needed to conclusively determine association (or lack of) between EFV and NTDs.

EFV should be avoided during 1st trimester whenever possible. However, EFV should be continued in women presenting in 1st-trimester on EFV-containing regimen and with maximal VL suppression.

After 1st-trimester, EFV may be considered if best choice compared with alternativesWomen of childbearing age trying to conceive or not using effective contraception should not use EFV unless other effective and acceptable regimens are not available

Recommend effective contraception if EFV is to be 

continued or initiated postpartum. Because EFV may decrease hormonal contraceptive efficacy, a reliable method of contraception (e.g., barrier) should be used in 

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

ALTERNATIVE

NEVIRAPINE(Viramune®, NVP)

Dose: 200 mg po qd for 14 d, then 200 mg po bidNote: If mild to moderate rash develops without constitutional symptoms, continue lead-in dosing until rash resolves, but no longer than 28 d totalFood requirements: Take without regard to mealsAvailable as:• Tabs: 200 mg• Oral suspension: 50 mg/5mL

Rash in 17% of patients (7% d/c’ed due to rash; many patients require hospitalization)Stevens-Johnson syndrome reported; transaminase elevation; severe hepatitis; fever; nausea; headacheWomen may be at increased risk of rash and liver toxicity, especially with CD4+ cell count >250/mm3 (AIDS

2002;16(11):1566; Clin Infect Dis 2001;32(1):124; J Acquir Immune Defic Syndr 2003;34 suppl 1:S21) or with baseline elevated liver enzymes (HIV Med 2010;11(10):650); unclear if pregnancy increases risk. This toxicity not reported in women receiving single-dose NVP for prophylaxis of perinatal transmission.

Placental transfer: HighPK: Not significantly altered in pregnancy; use standard doses.

Initiate NVP in pregnant women with CD4+ cell counts >250/mm3 only if benefit clearly outweighs risk, 

because of increased risk of potentially life-threatening hepatotoxicity in women with high CD4+ cell counts. Elevated transaminase levels at baseline also may increase the risk of NVP toxicity.Women who enter pregnancy on NVP regimens and are tolerating them well may continue therapy, regardless of CD4+ cell countMonitor LFTs q 2 wk x 1 mo, then q 1 mo x 4 mo, then q 1–3 moRepeat lead-in dosing period if therapy d/c’ed for >7 dNo evidence of human teratogenicity

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

INSUFFICIENT DATA TO RECOMMEND USE

RILPIVIRINE(Endurant, RPV)

Dose: 25 mg po qdFood requirements: Take with a mealAvailable as:• Tabs: 25 mg• Complera (RPV 25 mg/TDF 300 mg/FTC 

200 mg) 1 tab po qd with meal

Rash; depression, insomnia, headache

Placental transfer:UnknownPK: No pharmacokinetic studies in human pregnancy

Limited experience in human pregnancy. Safety and pharmacokinetic data in pregnancy are insufficient to recommend use during pregnancy.RPV not recommended with pretreatment HIV RNA >100,000 c/ml or CD4+ cell count <200 cells/microliter. Do not use with proton pump inhibitor.

NOT RECOMMENDEDETRAVIRINE(Intelence, ETR)

Dose: 200 mg po bidFood requirements: Take with foodAvailable as:• Tabs: 100 mg, 200 mg

Rash in up to 17%, severe in 1.3% of patients; generally occurs in first 2 wk and resolves within 1–2 wk on continued therapy, but 2% required ETR d/c

Stevens-Johnson syndrome 

reportedHypersensitivity reactions have been reported (rash; constitutional symptoms; and organ dysfunction, including liver failure)

Placental transfer:UnknownPK: Limited data in pregnancy suggests no change in dose needed (HIV Med 2011;12(4):257)

Not recommended in naïve adults as limited data. Limited experience in pregnancy

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

PIs: Protease inhibitors are recommended for use in combination regimens with 2 NRTI/NtRTI drugs. Hyperglycemia, new onset or exacerbation of diabetes mellitus, and diabetic ketoacidosis have been reported with PI use; unclear if pregnancy increases risk. Conflicting data regarding preterm delivery in women receiving PIs.PREFERREDATAZANAVIR(Reyataz®, ATV)

Dose: (ATV 300 mg po + RTV 100 mg po) qd2nd and 3rd trimesters: Some experts recommend increased dose (ATV 400 mg + RTV 100 mg po qd) in all pregnant women in the 2nd and 3rd trimestersNote: Increased dose (ATV 400 mg po + RTV 100 mg po) qd is recommended in the following situations:• With TDF or H2-receptor antagonist in 

ARV-experienced pregnant patients

• With EFV in ARV-naïve patientsConcurrent use of ATV with EFV in ARVexperienced patients is not recommended due to decreased ATV levelsFood requirements: Take with foodAvailable as:• Caps: 100 mg, 150 mg, 200 mg, 300 mg

Reversible benign hyperbilirubinemia (grade 3–4 occurring in 35%–47% of patients), jaundice, scleral icterusPR interval prolongation, 1st-degree AV block reportedNausea, vomiting, abdominal pain (generally better tolerated compared with LPV/r); skin rash (20%); headache; serum transaminase elevationClass adverse events such as hyperlipidemia, fat redistribution and hyperglycemiaATV alone has less impact on serum lipids, but elevated lipids can be a problem with RTV boosting

Placental transfer: LowPK: With standard ATV/r dosing, lower ATV concentrations during pregnancy as compared to nonpregnant adults (J Acquir Immune Defic Syndr2011;56(5):412; AIDS2007;21(18):2409). Use of an increased dose during 2nd and 3rd trimesters resulted in plasma concentrations equivalent to those in nonpregnant adults on standard dosing.ATV concentrations further reduced ~25% with concomitant TDF use (J Acquir Immune Defic Syndr2011;56(5):412; AIDS2007;21(18):2409)

Must be combined with low-dose RTV boostingTheoretical concern of increased indirect bilirubin exacerbating physiologic hyperbilirubinemia in neonates not observed in clinical trials to date (J Acquir Immune Defic Syndr 2011;56(5):412; AIDS 2007;21(18):2409)No evidence of human teratogenicity

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

LOPINAVIR/RITONAVIR(Kaletra®, LPV/r)

Dose: LPV 400 mg /r 100 mg (2 tabs or 5 mL) po bid2nd and 3rd trimesters: PK studies suggest dose should be increased to LPV 600 mg/r 150 mg po bid, especially in PI-experienced patientsIf standard dosing is used, monitor virologic response and LPV drug levels, if availableNote: Once-daily dosing (LPV 800 mg/r 200 mg) is not recommended during pregnancy because no data address whether drug levels are adequate with such administrationDose adjustment required if co-administered with NVP or EFV: LPV500 mg/r 125 mg po bidFood requirements: Tabs: Take without regard to foodOral sol: Take with foodAvailable as:• Tabs: (LPV 200 mg + RTV 50 mg) or 

(LPV 100 mg + RTV 25 mg)

• Oral solution: Each 5 mL contains 

(LPV 400 mg + RTV 100 mg)

Oral solution contains 42% alcohol and therefore may not be optimal for use in pregnancy

Generally well tolerated, good short-term safety profileDiarrhea in 13.8%–23.8% of patients; nausea, vomiting, abdominal pain, asthenia, headache, and rash reportedSerum transaminase elevationClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: LowPK: AUC decreased in 2nd and 3rd trimesters with standard dosing (AIDS2010;24(14):2193; AIDS2006;20(15):1931; HIV Med 2011;12(3):166). AUC with dose of LPV/r 600 mg/150 mg bid in 3rd trimester resulted in AUC similar to nonpregnant adults taking LPV/r 400 mg/100 mg bid (J Acquir Immune Defic Syndr2010;54(4):381).

No evidence of human teratogenicity. Short-termsafety demonstrated in Phase I/II studies.

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

ALTERNATIVE

DARUNAVIR(Prezista®, DRV)

Dose: Must be combined with low-dose RTV boosting:• ARV naïve: DRV 800 mg po + RTV 

100 mg po qd

• ARV experienced with no DRV resistance 

mutations: (DRV 800 mg po + RTV 100 mg po) qd

• ARV experienced and any DRV resistance 

mutations: (DRV 600 mg po + RTV 100 mg po) bid

Some experts recommend use of only bid dosing (DRV 600 mg po + RTV 100 mg po) during pregnancyFood requirements: Take with foodAvailable as:• Tabs: 75 mg, 150 mg, 400 mg, 600 mg

GI intolerance (20%); diarrhea, but less common than with LPV/r; headache (15%); rash (7%); contains a sulfa moietyStevens-Johnson syndrome and erythema multiforme have been reported; serum transaminase elevation and hepatitisClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: Minimal to lowPK: In the 3rd trimester and postpartum, decreased DRV levels, especially with qd dosing

Must be combined with low-dose RTV boostingUse with caution or avoid in patients with sulfa allergyLimited experience in human pregnancy

SAQUINAVIR(Invirase®, SQV)

Dose: (SQV 1000 mg po + RTV 100 mg po) bidUnboosted SQV is not recommended in pregnancyFood requirements: Take with meals or within 2 h after a mealAvailable as:• Caps (hard gel): 200 mg• Tabs: 500 mg

GI intolerance: nausea, diarrhea, abdominal pain; transaminase elevation; PR interval prolongation; QT interval prolongationClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: MinimalPK: Limited data on SQVHGC and 500 mg tablet suggest that (SQV 1000 mg + RTV 100 mg) bid achieves adequate drug levels in pregnancy

Must be combined with low-dose RTV boostingWell tolerated; short-term safety demonstrated for mother and infant for SQV in combination with lowdose RTVBaseline EKG recommended before starting because of potential PR and/or QT interval prolongations. Drug is contraindicated in patients with pre-existing conductionsystem disease.Insufficient data to assess for teratogenicity in humans

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

NOT RECOMMENDED

INDINAVIR(Crixivan®, IDV)

Dose: (IDV 800 mg po + RTV 100 mg-200 mg po) bidUnboosted IDV is not recommended in pregnancyMeals: Take without regard to mealsAvailable as:• Caps: 100 mg, 200 mg, 400 mg

Nephrolithiasis +/- hematuria in 5%–15% of patients; indirect hyperbilirubinemia (≥2.5 mg/dL in 10–15% of patients); transaminase elevationClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: MinimalPK: Significantly lower levels with standard dosing of IDV alone during pregnancy compared with postpartum. (Antimicrob Agents Chemother2007;51(2):783; AIDS2000;14(8):1061)With (IDV 400 mg + RTV 100 mg po) bid, 82% of women met target trough level (Antimicrob Agents Chemother2008;52(4):1542)

Because of 2x daily dosing, pill burden, and potential for renal stones and hyperbilirubinemia, IDV is not recommended in pregnancy.No evidence of human teratogenicity

NELFINAVIR(Viracept®, NFV)

Dose: 1250 mg po bid (750 mg po tid not recommended in pregnancy)Food requirements: Take with fatty mealAvailable as:• Tabs: 250 mg, 625 mg• Oral powder: 50 mg/g

Generally well toleratedDiarrhea; serum transaminase elevationClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: Minimal to lowPK: Adequate drug levels with 1250 mg po bid during 1st and 2nd trimester, but higher variability and lower concentrations observed during 3rd trimester compared with postpartum. NFV 1250 mg po bid was associated with lower blood levels in the 3rd trimester than in the 2nd trimester (Br J Clin Pharmacol2006;62(3):309; HIV Med2008;9(10):875).

Not recommended due to lower rate of viral suppression with NFV.In Antiretroviral Pregnancy Registry, a small increase in overall birth defect rates was noted. No specific pattern of defects was noted and clinical relevance is uncertain. Good short-term safety profile for mothers and infants.

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

NOT RECOMMENDED

RITONAVIR(Norvir®, RTV)

When used as lowdose booster with other PIs

Dose: RTV is used at low doses (i.e., 100–200 mg qd or bid) with other PIs as a pharmacologic enhancer or booster (refer to other PIs for specific dosing recommendations)Food requirements: Tabs: Take with foodCaps: Take with food if possible (may improve tolerability)Available as:• Caps: 100 mg• Tabs: 100 mg• Oral sol: 80 mg/mL (contains 43% alcohol 

and therefore may not be optimal for use in pregnancy)

GI intolerance: nausea, vomiting, diarrhea; abdominal painDose-dependent taste perversion; asthenia; circumoral and peripheral paresthesias; pancreatitis; transaminase elevationClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: MinimalPK: Lower drug concentrations during pregnancy compared with postpartum

Should be used only in combination with second PI as low-dose RTV “boost” because of low drug levels in pregnant women when used as a sole PI and poor tolerance when given at full doseRTV as a single PI is not recommended because of inferior efficacy and increased toxicityLimited experience at full dose in human pregnancyNo evidence of human teratogenicity

TIPRANAVIR(Aptivus®, TPV)

Dose: Must be combined with low-dose RTV boosting:(TPV 500 mg po + RTV 200 mg po) bidFood requirements: When taken with RTV tablets, take with meals; with RTV caps or sol, take without regard to mealsAvailable as:• Caps: 250 mg• Oral sol: 100 mg/mL

GI intoleranceLFTs elevation (17.5%) more common with TPV; severe hepatitisRash (8-14%); contains a sulfa moietyRare cases of intracranial hemorrhageClass adverse events such as hyperlipidemia, fat redistribution and hyperglycemia

Placental transfer:Moderate, based on very limited dataPK: Limited studies in human pregnancy

Not recommended in naïve adults and increased toxicity with higher ritonavir doseLimited experience in human pregnancyMust be combined with low-dose RTV boostingUse with caution or avoid in patients with sulfa allergyInsufficient data to assess for teratogenicity in humans

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

INSUFFICIENT DATA TO RECOMMEND USE

FOSAMPRENAVIR

(Lexiva®, FPV)

Dose:• ARV naïve: (FPV 1400 mg po + RTV 

100–200 mg po) qd

• or (FPV 700 mg po + RTV 100 mg po) bid• or FPV 1400 mg po bidARV experienced: (once daily dosing NOT recommended):• (FPV 700 mg po + RTV 100 mg po) bid• With EFV: (FPV 700 mg po + RTV 100 

mg po) bid

• or (FPV 1400 mg po + RTV 300 mg 

po) qd

Food requirements:Tabs: Take with meals when RTV-boostedOral suspension: Take without foodAvailable as:• Tabs: 700 mg• Oral suspension: 50 mg/mL

GI intolerance most common: nausea, vomiting, diarrhea; headache; rash (in 19% of patients) (contains a sulfa moiety), usually mild-moderate but Stevens-Johnson syndrome reported; serum transaminase elevationClass adverse events such as hyperlipidemia, fat redistribution, and hyperglycemia

Placental transfer: LowPK: With RTV boosting, AUC reduced in 3rd trimester; however, exposure is greater in 3rd trimester with boosting than in nonpregnant adults without boosting, and trough concentrations in 3rd trimester are adequate for patients without PI resistance mutations

Limited experience in human pregnancyRecommended to be given with low-dose RTV boostingUse with caution or avoid in patients with sulfa allergyInsufficient data to assess for teratogenicity in humans

Integrase InhibitorALTERNATIVERALTEGRAVIR(Isentress®, RAL)

Dose: RAL 400 mg po bid (with rifampin: 800 mg po bid)Food requirements: Take without regard to mealsAvailable as:• Tabs: 400 mg

Generally well tolerated with adverse effect rates comparable to placeboNausea, headache, diarrhea, pyrexiaReports of myopathy and rhabdomyolysisReports of CNS side effects (dizziness, ataxia, depression)

Placental transfer: Variable but highPK: Extensive variability in 3rd trimester, but RAL exposure not consistently altered compared with postpartum/historical data. Standard dosing recommended.

May be used when drug interactions with PI regimens a concernLimited experience in human pregnancyInsufficient data to assess for teratogenicity in humans

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

INSUFFICIENT DATA TO RECOMMEND USE

ELVITEGRAVIR (EVG)—currently only availabe as a co-formulation with Cobicistat (COBI/ TDF/FTC) Stribild

Dose: (EVG 150 mg + COBI 150 mg + 

TDF 300 mg + FTC 200 mg) po qd with food

GI intolerance (nausea, diarrhea)New onset or worsening renal impairmentPotential decrease in bone mineral densitySevere acute exacerbation of hepatitis may occur in HBV-coinfected patients who discontinue FTC and TDF

Placental transfer: No informationPK: No data in human pregnancy

No experience in human pregnancy

Entry InhibitorsNOT RECOMMENDEDENFUVIRTIDE(Fuzeon®, T-20)

Dose: T-20 90 mg (1 mL) subcut bid into upper arm, anterior thigh, or abdomen, with each injection given at a site different from the preceding injectionAvailable form: Single-use vial containing 108 mg of T-20 (as powder) to be reconstituted with 1.1 mL of sterile water for injection, with delivery of approx. 90 mg/mL

Local site reaction (grade 3 or 4) including pain (9%), erythema (32%), pruritus (4%), induration (57%), and nodules or cysts (26%) (with 3% requiring d/c)Bacterial pneumonia (reported in 4.68 events vs. 0.61 events per 100 pt-y)Hypersensitivity reaction (<1%); symptoms may include rash, fever, nausea, vomiting, chills, hypotension, elevated transaminases; may recur on rechallenge

Placental transfer: None, but limited dataPK: Limited data in human pregnancy

Not recommended due to lack of data in ART-naïve adultsMinimal data in human pregnancyInsufficient data to assess for teratogenicity in humansRequires twice daily injections

continued

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Table 8-7

Antiretroviral Drugs in Pregnancy and Recommendations for Antiretroviral Naïve WomenDrug Name Dosing and Available Formulations Adverse Effects Placental Transfer and 

PK in Pregnancy

Notes Regarding Use in Pregnancy

INSUFFICIENT DATA TO RECOMMEND USE

MARAVIROC(Selzentry®, MVC)

Dose:

• MVC 150 mg po bid when given with strong 

CYP3A inhibitors, with or without CYP3A 

inducers, including PIs (except TPV/r)

• MVC 300 mg po bid when given with NRTIs, 

NVP, RAL, T-20, TPV/r, and other drugs that are not strong CYP3A inhibitors or inducers

• MVC 600 mg po bid when given with 

CYP3A inducers, including EFV, ETR (without a CYP3A inhibitor)

Food requirements: Take without regard to mealsAvailable formulation:• Tabs: 150 mg, 300 mg

Generally well toleratedAbdominal pain; cough; upper respiratory tract infections; musculoskeletal symptoms; pyrexia; rash; dizziness, orthostatic hypotension (especially with chronic renal insufficiency)Rare cases of hepatotoxicity

Placental transfer:UnknownPK: No data in human pregnancy

Limited experience in human pregnancyInsufficient data to assess for teratogenicity in humans

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixAdapted from: Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

continued

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For ARV-naïve pregnant women, preferred or alternative regimens include one 

of the preferred or alternative PIs, NNRTIs or integrase inhibitors, as noted in 

Table 8-7, combined with a 2 NRTI backbone. This backbone may be ZDV/3TC, 

ABC/3TC or TDF/FTC. 3TC and FTC can substitute for each other. TDF/FTC and 

ABC/3TC may be preferred because of once daily co-formulations and less 

frequent toxicity than ZDV-containing regimens, but there is less experience with 

use of these regimens in pregnancy. ABC should NOT be used in patients who 

test positive for HLA-B*5701. Drugs listed in the Do Not Recommend category 

are placed in that category either because of toxicity or lower rate or viral 

suppression, or because they are not currently recommended in naïve adults 

and adolescents due to limited data. The latter group may eventually move to 

a different category as more data becomes available.

Special Considerations

Pharmacokinetics: Physiologic changes that occur during pregnancy may affect 

the kinetics of drug absorption, distribution, biotransformation, and elimination, 

thereby also affecting requirements for drug dosing and potentially altering 

a pregnant woman’s susceptibility to drug toxicity (Clin Pharmacokinet

2004;43(15):1071; Br J Clin Pharmacol 2008;66(2):179). In general, the 

pharmacokinetics of NRTI and NNRTI drugs are similar in women who are and 

are not pregnant; protease inhibitor (PI) pharmacokinetics are more variable, 

particularly in later pregnancy. The need for a dose adjustment depends 

on the PI, the patient’s treatment experience, and the use of interacting 

concomitant medications (Reyataz [package insert]. Princeton, NJ: BristolMyers Squibb; 2011. http//www packageinserts.bms.com/pi/pi_reyataz.

pdf. Accessed 7/11/2012; AIDS 2006;20(15):1931; Br J Clin Pharmacol

2006;62(3):309; Br J Clin Pharmacol 2006;62(3):309; J Acquir Immune Defic 

Syndr 2008;49(5):485; J Antimicrob Chemother 2009;63(6):1223; J Acquir 

Immune Defic Syndr 2010;54(4):381).

Gastrointestinal upset and/or hyperemesis: ARV drugs that cause 

gastrointestinal upset may not be well tolerated in early pregnancy, when 

morning sickness is common, and may increase risk for nonadherence or 

inadequate absorption. Some pregnant women also develop hyperemesis in 

early pregnancy, though there is no evidence this is increased in the setting 

of HIV. If antiemetics are not effective, consideration should be given to 

temporary discontinuation of all ARVs, in which case, all drugs should be 

stopped simultaneously and restarted simultaneously when nausea and 

vomiting have resolved or been effectively treated.

Teratogenicity: The potential harm to the fetus from maternal intake of a 

specific drug depends on a number of factors: the drug itself, dose, gestational 

age at exposure, duration of exposure, interaction with other agents to which 

the fetus is exposed, and, to an unknown extent, the genetic makeup of the 

mother and fetus. Of the currently FDA-approved ARV drugs available in 

the United States, only EFV is considered to have significant teratogenic 

potential. Primate studies have demonstrated an increase in significant 

malformations (anencephaly, anophthalmia/microophthalmia, cleft palate) 

at doses similar to human therapeutic exposures, and both retrospective and 

prospective studies have reported CNS defects in human infants exposed to 

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EFV in utero. The magnitude of the risk is not known, however, and may be 

low. A recent systematic review and meta-analysis of data from 21 studies 

reporting on first-trimester exposures did not indicate an increased risk of 

birth defects among infants born to women taking EFV during the first trimester 

compared with those taking other ARVs during the first trimester (AIDS

2011;25(18):2301); one neural tube defect occurred among 1,437 live births 

(incidence 0.07%). No visible anomalies were found among 147 infants in a 

West African cohort born after first-trimester use of EFV, whereas an analysis 

of the PACTG219 database found a significantly increased risk of birth 

defects (including one neural tube defect) among 5 of 32 infants exposed to 

EFV in the first trimester (Pediatr Infect Dis J 2010;29(8):721; J Acquir Immune 

Defic Syndr 2011;56(2):183).

EFV has been classified as an FDA Pregnancy Category D drug. Because of the 

potential for teratogenicity, women who are taking EFV should avoid pregnancy 

and use of EFV should whenever possible be avoided during the first trimester, 

which is the primary period of fetal organogenesis; however, EFV can be 

continued in women who present for care in the first trimester on EFV-containing 

regimens that are effective in suppressing VL. This is because the risk of neural 

tube defects is restricted to the first 5-6 weeks of pregnancy (and pregnancy 

is rarely recognized prior to this) and unnecessary ARV drug changes during 

pregnancy may be associated with a loss of virologic control and may thus 

increase the risk of transmission to the infant (HIV Clin Trials 2010; 11:303). 

Initiation after the first trimester can be considered if, after considering other 

alternatives, EFV is the best choice for an individual woman. If EFV is to be 

continued postpartum, adequate contraception should be assured.

Adverse Pregnancy Outcomes

Preterm birth: Although currently published data show conflicting results, there 

may be a small increased risk of preterm birth in pregnant women who are 

taking PI-based combination ART or prophylaxis (AIDS 2007;21(5):607; 

AIDS 2006;20(18):2345; AIDS 2004;18(17):2337; N Engl J Med

2002;346(24):1863; J Acquir Immune Defic Syndr 2005;38(4):449). A 

variable that may confound published observational studies is the increased 

rate of preterm birth if combination ART is started before conception, as 

compared with later in pregnancy, which itself may reflect confounding by 

severity or indication (Sex Transm Infect 2009;85(2):82). When data from 

the IMPAACT P1025 observational cohort were examined by multivariable 

analysis to correct for HIV disease stage, excluding delivery initiated at 

preterm gestation due to medical or obstetrical factors, PI-based combination 

ART was no more likely than non-PI-based combination ART to be associated 

with spontaneous preterm birth (odds ratio [OR] 1.22; 95% confidence interval 

[CI], 0.70–2.12) (J Infect Dis 2010;201(7):1035). A recent combined analysis 

of three large studies, two from Europe and one from the United States, found 

that injection drug use and more advanced HIV disease were associated with 

preterm birth in all three cohorts (BJOG 2010;117(11):1399). Given the clear 

benefits of such therapy for both a woman’s health and prevention of MTCT, 

PIs should not be withheld for fear of altering pregnancy outcome.

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Hyperglycemia and/or diabetes: Although hyperglycemia and diabetes 

have been reported in individuals on PIs and pregnancy is a risk factor 

for hyperglycemia (Ann Intern Med 1997;127(10):948; AIDS Clin Care

1998;10(6):41), the majority of studies to date have not shown an 

increased risk of glucose intolerance associated with PI-based regimens 

in pregnancy (Infect Dis Obstet Gynecol 2002;10(4):187; Obstet Gynecol

2006;107(50):1115; Am J Obstet Gynecol 2007;196(4):331).

Secondary analyses of two large cohorts did not find an association with type 

of ART and gestational diabetes, except for an association of PI initiation 

before pregnancy or during the first trimester with gestational diabetes in the 

PACTG 316 cohort (Am J Obstet Gynecol 2004;190(2):506; J Acquir Immune 

Defic Syndr 2005;38(4):449). Standard glucose screening at 24–28 weeks 

of gestation should be performed in HIV infected women who are taking 

ART during pregnancy. Some experts recommend earlier glucose screening in 

women who continue PI-based therapy that was initiated prior to pregnancy 

(particularly in women of minority race/ethnicity); this approach is similar to 

the recommendations for women with risk factors for glucose intolerance, such 

as maternal obesity, advanced maternal age, and family history of type II 

diabetes mellitus (Recommendations for Use of Antiretroviral Drugs in Pregnant 

HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal 

HIV Transmission in the United States. 2012. http://www.aidsinfo.nih.gov).

Mitochondrial toxicity (maternal risk): NRTI drugs are known to induce 

mitochondrial dysfunction; risk varies by specific drug and is associated with 

long-term use. In one study, ddI and ddI-containing regimens were associated 

with the greatest degree of mitochondrial suppression (Antimicrob Agents 

Chemother 2008;52(8):2825). Clinical disorders linked to mitochondrial 

toxicity include neuropathy, myopathy, cardiomyopathy, pancreatitis, hepatic 

steatosis, and lactic acidosis. Among these disorders, symptomatic lactic acidosis 

and hepatic steatosis may occur more frequently in women (Clin Infect Dis

2007;45(2):254; Clin Infect Dis 2007;45(2):261). Typical initial symptoms 

are relatively nonspecific and include nausea, vomiting, abdominal pain, 

dyspnea, and weakness. Metabolic acidosis with elevated serum lactate and 

liver enzymes is common. Bristol-Myers Squibb has reported several maternal 

deaths due to lactic acidosis/hepatic steatosis, all in women who were taking 

a combination of d4T/ddI as part of their ARV regimen at the time of 

conception and for the duration of pregnancy (the d4T/ddI combination is no 

longer recommended for HIV infected adults, pregnant or not). Other nonfatal 

cases of lactic acidosis have been reported in pregnant women taking this 

combination (Sex Transm Infect 2002;78(1):58; AIDS 2003;17(2):272). Cases 

of lactic acidosis have also been described with exposure to other NRTIs 

(Lancet 1999;353(9156):901). It is not known if pregnancy increases the 

incidence of this syndrome; however, pregnancy itself can mimic some of the 

early symptoms of lactic acidosis/hepatic steatosis and is also associated with 

several rare but life-threatening disorders of liver metabolism (acute fatty liver 

of pregnancy, hemolysis, elevated liver enzymes and low platelets—the HELLP 

syndrome). Data suggest that a disorder of mitochondrial fatty acid oxidation 

in the mother or her fetus during late pregnancy may play a role in the 

development of these disorders, as well as ARV-related mitochondrial toxicity 

(Proc Natl Acad Sci USA 1995;92(3):841; N Engl J Med 1999;340(22):1723; 

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Semin Perinatol 1999;23(2):100; Mol Genet Metab 2000;71(1-2):182). 

Therefore, obstetric providers should be aware of lactic acidosis/hepatic 

steatosis syndrome, be alert to and educate patients about suggestive signs 

and symptoms, and consider it in their differential diagnosis when appropriate. 

If the diagnosis is suspected, then serum lactate, liver enzymes, and electrolyte 

levels should be obtained, expert consultation engaged, and all ARV drugs 

should be discontinued.

Mitochondrial toxicity (infant risk): Some studies suggest that mitochondrial 

dysfunction might develop in infants with in utero exposure to NRTI drugs (AIDS

2003;17(12):1769; Lancet 2002;359(9306):583; AIDS 2003;17(14):2053), 

generally presenting as neurologic disease, and in some cases resulting in 

death; however, results from large clinical studies from the United States and 

Europe have been reassuring (J Acquir Immune Defic Syndr 2000;25(3):261; 

J Acquir Immune Defic Syndr 2003;32(4):380). Several studies, often 

small, have reported laboratory abnormalities without clinical symptoms 

(differences in mtDNA, lactate levels, echocardiographic abnormalities, 

and hematologic parameters) among infants with perinatal ARV exposure 

compared with unexposed infants (Pediatrics 2009;124(6):e1189; J Infect 

Dis 2008;198(6):851; Environ Mol Mutagen 2007;48(3-4):201; Environ 

Mol Mutagen 2007;48(3-4):173; AIDS 2005;19(10):1071; J Infect Dis

2006;194(8):1089; J Am Coll Cardiol 2011;57:76). The clinical significance 

of these laboratory findings is unclear. Even if an association is more 

clearly demonstrated, the development of severe or fatal mitochondrial 

disease appears to be extremely rare and the benefit of reduced perinatal 

transmission is thought to clearly outweigh the risk. Mitochondrial dysfunction 

should be considered in uninfected children with perinatal ARV exposure who 

present with severe clinical findings of unknown etiology, particularly neurologic 

findings. Current recommendations call for long-term clinical follow-up for any 

child with in utero exposure to ARVs.

Hepatotoxicity and/or skin rash: Although all ARV drugs may cause liver 

toxicity, special concerns have been raised regarding the use of NVP. Several 

studies have demonstrated an increased risk of developing symptomatic, often 

rash-associated, NVP-related hepatotoxicity among women, particularly those 

with CD4+ cell counts >250/mm3 (J Acquir Immune Defic Syndr 2004;35:538; 

Clin Infect Dis 2001;32:124; J Acquir Immune Defic Syndr 2003;34:S21). 

Deaths from hepatic failure have been reported in pregnant women taking 

ARV regimens that include NVP (J Acquir Immune Defic Syndr 2004;36:772; 

HIV Med 2006;7:255). In general, in controlled clinical trials, hepatic events, 

regardless of severity, have occurred in 4.0% (range 0%–11.0%) of patients 

on NVP and severe or life-threatening rash has occurred in approximately 

2% of patients taking NVP (Viramune package insert. Ridgefield, CT: 

Boehringer Ingelheim Pharmaceuticals, Inc.; 2011. http://bidocs.boehringeringelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/

Prescribing+Information/PIs/Viramune/Viramune.pdf. Accessed 7/11/2012).

In a recent analysis of two multi-center prospective cohorts, pregnancy itself 

was a risk factor for liver enzyme elevations (RR 4.7; 95% CI; 3.4–6.5) but 

NVP use was not, regardless of pregnancy status (AIDS 2010;24(1):109). 

Nevertheless, because some of the early symptoms of hepatotoxicity are 

relatively nonspecific and can be confused with common symptoms during 

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pregnancy, care providers should be aware of potential liver toxicity with 

or without rash if NVP is used in pregnancy and should conduct frequent 

and careful monitoring of clinical symptoms and liver enzymes (i.e., ALT and 

AST), particularly during the first 18 weeks of therapy. NVP should be used 

only as a component of a combination regimen when ART is being initiated 

in women with CD4+ cell counts >250 cells/mm3 if the benefit clearly 

outweighs the risk. In patients with pre-existing liver disease, monitoring 

should be performed more frequently when initiating therapy and monthly 

thereafter (Semin Liver Dis 2003;23(2):173). Liver enzyme levels should be 

checked in all women who develop a rash while taking NVP. Patients who 

develop suggestive clinical symptoms accompanied by elevation in serum 

transaminase levels (ALT and/or AST) or who have asymptomatic but severe 

liver enzyme elevations (i.e., more than 5X the upper limit of normal) should 

stop NVP and should not take NVP in the future. Hepatic toxicity has not 

been seen in women receiving single-dose NVP during labor for prevention 

of perinatal transmission of HIV (Drug Saf 2009;32(2):147). Women who 

enter pregnancy on NVP-containing regimens and are tolerating them well 

may continue therapy, regardless of CD4+ cell count.

Anemia: Several ARVs, and ZDV in particular, may cause bone marrow 

suppression and result in anemia. Pregnant women are at increased risk for 

anemia because of increased demands on nutritional stores, including iron and 

folic acid; the addition of ARV regimens that include ZDV may exacerbate 

anemia. Nutritional counseling, along with iron and folate supplementation, 

should be provided to ensure adequate intake of other nutrients. Administration 

of ZDV is usually associated with macrocytosis. When evaluating anemia in a 

pregnant woman who is taking ZDV, the presence of macrocytosis should not 

exclude consideration and evaluation of causes of anemia usually resulting 

in microcytic or normocytic red blood cell indices; nor should the presence 

of macrocytosis result in an assumption of more typical causes of macrocytic 

anemia, such as folate or B12 deficiency. Depending on severity, anemia 

should be treated and a non-ZDV-containing regimen may be considered.

Guidelines for Antepartum Care

History and Physical Examination

The following is the key information that should be obtained from the initial 

and follow-up history and physical evaluation for the HIV infected pregnant 

woman. Certain symptoms of HIV disease, ARV toxicity, and normal or 

abnormal pregnancy may overlap, resulting in possible delays in appropriate 

diagnosis and management. (See also Chapter 4, Primary Medical Care.)

HIV History

• Date of diagnosis

• History of HIV-related symptoms, OIs, or malignancies

• CD4+ cell count nadir and current value

• Current and highest VL

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• Results of any prior drug resistance testing

• Complete ARV history, including specific drugs, side effects or toxicity, length of 

treatment, adherence, response to treatment, and reasons for any changes

• Partner’s HIV status

• Disclosure of HIV status: to whom

Pregnancy History

• Previous pregnancies and outcomes

• Pregnancy complications

• Mode(s) of delivery

• Use of ARV prophylaxis or ART in previous pregnancy(ies)

• HIV status of other children

Family History

• Relevant family history of possible heritable diseases

Signs and Symptoms of HIV/AIDS (initial and follow-up visits)

• Generalized lymphadenopathy

• Thrush

• Constitutional symptoms, such as fever (38.5°C) or diarrhea >1 mo

• Herpes zoster involving 2 episodes or >1 dermatome

• Peripheral neuropathy

• Wasting

• Dysphagia

• Dyspnea

• Persistent mucocutaneous herpetic ulcerations

• Cognitive dysfunction

Signs and Symptoms of Pregnancy-Related Complications

• Elevated blood pressure

• Significant edema

• Severe headache

• Vaginal bleeding or fluid leakage

• Intractable nausea and vomiting

• Dysuria

• Abnormal vaginal discharge

• Persistent abdominal or back pain or cramping

• Decreased fetal movement

Signs or Symptoms of ARV Toxicity

• Nausea/vomiting

• Abdominal pain

• Jaundice

• Extreme fatigue

• Skin rash

Laboratory Examination

Recommended laboratory evaluations for HIV infected pregnant women 

are listed in Table 8-8.

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Table 8-8

Recommended Laboratory Evaluations for the HIV Infected Pregnant 

Woman

Upon Entry into Prenatal Care and Ongoing

Test Frequency and Comments

HIV serology • Test at initial visit if HIV infection not previously confirmed

• Test if there is positive rapid or screening test without 

confirmatory assay 

CD4+ cell count 

and/or CD4+% • At baseline and every 3 mo during pregnancy

• Consider repeat test if significant change in clinical status 

or near milestones for therapeutic decisions (e.g., OI 

prophylaxis)

• Consider extending test interval to every 6 mo for 

patients who are adherent to therapy, with sustained viral 

suppression and stable clinical status >2–3 y

HIV RNA • At baseline

• 2–4 wk after initiating or changing ART (should see decrease by minimum of 1 log 10 copies/mL by 1 mo after 

start of potent regimen)

• Monthly until RNA levels are undetectable

• At least every 3 mo during pregnancy

• At 36 wk to determine mode of delivery

• More frequently if adherence is a concern

ARV resistance 

assay • At baseline with VL >500–1000 c/mL, whether ARV naïve 

or currently on therapy

• Repeat with virologic failure

• Genotypic testing preferred over phenotypic

CBC • At baseline

• Repeat (at least) every trimester in women on stable ARV 

regimen

• Consider more frequent testing if marrow-toxic drugs (e.g., 

ZDV) are used or with anemia

Liver enzymes • At baseline

• Repeat at least every trimester in women on stable ARV 

regimen

• More frequent monitoring with initiation of NVP or with clinical signs/symptoms of hepatotoxicity

• Repeat as indicated with abnormal results or use of other 

hepatotoxic drugs

Electrolytes, BUN, 

creatinine • At baseline

• Repeat as indicated with abnormal results or use of 

potentially nephrotoxic drugs

Urinalysis, 

calculated 

creatinine clearance

• At baseline in newly diagnosed patients and those not 

previously evaluated, in Black patients and in those with 

advanced HIV or comorbid conditions

• Consider prior to initiating regimens containing TDF or IDV

Syphilis serology • At baseline

• Repeat, as noted below, on the basis of gestational age

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Table 8-8

Recommended Laboratory Evaluations for the HIV Infected Pregnant 

Woman

Upon Entry into Prenatal Care and Ongoing

Test Frequency and Comments

Hepatitis serology:

• HBsAg

• HBcAb

• HBsAb

• HCV Ab

• HAV Ab

• Initiate HBV vaccine series if negative for HBsAg, HBcAb, 

and HBsAb

• Initiate HAV vaccination if negative HAV Ab, particularly in 

the setting of HBV or HCV Infection

• If anti-HCV+, order HCV RNA

• Consider HCV RNA with negative HCV Ab with risk factors 

for HCV or unexplained liver enzyme abnormalities, 

especially with CD4+ cell count <200/mm3

Rubella, blood type 

and Rh, antibody 

screen, urine culture, 

GC/chlamydia, Pap 

smear

• At baseline

• Repeat antibody screen, as noted below, on the basis of 

gestational age

• Repeat urine culture as needed with symptoms

• Repeat GC/chlamydia, as noted below, on the basis of gestational age; as needed with signs/symptoms of 

infection; or on the basis of risk factors

• Cytobrush can be used for Pap smear during pregnancy

PPD or interferongamma release 

assay

• Positive skin test = ≥5 mm induration

• Anergy testing not indicated and prior BCG vaccination not 

contraindication to skin testing

• Positive results: obtain CXR and other evaluation to rule out 

active TB

• Consider repeat testing if recent TB exposure

Hemoglobin 

electrophoresis, red 

blood cell indices

• Perform in women at increased risk for hemoglobinopathies

G6PD • Consider screening women with predisposing racial/ethnic 

background (e.g., Black, Middle Eastern) before receiving 

oxidant drugs (e.g., dapsone, sulfonamides)

CMV IgG • Consider baseline serology in patients at low risk for CMV 

(non-IDU)*

Toxoplasmosis IgG • Screen all patients with initial HIV diagnosis

• Repeat with CD4+ cell count <100/mm3 if not on TMP-SMZ, 

or with symptoms suggestive of toxoplasmic encephalitis

Varicella zoster 

virus IgG • Consider if no history of chicken pox or shingles

• Consider for post-exposure prophylaxis considerations

Urine toxicology 

screen • As indicated on the basis of patient history, signs/symptoms, 

and local protocols

Serum screening for 

Tay-Sachs disease • Consider screening both partners if at increased risk (i.e., 

Ashkenazi Jewish, French-Canadian, or Cajun descent)

Bacterial vaginosis 

screening • Perform if signs/symptoms of vaginitis

Ultrasound • Perform in first trimester for confirmation of gestational age

continued

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Table 8-8

Recommended Laboratory Evaluations for the HIV Infected Pregnant 

Woman

Upon Entry into Prenatal Care and Ongoing

Test Frequency and Comments

Nuchal translucency, 

PAPP-A, free or 

total beta-hCG

• Voluntary; requires counseling

• Screening for Down syndrome; abnormal result requires 

further evaluation

At 16–20 Weeks

Ultrasound • Anomaly screen

• Repeat as indicated to monitor fetal growth

Maternal serum 

alpha-fetoprotein • Voluntary; requires counseling

• Screening test for neural tube and abdominal wall defects

• Abnormal result (usually >2.5 multiple of the median) 

requires further evaluation

Quadruple screen 

(hCG, unconjugated 

estriol, MSAFP, 

Inhibin A)†

• Voluntary; requires counseling

• Noninvasive test to determine risk of neural tube and 

abdominal wall defects, Down syndrome, and trisomy 18

• Abnormal result requires further evaluation

At 24–28 weeks

CBC, syphilis serology, antibody screen

Diabetes screen • Glucose 1 h after 50 g Glucola ; 3 h oral GTT if abnormal 

(an alternative screen is a “one-step” 75 g oral GTT, 

recently endorsed for non-HIV-infected pregnant women 

by the American Diabetes Association and the International 

Association of Pregnancy Study Groups [Am J Obstet 

Gynecol 2010; 202(6):654.e1; Diabetes Care 2010; 

33(3):676]).

• Consider earlier screening in women with ongoing PI-based 

therapy initiated prior to pregnancy or other high-risk 

factors for glucose intolerance.

At 32–36 weeks

GC/chlamydia 

testing

Group B 

streptococcus 

culture – 35–37 

wk; vaginal and 

rectal

• Recommend intrapartum chemoprophylaxis with IV PCN G 

(2.5 million units q 4 h) if positive (or if GBS bacteriuria 

during current pregnancy or with previous infant with 

invasive GBS disease

• If unknown GBS status, IP prophylaxis: with delivery <37 

wk gestation, membrane rupture ≥18 h, or IP temperature 

≥100.4oF/38.0oC or positive intrapartum GBS nucleic 

acid amplification test (ACOG Practice Bulletin No. 485, 

April 2011. Available at http://www.acog.org/Resources_

And_Publications/Committee_Opinions/Committee_on_

Obstetric_Practice/Prevention_of_Early-Onset_Group_B_

Streptococcal_Disease_in_Newborns. Accessed 6/26/2012)

HIV RNA • Results may influence decisions about mode of delivery

Syphilis serology • Consider in high-risk patients or populations

continued

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Table 8-8

Recommended Laboratory Evaluations for the HIV Infected Pregnant 

Woman

Upon Entry into Prenatal Care and Ongoing

Test Frequency and Comments

Other Considerations

HLA B*5701 • Obtain prior to starting ABC

Coreceptor tropism 

assay • Obtain prior to prescribing CCR5 entry inhibitor

Serum lactate, 

electrolytes, liver 

enzymes; consider 

anion gap, CPK, 

amylase, lipase

• Signs or symptoms suggest possible lactic acidosis in setting 

of NRTI therapy, especially if long term

Fasting lipid profile • May delay until postpartum, unless baseline history of hyperlipidemia +/- treatment

• If obtained, subsequent measurements on the basis of 

history and initial results

Liver enzymes 

(ALT, AST) • With initiation of NVP (does not apply to single-dose 

prophylactic therapy in labor); q 2 wk during mo 1; monthly 

through mo 4; every 1–3 mo thereafter. More frequently in 

patients with pre-existing liver disease.

Type-specific HSV 

serology • May be useful to identify women at risk for HSV and to 

guide counseling, especially if sexual partner has HSV 

infection

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

* Seroprevalence CMV IgG in US adults is 50–60%; IDU patients ≥90%

† Accurate gestational age is essential for interpretation

Antepartum Fetal Surveillance and Testing

The general purpose of antepartum fetal surveillance and testing is to identify 

fetal abnormalities or compromise so that appropriate interventions can be 

undertaken to optimize fetal health and prevent fetal damage or death. In 

some instances, the purpose is to aid in decisions regarding continuation of the 

pregnancy versus early delivery (ACOG Practice Bulletin No. 9; Int J Gynaecol 

Obstet 2000;68(2):175; reaffirmed 2009).

continued

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Indications for antepartum fetal surveillance and testing:

• Maternal conditions that increase risk of fetal death: include but are 

not limited to the following conditions: hemoglobinopathies, chronic renal 

disease, systemic lupus erythematosus, hypertension, and diabetes

• Pregnancy-related conditions that increase risk of fetal death:

include pregnancy-induced hypertension, decreased fetal movement, 

oligohydramnios, polyhydramnios, intrauterine growth retardation, postterm pregnancy, mild to moderate isoimmunization, previous fetal death, 

and multiple gestation

• HIV considerations: Data are lacking specifically on the need for 

and use of fetal surveillance techniques in HIV infected women during 

pregnancy. HIV infection per se is not an indication for fetal testing; 

however, fetal surveillance should be performed in HIV infected women 

with comorbidities that may increase fetal risk. Furthermore, HIV infection, 

especially when more advanced or associated with substance abuse, may 

be associated with increased risk for poor fetal growth, which places the 

fetus at increased risk. Fetal surveillance may be considered for pregnant 

women on ART, particularly when the mother’s regimen contains newer 

agents with which there is little experience in pregnancy. Ultimately, the 

need for fetal surveillance should be determined case by case.

Fetal surveillance techniques include the following:

• Fetal movement assessment: Also known as kick counts; the perception 

of 10 distinct movements in a period of up to 2 hours is reassuring.

• Nonstress test (NST): A reactive or reassuring result is defined as two 

or more fetal heart rate accelerations (at least 15 beats/minute above 

baseline and lasting at least 15 seconds on a fetal monitor) within a 

20-minute period.

• Contraction stress test (CST): A negative or reassuring result is the 

absence of late or significant variable fetal heart rate decelerations 

with at least three contractions (lasting at least 40 seconds) within 

10 minutes.

• Biophysical profile: Consists of an NST combined with observations of 

fetal breathing, fetal movements, fetal tone, and amniotic fluid volume 

by real-time ultrasonography. Each component is assigned a score of 2 

(normal or present) or 0 (abnormal or absent); a composite score of 8 

or 10 is normal.

• Modified biophysical profile: Combines NST and amniotic fluid index 

(AFI), which is the sum of measurements of the deepest amniotic fluid 

pocket in each abdominal quadrant; normal AFI is >5 cm. This test 

combines a short-term indicator of fetal acid-base status (NST) and an 

indicator of long-term placental function (AFI); placental dysfunction 

often leads to poor fetal growth and oligohydramnios.

• Umbilical artery Doppler velocimetry: Evaluation of flow velocity wave 

forms in the umbilical artery, which is characterized by high-velocity 

diastolic flow in a normally developing fetus. This technique is beneficial 

only in pregnancies complicated by intrauterine growth restriction.

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Although data from randomized clinical trials are lacking, antepartum fetal 

surveillance has been consistently associated with lower rates of fetal death 

when compared with rates among untested pregnancies from the same 

institution or among historic controls with similar complicating factors. Testing 

should be initiated at 32–34 weeks’ gestation, but may be started as early 

as 26–28 weeks’ gestation in very high-risk pregnancies. When the condition 

prompting testing persists, testing should be repeated periodically (weekly 

or, in some cases, twice weekly) until delivery. Fetal reevaluation should also 

be repeated if the mother’s medical condition deteriorates significantly or if 

there is an acute decrease in fetal movement, regardless of the amount of time 

elapsed since the previous test.

NST, CST, biophysical profile, and modified biophysical profile are the most 

commonly used forms of testing; they have a negative predictive value >99%. 

They are not predictive of acute events, however, such as placental abruption 

or umbilical cord accidents. On the other hand, the positive predictive value 

of an abnormal test can be quite low and the response to an abnormal result 

should be dictated by the individual clinical situation. Any abnormal test result 

requires further evaluation or action. Management should be based on test 

results, gestational age, degree of oligohydramnios (if assessed), and maternal 

condition. Oligohydramnios should prompt evaluation for membrane rupture. 

Depending on the degree of oligohydramnios, gestational age, and maternal 

medical condition, oligohydramnios warrants either delivery or close maternal/

fetal surveillance.

Ultrasound: There are many indications for obstetric ultrasound; some of the 

more common include the following (Obstet Gynecol 2009;113(2 Pt 1):451):

• Pregnancy dating

• Evaluation of fetal growth

• Evaluation of vaginal bleeding during pregnancy

• Determination of fetal presentation

• Suspected multiple gestation

• Significant uterine size/clinical dates discrepancy

• Pelvic mass

• Suspected ectopic pregnancy

• Documentation of fetal viability and/or to rule out fetal death

• Biophysical profile for antepartum fetal surveillance

• Suspected polyhydramnios and/or oligohydramnios

• Placental localization

• Abnormal serum alpha-fetoprotein or quadruple screen

• Evaluation for fetal anomalies

• Evaluation of fetal condition in late registrants for prenatal care

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With transvaginal ultrasound, an intrauterine gestational sac can be seen 

as early as 5 weeks after the woman’s last menstrual period and fetal 

heart activity can be detected by 6 weeks. First-trimester bleeding is the 

most common indication for early ultrasound, when the major differential 

diagnoses are threatened abortion (miscarriage) and ectopic pregnancy. 

Accurate pregnancy dating is best accomplished late in the first trimester or 

in the second trimester; screening for anomalies is best performed at 16–20 

weeks’ gestation. A third-trimester (or other follow-up) ultrasound(s) should be 

considered, particularly in women with more advanced disease and/or other 

maternal pregnancy-related factors that could affect fetal growth.

Amniocentesis, chorionic villus sampling, cordocentesis: Though data are 

still somewhat limited, risk of MTCT does not appear to increase during 

amniocentesis or other invasive diagnostic procedures among women who 

are on effective combination ART. HIV infected women who have indications 

for invasive testing in pregnancy, such as abnormal ultrasound or aneuploidy 

screening, should be counseled about the potential risk of HIV transmission 

along with other risks of the procedure so they can make an informed decision 

about testing. Ideally, a woman should have an undetectable VL at the time of 

any procedure. Procedures should be performed under continuous ultrasound 

guidance and, if possible, the placenta should be avoided. Some experts 

consider chorionic villus sampling and cordocentesis too risky to offer to HIV 

infected women and recommend limiting procedures to amniocentesis (Am J 

Obstet Gynecol 2006;194(1):192).

Prevention for Positives

All HIV infected pregnant women should be encouraged to disclose their 

HIV status to their sexual partners, with assistance if needed, and HIV 

testing should be encouraged for partners. Condom use during pregnancy is 

recommended, particularly if partners are serodiscordant; recent data suggest 

that pregnancy may increase risk of female-to-male HIV transmission (AIDS

2011;25 (15):1887). However, even when both partners are HIV infected, 

condom use is encouraged to prevent both acquisition of other STIs and 

potential reinfection with another HIV strain. Women who have active substance 

abuse problems should be encouraged and assisted in accessing treatment, 

including opioid-assisted therapy if indicated. Harm reduction practices, such as 

needle exchange and not sharing injection equipment, should be discussed and 

encouraged in IDUs who are not able or not willing to stop using altogether.

Antepartum Scenarios for Antiretroviral Drug Use

(Source: Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-

Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV 

Transmission in the United States. 2012. http://www.aidsinfo.nih.gov)

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ARV naïve (no prior experience with ARVs): Current adult treatment 

guidelines are updated regularly and can be accessed online at http://

aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatmentguidelines/0/.

• HIV infected pregnant women should be prescribed standard potent 

combination ART, taking into account current information about use in 

pregnancy, including safety and risk of teratogenicity. (See Table 8-7.)

• Current adult treatment guidelines recommend ART for all HIV-infected 

individuals. The strength of this recommendation varies on the basis of 

the pretreatment CD4+ cell count (see Chapter 4 Primary Medical Care).

- CD4+ cell count ≤500 cells/mm3 (strong recommendation)

- CD4+ cell count >500/mm3 (moderate recommendation)

- ART also is recommended for HIV-infected individuals for the prevention 

of transmission of HIV (strong recommendation) and therefore should 

be recommended for women with partners who are HIV-negative or of 

unknown status, without regard to CD4+ cell count.

- Patients starting ART should be willing and able to commit to lifelong 

treatment and should understand the benefits and risks of therapy 

and the importance of adherence. The potential benefits of early 

therapy must be weighed against possible drug toxicity, cost, and the 

patient’s risk of developing viral resistance with suboptimal adherence, 

which may be more likely during the postpartum period (AIDS Care

2008;20(8):958; J Acquir Immune Defic Syndr 2008;48(4):408; Curr 

Opin Infect Dis 2012;25(1):58; J Womens Health 2010;19(10):1863; 

AIDS 2012:26:2039).

• In women who require immediate initiation of therapy for their own 

health, ART can begin in the first trimester, but use of EFV should be 

avoided in the first trimester.

• Pregnant women with CD4+ cell counts >500/mm3 should be counseled 

about current treatment recommendations, the potential risks and benefits 

of stopping and continuing with an ART regimen following delivery, and 

the need for strict adherence if the regimen is continued postpartum.

• The use of raltegravir in late pregnancy for women who are diagnosed 

late in pregnancy and have high viral loads has been suggested because 

of its ability to rapidly suppress viral load (approximately 2-log copies/

mL decrease by Week 2 of therapy). (AIDS Patient Care STDS 2012; 

26(12):717; J Antimicrob Chemother 2010;65(9):2050;. AIDS 2010; 

24(15):2416). However, this approach has only been described in 

anecdotal reports and efficacy and safety of this approach is unclear; it 

is not routinely recommended and should only be used in consultation with 

an expert.

• While it is considered suboptimal to use a non-HAART regimen (i.e., 

triple NRTIs, ZDV only) for prophylaxis alone during pregnancy, with ARV 

discontinuation after delivery, that approach may be considered in some 

limited circumstances.

• The decision to start the ARV regimen in the first trimester or delay until 

12 weeks of gestation will depend on CD4+ cell count, VL, and maternal 

conditions such as nausea and vomiting. Earlier initiation of a combination 

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ARV regimen may be more effective in reducing in utero transmission, but 

the benefit must be weighed against the potential long-term effects of 

first-trimester drug exposure.

• If possible, one or more NRTIs with high levels of placental transfer to the 

fetus should be included to provide pre-exposure prophylaxis (ZDV, 3TC, 

FTC, d4T, TDF, ABC).

• If VL is above the threshold for resistance testing (e.g., >500–1000 c/

mL), ARV drug resistance studies should be performed before therapy is 

initiated. If HIV is diagnosed late in pregnancy, the ARV regimen should 

be initiated promptly without waiting for the results of resistance testing.

• NVP may be used as a component of initial therapy for pregnant women 

with CD4+ cell counts <250/mm3; however, due to an increased risk of 

hepatic toxicity, NVP should be used as a component of ART in pregnant 

women with CD4+ cell counts >250 cells/mm3 only if the benefit clearly 

outweighs the risk.

ARV experienced (currently on ART):

• In general, a pregnant woman who is taking and tolerating an ART 

regimen that is effective in suppressing her VL should continue on the 

regimen. Discontinuation or interruption of therapy may lead to an 

increase in VL, with possible disease progression and a decline in 

immune status, and has been associated with increased risk of perinatal 

transmission (Clin Infect Dis 2009;48(9):1310).

• ARV drug resistance testing is recommended if a pregnant woman has 

detectable viremia (e.g., >500–1000 copies/mL) on therapy. Results of 

this testing can be used to select a regimen that may be more effective in 

suppressing VL to an undetectable level.

• If a woman is taking EFV and her pregnancy is recognized during the first 

trimester, EFV should be continued if there is maximal VL suppression and 

the regimen is well tolerated.

- Treatment changes during pregnancy increase the risk of incomplete 

viral suppression at the end of pregnancy (HIV Clin Trials

2010;11(6):303).

- The risk of neural tube defects is restricted to the first 5–6 weeks of 

pregnancy and pregnancy is rarely recognized prior to 4–6 weeks of 

pregnancy.

• If a pregnant woman has an undetectable VL and is taking and tolerating 

NVP, she should continue with that ARV regimen regardless of CD4+ cell 

count. Increased risk of hepatic toxicity has not been seen in pregnant 

women who are taking and have achieved immune reconstitution with 

NVP-based therapy.

Prior ART for treatment or prophylaxis:

• If a patient has taken ARVs in the past for treatment or prophylaxis, 

the care provider should obtain an accurate history of all prior ARV 

use, including tolerance; clinical, virologic, and immunologic efficacy; the 

indication for stopping therapy; and results of prior resistance testing.

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• Perform HIV ARV resistance testing prior to initiating repeat ARV 

prophylaxis or therapy if VL >500-1000 c/mL. In women who present 

late in pregnancy, treatment or prophylaxis should be initiated promptly, 

based on available history, without waiting for the results of resistance 

testing. Limited data regarding rates of resistance after pregnancylimited use of combination ARV regimens for prophylaxis, particularly 

with documented virologic suppression at the time of labor, suggest 

that PI-based regimens may be less likely than NNRTI-based regimens 

to be associated with detection of resistance mutations (Clin Infect Dis

2010;50(6):890; AIDS 2010;24(1):45; J Acquir Immune Defic Syndr

2009;51(5):522; AIDS Res Hum Retroviruses 2010;26(3):293). This 

may be related to the longer half-life of NNRTIs, resulting in functional 

monotherapy if the regimen is stopped abruptly (see Guidelines for 

Postpartum Care, p. 333, for discussion of strategies to prevent resistance 

with NNRTI regimens). No data exist to guide the choice of ARV regimens 

for women with prior experience taking ARVs as pregnancy-limited 

prophylaxis solely for prevention of MTCT.

• Data are limited on ART efficacy following the use of ARV solely for 

prevention of MTCT. Most experience is with NVP-based ART regimens 

initiated after peripartum single-dose NVP. Data suggest decreased 

virologic and clinical efficacy when regimens are started within 12–24 

months after delivery (N Engl J Med 2010;363(16):1499; PLoS 

Med 2010;7(2):e1000233; AIDS 2007;21(8):957; N Engl J Med

2007;356(2):135). Investigators recently assessed data from the French 

Perinatal Cohort on virologic suppression with PI-based ART administered 

for prevention of MTCT to women who had received ARV prophylaxis 

during a previous pregnancy; no differences were seen in rates of 

VL suppression at delivery among ARV-naïve women compared with 

those who had received previous prophylaxis or according to previous 

prophylaxis regimens (J Acquir Immune Defic Syndr 2011;57(2):126).

• If a woman is ARV-experienced and requires ART for her own health, 

her care provider should perform a thorough clinical evaluation 

(including assessment of liver, renal, and cardiovascular function) prior 

to reinitiating ART.

• Initiate a combination ARV drug regimen, with the regimen chosen on 

the basis of resistance testing and prior ART history (including efficacy 

and toxicity), avoiding EFV in the first trimester or drugs with known risk 

for the pregnant woman (e.g., combination ddI/d4T). Virologic response 

should be monitored carefully; if virologic response is inadequate, 

resistance testing should be repeated.

• Expert consultation is recommended when choosing ARVs for pregnant 

women with prior ARV experience.

Stopping ART During Pregnancy

HIV infected women taking ART who present for care during the first trimester 

should generally not discontinue or interrupt treatment during pregnancy. 

Women who present in the first trimester and are taking an EFV-containing 

regimen should not interrupt therapy but can continue on treatment if VL is 

suppressed. A recent analysis from a prospective cohort of 937 HIV infected 

mother-child pairs found that interruption of ART during pregnancy, including 

interruption in the first and third trimesters, was independently associated 

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with perinatal transmission (Clin Infect Dis 2009;48(9):1310). Furthermore, 

unnecessary ARV drug changes during pregnancy may be associated with a 

loss of virologic control and thus may increase the risk of MTCT (HIV Clin Trials

2010;11(6):303).

If an ARV regimen for therapy and/or prophylaxis is stopped abruptly for 

severe or life-threatening toxicity, severe pregnancy-induced hyperemesis 

unresponsive to anti-emetics, or other acute illnesses precluding oral intake, all 

ARVs should be stopped at the same time and reinitiated at the same time.

If an ARV regimen is being stopped electively and the patient is receiving an 

NNRTI, then one of the following options should be considered: (1) stop the 

NNRTI first and continue other ARVs for a period of time; or (2) switch from 

an NNRTI to a PI prior to interruption and continue the PI with the other ARVs 

for a period of time before electively stopping. The optimal interval between 

stopping an NNRTI and stopping other ARVs is not known, but a period of 

at least 7 days is recommended. Given the potential for prolonged (i.e., >3 

weeks) detectable EFV concentrations, some experts recommend continuing 

the other ARVs or substituting a PI plus two other agents for up to 30 days. A 

recent study of 412 women who received single-dose nevirapine and were 

randomized to receive zidovudine/lamivudine, tenofovir/emtricitabine, or 

lopinavir/ritonavir for either 7 or 21 days found an overall new nevirapine 

resistance mutation rate of 1.2% when assessed by population genotype at 2 

and 6 weeks following completion of treatment, with no difference by length 

of treatment. However, low-frequency nevirapine-resistant mutations at codons 

103, 181, and 184 detected using allele-specific PCR emerged significantly 

more often in the 7-day arms (13/74 [18%]) than in the 21-day arms (3/66 

[5%], P = .019). (Clin Infect Dis 2013;56(7):1044).

If NVP is stopped and more than 2 weeks have passed prior to restarting 

therapy, then NVP should be restarted with the 2-week dose escalation period.

Failure of Viral Suppression in Pregnancy

Women on antiretroviral (ARV) regimens who have detectable virus at any time 

during pregnancy using ultrasensitive assays should 

• be evaluated for resistant virus (if plasma HIV RNA is 

>500–1,000 copies/mL); 

• be assessed for adherence, tolerability, incorrect dosing, or 

potential problems with absorption (such as with nausea/

vomiting or lack of attention to food requirements); 

• be considered for ARV regimen modification.

Treatment modification during pregnancy has been independently associated 

with an HIV-1 RNA level >400 copies/mL in late pregnancy highlighting the 

importance of using potent and well-tolerated regimens during pregnancy to 

maximize effectiveness and minimize need to modify treatment. (HIV Clin Trials 

2010;11(6):303–311.)

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Baseline HIV RNA levels have been shown to affect the time to response; most 

patients with an adequate viral response at 24 weeks have had at least a 

1-log copies/mL HIV RNA decrease within 1–4 weeks after starting therapy. 

In a retrospective multicenter cohort of 378 pregnant women, 77.2% achieved 

HIV RNA <50 c/ml by delivery, with success of viral suppression varying by 

baseline HIV RNA level: with baseline <10,000 c/ml, gestational age at 

initiation did not affect success up to 26.3 weeks but with baseline >10,000 

c/ml, delaying initiation past 20.4 weeks significantly reduced ability for 

maximal suppression at deliver. (AIDS 2012;26(9):1095) 

A recent systematic review and meta-analysis of adherence to antiretroviral 

regimens during and after pregnancy in low-, middle- and high-income 

countries (27% of studies were from the US) found a pooled estimate of 

73.5% adherence during pregnancy (threshold defining good adherence 

to ART varied across studies from >80–100%) (AIDS 2012;26(16):2039)

Therefore, evaluation of and support for adherence during pregnancy is 

critical to achievement and maintenance of maximal viral suppression.

The addition of raltegravir in late pregnancy has been suggested for women 

who have high viral loads and/or in whom multiple drug-resistant mutations 

have resulted in incomplete suppression of viremia because of the ability of 

raltegravir to rapidly suppress viral load. In the setting of a failing regimen 

related to nonadherence and/or resistance, there are concerns that the 

addition of a single agent may further increase risk of resistance and potential 

loss of future effectiveness with raltegravir. A recent report found 10–23-

fold increase in transaminase levels following introduction of a raltegravircontaining regimen in late pregnancy, with return to normal levels after 

raltegravir discontinuation. (J Obstet Gynaecol Can 2013;35(1):68). Therefore, 

at the current time, this approach cannot be recommended.

Scheduled cesarean delivery is recommended for HIV-infected pregnant 

women who have HIV RNA levels >400 copies/mL near the time of delivery.

Special Situations

Acute infection: Preventing HIV acquisition is a subject that should be 

addressed with all pregnant and breastfeeding women. Several studies 

suggest that pregnancy may be a time of increased risk for HIV transmission 

(Lancet 2005;366(9492):1182; AIDS 2009;23(10):1255; J Clin Virol

2010;48(3):180), even when controlling for sexual risk behaviors (Lancet

2005;366(9492):1182). Primary or acute HIV infection in pregnancy or while 

a woman is breastfeeding is associated with an increased risk of perinatal HIV 

transmission and may represent a significant proportion of residual MTCT in 

the United States. This high rate of transmission is likely related to two factors: 

1) the high VL of plasma, breast milk, and the genital tract associated with 

acute infection; and 2) the difficulty of diagnosis. Because acute infection 

is easily missed, opportunities for prevention are missed as well (AIDS

2002;16(8):1119; AIDS 2010;24(4):573).

All pregnant women with acute or recent HIV infection should start combination 

ART as soon as possible to prevent MTCT, with the goal of suppressing plasma 

HIV RNA levels to below detectable levels.

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Data from the United States and Europe indicate that transmitted virus 

may be resistant to at least one ARV in 6%–16% of patients (J Infect Dis

2005;192(6):958; AIDS 2010;24(8):1203). Genotypic resistance testing 

should be performed at baseline, simultaneously with initiation of ART or 

prophylaxis, with a subsequent adjustment in ARV regimen if needed to 

optimize virologic response. Because clinically significant PI resistance is less 

common than NNRTI resistance in ARV-naïve patients, an RTV-boosted PI-based 

regimen should generally be initiated.

Healthcare providers should maintain a high level of suspicion of acute HIV 

infection in pregnant or breastfeeding women who have a compatible clinical 

syndrome (e.g., fever, lymphadenopathy, pharyngitis, skin rash, myalgias/

arthralgias) even in the absence of reported high-risk behaviors.

When acute retroviral syndrome is suspected in pregnancy or during 

breastfeeding, a plasma HIV RNA test should be obtained in conjunction with 

an HIV antibody test. A low-positive HIV RNA level (<10,000 copies/mL) may 

represent a false-positive test because values in acute infection are generally 

very high (i.e., >100,000 copies/mL) (Ann Intern Med 2001;134(1):25; AIDS

2002;16(8):1119); however, non-B HIV-1 subtypes may not amplify as well as 

subtype B, which may result in a lower HIV RNA level, even with acute infection.

If seroconversion is suspected in nursing mothers, breastfeeding should 

be interrupted until definitive confirmation of infection is obtained; if 

seroconversion is confirmed, breastfeeding should not be resumed.

Hepatitis B infection: Women with chronic HBV infection (persistent hepatitis B 

surface antigenemia for at least 6 months) and who are hepatitis A virus (HAV) 

IgG negative should receive the HAV vaccine series because of the added 

risk of acute HAV in people with chronic viral hepatitis. This vaccine can be 

given safely during pregnancy (ACOG Practice Bulletin No. 86; Obstet Gynecol

2007;110(4):94; reaffirmed 2009).

An ART regimen that includes drugs active against both HIV and HBV (i.e., TDF 

+ 3TC or FTC) is recommended for pregnant women with HIV/HBV co-infection 

to avoid reactivation of HBV and development of immune reconstitution 

inflammatory syndrome (IRIS). An IRIS-related flare of HBV activity during 

pregnancy can occur even among women with relatively high CD4+ cell counts. 

Use of ARVs that have anti-HBV activity will also reduce HBV viremia and may 

decrease the risk of failure of neonatal HBV immune globulin (HBIG) and HBV 

vaccine for prevention of perinatal transmission of HBV.

Elevation of hepatic enzymes after ART initiation may be related to HBV flare 

due to immune reconstitution with effective ARV regimens; HBV infection also 

increases hepatotoxic risk of PIs and NVP. Liver enzymes should be assessed 

2–4 weeks after initiation of ARVs and then at least every 3 months. If hepatic 

toxicity occurs, consultation with an expert in HIV and HBV co-infection is 

strongly recommended. Pregnant women with HBV/HIV co-infection should 

be counseled about signs and symptoms of liver toxicity and advised to 

avoid alcohol. If ARVs are discontinued postpartum in women with HIV/HBV 

co-infection, frequent monitoring of liver function tests for potential HBV flare is 

recommended, with prompt re-initiation of treatment for both HIV and HBV if 

a flare is suspected.

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Interferon (IFN) and peg-IFN are not recommended for use in pregnancy 

because of direct antigrowth and antiproliferative effects and should be used 

only if the potential benefit outweighs the risk (Neurology 2005;65(6):807).

All infants born to mothers who are HBsAg+ should receive hepatitis B immune 

globulin (HBIG) and should receive an initial dose of HBV vaccine within 12 

hours after birth. The second and third doses of vaccine should be administered 

at 1 and 6 months of age, respectively. This regimen is >95% effective in 

preventing HBV infection in these infants.

Hepatitis C infection: Because of an increased risk for fulminant HAV or HBV 

in patients infected with HCV, HAV vaccination is recommended for HCV 

infected women who are anti-HAV-negative; HBV vaccination is recommended 

for women who are HBV uninfected. These vaccinations may be given 

safely during pregnancy (ACOG Practice Bulletin No. 86; Obstet Gynecol

2007;110(4):94; reaffirmed 2009).

Treatment of HCV aims to eradicate infection and prevent the long-term 

complications of progressive liver disease. It generally includes combination 

therapy with pegylated interferon plus ribavirin; however, treatment with these 

agents is not recommended during pregnancy (Recommendations for Use of 

Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health 

and Interventions to Reduce Perinatal HIV Transmission in the United States. 

Updated Sept. 14, 2011; http://www.aidsinfo.nih.gov/Guidelines/HTML/3/

perinatal-guidelines/188/initial-postnatal-management-of-the-hiv-exposedneonate). Ribavirin is teratogenic at low doses in multiple animal species. Both 

women and men of childbearing potential who are receiving ribavirin should 

be counseled about the need to use effective contraception during therapy 

and for 6 months after completion. Interferons are not recommended for use 

in pregnancy because of direct antigrowth and antiproliferative effects. The 

recently FDA-approved drugs boceprevir and telaprevir should be used only 

in combination with interferon and ribavirin and therefore should not be used 

in pregnancy. Evaluation for treatment, including liver biopsy, can be delayed 

until 3 months or more after delivery to allow pregnancy-related changes in 

disease activity to resolve.

A European study of perinatal HCV transmission found that the use 

of effective combination ART was associated with a strong trend for 

reduction in HCV transmission [OR 0.26, 95% CI, 0.07–1.01] (J Infect Dis

2005;192(11):1872).Therefore, standard recommendations for ARV drug 

use during pregnancy for treatment of HIV and/or prevention of MTCT HIV 

transmission should be followed.

As with HBV infection, elevation in hepatic enzymes may occur after starting 

ARVs; this may be related to HCV flare due to immune reconstitution with 

effective ARV regimens or to greater vulnerability to hepatotoxicity with 

ARVs drugs.

Liver enzymes should be assessed 2–4 weeks following initiation of ARVs 

and then at least every 3 months. (Recommendations for Use of Antiretroviral 

Drugs in Pregnant HIV-1 Infected Women for Maternal Health and Interventions 

to Reduce Perinatal HIV Transmission in the United States). If hepatic toxicity 

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occurs, consultation with an expert in HIV and HCV co-infection is strongly 

recommended. Pregnant women with HCV/HIV co-infection should be counseled 

about signs and symptoms of liver toxicity and advised to avoid alcohol.

Internal fetal monitoring, amniocentesis, and duration of membrane rupture 

greater than 6 hours may increase risk of HCV transmission (J Infect Dis

2005;192(11):1880; Ann Hepatol 2010;9 suppl:92). Most studies that have 

included both HIV infected and uninfected pregnant women with HCV have 

found that elective CS delivery does not reduce the risk of perinatal HCV 

transmission (AIDS 2007;21(13):1811; Am J Obstet Gynecol 2008;199(3):315; 

Arch Gynecol Obstet 2011;283:255).

HIV-2 infection: HIV-2 infection is endemic in some West African countries 

and in parts of India (JAMA 1993;270(17):2083; AIDS 1989;3 suppl 

1:S89). It also occurs in countries with large numbers of immigrants from these 

regions (Bull Epidemiol Hebd 2007;46-47:386). HIV-2 is less infectious than 

HIV-1, with a 5-fold lower rate of sexual transmission and a 20–30-fold 

lower rate of vertical transmission (Lancet 1990;335(8697):1103; Lancet

1994;343(8903):943).

HIV-2 infection should be suspected if a pregnant women or her partner 

is from an endemic country and presents with the following pattern of HIV 

testing: a positive test on HIV screening assay with a repeatedly indeterminate 

HIV-1 western blot and HIV-1 RNA VL at or below the limit of detection. 

Although most commercially available HIV screening tests can detect both 

HIV-1 and HIV-2, the Bio-Rad Laboratories Multispot HIV1/2 test is the only 

FDA-approved antibody test that can distinguish between HIV-1 and HIV-2; in 

some laboratories HIV-2 supplemental tests such as HIV-2 immunoblot or HIV-2-

specific western blot are available, but these tests do not have FDA approval 

for diagnosis. One HIV-2 VL assay is now commercially available in the United 

States; it can be ordered through the University of Washington (1-800-713-

5198 or commserv@u.washington.edu).

For HIV-2+ pregnant women who require treatment for their own health (e.g., 

significant clinical disease or CD4+ cell count <500/mm3), two NRTIs and a 

boosted PI are currently recommended for treatment. On the basis of available 

safety data in pregnancy, ZDV/3TC + LPV/r, or, alternatively, TDF/FTC + LPV/r 

or TDF + 3TC + LPV/r is recommended for treatment during pregnancy.

Optimal prophylaxis regimens for HIV-2+ pregnant women (without HIV-1 

co-infection) who do not require treatment for their own health (e.g., CD4+ cell 

count >500/mm3 and no significant clinical disease) have not been defined. 

Some experts would use a boosted PI-based regimen for prophylaxis and stop 

the drugs postpartum. Other experts would use ZDV prophylaxis alone during 

pregnancy and intrapartum (Clin Infect Dis 2010;51(7):833). Some experts 

would not provide any drug prophylaxis because the risk of transmission from 

such women is very low (HIV Med 2008;9(7):452). The infant should receive 

the standard 6-week ZDV prophylactic regimen. Expert consultation is advised.

NNRTIs and ENF are not active against HIV-2 and should not be used for 

treatment or prophylaxis.

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Infants born to HIV-2+ mothers should be tested with HIV-2-specific virologic 

assays at similar time points as HIV-1 testing would be conducted. Because 

these tests are not commercially available, testing must be referred to 

academic or research laboratories. Determining loss of HIV-2 antibodies by 

age 18 months is also recommended (HIV Med 2008;9(7):452). Breastfeeding 

is not recommended for infants of HIV-2+ mothers.

Opportunistic Infections

Prophylaxis indications and recommendations for primary prophylaxis of OIs 

in pregnancy are noted in Table 8-9. Once an individual has had the listed 

infections, prophylaxis to prevent recurrence is recommended as standard of 

care. Criteria for discontinuation of secondary prophylaxis vary by infection. 

See the USPHS Guidelines for Prevention and Treatment of Opportunistic 

Infections in Adults and Adolescents (http://aidsinfo.nih.gov/Guidelines/) for 

current recommendations for treatment and secondary prophylaxis of each OI 

In pregnancy.

Table 8-9

Primary Prophylaxis for Opportunistic Infections in Pregnant 

Women*

Pathogen Indication Regimen Alternatives1 Comment

Pneumocystis 

pneumonia

Strong recommendation:

CD4+ cell 

count <200 c/

mm3 or oral 

thrush

Moderate 

recommendation:

CD4+% <14% 

or history of 

AIDS-defining 

illness

TMP-SMZ DS 

or SS 1 po qd

Dapsone

Atovaquone

Test for G6PD 

deficiency 

before 

administration 

of dapsone

Criterion 

for stopping 

primary 

prophylaxis: 

CD4+ cell 

count >200 

c/mm3 for 

>3 mo in 

response to 

ART

Toxoplasma 

gondii

Strong recommendation:

Toxoplasma 

IgG+ with 

CD4+ cell 

count <100 

c/mm3 or if 

toxoplasma 

seroconversion 

occurs

TMP-SMZ DS 

1 po qd

TMP-SMZ 

(alternate 

dosing)

Dapsone + 

pyrimethamine 

+ leucovorin

Test for G6PD 

deficiency 

before 

administration 

of dapsone

Criterion for 

stopping 

primary 

prophylaxis: 

CD4+ cell 

count >200 c/

mm3 for >3 

mo in response 

to ART

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Table 8-9

Primary Prophylaxis for Opportunistic Infections in Pregnant 

Women*

Pathogen Indication Regimen Alternatives1 Comment

Mycobacterium 

tuberculosis

Strong recommendation:

Positive 

diagnostic 

test for latent 

TB (e.g., TST 

reaction ≥ 

5 mm or (+) 

interferon 

gamma 

release assay), 

no prior 

treatment for 

active or latent 

TB and no 

evidence of 

active TB, or

Negative 

diagnostic test 

for latent TB 

but contact 

with active 

TB and no 

evidence of 

active TB

INH 300 mg 

qd or 900 

mg twice 

weekly plus 

pyridoxine 

25 mg qd for 

9 mo

Rifampin

Rifabutin

Must rule 

out active 

TB prior to 

beginning 

prophylaxis; 

for persons 

exposed to 

drug-resistant 

TB, select 

drugs with 

consultation

Mycobacterium 

avium complex 

Strong recommendation:

CD4+ cell 

count <50 c/

mm3

Azithromycin 

1200 mg po 

once weekly 

or 600 mg po 

twice weekly

Rifabutin 

(must rule out 

active TB)

Must rule out 

active MAC 

infection

Criterion 

for stopping 

primary 

prophylaxis: 

CD4+ cell 

count >100 

c/mm3 for 

>3 mo in 

response to 

ART

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

* See OI Guidelines for Dosing (http://aidsinfo.nih.gov/Guidelines) (accessed 5/20/13)

Immunizations

See the USPHS Guidelines for Prevention and Treatment of Opportunistic 

Infections in Adults and Adolescents (http://aidsinfo.nih.gov/Guidelines/) for 

current recommendations for immunizations in pregnancy.

continued

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Immunization should be considered in pregnancy when the risk for exposure 

or maternal and/or fetal infection is high and the vaccine is thought unlikely to 

cause harm. Immune-suppressed HIV infected patients and pregnant women 

should avoid live-virus or live-bacteria vaccines. HIV-infected patients who are 

symptomatic or have low CD4+ cell counts may have suboptimal responses 

to vaccination. Some, but not all, studies have shown a transient (<4 weeks) 

increase in VL after immunization. This increase in viremia may be prevented 

with appropriate ART (Medical Management of HIV Infection, 2009–2010. 

Johns Hopkins University School of Medicine). For this reason, clinicians may 

consider deferring routine vaccination until after the patient is on an effective 

ARV regimen and avoiding administration late in pregnancy (i.e., close to 

delivery), when most transmission is thought to occur. Table 8-10 presents 

current immunization recommendations for HIV-infected pregnant women.

Table 8-10

Immunizations Recommended for HIV Infected Pregnant Women

Vaccines Recommendation Comments

Pneumococcal 

(see Table 4-9)

Recommended if patient 

has not received the 

vaccine during the 

previous 5 y

Influenza Recommended Administer annually 

before flu season begins

Use of live attenuated 

influenza vaccine is 

contraindicated

Tetanus-diphtheriapertussis (Tdap)Recommended with each 

pregnancy

• optimal timing is 27–36 

weeks gestation

• if tetanus booster 

indicated for wound 

management, administer 

at any time

• if unknown or incomplete 

tetanus vaccination, 

administer 3 vaccinations 

containing tetanus and 

diphtheria (Td) toxoids 

with recommended 

schedule 0, 4 weeks, 

6–12 mo. Tdap should 

replace 1 dose of Td, 

preferably between 

27–36 wks gestation

Pregnant women who 

have not already received 

Tdap should receive a 

dose as soon as possible 

after delivery to ensure 

pertussis immunity and 

reduce the risk for 

transmission of Td to the 

newborn

HBV Recommended for all 

susceptible patients

3 doses: at 0, 1 mo, 6 mo 

of pregnancy

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Table 8-10

Immunizations Recommended for HIV Infected Pregnant Women

Vaccines Recommendation Comments

HAV Recommended for 

all susceptible (HAV 

Ab-negative) patients with 

chronic HCV or HBV; also 

indicated before travel 

to endemic areas, in 

IDUs, and with community 

outbreaks

2 doses: at 0, 6 mo of 

pregnancy

Enhanced-potency 

inactivated polio vaccine

Use if not previously 

immunized and traveling 

to areas where risk for 

exposure is high

Oral polio vaccine is a 

live virus vaccine and is 

contraindicated in HIV 

infected people

Immune Globulins

Recommended for measles 

exposure in persons with 

symptomatic HIV

Recommended for HAV, 

with exposure to HAV 

in close contact/sex 

partner, or with travel to 

underdeveloped country 

(especially in patients 

with advanced HIV, who 

may have poor antibody 

response to vaccine)

Recommended for rubella, 

within 72 h of exposure

Hyperimmune Globulins

Varicella-zoster virus 

(VZV) immune globulin

Recommended for 

susceptible adults (i.e., 

undetectable antibodies 

to VZV or no history of 

either chickenpox or 

shingles) after significant 

exposure to chickenpox or 

VZV (significant exposure 

= household, hospital 

room, close indoor contact 

>1 h, prolonged face-toface contact)

Give within 96 h of 

exposure

Hepatitis B immune 

globulin

Recommended for 

needlestick or sexual 

contact with HBsAg+ 

person in susceptible 

individuals

Give HBIG; start HBV 

vaccine series within 14 d 

of exposure

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

continued

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Frequency of Visits

The frequency of prenatal care visits depends on several factors specific to 

each patient, including the health of the mother, gestational age, presence of 

pregnancy-related complications, ARV regimen and response, and psychosocial 

needs. In uncomplicated pregnancies, visits generally are scheduled monthly in 

early pregnancy and every 1–2 weeks from 28–30 weeks of gestation until 

delivery; when possible, they should be coordinated with other healthcare visits.

Consultations to Consider During Pregnancy

HIV infected women may need certain specialty consultations during 

pregnancy. Ideally, many of these consultations can be handled within the 

same clinic or center where the patient is seen for obstetrical or primary 

medical care. When possible, referral of the HIV infected pregnant woman to 

an obstetrician with HIV expertise and experience is advised, in which case the 

obstetrician may manage many of the patient’s HIV-specific treatment issues.

In general, consultative needs may include the following:

• Perinatology to address special obstetrical concerns, including use of 

HIV-related or other medications in pregnancy, discussions about fetal 

monitoring/evaluation, other appropriate antepartum/intrapartum 

evaluation and management. When indicated, consultation should 

ideally be with a perinatologist who has HIV experience/expertise.

• Infectious disease/HIV specialist to address HIV-related treatment 

issues, including choice of ARV regimen and need for OI prophylaxis 

or treatment. This consultation is particularly important if the patient is 

newly diagnosed with HIV infection during pregnancy.

• Pediatrics to address care of the infant after birth, including testing 

for HIV, use of ZDV, and Pneumocystis jirovecii pneumonia (PCP) 

prophylaxis in exposed infants

• Nutrition to address proper diet, the need for nutritional or vitamin/

mineral supplementation, and food safety issues when needed

• Substance abuse management when indicated

• Psychiatry/psychology to address signs/symptoms of depression and 

other psychiatric disorders and their management, if needed

• Social services to address needs related to housing, transportation, 

domestic violence, access to medications and medical care, etc.

Counseling and Support

Support systems: At the initial visit, the healthcare provider should assess a 

patient’s support systems (i.e., determine who knows the patient’s HIV status, 

what problems she has encountered with disclosure, which family members 

and/or friends provide ongoing support, and what barriers exist to disclosing 

her HIV status to sexual or needle-sharing partners). These issues should be 

readdressed at intervals throughout pregnancy as needed. The use of peer 

counselors may be especially helpful.

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Contraception use postpartum: Discussion about postpartum contraceptive 

plans should be initiated in early to mid-pregnancy to allow time for 

comprehensive education and counseling about available options and 

adequate time for informed decision making. Women who receive family 

planning counseling during prenatal care are more likely to use effective 

contraception postpartum (Thromb Res 2011;127 Suppl 3:s35).

Condom use during pregnancy: Sexual activity should be reviewed at each 

visit and condom use reinforced.

Drug use/treatment: History of and/or ongoing substance abuse, including use 

of tobacco and alcohol as well as illicit drugs, should be assessed at the initial 

visit and at intervals during prenatal care, if indicated. Type of substance(s), 

amount of use, route of administration, and prior drug or alcohol treatment 

should be documented. The patient should be counseled about specific risks 

associated with substance abuse in pregnancy (see Chapter 9, Psychosocial 

Issues) and drug or alcohol treatment during pregnancy should be encouraged 

and facilitated for active problems.

Adherence: Before initiating an ARV regimen, each patient should be educated 

and counseled about the importance of adherence to prescribed medications, 

and medication adherence should be assessed and reinforced at each visit 

(see Chapter 5, Adherence).

Clinical trials: Pregnant HIV infected women should be informed about the 

availability of and offered participation in clinical trials for which they are 

eligible.

Advance directives: The issue of advance directives for care in the event of 

sudden deterioration in the woman’s health, as well as guardianship plans 

for children in the event of the mother’s incapacitation or death, should be 

discussed, and legal assistance should be facilitated, if needed.

Guidelines For Intrapartum Care

The goals of intrapartum management are to further reduce the risk of 

perinatal transmission and minimize the risk of maternal and neonatal 

complications.

Universal Precautions

Gowns, gloves, and eye protection should be used in all deliveries and in 

examinations or procedures likely to generate splashing blood or amniotic 

fluid. (See Chapter 12, Occupational Exposure.) When used, this should 

provide adequate protection for healthcare workers. Medical care should not 

be altered because of considerations of potential occupational exposure.

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Intrapartum ART and Prophylaxis (http://aidsinfo.nih.gov)

Intravenous (IV) ZDV is recommended during the intrapartum period for 

HIV infected pregnant women with VL ≥ 400 c/mL (or unknown VL), 

regardless of their antepartum regimen or mode of delivery, to reduce 

perinatal HIV transmission.

• Administer a loading dose of 2 mg/kg IV over 1 hour, followed by 

continuous infusion of 1 mg/kg/hour until delivery.

• For a scheduled CS delivery, IV ZDV should begin 3 hours before 

surgery; with unscheduled CS, consideration may be given to 

shortening this interval, depending on the indications for CS.

• IV ZDV should be given even with documented or suspected 

ZDV resistance.

However, IV ZDV is not required for HIV infected women receiving combination 

ARV regimens who have HIV RNA <400 copies/mL near delivery. In a 

study from the French Perinatal Cohort, intrapartum prophylaxis was not 

associated with transmission in women with VL <400 c/mL at delivery (AIDS

2008;22(2):289).

Women who are taking an antepartum combination ARV regimen should 

continue it on schedule, to the degree possible, during labor and prior to 

scheduled CS delivery to maximize virologic efficacy and minimize the 

development of resistance. If oral ZDV is a part of the antepartum regimen 

and IV ZDV is indicated, the oral ZDV component of the regimen can be 

stopped while the patient receives IV ZDV. For women who are receiving a 

d4T-containing antepartum regimen, d4T should be discontinued during labor if 

IV ZDV is being administered. If maternal ART must be interrupted temporarily 

(e.g., for less than 24 hours) in the peripartum period, all drugs (except for 

intrapartum IV ZDV, when indicated) should be stopped and reinstituted 

simultaneously to minimize the chance of developing resistance.

When CS delivery is planned, oral medications may be continued 

preoperatively with sips of water. Medications requiring food ingestion 

for absorption can be taken with liquid dietary supplements, contingent on 

consultation with the attending anesthesiologist during the preoperative period.

HIV infected women in labor who have not received antepartum ARV drugs 

should receive IV ZDV during labor, with subsequent infant combined ARV 

prophylaxis for 6 weeks. Women of unknown HIV status who present in labor 

should have a rapid HIV test performed. If the test is positive, a confirmatory 

HIV test should be sent as soon as possible and maternal/infant ARVs should 

be initiated without waiting for results of the confirmatory test. Rapid HIV 

testing (see http://www.cdc.gov/hiv/topics/testing/rapid/index.htm. Accessed 

4/10/12) should be available on a 24-hour basis at all facilities with a 

maternity service and/or neonatal intensive care unit. The National HIV/AIDS 

Clinicians’ Consultation Center website provides information on state HIV testing 

laws (http://www.nccc.ucsf.edu/consultation_library/state_hiv_testing_laws. 

Accessed 4/10/12).

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Mode of Delivery

(Current recommendations: Public Health Service Task Force Recommendations 

for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal 

Health and Interventions to Reduce Perinatal HIV Transmission in the United 

States, http://www.aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf. Accessed 

4/9/12)

Planned vaginal delivery: Vaginal delivery can generally be safely planned 

in women who are taking combination ARV regimens and who have plasma 

HIV RNA levels <1000 copies/mL near the time of delivery because of the 

low rate of transmission among this group and the lack of data that establish 

the additional benefit of CS in this situation. Recent studies indicate that the use 

of combination ARV regimens and attainment of a very low or undetectable 

HIV VL are associated with very low rates of perinatal HIV transmission. These 

include a recent report from a comprehensive national surveillance system in 

the United Kingdom and Ireland, where HIV transmission occurred in three 

(0.1%) of 2,309 and 12 (1.2%) of 1,023 infants born to women with HIV 

RNA of <50 copies/mL and 50–999 copies/mL, respectively. The transmission 

rate among all women who received at least 14 days of ART was 40 (0.8%) 

of 4,864, regardless of mode of delivery (AIDS 2008;22(8):973). In this and 

another large cohort (Clin Infect Dis 2005;40(3):458), there were no significant 

differences in transmission rates by mode of delivery when VL and the use of 

combination ARV regimens were taken into account.

Scheduled cesarean section: Scheduled CS at 38 weeks’ gestation is 

recommended for women with HIV RNA levels >1000 copies/mL near the time 

of delivery (whether on ARVs or not) and for women with unknown HIV RNA 

levels near the time of delivery. Early studies, performed before VL testing 

and the use of optimal combination ARV regimens became the standard of 

care, found that scheduled CS, when performed before the onset of labor 

and/or membrane rupture, reduced MTCT by 55% to 80% in the absence of 

ARV prophylaxis and with ZDV alone (Lancet 1999;353:1035; N Engl J Med

1999;340:977).

When CS is performed to prevent HIV transmission, it should be scheduled at 

38 weeks’ gestation to decrease the likelihood of labor onset or membrane 

rupture before delivery. In a study of 1,194 infants born to HIV infected 

mothers, no statistically significant association was observed between mode 

of delivery and infant respiratory distress syndrome when adjusted for 

gestational age and birthweight (Obstet Gynecol 2010;116 2 Pt 1:335).

For women who are not HIV infected, ACOG recommends that planned 

CS not be performed before 39 weeks’ gestation due to the risk of 

iatrogenic prematurity (Obstet Gynecol 2008;112(3):717; N Engl J Med

2009;360(2):111). When CS is performed for standard obstetrical indications 

(e.g., malpresentation), it should be scheduled at 39 weeks, with timing based 

on menstrual dating and ultrasound.

For HIV infected women presenting in late pregnancy and not taking ARVs, 

scheduled CS is likely to provide additional benefit in reducing risk of 

perinatal transmission of HIV unless viral suppression can be documented 

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prior to 38 weeks. Depending on the baseline RNA level, reduction in plasma 

HIV RNA to undetectable levels usually takes several weeks (Clin Infect Dis

2007;44(12):1647).

It is not clear whether CS after membrane rupture or labor onset provides 

benefit in preventing perinatal transmission. Management of women originally 

scheduled for CS who present with ruptured membranes or in labor must be 

individualized on the basis of the duration of rupture, progress of labor, plasma 

HIV RNA level, current ARV therapy or prophylaxis, and other clinical factors.

When preterm membrane rupture occurs (<37 weeks’ gestation), decisions 

about delivery should be made on the basis of gestational age, HIV VL level, 

current ARV regimen, and evidence of acute infection (e.g., chorioamnionitis). 

Expert consultation is recommended. The ARV regimen should be continued and 

initiation of IV ZDV, if indicated, considered if imminent delivery seems possible.

Maternal morbidity and mortality are increased with CS compared 

with vaginal delivery (Obstet Gynecol 1999;94:942). Most studies have 

demonstrated that HIV infected women have increased rates of postoperative 

complications, mostly infectious, compared with women who do not have 

HIV infection, and that the risk of complications is related to the degree of 

immunosuppression (Acta Obstet Gynecol Scand 1999;78(9):789; Eur J Obstet 

Gynecol Reprod Biol 2000;90(1):73; Int J Gynaecol Obstet 2001;74(1):9; Am J 

Obstet Gynecol 2001;184(6):1108).

A Cochrane review of six studies of HIV infected women concluded that urgent 

CS delivery was associated with the highest risk of postpartum morbidity, 

that scheduled CS was intermediate in risk, and that vaginal delivery had the 

lowest risk of morbidity (Cochrane Database Syst Rev 2005;(4):CD005479).

Complication rates in most studies (Am J Obstet Gynecol 2000;183(1):100; 

J Acquir Immune Defic Syndr 2001;26(3):236; Am J Obstet Gynecol

2002;186(4):784; AIDS 2004;18(6):933) were within the range reported in 

populations of women who were not HIV infected but had similar risk factors, 

and were not of sufficient frequency or severity to outweigh the potential 

benefit of reduced transmission.

Most complications relate to postpartum infections (e.g., endometritis, wound 

infection, urinary tract infection, pneumonia) but also include complications 

related to hemorrhage, since blood loss is generally greater with CS. Factors 

that increase the risk of complications include low socioeconomic status, genital 

infections, malnutrition, smoking, and prolonged labor or membrane rupture, 

some of which may be more common in the setting of HIV infection.

Prophylactic antibiotics should be given when CS is performed for prevention 

of HIV transmission.

Women should be counseled about the risks and potential benefits of CS 

for the purpose of reducing perinatal HIV transmission; decisions should be 

individualized on the basis of this discussion and the specific situation. The 

woman’s autonomy to make an informed decision regarding route of delivery 

should be respected and honored.

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Other Intrapartum Considerations

If spontaneous membrane rupture occurs before or early in the course of labor, 

interventions to decrease the interval to delivery, such as administration of 

oxytocin, may be considered in women without indications for CS.

Absent clear obstetric indications , the following procedures should generally 

be avoided because of potential increased risk of transmission: artificial 

rupture of membranes, routine use of fetal scalp electrodes, operative delivery 

with forceps or vacuum extractor, or episiotomy.

Delayed cord clamping has been associated with improved iron status and 

additional benefits (e.g., decreased risk of intraventricular hemorrhage) 

in both term and preterm births to HIV uninfected mothers (Pediatrics

2006;117(4):1235; Neonatology 2007;93(2):138; J Perinatol 2011;31 suppl 

1:S68). Although HIV-specific data are lacking, there is no reason to modify 

this practice when the mother is HIV infected.

Treatment for postpartum hemorrhage due to uterine atony: If a woman is 

receiving a CYP3A4 enzyme inhibitor (e.g., PI), methergine should not be used 

unless alternative treatments for postpartum hemorrhage (e.g., prostaglandin 

F2-alpha, misoprostol, oxytocin) are not available and if the need for 

pharmacologic treatment outweighs the risks. If used, methergine should be 

administered in the lowest effective dose for the shortest duration possible. 

If she is receiving a CYP3A4 enzyme inducer (e.g., NVP, EFV, etravirine), the 

potential exists for decreased methergine levels and inadequate treatment 

effect; therefore, additional uterotonic agents may be needed.

Postnatal Care for the HIV-Exposed Infant

Antiretroviral prophylaxis

The 6-week neonatal component of the ZDV prophylaxis regimen is 

recommended for all HIV exposed neonates. Short-term toxicity of infant ZDV 

prophylaxis has been minimal, consisting primarily of transient hematologic 

toxicity, mainly anemia, which generally resolves by age 12 weeks.

A 4-week neonatal ZDV prophylaxis regimen is recommended in the United 

Kingdom and several European countries when the mother has taken ARVs 

prenatally (HIV Med 2008;9(7):452; Pediatr Infect Dis J 2011;30(5):408). 

This approach may be considered if there are concerns about adherence or 

toxicity with the 6-week regimen. The 4-week ZDV regimen may allow earlier 

recovery of anemia in otherwise healthy infants compared with the 6-week 

ZDV course (Pediatr Infect Dis J 2010;29(4):376). Consult with a pediatric HIV 

specialist if early discontinuation of infant prophylaxis is considered.

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Table 8-11 presents recommendations for neonatal ZDV dosing to prevent 

MTCT; Table 8-12 presents recommended neonatal combination antiretroviral 

regimens for use in special circumstances.

Table 8-11

Recommendations for Neonatal Zidovudine Dosing to Prevent 

Mother-to-Child Transmission of HIV

Age Dosing Duration

>35 wk gestation • 4 mg/kg body weight per dose, 

po bid

• Start as close to the time of birth as 

possible and within 12 h of delivery

• If unable to tolerate oral agents: 

3 mg/kg body weight per dose given 

IV, started within 6–12 h of delivery, 

then q 12 h

Birth through 6 wk

<35–>30 wk 

gestation • 2 mg/kg body weight per dose po or

• 1.5 mg/kg body weight per dose IV

• Start within 6–12 h of delivery, then 

q 12 h

• Advance to 3 mg/kg per dose po (or 2.3 mg/kg per dose IV) q 12 h at 15 

days of age

Birth through 6 wk

<30 wk gestation • 2 mg/kg body weight per dose po or

• 1.5 mg/kg body weight per dose IV

• Start within 6–12 h of delivery, then 

q 12 h

• Advance to 3 mg/kg per dose po (or 2.3 mg/kg per dose IV) q 12 h at 4 

wk of age

Birth through 6 wk

Source: Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women 

for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United 

States. Sept 14, 2011. http://aidsinfo.nih.gov/content files/PerinatalGL.pdf

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Table 8-12

Recommended Neonatal Combination Antiretroviral Regimens for 

Use in Special Circumstances

Regimen Administration Notes

ZDV 4 mg/kg bid 

+ NVP

• 12 mg po if birth 

weight >2 kg

• 8 mg po if birth 

weight 1.5–2.0 kg

• Give birth through 6 wk

• Administer 3 doses in first 

week of life:

- Dose 1: Give within 48 h 

of birth (birth–48 h)

- Dose 2: Give 48 h after 

Dose 1

- Dose 3: Give 96 h after 

Dose 2

• ZDV dosing regimen is 

for infants >35 weeks’ 

gestation. See Table 

8-11 for recommended 

doses for premature 

infants.

• NICHD HPTN 040/

PACTG 1043 used NVP 

12 mg po bid if birth 

weight >2 kg and 8 mg 

po bid if birth weight 

1.5-2.0 kg

Source: NICHD HPTN 040/PACTG 1043. 18th Conference on Retroviruses and 

Opportunistic Infections. Boston, MA, 2011.

ZDV should be initiated as close to the time of birth as possible, preferably 

within 6–12 hours. The 6-week ZDV prophylaxis regimen is recommended at 

gestational age-appropriate doses (see Table 8-11). Use of ARVs other than 

ZDV and nevirapine is not recommended in premature infants because of a 

lack of dosing and safety data. The use of neonatal ZDV is recommended 

regardless of maternal ZDV resistance history.

Infants born to HIV infected women who have not received antepartum or 

intrapartum ARVs or who have received only intrapartum ZDV should receive 

prophylaxis with a combination ARV regimen started as close to the time of 

birth as possible. This recommendation is based on a phase III randomized 

trial conducted in 4 countries (see Table 8-12) (N Engl J Med 2012 Jun 

21;366(25):2368), which enrolled 1,746 infants born to HIV infected women 

who did not receive any ARVs during pregnancy prior to labor. The study 

compared the standard 6-week ZDV regimen alone with two different 

combination regimens: 6 weeks of ZDV plus three doses of NVP; or 6 weeks 

of ZDV plus 2 weeks of 3TC and NFV. In this trial, 41% of women received 

ZDV during labor and transmission rates did not vary by whether intrapartum 

ZDV was given. The overall HIV transmission rate was significantly lower in the 

two- and three-drug arms compared with the ZDV-alone arm; however, the 

two-drug regimen (ZDV plus NVP) was less toxic than the three-drug regimen 

(ZDV plus 3TC plus NFV). Although transmission rates with the two combination 

regimens were similar, neutropenia was significantly more common with the 

three-drug regimen compared with the two-drug regimen (27.5% vs. 15%, p 

< .0001). Furthermore, NFV powder is no longer commercially available in the 

United States.

No specific data address whether a more intensive combination infant 

prophylaxis regimen provides further protection against transmission when the 

mother receives antepartum/intrapartum prophylaxis but has suboptimal viral 

suppression near delivery, particularly in the absence of scheduled CS, or when 

the mother has ARV drug-resistant virus. On the basis of extrapolated findings 

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from the NICHD HPTN 040/PACTG 1043 study, the use of a combination 

infant prophylaxis regimen should be considered, depending on risk assessment 

(e.g., maternal VL and mode of delivery). Expert consultation is advised. The 

decision to use other drugs with 6 weeks of ZDV in other scenarios should be 

made only after expert consultation and a discussion of risks and benefits with 

the mother, preferably before delivery.

Appropriate drug formulations and dosing regimens for neonates are 

incompletely defined and minimal data are available concerning the safety of 

combination drugs in the neonate. Neonatal dosing information is not available 

for currently available boosted PIs; both RTV and LPV/r have been associated 

with cardiac toxicity, lactic acidosis, acute renal failure, CNS depression and 

respiratory complications leading to death, predominantly in preterm neonates. 

The FDA now recommends that LPV/r not be administered to neonates before 

a postmenstrual age (first day of the mother’s last menstrual period to birth 

plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 

14 days has been attained.

Infants of women with positive HIV rapid test results while the mother is in labor 

should begin combination ARV prophylaxis as described above. If the maternal 

confirmatory HIV test is positive, then ARVs should be continued in the infant for 

6 weeks; if the test is negative, the infant ARVs should be stopped.

Initiation of ART is recommended for infected infants aged <12 months, 

regardless of clinical status, CD4+ percentage, or VL. If the infant becomes 

infected despite combination prophylaxis that includes NVP, the risk of NVP 

drug resistance is increased; expert consultation is advised when choosing 

ARV regimens.

Neonatal Evaluation

A baseline complete blood count (CBC) and differential should be performed 

on the newborn. Decisions about the timing of subsequent hematologic testing 

depend on baseline results, gestational age at birth, clinical condition, dose 

of ZDV being administered, receipt of other ARV drugs and concomitant 

medications, and maternal antepartum therapy. Some experts recommend 

more intensive monitoring of hematologic, serum chemistry and liver function 

assays at birth and when diagnostic HIV PCR tests are obtained for infants 

exposed to combination ART in utero or during the neonatal period. Because 

of the potential for enhanced hematologic toxicity in infants receiving 

a zidovudine/lamivudine-containing prophylaxis regimen, a recheck of 

hemoglobin and neutrophil counts is recommended 4 weeks after initiation 

of prophylaxis. If hematologic abnormalities are identified while the infant 

is receiving prophylaxis, decisions regarding continuation of prophylaxis 

should be individualized. Expert consultation is advised if discontinuation 

of prophylaxis is considered. Routine measurement of serum lactate is not 

recommended; but measurement of serum lactate may be considered if an 

infant develops severe clinical symptoms, particularly neurologic symptoms, of 

unknown etiology.

Follow-up of children with ARV exposure should continue into adulthood 

because of the unknown long-term effects of these drugs.

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Diagnosis of HIV

Source: Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection; 

http://aidsinfo.nih.gov/guidelines/html/2/pediatric-treatment-guidelines/0/. 

Accessed 6/27/12)

HIV infection can be definitively diagnosed with virologic assays in most 

nonbreastfed HIV infected infants by 1 month of age and in virtually all 

infected infants by 4 months of age. Because of transplacental passage, HIV 

antibody tests will be positive up to 18 months after birth and therefore are 

not valid for infant diagnosis. Virologic assays (HIV DNA PCR or HIV RNA 

assay) are used to diagnose HIV infection in infants younger than 18 months.

HIV DNA PCR or HIV RNA assay in HIV exposed infants is recommended 

at age 14–21 days, 1–2 months, and 4–6 months. Virologic testing at birth 

should be considered for infants at high risk of HIV infection (e.g., born 

to HIV infected mothers who did not receive prenatal ARV drugs and/or 

those with high VLs at the time of labor/delivery). Data do not indicate 

any delay in HIV diagnosis with HIV DNA PCR assays in infants who have 

received the ZDV regimen (Pediatr Infect Dis J 1995;14(11):948); however, 

the effect of combination ART in the mother or newborn on the sensitivity of 

infant virologic diagnostic testing, particularly HIV RNA assays, is unknown. 

Therefore, although HIV RNA assays may be acceptable for diagnosis 

(particularly in older infants) HIV DNA PCR assays may be optimal for 

diagnosing infection in the neonatal period.

Confirmation of HIV infection should be based on two positive virologic tests 

from separate blood samples. Definitive exclusion of HIV infection should be 

based on at least two negative virologic tests (at >1 month and >4 months of 

age). Consider confirmation of HIV status with HIV antibody testing at 12–18 

months in infants with prior negative virologic tests. In children aged ≥18 

months, HIV antibody assays alone can be used for diagnosis.

Pneumocystis jirovecii Pneumonia Prophylaxis

To prevent Pneumocystis jirovecii pneumonia (PCP; formerly known as 

Pneumocystis carinii pneumonia), all infants born to women with HIV infection 

should begin PCP prophylaxis with TMP-SMZ (150/750 mg/m2/day in 

two divided doses po three times weekly on consecutive days) at age 

4–6 weeks, after completing 6 weeks of ZDV, unless there is adequate 

test information to presumptively exclude HIV infection. Dapsone and 

atovaquone are alternatives.

Guidelines for Postpartum Care

Infant feeding: Breastfeeding (BF) by HIV infected mothers is not recommended 

in the United States, even for women who are on ART and have undetectable 

VL, because of potential toxicity arising from drug transmission via breast milk 

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and the risk of drug resistance due to insufficient drug levels in breast milk if 

the baby is infected despite prophylaxis. Furthermore, ART may not affect the 

presence of cell-associated virus (intracellular HIV DNA) in breast milk, which 

may therefore continue to pose a transmission risk (J Acquir Immune Defic Syndr

2004;35(2):178).

Late HIV transmission events in infancy have recently been reported among 

HIV infected children suspected to have acquired HIV infection as infants as a 

result of consuming premasticated food; this was supported by phylogenetic 

comparisons of virus from cases and suspected sources and supporting clinical 

history. Healthcare providers should routinely inquire about this feeding 

practice and instruct HIV infected caregivers to avoid this practice and advise

on safe feeding options (Pediatrics 2009;124(2):658; J Acquir Immune Defic 

Syndr 2012;59(2):207).

In most low-resource settings internationally, however, BF has significant benefits 

that outweigh the risks, including provision of ideal infant nutrition in the first 6 

months of life, reduction of infant morbidity and mortality through protection 

against both diarrhea and respiratory-associated mortality in the first year 

of life (Lancet 2000;355:451), delays in the return of fertility with exclusive 

breastfeeding (promotes child spacing and maternal recovery from blood loss), 

low cost, and cultural acceptability. Therefore, current WHO recommendations 

regarding BF for HIV infected mothers include the following:

• When infants are HIV uninfected or of unknown status:

- Exclusive BF for the first 6 months of life unless 

replacement (formula) feeding is acceptable, feasible, 

affordable, sustainable, and safe

- At 6 months, introduce appropriate complementary foods 

and continue BF for the first 12 months of life. All BF 

should then stop once a nutritionally adequate and safe 

diet without breast milk can be provided.

• When infants are HIV infected:

- Exclusive BF for the first 6 months of life and continue BF 

as per recommendations for the general population (up to 

2 years or beyond)

In addition, data from several recent randomized controlled trials support the 

use of extended infant NVP prophylaxis or continuation of maternal triple ARV 

prophylaxis throughout BF to further reduce the risk of perinatal transmission 

(Lancet 2008;372(9635):300; N Engl J Med 2010;362:2271; N Engl J Med

2010;362:2282; N Engl J Med 2008;359:119). The WHO now recommends 

one of these two strategies when ongoing maternal ART is not indicated 

(World Health Organization. Antiretroviral Drugs for Treating Pregnant Women 

and Preventing HIV Infection in Infants. 2010 version. http://whqlibdoc.who.int/

publications/2010/9789241599818_eng.pdf. Accessed 3/26/12).

Care for mother and infant: HIV infected mothers may neglect their own care 

while trying to provide appropriate care for their infants and other children 

or family members. The immediate postpartum period is an important time 

to assess new mothers’ psychological, emotional, and physical health. New 

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mothers should be monitored for signs of postpartum depression or worsening 

of underlying psychiatric disorders and referred to mental health services if 

necessary. In addition, this is an important time to review the completeness of 

preventive health interventions, including immunizations and cervical cancer 

screening. The care of other chronic medical conditions should be reviewed. It 

is essential that women be linked with comprehensive medical and supportive 

care services, including HIV specialty care; primary medical and gynecologic 

care; family planning; mental health or substance abuse treatment services; 

and assistance with food, housing, transportation, and legal/advocacy services, 

if needed. A team approach with multiple support services may also help to 

provide optimal care. Similarly, the HIV-exposed infant should be linked into 

ongoing pediatric care, with HIV diagnostic tests as described above and 

appropriate HIV specialty care if HIV infected.

Antiretroviral Treatment

Whether to continue or discontinue ARVs after delivery: Decisions regarding 

continuation of ARV drugs after delivery should take the following into account: 

current recommendations for initiation of ART (available at http://www.

aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 5/17/13), 

current and nadir CD4+ cell counts and trajectory, HIV RNA levels, clinical 

symptoms/disease stage, presence of other indications for ART (e.g., chronic 

hepatitis B, HIV-associated nephropathy), adherence issues, HIV infection status 

of the woman’s sexual partner, and patient decision after careful counseling.

Following delivery, women who meet the indications for ART should continue 

therapy without interruption. Doses of some PIs may be increased during 

late pregnancy; for women continuing therapy, available data suggest that 

standard doses can be used again starting immediately after delivery.

When ARV drugs have been given in pregnancy to women with CD4+ 

cell count >500 cells/microliter, the decision to stop or to continue ARV 

drugs postpartum has become increasingly controversial because of 

increasing evidence of benefit in starting therapy at higher CD4+ levels 

and recommendations for earlier initiation of ART (http://aidsinfo.nih.gov/

guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/. Accessed 

5/17/13) and because therapy interruption when ART has been given for 

treatment in nonpregnant adults has been associated with increased morbidity 

(J Infect Dis 2008;197:1145).

At issue is the potential impact of postpartum ARV discontinuation on the 

short- and long-term health of the mother. This is especially important as 

women may have multiple pregnancies, resulting in episodic receipt of ARVs. 

To date, studies of pregnant women with relatively high CD4+ cell counts 

who stop therapy after delivery have not shown a risk for increased disease 

progression (J Infect Dis 2007;196(7):1044; HIV Med 2009;10(3):157; Infect 

Dis Obstet Gynecol 2009:456717). Unplanned changes in ARV regimens and 

discontinuations of treatment in the postpartum period have led to viral load 

rebound (HIV Clin Trials 2011;12(1);9).The risks versus benefits of stopping 

therapy postpartum in women with high CD4+ counts is being evaluated in the 

ongoing PROMISE study.

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The potential benefits of continuing ART in women with higher CD4+ 

counts must be weighed against possible drug toxicity, cost, and the risk of 

development of viral resistance with suboptimal adherence, which may be 

more likely during the postpartum period (AIDS Care 2008;20(8):958; 6th 

International AIDS Society Conference on HIV Pathogenesis and Treatment and 

Prevention 2011; Abstract #1016).

Women who have uninfected sexual partners should continue ART postpartum 

to reduce risk of HIV transmission (New Engl J Med 2011;365:493). Safe 

sexual practices should continue to be recommended.

The decision to continue therapy after delivery should be discussed with 

the woman and decisions made prior to delivery. Until definitive evidence 

is available to guide this decision, continuation of therapy in women with 

high CD4+ cell counts should be based on individualized discussions with the 

woman and consideration of willingness and ability to commit and adhere to 

lifelong therapy.

Stopping ARV Drugs Postpartum

For women whose antepartum regimen included an NNRTI and who plan to 

stop ARV prophylaxis after delivery, consider one of the following two options: 

1) stop the NNRTI first and continue other ARVs for a period of time; or 2) 

switch from an NNRTI to a PI prior to interruption and continue the PI with 

the other ARVs for a period of time before electively stopping. The optimal 

interval between stopping an NNRTI and the other ARV drugs is not known; at 

least 7 days is recommended. Given the potential for prolonged detectable 

NNRTI concentrations for more than 3 weeks in patients taking EFV-based 

therapy, some experts recommend continuing the other ARVs or substituting a 

PI plus two other agents for up to 30 days. A recent study of 412 women who 

received single-dose nevirapine and were randomized to receive zidovudine/

lamivudine, tenofovir/emtricitabine, or lopinavir/ritonavir for either 7 or 21 

days found an overall new nevirapine resistance mutation rate of 1.2% when 

assessed by population genotype at 2 and 6 weeks following completion of 

treatment, with no difference by length of treatment. However, low-frequency 

nevirapine-resistant mutations at codons 103, 181, and 184 detected using 

allele-specific PCR emerged significantly more often in the 7-day arms (13/74 

[18%]) than in the 21-day arms (3/66 [5%], P = .019). (Clin Infect Dis 2013; 

56(7):1044).

Women whose antepartum regimen did not include an NNRTI and who plan to 

stop ARV prophylaxis after delivery should stop all ARVs at the same time.

Adherence support: For women continuing ARVs postpartum, adherence 

support should be available during the postpartum period and adherence 

should be assessed at each clinical visit. Because of the physical recovery from 

giving birth, the stresses and demands of caring for a new baby, and possible 

postpartum depression, the new mother may be particularly vulnerable to 

problems with adherence to ARV treatment. Providers should be especially 

aware that depression or drug or alcohol use/abuse may negatively affect 

adherence and should screen postpartum women for these conditions.

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It is essential that access to and continuity of ART as needed for maternal 

health be ensured. Simplification of an ARV regimen may be considered. If a 

woman is not able to adhere to her regimen, temporary interruption of ART 

may be needed while strategies are devised to improve adherence.

Contraception and Condom Use

Discussions about contraception and safe sexual practices should continue 

throughout pregnancy and should be reviewed and reinforced at the 

postpartum visit. Lack of breastfeeding is associated with earlier return of 

fertility; ovulation returns as early as 6 weeks postpartum and potentially 

even earlier in some women, putting them at risk for pregnancy shortly 

after delivery (Obstet Gynecol 2011;117(3):657). Interpregnancy intervals 

<18 months have been associated with increased risk of poor perinatal 

and maternal outcomes in HIV-uninfected women (J Obstet Gynaecol

2010;30(2):107). Because of the stresses and demands of a new baby, women 

may be both more receptive to the use of effective contraception and more 

at risk for nonadherence to contraceptive methods and unintended pregnancy. 

This is an important concern when the woman is on an EFV-containing regimen 

or other drugs that are potential teratogens. An ideal contraceptive strategy 

for women with HIV infection is to provide simultaneous protection against both 

unintended pregnancy and HIV transmission or sexually transmitted disease 

acquisition or transmission, often called “dual protection” (i.e., condoms plus a 

highly effective contraceptive) (Sex Transm Dis 2002;29(3):168). The use of 

longer-term, reversible contraceptive methods (e.g., injectable, implants, and/or 

IUD) should be included as options.

National Perinatal HIV Hotline

This toll-free hotline provides free clinical consultation on all aspects of 

perinatal HIV, including infant care: 1-888-448-8765.

Dolutegravir (Tivicay, DLG)

FDA approved 8/13. It is classified as FDA Pregnancy Category B. 

Standard adult dose: ARV-naïve or ARV-experienced but integrase inhibitor 

naïve patients: DLG 50 mg once daily

ARV-naïve or ARV-experienced but integrase inhibitor naïve if given with EFV, 

fos-APV/r, TPV/r, or rifampin; or integrase inhibitor experienced: DLG 50 mg 

twice daily

Formulation: 50 mg tablets

Adverse effects: The most common adverse reactions of moderate to severe 

intensity and incidence ≥2% are insomnia and headache. Hypersensitivity 

reactions have been reported in 1% or fewer study subjects and were 

characterized by rash, constitutional findings, and sometimes organ dysfunction, 

including liver injury. Patients with underlying hepatitis B or C may be at 

increased risk for abnormal liver enzymes. 

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Drug Interactions: Drugs that are metabolic inducers may decrease the plasma 

concentrations of dolutegravir. Dolutegravir should be taken 2 hours before or 

6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron 

supplements, oral calcium supplements, or buffered medications. DLG should be 

given as 50 mg twice daily when coadministered with rifampin. 

Use in pregnancy: Insufficient data to recommend use: No studies of 

dolutegravir use in human pregnancy. Insufficient data to assess for 

teratogenicity in humans. No evidence of teratogenicity in mice, rats, or rabbits.

Placental transfer and PK in pregnancy are unknown

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Chapter 9:

Psychosocial Issues, Mental Health, 

and Substance Abuse

Julie Barroso, PhD, ANP, APRN, BC, FAAN

Associate Professor and Research Development Coordinator

Duke University School of Nursing

Senior Research Fellow

Sanford School of Public Policy, Duke University

The author declares no conflict of interest

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Chapter 9: Psychosocial Issues, Mental Health, 

and Substance Abuse

Chapter 9 at a Glance

Psychosocial Issues, Mental Health, and Substance Abuse......................341

Major Psychosocial and Cultural Issues Faced by Women 

with HIV Infection.......................................................................................................................................341

Special Considerations..............................................................................................................................344

Mental Health Issues...............................................................................................................................345

General Considerations...........................................................................................................................345

Assessment..............................................................................................................................................................346

Specific Mental Health Conditions...........................................................................................349

Depression..............................................................................................................................................................349

Anxiety.......................................................................................................................................................................352

Psychopharmacology.............................................................................................................................355

General Guidelines......................................................................................................................................355

Common Psychiatric Medications...................................................................................................356

Substance Abuse..........................................................................................................................................361

Substance Abuse and Substance Dependence: DSM-IV-TR Criteria ......361

Substance Abuse Comorbidities......................................................................................................363

Identification of Substance Abuse ................................................................................................365

Drug Testing..........................................................................................................................................................367

Treatment Readiness and Harm Reduction ..........................................................................368

Pharmacologic Interventions for Addiction..........................................................................369

Nonpharmacologic Approaches......................................................................................................372

Pregnancy and Substance Abuse..................................................................................................372

Treatment Retention and Relapse..................................................................................................374

Antiretroviral Therapy and Substance Abuse...................................................................374

Tobacco.....................................................................................................................................................................375

Conclusion...........................................................................................................................................................376

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Psychosocial Issues, Mental Health, and Substance Abuse

Although healthcare providers for women living with HIV focus primarily on the 

physical manifestations of the condition, understanding the psychosocial, cultural, 

mental health, and substance abuse issues faced by HIV infected women is 

important to optimizing care. By developing a comprehensive treatment plan 

for the HIV infected woman that includes emotional support and treatment for 

coexisting psychosocial and mental health conditions, the care provider can 

help the woman to feel that the entirety of her experience is being addressed. 

This chapter reviews the principal psychosocial, cultural, mental health, and 

substance abuse issues relevant to women with HIV infection and makes 

recommendations for provider response, evaluation, and management.

Major Psychosocial and Cultural Issues Faced by Women 

with HIV Infection

A woman with HIV infection potentially faces many psychosocial issues that can 

significantly affect her ability to access or accept care. For many women, HIV 

infection is just one additional challenge in a life filled with poverty, abuse, 

substance use, and other hardships, and it may not even be perceived as the 

biggest problem.

Gender inequality: Gender inequality contributes to the spread of HIV 

infection (Table 9-1) and magnifies many of the problems women experience 

after becoming infected. Compared with men, women often have both less 

control over their sexuality and less power in many other spheres of their lives.

Table 9-1

Gender Norms that Contribute to the Spread of HIV Infection

Men

• Gender norms related to masculinity can encourage men to have more sexual 

partners and older men to have sexual relations with much younger women

• Homophobia stigmatizes men who have sex with men, making them more likely to 

keep such activity covert and to have a female partner as a cover

Women

• Women and girls often have less information about HIV and fewer resources to 

take preventive measures

• Because of economic dependency and unequal power relations, women are often 

unable to negotiate safer sex practices

• Women may be subjected to forced sex, which can cause tears and lacerations in 

the vaginal mucosa and anal lining, thereby increasing the risk of HIV transmission

• Women who fear interpersonal violence may be less likely to disclose their 

HIV serostatus

Sources: Adapted from Gender Issues–HIV & AIDS. United Nations Development Fund 

for Women; Gender, Women, and Health: Gender Inequalities and HIV. World Health 

Organization (WHO). 2012

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Race/ethnicity: In the United States, women living with HIV are 

disproportionately African-American or Hispanic. Many of these women 

have experienced stigma related to their race, ethnicity, or country of origin, 

and HIV may be particularly stigmatizing within their own communities. 

Language and cultural beliefs about health may act as barriers to care, 

and there may be lack of awareness and health literacy definicts, as well 

as other myriad social and structural barriers. Recent studies also highlight 

sometimes disparate treatment by health care providers. Healthcare providers 

must offer respect, awareness, and acceptance of cultural differences and 

proactively address these health disparities. They should develop a basic 

knowledge of a patient’s culture, such as the involvement of family members 

in decision making (important in many Hispanic cultures), the use of alternative 

therapies or traditional healers (common in some African cultures), and rituals 

relating to birth and death. Language differences should be addressed with 

appropriately trained medical interpreters; in general, family members should 

not be asked to interpret.

Economic problems: HIV infected women are more likely than HIV infected 

men to be poor, unemployed, and uninsured or under-insured (Clin Inf Dis

2007;45:S255); women may be less likely to be able to keep their healthcare 

appointments because of a lack of transportation and may be unable to 

afford their medications. Poverty may lead some women to exchange sex 

for money, food, or other material support, placing them at increased risk for 

acquiring HIV. Poverty may also lead women to stay in abusive relationships.

Childbearing and childcare: The woman with HIV infection often has children, 

one or more of whom may also be HIV infected. She may be stigmatized if 

she becomes pregnant or expresses the desire to have children. Caring for her 

children will generally take precedence over caring for herself and lack of 

childcare may be a further barrier to accessing care.

Other caretaking: The woman with HIV is often a caretaker for other family 

members, who may include her husband or partner, aging parents, and/

or grandchildren. Attending to these responsibilities may take priority over 

meeting her own needs and may result in the woman neglecting her own care.

Cultural issues and societal perceptions/pressures: Perceptions and 

expectations of women, including HIV infected women, vary in different 

cultures and societies. These expectations commonly center on childbearing, 

sexuality, and submission to men. Women are often expected to be virgins 

when they marry, to have several children after marriage, and to submit to sex 

or violence within relationships without complaint or choice. When women do 

not meet the expectations placed on them, they may feel guilt and shame and 

may pay a heavy price in terms of stigma or even safety.

Stigma/disclosure: Stigma has profoundly adverse effects on the prevention 

and treatment of HIV in women. For example, disclosure of one’s HIV status can 

help with medication adherence, relationship authenticity, and prevention of 

transmission (J Nurs Scholarsh 2004;36(2):122); however, because of stigma, 

women who are infected may not disclose their status to a partner, family, 

or friends for fear of rejection, abandonment, or violence. The HIV infected 

woman may not feel comfortable insisting that her partner use a condom, 

fearing that the request may arouse suspicion about her serostatus. She may 

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be at increased risk for nonadherence because she does not want to take 

her antiretroviral medications in front of others, fearing that people may ask 

questions about the pills and her reasons for taking them. Table 9-2 presents 

issues women may need to consider prior to disclosing their HIV serostatus.

Table 9-2

Decisions and Considerations Regarding Disclosure of HIV Status

Decisions Considerations

Who will make the disclosure? Will the patient disclose for herself or 

designate someone else to do so on her 

behalf?

Who will be told? Partners? Children? Family? Friends? 

Employer? Coworkers? Health care providers?

When will disclosure take place? Immediately after diagnosis or after a 

period of adjustment? Before disclosure is 

made by someone else? Any time that feels 

right?

Under what circumstances will 

disclosure be made?

What are the necessary conditions for 

disclosure to occur?

How much information will be 

shared?

Will the patient tell all the details of her 

diagnosis?

What are the reasons for 

disclosure?

Is disclosure necessary to obtain needed 

services? To have the support of friends and 

family? To prevent transmission of infection? 

To prevent someone else from telling?

Are there any reasons not to 

disclose HIV status?

What are the times and circumstances when 

it may be best not to disclose (e.g., is there a 

possibility of harm?)?

Source: Qual Health Res 2006;16(10):1350

Interpersonal violence: More than four million women a year in the United 

States are harmed by their husbands, boyfriends, or other intimate partners 

(JAMA 2010;304:596). Although no statistics are available on the number of 

HIV infected women who are victims of interpersonal violence (IPV), Gielen 

et al. (Trauma Violence Abuse 2007;8:178) found in a review of studies on 

IPV and HIV that HIV infected women appear to experience IPV at the same 

rates as uninfected women. Rates of adult lifetime physical or sexual IPV were 

roughly equivalent across studies and between HIV infected and uninfected 

women; more than 60% of women, regardless of HIV status, reported 

experiencing IPV. Abuse was both more frequent and more severe among HIV 

infected women, however, than among HIV uninfected women.

IPV is more complex for HIV infected than uninfected women. Those who are 

in abusive relationships are at risk for potential re-infection with HIV and 

for infection with other STDs because men who are violent are more likely 

to engage in risky sexual practices (Sex Health 2010;7:25). Abusive male 

partners are more likely than other men to be HIV infected; therefore, women 

who experience IPV have a higher incidence and prevalence of HIV (Science

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2010;329:145). Women learn the futility of resisting their partners’ attempts 

to control the timing and circumstances of sex because of their experiences of 

male dominance in sexual relationships. Women who are depressed, abusing 

substances, or dissociating from post-traumatic stress disorder (PTSD) are more 

likely to be at risk of IPV (Science 2010;329:145).

Because IPV is so common in many women’s lives and because there is help 

available for women who are being abused, care providers should ask every 

patient about domestic violence, with such questions as the following: (ACOG 

Committee Opinion No. 518; Obstet Gynecol 2012;119:412)

• Within the past year, have you been hit, slapped, kicked, or otherwise 

physically hurt by someone?

• Are you in a relationship with a person who threatens or physically 

hurts you?

• Has anyone forced you to have sexual activities that made you feel 

uncomfortable?

• Have you ever been the perpetrator of violence?

If the woman is newly diagnosed, the clinician should ask about concerns she 

may have if/when her partner learns of her HIV serostatus.

Special Considerations

Homelessness: Structural and societal factors contribute to the increased 

numbers of homeless women, particularly since the economic recession of 2008 

(Curr HIV/AIDS Rep 2007;4:181). The deinstitutionalization of mental health 

services, low wages, limited employment opportunities for women with few job 

skills, and difficulties receiving and maintaining government entitlements all 

contribute to homelessness among women.

Women are particularly susceptible to less visible forms of homelessness, 

such as staying with friends or family, “couch surfing,” or exchanging sex for 

shelter. Transitions in and out of homelessness occur frequently for women in this 

vulnerable position. Riley et al. reported that female gender was one of the 

strongest predictors of poor health among homeless adults (Curr HIV/AIDS Rep

2007;4:181).

Women without stable housing are more likely to use illicit drugs, have multiple 

sex partners, and report poor physical and mental health compared with their 

sheltered counterparts. Exchanging sex for money, drugs, housing, food, and 

safety exposes women to violence and sexually transmitted infections, including 

potential infection or re-infection with HIV, yet women without stable housing 

may resort to this strategy for survival and may be unable to negotiate safer 

sexual practices. With competing needs for housing and food, and perhaps 

also for the care of children, appropriate health care may not be a priority 

for HIV infected women, especially if they are asymptomatic. Women who 

are homeless are more likely to use emergency health care services and to 

use health services in general inconsistently. They may feel that the stigma 

they already experience as a result of HIV infection is compounded by their 

marginal housing situation and may be less likely to search for assistance with 

either housing or health care (Curr HIV/AIDS Rep 2007;4:181). Care providers 

should be consistent in asking about their HIV infected patients’ living situations, 

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whether or not they have enough food, and whether or not they have access 

to electricity and water, as these basic needs must be met before women can 

effectively manage their HIV infection.

Incarceration: The prevalence of HIV infection among incarcerated women 

is roughly double that among incarcerated men (J Assoc Nurses AIDS Care

2009;20:50). Life circumstances outside of prison tend to be very different 

for incarcerated women than for incarcerated men: women have higher levels 

of poverty, more exposure to violence and abuse, more substance abuse, and 

are more likely to face unstable living conditions. Incarcerated women also 

are more likely than incarcerated men to have used sex work to buy food and 

drugs; they are thus at greater risk than men for HIV infection.

Privacy is necessarily limited in prison, which may make inmates who are 

concerned about disclosure of their HIV status reluctant to access healthcare. 

Lack of medical privacy, or the lack of privacy when taking one’s medications 

in prison, has been shown to be a barrier to adherence to antiretroviral 

therapy (ART) for the imprisoned (J Assoc Nurses AIDS Care 2009;20:50). By 

denying medical privacy to inmates, prisons inadvertently may be reducing 

ART adherence rates and increasing the risks of treatment failure and drug 

resistance, which could have public health consequences upon the release 

of inmates to the community. Positive interactions with prison healthcare 

providers, including time for private conversations about medications, can 

help HIV infected incarcerated women adhere to an ART regimen. Similarly, 

individualized decisions regarding the method of medication administration 

(e.g., keeping one’s own medications, directly observed therapy) can also 

improve adherence. Education of prison staff, healthcare providers, and 

inmates can reduce the stigma associated with HIV infection, improve a 

woman’s desire to protect her health, and increase adherence behaviors 

(J Assoc Nurses AIDS Care 2009;20:50).

Lesbian and transgender patients: Special issues, particularly relating to 

stigma and discrimination, face the HIV infected patient who is lesbian or 

transgendered. It is important that healthcare providers inquire about sexual 

practices in a nonjudgmental fashion (e.g., “Do you have sex with men, 

women, or both?”) and also ask about specific practices in order to best 

advise about safe sex. Because many of these patients have had negative 

experiences with the healthcare system or with individual healthcare 

providers, it is critical to openly discuss concerns they may have related to 

care as a lesbian or transgendered person and to actively work to build 

trust and foster mutual respect.

Mental Health Issues

General Considerations

Mental health problems are common in the setting of HIV infection in women. 

Psychiatric illnesses often co-occur with HIV infection and have been linked 

with poor medication adherence and with the risk of suicide (AIDS Care

2009;21:1432). In one study of subjects with a dual diagnosis of HIV and 

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mental illness, HIV infected women were more likely than HIV infected men 

to have a serious mental illness, defined as a diagnosis of schizophrenia or 

major affective disorder, and at least one inpatient or two outpatient treatment 

contacts with healthcare providers related to these diagnoses (Psychiatr Ser

2009;60:974). The most common causes of psychiatric hospitalizations for 

HIV infected women include mood, anxiety, and psychotic disorders. Alcohol/

substance abuse is significantly associated with mood, adjustment, anxiety, 

personality, and psychotic disorders. The most vulnerable women are those who 

are triply diagnosed (i.e., with HIV infection, a chronic mental illness, and a 

substance abuse disorder).

The cost of managing patients with multiple diagnoses is high. One study 

found that health care expenditures for triply diagnosed patients were nearly 

twice as high as those for people with HIV infection in general (AIDS Care

2009;21:1547). Inpatient care (36%), medications (33%), and outpatient 

services (31%) each accounted for roughly one-third of expenditures; costs 

were highest for patients on Medicare or Medicaid, not in stable residences, 

or with poor physical health or high viral loads (AIDS Care 2009;21:1547). 

Women were more likely than men to have poor access to care, defined 

as no outpatient medical visits, at least one emergency room visit without 

an associated hospitalization, and at least one hospitalization (AIDS Care

2009;21:1547).

Both men and women with HIV are more likely to experience a range of 

mental health issues, which most commonly include feelings of acute emotional 

distress, depression, anxiety, PTSD, and cognitive impairment (Mental Health 

Screening: A Quick Reference Guide for HIV Primary Care Clinicians. New York 

State Department of Health. 2012; http://www.hivguidelines.org/wp-content/

uploads/mental-health-screening-06-21-2012.pdf. Accessed 7/18/2012).

Psychosis is more common among patients with HIV who abuse substances, 

particularly stimulants, than in the general population. With any change in 

mental status, a medical cause should be considered before determining that 

the cause is solely psychiatric.

Assessment

It is helpful to assess a patient’s general psychosocial status by inquiring about 

the following:

• Who does the patient consider to be family?

• Does she have a social support system?

• Does she have a partner?

• What kind of work does she do? If unemployed, how does she spend 

her time?

• Does she have children? If yes, how many?

The care provider should also inquire about the patient’s living situation, 

transportation needs, income adequacy, concerns for the future (including 

advance directives for healthcare planning), spiritual/religious support, and 

disclosure status.

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It is important to obtain a detailed psychiatric history, including any prior use 

of psychotropic medications and any history of hospitalizations for mental 

health issues. Depression in particular can be a recurring problem and it will 

be helpful to know what medications or other treatments were effective for this 

disorder in the past. Complex psychiatric disorders require an interdisciplinary 

approach. Table 9-3 lists mental health disorders that should be assessed at 

baseline and at least annually in the HIV infected female patient.

Table 9-3

Screening for Mental Health Disorders

Condition Screening Considerations

Alcohol 

and/or 

Substance 

Abuse

• The provider should inquire as to type, quantity, and frequency 

of alcohol and other substance use and whether the patient has 

experienced adverse consequences from this use

• Addiction to alcohol and recreational drugs and the work required 

to obtain these substances can become the driving force in a 

patient’s life, resulting in neglect of a woman’s health and/or that 

of her children

Anxiety • Anxiety is a common symptom in HIV infected patients; if it is 

severe or persistent, the patient may have an anxiety disorder. 

Other psychiatric disorders can also present with significant 

anxiety.

• Anxiety can present with a wide range of physiological manifestations, including shortness of breath, chest pain, racing/

pounding heart, dizziness, diaphoresis, numbness/tingling, nausea, 

or a sensation of choking. A medical etiology for such symptoms 

should first be ruled out.

• Other possible presentations include fear, worry, insomnia 

or excessive sleeping, impaired concentration and memory, 

ruminations, compulsive rituals, and avoidant coping

• Appetite may be affected; people may eat more or less than 

usual when depressed or anxious. A 24-hour diet recall or an 

inquiry about how a patient’s clothes are fitting can help to assess 

changes in appetite.

Cognitive 

Impairment • Because cognitive impairment may have an organic cause, current 

immune- system status and other symptoms should be considered

• It is often helpful to ask significant others and/or family members 

if they have noted any change in the patient’s cognitive status

• The Mini Mental State Exam is a good, reliable tool for assessing 

cognitive impairment

Depression • Depression is the most common mental health disorder in the HIV 

infected patient population, Depression may, however, be difficult 

to distinguish from symptoms such as fatigue.

• People may eat or sleep more or less than usual when depressed

• With depression it is common to wake earlier than usual and be 

unable to go back to sleep or to have repeated awakenings 

during the night

• Asking two simple questions about mood and anhedonia (“Over the 

past 2 weeks, have you felt down, depressed, or hopeless?” and 

“Over the past 2 weeks, have you felt little interest or pleasure 

in doing things?”) may be as effective as using more formal 

instruments to screen for depression (Screening for Depression in 

Adults: Recommendation Statement. U.S. Preventive Services Task 

Force. 2009; http://www.uspreventiveservicestaskforce.org/

uspstf09/adultdepression/addeprrs.htm. Accessed 7/16/2012)

• To obtain more information and track treatment efficacy, the 

Patient Health Questionnaire (see p. 350) may be helpful

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Table 9-3

Screening for Mental Health Disorders

Condition Screening Considerations

PostTraumatic 

Stress 

Disorder

• Because many HIV infected women have experienced a great deal 

of childhood and/or adult trauma, it is important to determine if 

the patient has symptoms of PTSD. These symptoms can become 

overwhelming and can make it difficult for the woman to cope with 

daily living, including the self-care (e.g., taking regular medications, 

making medical-care visits) required for a chronic illness.

• Management may require an interdisciplinary approach, including 

counseling to resolve the underlying cause(s) of PTSD symptoms

• PTSD may produce a variety of physical symptoms (e.g., insomnia, fatigue, headaches, muscle/joint pain, gastrointestinal upset). If no 

physiological factors are found that account for these symptoms, 

the provider should consider that the cause may be PTSD.

Psychosis • Physiologic cause(s) of symptoms must first be ruled out, 

particularly with an acute onset of symptoms that may include

- Delusions, grandiosity, or false beliefs

- Hallucinations, which are most commonly auditory but can 

affect any of the senses

- Agitation

- Suspiciousness, or being mistrusting and very guarded

- Hostility, or acting in an abusive or uncooperative manner

- Lack of drive or initiative

- Social withdrawal

- Emotional flatness or unresponsiveness

- Lack of spontaneity

- Concrete thought or difficulty in thinking abstractly

- Paucity of speech

- Poor communication skills

- Stereotyped thought or inflexible thinking that may seem 

unreasonable

- Physical symptoms that may involve poor grooming and hygiene

Suicidal 

and/or 

Violent 

Ideation

Determine at baseline and at periodic intervals if the patient either 

has a history of or is currently experiencing suicidal/violent ideation.

This is particularly important in circumstances that may exacerbate a 

mental health disorder (see below). Suicidal and/or violent ideation 

may be recurring features of depression. If these features are 

present, emergency psychiatric care is needed.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: HIV and Suicide: Risk Assessment & Intervention. Mountain Plains AIDS Education 

and Training Center. 2007

Triggers that may exacerbate an existing mental health disorder among 

women with HIV include the following (The Role of the Primary Care Practitioner 

in Assessing and Treating Mental Health in Persons With HIV. © New York State 

Department of Health AIDS Institute, 2000-2012; http://www.hivguidelines.

org/clinical-guidelines/hiv-and-mental-health/the-role-of-the-primary-carepractitioner-in-assessing-and-treating-mental-health-in-persons-with-hiv/. 

Accessed 8/1/2012):

continued

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• Learning of an HIV diagnosis

• Disclosing HIV status to others

• Beginning ART

• Physical illness, new symptoms, signs of disease progression, adverse 

changes in lab values

• Hospitalization

• Death of a significant other

• Lifestyle changes, e.g., loss of job, loss of income, end of relationship, 

relocation, birth of a child

• Making end-of-life and permanency planning decisions

• Any major problems with children, e.g., poor performance in school, 

acting out, illnesses

Specific Mental Health Conditions

Depression

Women with HIV infection have high rates of depression. In a longitudinal 

examination of data collected from the WIHS, which followed a 

representative sample (n=2,792) of HIV infected U.S. women for 10 years, 

53% of the women were depressed at baseline and depressive symptoms 

were an independent predictor of mortality (J Acquir Immune Defic Syndr

2009;51:399). HIV infected people with depression are also less adherent 

to ARV regimens (Psychiatr Q 2009;80:131; AIDS Patient Care STDS

2008;22:313). It is therefore important to assess for depression at baseline 

and at least annually; in a woman with a history of depression, assessment 

should occur at each visit. A positive response to two questions (“During 

the past 2 weeks, have you experienced little interest or pleasure in doing 

things?” “Have you felt down, depressed, or hopeless?”) should prompt a more 

thorough assessment.

Screening tools: Although many well-established depression screening tools are 

available, many of them include somatic items similar to HIV-related symptoms 

or to the side effects of some ARV medications. See Table 9-4 for the Patient 

Health Questionnaire (PHQ), a tool that is designed to approximate the 

Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for 

depression but that is free of somatic items. Specifically designed for use in the 

primary care setting, the PHQ has been studied in 5,780 patients in primary 

care and medical specialty outpatient centers (Cancer 2011;117(1):218). A 

Spanish version has also been validated (Textbook of Psychosomatic Medicine. 

Arlington VA: American Psychiatric Publishing, Inc.; 2005).

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Table 9-4

Patient Health Questionnaire

Instructions: How often have you been bothered by each of the following symptoms 

during the past 2 weeks? For each symptom put an “X” in the box beneath the 

answer that best describes how you have been feeling.

Symptoms Frequency in Past 2 Weeks

Not At 

All

Several 

Days

More 

than 

Half the 

Days

Nearly 

Every 

Day

1. Little interest or pleasure in doing things

2. Feeling down, depressed, or hopeless

3. Trouble falling or staying asleep, or 

sleeping too much

4. Feeling tired or having little energy

5. Poor appetite or overeating

6. Feeling bad about yourself, or that you 

are a failure, or have let yourself or 

your family down

7. Trouble concentrating on things, such 

as reading the newspaper or watching 

television

8. Moving or speaking so slowly that other 

people could have noticed—or the 

opposite: being so fidgety or restless 

that you have been moving around a 

lot more than usual

9. Thoughts that you would be better off 

dead or of hurting yourself in some 

way*

10. If you are experiencing any of the 

problems listed above, how difficult

have these problems made it for you 

to do your work, take care of things at 

home, or get along with other people?

 Not difficult at all

 Somewhat difficult

 Very difficult

 Extremely difficult

11. If these problems have caused you 

difficulty, have they caused you 

difficulty for 2 years or more?

 Yes, I have had difficulty with these 

problems for 2 years or more.

 No, I have not had difficulty with 

these problems for 2 years or more.

* If you have had thoughts that you would be better off dead or of hurting 

yourself in some way, please discuss this with your health care provider, go to 

a hospital emergency room, or call 911.

Severity scores: For each reply, not at all = 0; several days = 1; more than half the 

days = 2; nearly every day = 3

Number of Symptoms: Severity Score:

Source: JAMA 1999;282(18):1737

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Scoring the PHQ: The PHQ can assist in diagnosing depression as well as 

in planning and monitoring depression treatment. The PHQ score has three 

components: 1) number of depressive symptoms; 2) severity score; and 3) 

functional assessment. The number of depressive symptoms is used to aid in 

making the diagnosis of depression. The severity score and functional assessment 

are measured at initial assessment and regularly after treatment begins to 

determine baseline depression severity and assess ongoing patient progress.

Diagnosis (number of depressive symptoms): For questions 1–8, count the number 

of symptoms for which the patient checks “More than half the days” or 

“Nearly every day.” For question 9, count the question positive if the patient 

checks “Several days,” “More than half the days, or “Nearly every day.” Use 

the following interpretation to diagnose depression subtypes:

• 0–2 PHQ symptoms: not clinically depressed

• 3–4 PHQ symptoms: other depressive syndrome (items 1 and 2 must be 

among the symptoms checked)

• 5 or more PHQ symptoms: major depression (items 1 and 2 must be 

among the symptoms checked)

Severity score: Assign a score to each response using the following number values:

• Not at all = 0

• Several days = 1

• More than half the days = 2

• Nearly every day = 3

Total these values to obtain the severity score. Use the following interpretation 

to determine severity:

• 0–4: not clinically depressed

• 5–9: mild depression

• 10–14: moderate depression

• 15 or higher: severe depression

Functional assessment: The final two questions on the PHQ ask the patient how 

emotional difficulties or problems affect work, home life, or relationships with 

other people, and if the difficulty has lasted for 2 years or more.

1. If the patient responds to question 10 with “Very difficult” or 

“Extremely difficult,” then his/her functionality at work, at home, or 

in relationships with other people is significantly impaired.

2. If the patient has had difficulty with these problems for 2 years 

or more (question 11), then consider the diagnosis of dysthymia 

(chronic depression), which may require different management 

strategies from those used to treat acute depression.

Several general medical disorders may be considered in the differential 

diagnosis of major depressive disorder (Table 9-5).

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Table 9-5

Differential Diagnosis of Major Depressive Disorder 

Condition How Differentiated from MDD 

Adjustment 

disorder with 

depressed mood

Sadness is rarely as profound as with MDD; little anhedonia; 

no vegetative symptoms; identifiable precipitant; responsive 

to environmental change; suicidal ideation and intent may still 

occur; severe cases may respond to antidepressants

Bipolar disorder Racing thoughts; increased energy; decreased need for sleep; 

irritability or angry outbursts; hypersexuality; symptoms may 

coexist with depressed mood in a mixed bipolar state

Delirium Fluctuating mental status with altered level of consciousness; 

distractibility; inability to focus or sustain attention; dysarthric 

speech; agitation; medical etiology; onset usually acute

Dementia Less concern with cognitive decline; more gradual changes; may 

respond with laughter; worse at night; specific neurological 

deficits; CT or MRI scan often abnormal

Grief Onset associated with loss; able to respond to positive changes 

in the environment with enjoyment or less sadness; decreasing 

severity over time; preoccupation with deceased or loss; 

“psychotic” symptoms related to the deceased (i.e, seeing or 

being visited by the deceased); rare suicidal intent, although 

reunion fantasies may exist

Medication- or 

substanceinduced mood 

disorders

Onset with use of steroids, anticholinergics, sedative-hypnotics, 

anticonvulsants, anti-Parkinsonian drugs, beta-blockers, anti-TB 

medications, sympathomimetics, AZT, d4T, and all illicit drugs 

(urine toxicology screen, medication history)

Organic mood 

disorder

Identifiable etiology linked by time; may be associated with 

cognitive deficits; test for specific medical conditions (e.g., TSH, 

B12, VDRL or RPR, CNS evaluation); no family history

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Source: Adapted from Guide to the Clinical Care of Women with HIV, 5th ed. 2005;364.

Anxiety

Although depression is the most prevalent mental health problem experienced 

by HIV infected women, anxiety can be a problem as well. HIV infected 

women had significantly higher anxiety symptom scores than uninfected 

women (Am J Psychiatry 2002;159:789). Because anxiety and depression 

are considered by many to be two faces of a single disorder, clinicians should 

assess for both depression and anxiety if a woman exhibits symptoms of either 

disorder. Symptoms of anxiety can be very troubling for women and may 

require intervention. Women with HIV infection may become anxious thinking 

about the future, may feel uncertain about what will happen to them, and may 

shut down because they believe they cannot cope. Women with limited social 

support may be particularly susceptible to developing anxiety symptoms. 

Often the victims of neglectful or abusive parents themselves, many women with 

HIV have not been taught the coping skills that would help them successfully 

negotiate life’s hurdles. When anxiety symptoms are severe or persistent, a 

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woman may have an anxiety disorder, which may manifest as generalized 

anxiety disorder, panic disorder, obsessive-compulsive disorder, or PTSD 

(Anxiety Disorders. National Institute of Mental Health. 2009; http://www.

nimh.nih.gov/health/publications/anxiety-disorders/nimhanxiety.pdf. Accessed 

7/17/2012).

Screening for anxiety: Questions to ask include the following (DSM-IV-TR; 

Arlington, VA: American Psychiatric Association; 2000):

• Do you often worry or feel nervous?

• Are you often fearful of interacting with other people?

• Do you ever feel jittery, short of breath, or like your heart is racing?

• Do you ever feel as if you might lose control or fear that you may 

be “losing it”?

Screening for PTSD: If there is reason to suspect PTSD, the following questions 

may be helpful in screening for that disorder (DSM-IV-TR; Arlington, VA: 

American Psychiatric Association; 2000):

• In your life, have you ever had any experience that was so upsetting, 

frightening, or horrible that you

- Have nightmares about it or think about it when you 

do not want to?

- Try hard not to think about it or go out of your way to 

avoid situations that remind you of it?

- Are constantly on guard, watchful, or easily startled?

- Feel numb or detached from others, activities, or your 

surroundings?

Wide range of manifestations: Anxiety can present with a wide range of 

physiologic manifestations, as outlined in Table 9-3. Just as with depression, 

women with a history of anxiety are susceptible to symptom recurrence. An 

anxiety disorder occurs when symptoms interfere with a woman’s daily function, 

interfere with personal relationships, or cause marked subjective distress. 

Anxiety-like symptoms may be caused by other mental health disorders, 

making it difficult, for example, to distinguish depression with agitation from 

an adjustment disorder with anxious mood. Adjustment reactions, however, 

usually follow a stressful event, which is rarely the case with clinical depression. 

Moreover, adjustment reactions are less likely to present with the vegetative 

symptom complex seen in depression, including insomnia, diminished appetite, 

loss of pleasure/interest, feelings of guilt, and fatigue (The Role of the Primary 

Care Practitioner in Assessing and Treating Mental Health in Persons With HIV. 

© New York State Department of Health AIDS Institute, 2000-2012. Accessed 

8/1/2012).

Underlying medical conditions, such as CNS pathologies, systemic or metabolic 

illness, endocrine disorders, respiratory or cardiovascular conditions, or 

substance intoxication/withdrawal, can cause anxiety-like symptoms, as can 

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certain medications. Once these have been ruled out as the source of symptoms, 

the clinician should determine which anxiety disorder is causing the symptoms. 

Table 9-6 outlines how to distinguish among various anxiety disorders.

Table 9-6

Distinguishing Among Anxiety Disorders

Disorder Distinguishing Characteristics

Adjustment 

disorder with 

anxious mood

History of stressful situations causing nervousness or upset

Generalized 

anxiety disorder

Worrying/ruminating about a variety of things for months

Obsessivecompulsive 

disorder

Intrusive, disturbing thoughts; compulsive rituals

Panic attacks/

panic disorder

Discrete episodes of intense anxiety/fear with chest pain, 

pounding heart, diaphoresis, shortness of breath

Phobia Fear/avoidance of certain situations, places, or objects

PTSD History of a traumatic event that continues to cause great 

distress, with symptoms lasting more than 1 mo (if the event 

occurred less than 1 mo ago, this is an acute stress disorder)

Source: The Role of the Primary Care Practitioner in Assessing and Treating Mental Health in 

Persons With HIV. © New York State Department of Health AIDS Institute, 2000-2012

For some patients, if symptoms are mild, basic supportive and behavioral 

interventions may be sufficient. A variety of strategies may be helpful, 

including the following:

• Express empathy

• Educate the patient about anxiety

• Reassure the patient that anxiety can be the cause of somatic symptoms

• Identify the psychological factors that contribute to anxiety

• Prepare the patient for stressful situations and assist in the development 

of positive coping mechanisms

• Teach her simple breathing exercises; slow, deep, focused breathing 

can be helpful

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Psychopharmacology

General Guidelines

The following general principles should guide the prescription of psychotropic 

drugs to HIV infected women (Guide to the Clinical Care of Women with HIV, 

5th ed. 2005;365)

• Start low, go slow: Evidence indicates that, in general, women 

require lower doses of antipsychotic medications than men. Use 

slow upward titration as with geriatric patients (Diabetes Care

2004;27:596; Am J Psychiatry 2004;161:1324).

• Expect the unexpected: HIV infected patients often experience 

unusual side effects, common side effects at low doses, or 

complicated drug-drug interactions

• Monitor dynamically: Changes in weight or metabolism, changes in 

other medications, or episodes of medical illness require frequent 

updating and re-evaluation of dosing or choice of medications. This 

is particularly important with increased weight or abdominal girth, 

new onset of hyperlipidemia, or hyperglycemia.

• Coordinate among disciplines: Psychiatrists and primary health care 

providers should be in regular communication with each other about 

clinical updates, dosing changes, and major medical events

• Suspect substances: Depression may be complicated by alcohol use, 

anxiety by withdrawal syndromes, and mania by psychostimulant 

use. Patients often forget that when their substance consumption has 

decreased, their CNS sensitivity to the effects of these substances 

increases over time.

• Address medication adherence: Use medication boxes, simple 

regimens, written instructions, coordination with antiretroviral 

therapies, and patient education. Nonadherence or discontinuation 

may diminish the overall treatment effect if adherence is not 

specifically targeted (J Clin Psychiatry 1999;60:741).

• Attend to potential drug-drug interactions: Drug-drug interactions 

are a concern when coprescribing psychotropic and antiretroviral 

(ARV) medications. The primary cytochrome P450 systems at issue 

with psychiatric medications are CyP2D6 and CyP3A4 (Guide to the 

Clinical Care of Women with HIV, 5th ed. 2005;365). Most studies 

that have examined the concurrent use of antiretroviral (ARV) drugs 

and psychotropic medications have included few women. For drug 

interactions between psychotropic medications and ARVs, see Table 

13-8, p. 500.

SSRIs: Selective serotonin reuptake inhibitors (SSRIs), the drugs most commonly 

used to treat depression, are also effective against a variety of anxiety 

disorders (Depress Anxiety 2007;24:185). The SSRIs have a range of effects, 

from activating or stimulating to sedating.

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Bupropion: Bupropion is often used for smoking cessation; it has no known 

drug-drug interactions and no sexual side effects. It may be helpful to 

decrease craving in patients with a history of substance abuse.

Antipsychotics: Second-generation antipsychotic agents (e.g., aripiprazole) 

are routinely recommended over traditional antipsychotics (e.g., haloperidol), 

except for acute or short-term use, because of their potential to improve 

psychotic symptoms and the lower associated incidence, compared with 

traditional antipsychotic agents, of extrapyramidal side effects and long-term 

risk of dyskinesia.

Side effects: Common potential side effects of all antidepressant medications 

include agitation, irritability, sedation, sexual dysfunction, weight gain, 

headache, gastrointestinal distress, dry mouth, and activation of mania. 

Benzodiazepine use may be complicated by tolerance, dependence and 

withdrawal syndromes, including rebound anxiety, and patients should be 

warned about sedation, cognitive effects, and slowed reflexes when using these 

agents. Patients who experience severe or unusual side effects, have multiple 

diagnoses, require multiple medications, or are not responding to routine doses 

of initial medications should be referred for psychiatric consultation (Guide to 

the Clinical Care of Women with HIV, 5th ed. 2005;366).

Common Psychiatric Medications

Table 9-7 lists common psychiatric medications (in alphabetical order within 

drug classes; order does not indicate priority for use).

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Table 9-7

Common Psychiatric Medications

Disorder Medications and Common Dosing Ranges*

Alcohol Dependence

Initiate only after 

alcohol withdrawal 

for maintenance of 

abstinence

• Acamprosate (Campral): 333 mg tid; continue even if relapse

• Disulfiram (Antabuse): up to 500 mg qd x 1–2 wk; 

maximum 500 mg qd

• Naltrexone (Revia): 50 mg qd; must also be opioid-free 

x 7–10 d

Alcohol Withdrawal

Doses needed may 

be higher with 

significant tolerance 

or combined alcohol 

and benzodiazepine/

barbiturate 

dependence

Observe carefully 

and stop treatment if 

signs of respiratory 

depression or if 

patient is difficult to 

arouse

• Alprazolam (Xanax): 0.5–1 mg bid x 7–10 d

• Chlordiazepoxide (Librium): 50–100 mg initially, to be 

followed by repeated doses as needed until agitation is 

controlled; dosage then may be reduced to maintenance 

levels; maximum dose 300 mg qd. In acute setting, initial 

doses may be given IM or IV.

• Clorazepate dipotassium (Tranxene): Maximum 90 mg qd; 

divide doses bid-tid:

- Day 1: initial, 30 mg; then 30–60 mg

- Day 2: 45–90 mg qd

- Day 3: 22.5–45 mg qd

- Day 4: 15–30 mg qd

- Day 5 and after: 7.5–15 mg qd until patient’s condition 

is stable

• Avoid excessive reductions on successive days

• Lorezapam (Ativan): 2 mg q 6h for 4 doses, then 1 mg q 

6h for 8 doses 

Anxiety Disorders, 

Panic Attacks, PTSD

Unless otherwise 

noted, increase dose 

gradually to lowest 

effective dose

• Citalopram† (Celexa): For panic disorder, 20–30 mg qd; 

maximum dose 60 mg qd

• Escitalopram† (Lexapro): For generalized anxiety disorder, 

10–20 mg qd

• Fluoxetine† (Prozac): For panic disorder, 10–60 mg qd

• Paroxetine† (Paxil):

- Generalized anxiety disorder: 20–60 mg qd

- Panic disorder: 10–60 mg qd (immediate release); 12.5–

75 mg qd (controlled release)

- PTSD: usual effective dose is 20 mg qd

• Sertraline† (Zoloft): For panic disorder and/or PTSD, 

25–200 mg qd A.M.

• Venlafaxine† (Effexor): For generalized anxiety and/or 

panic disorder, 37.5–225 mg qd in single dose (extended 

release)

• Alprazolam† (Xanax):

- Anxiety: 0.25–0.5 mg tid to maximum 4 mg qd in divided 

doses (immediate release or orally disintegrating tablet)

- Panic disorder: 0.5 mg tid (immediate-release or orally 

disintegrating tablet) to maximum 10 mg qd in divided 

doses; 0.5–1 mg qd (extended release); usual dosing 

range 3–6 mg qd

• Clonazepam† (Klonopin): For panic disorder, 0.25 mg bid 

up to maximum 4 mg qd in 2–3 divided doses

• Lorazepam† (Ativan): For anxiety, 2–10 mg qd divided 

bid-tid

• Buspirone (Buspar): For anxiety, 5 mg bid-tid or 7.5 mg 

bid–60 mg qd in 2–3 divided doses

• Duloxetine† (Cymbalta): For generalized anxiety disorder, 

30–120 mg qd; delayed-release capsules should be 

swallowed whole—do not cut, crush, chew, or sprinkle

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Table 9-7

Common Psychiatric Medications

Disorder Medications and Common Dosing Ranges*

Bipolar Mood 

Disorder

Unless otherwise 

noted, increase dose 

gradually to lowest 

effective dose

• Aripiprazole (Abilify): For mania or mixed episodes, 

15–30 mg qd

• Carbamazepine (Tegretol): 800–1600 mg in divided 

doses; may increase in increments of 200 mg qd, titrated 

slowly by blood levels (4–12 mcg/ml)

• Lamotrigine (Lamictal): 25–200 mg qd

• Lithium carbonate: Use requires ability to obtain lithium levels, 

as toxicity can occur at doses close to therapeutic levels

- Acute mania: 600 mg tid (immediate-release tablet and 

capsule); 1800 mg qd (extended-release tablet) in 2–3 

divided doses; desired serum level 1–1.5 mEq/L

- Maintenance therapy: 300 mg 3–4 x qd (immediaterelease tablet and capsule); 900–1200 mg qd 

(extended-release tablet) in 2–3 divided doses; desired 

serum level 0.6–1.2 mEq/L

• Olanzapine (Zyprexa): 10–15 mg qd; increase in 5 mg 

increments at intervals not less than 24 h; maximum dose 

20 mg qd

• Quetiapine (Seroquel):

- Depression phase: 50 mg qd (regular release and 

extended release), with rapid scale-up in initiation phase; 

usual maintenance dosage range is 400–800 mg qd, 

given in divided doses bid

- Manic phase: 50 mg bid (regular release); increase 

over 4–6 d, usual dosage range 400–800 mg qd, given 

in divided doses bid; 300 mg qd (extended release); 

increase over 3 d; usual dosage range 400–800 mg qd

• Risperidone (Risperdal): 2–3 mg qd; may increase in 

increments of 1 mg qd to maximum 6 mg qd

- Valproate/valproic acid (Depakote): For acute mania, 

250 mg tid (delayed release); increase rapidly to 

lowest effective dose; maximum 60 mg/kg/d; usual 

trough plasma level 50–125 mcg/mL; 25 mg/kg/d qd 

(extended release); increase rapidly to lowest effective 

dose; maximum dose 60 mg/kg/d; usual trough plasma 

level 85–125 mcg/mL

• Ziprasidone (Geodon): For acute mania or mixed episodes, 

40 mg bid with food; titrate rapidly to lowest effective 

dose; maximum dose 80 mg bid 

Insomnia • Diphenhydramine: 25–100 mg q hs

• Eszopiclone (Lunesta): 2–3 mg q hs

• Lorazepam (Ativan): 2–4 mg q hs

• Temazepam (Restoril): 7.5–30 mg q hs

• Trazodone (Desyrel, Oleptro): 25–50 mg q hs

• Zolpidem (Ambien): 5–10 mg q hs (immediate release); 

6.25–12.5 mg q hs (extended release); also available 

as oral spray and sublingual tablet with maximum 

10 mg q hs

continued

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Table 9-7

Common Psychiatric Medications

Disorder Medications and Common Dosing Ranges*

Major Depressive 

Disorder (with or 

without anxiety)

Unless otherwise 

noted, increase dose 

gradually to lowest 

effective dose

• SSRIs:

- Citalopram† (Celexa): 20–40 mg qd

- Escitalopram† (Lexapro): 10–20 mg qd

- Fluoxetine† (Prozac): 20–80 mg qd in A.M. or 90 mg q wk

- Paroxetine† (Paxil): 20–50 mg qd (immediate release); 

25–62.5 mg qd in A.M. (controlled release)

- Sertraline† (Zoloft): 50–200 mg qd

• Bupropion† (Wellbutrin):

- 100 mg bid (immediate release); increase slowly to 

maximum 450 mg qd in 3–4 divided doses

- 150 mg once qd (sustained release); increase slowly to 

maximum 200 mg bid

- 150 mg qd (extended release); increase slowly to 

maximum 450 mg qd, given as single dose

• Duloxetine† (Cymbalta): Start with 20 mg bid; maintenance 

dose 60 mg qd; maximum dose 120 mg qd

• Mirtazapine† (Remeron): 15–45 mg q hs

• Venlafaxine† (Effexor):

- 75–225 mg qd (immediate release) in 2–3 divided doses

- 37.5–225 mg qd (extended release) in single dose

Opiate Dependence • Buprenorphine: Prescribing of buprenorphine for this 

indication is limited to qualifying physicians who have 

notified HHS of their intent

- Induction: 12–16 mg/d SL; adjust dose in 2–4 mg 

increments to level that suppresses opioid withdrawal 

effects (typical range 4–24 mg qd)

- Rapid detoxification (with naltrexone and clonidine): 

3 mg/d SL for 3 d

- Methadone maintenance therapy:

o Start 15–30 mg x 1, then 5–10 mg prn q 2–4 h prn; 

maximum 40 mg on day 1

o Adjust dose to prevent withdrawal symptoms x 24 h, 

block euphoric opioid effects

o Stabilize dose x 10–14 d, then decrease dose by up to 

10% q 10–14 d

o Doses >100 mg/d require documentation; maintenance 

therapy permitted only in FDA-approved program

• Naltrexone:

- Do not attempt treatment unless patient has remained 

opioid-free for at least 7–10 d. Verify self-reporting of 

abstinence from opioids in opioid addicts by analysis of 

urine for absence of opioids.

- Patient should not be manifesting withdrawal signs or 

reporting withdrawal symptoms. If there is any question of 

occult opioid dependence, perform naloxone challenge test. 

If signs of opioid withdrawal are still observed following 

naloxone challenge, do not attempt treatment with 

naltrexone. Naloxone challenge can be repeated in 24 h.

- Initiate treatment carefully, with an initial dose of 25 mg 

qd. If no withdrawal signs occur, patient may be started 

on 50 mg qd thereafter

- Extended-release naltrexone also available

continued

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Table 9-7

Common Psychiatric Medications

Disorder Medications and Common Dosing Ranges*

Opiate Withdrawal • Clonidine: 0.3–0.6 mg in 3 divided doses

• Methadone:

- Short-term detoxification:

o 15–30 mg as initial dose, then 5–10 mg q 2–4 h prn; 

maximum 40 mg on day 1; adjust dose to suppress 

withdrawal symptoms

o Stabilize dose x 2–3 days, then decrease dose by up 

to 20% q 24–48 h

o Doses >40 mg/d require documentation

- Drug detoxification:

o Opioid abuse: Initial dose 15–30 mg orally; additional 

5–10 mg can be given 2–4 h later if needed

o Adjust dose cautiously over first week based upon 

control of withdrawal 2–4 h post dose

o Usual total daily dose 40 mg qd; keep on stable dose 

for 2–3 d, then decrease in 1–2-d intervals according 

to response

o Detoxification treatment usually occurs over 21 d

- Opioid abuse, maintenance therapy:

o Individualize maintenance doses

o Titrate to a dose that prevents symptoms for 24 h

o Usual maintenance doses range from 80–20 mg qd 

Psychotic 

Symptoms and/or 

Schizophrenia

Unless otherwise 

noted, increase dose 

gradually to lowest 

effective dose

Periodically reassess 

need for treatment; 

d/c if ANC <1000; 

consider d/c 

if unexplained 

decrease in WBC

• Aripiprazole (Abilify): 10–15 mg qd; maximum 30 mg qd

• Olanzapine (Zyprexa): 5–10 mg qd; maximum 20 mg qd

• Paliperidone (Invega): 6 mg qd A.M. (extended release); 

maximum 12 mg qd; do not cut, crush, or chew

• Quetiapine (Seroquel):

- Start at 25 mg bid (regular release); usual effective 

range is 150–750 mg qd, in divided doses; maximum 

800 mg qd

- With extended-release formulation, start at 300 mg qd; target dose range 400–800 mg/d; maximum 800 mg/d

• Risperidone (Risperdal): Start at 1 mg qd or bid; maximal 

effect usually seen with 4–8 mg qd; do not cut or chew 

orally disintegrating tablet

• Ziprasidone (Geodon): Start at 20 mg bid with food; 

maximum 80 mg bid

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

*All doses are for oral administration, unless otherwise noted. Many psychiatric medications 

are now available in extended-release, rapidly dissolving, liquid, and parenteral forms.

†Taper dose gradually to discontinue

Source: Adapted from Guide to the Clinical Care of Women with HIV, 5th ed. 2005;367. 

Dosing recommendations from Epocrates® Online

continued

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Substance Abuse

Substance abuse is differentiated from substance dependence; in the latter 

the impairment is more pervasive and includes physical dependence and 

withdrawal symptoms.

Substance Use and Addictive Disorders: DSM-V-TR Criteria

(DSM-V-TR; Arlington, VA: American Psychiatric Association; 2013)

The old categories of substance abuse and dependence have been replaced 

with the new “substance use and addictive disorders” classification. The term 

“dependence” was felt to be misleading, often applied to tolerance and 

withdrawal, which are normal responses to prescribed medications that affect 

the central nervous system. The new category for addictive diseases includes a 

variety of “substance-use disorders” broken down by drug type. 

Substance use disorder:

A. A maladaptive pattern of substance use leading to clinically 

significant impairment or distress, as manifested by two or more of 

the following, occurring within a 12-month period:

1. Recurrent substance use resulting in a failure to fulfill major role 

obligations at work, school, or home (e.g., repeated absences 

or poor work performance related to substance use; substancerelated absences, suspensions, or expulsions from school; neglect 

of children or household)

2. Recurrent substance use in situations in which it is physically 

hazardous (e.g., driving an automobile or operating a machine 

when impaired by substance use)

3. Continued substance use despite having persistent or recurrent 

social or interpersonal problems caused or exacerbated by 

the effects of the substance (e.g., arguments with spouse about 

consequences of intoxication, physical fights)

Tolerance, as defined by either of the following:

• Need for markedly increased amounts of the substance to achieve 

intoxication or desired effect

• Markedly diminished effect with continued use of the same amount 

of the substance

Withdrawal, as manifested by either of the following:

• Characteristic withdrawal syndrome for the substance

• Same or a closely related substance is taken to relieve or avoid 

withdrawal symptoms

• Substance is often taken in larger amounts or over a longer period 

than was intended

• Persistent desire or unsuccessful efforts to cut down or control 

substance use

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• A great deal of time is spent on activities necessary to obtain the 

substance (e.g., visiting multiple doctors or driving long distances), 

use the substance (e.g., chain smoking), or recover from its effects

• Important social, occupational, or recreational activities are given up 

or reduced because of substance use

• Substance use is continued despite knowledge of having a persistent 

or recurrent physical or psychological problem that is likely to have 

been caused or exacerbated by the substance (e.g., current cocaine 

use despite recognition of cocaine-induced depression, continued 

drinking despite recognition that an ulcer was made worse by 

alcohol consumption)

• Craving or strong desire or urge to use a specific substance

Women who have a substance use disorder expend an extraordinary amount 

of time and energy in pursuit of their drug of choice at the expense of their 

own health and the health and well-being of their children.

Scope of the problem: An estimated one in five new HIV diagnoses in women 

is related to injection drug use (HIV/AIDS among Women. U.S. Centers for 

Disease Control and Prevention [CDC] HIV/AIDS Fact Sheet. 2008; http://

www.cdc.gov/hiv/topics/women/pdf/women.pdf. Accessed 7/26/2012) 

and 60% of new AIDS cases in women represent sexually acquired HIV from 

drug-using partners (Medical Care of HIV-Infected Substance-Using Women. 

© New York State Department of Health AIDS Institute, 2000-2012; http://

www.hivguidelines.org/clinical-guidelines/womens-health/medical-care-of-hivinfected-substance-using-women/. Accessed 7/26/2012). Few specific data 

exist on substance abuse disorders in HIV infected women. The WIHS found 

that 27% of HIV infected women reported crack, cocaine, or injection drug 

use (AIDS 1999;13:591). Crack cocaine in particular has disproportionately 

affected African-American women. Women who smoke crack are more likely 

than other women to sell sex or have an STD; women who smoke crack also 

have more sexual partners (Health and Human Rights 1998;2(4):42).

Methamphetamine (i.e., meth, speed, ice, crystal, crank) abuse is a significant 

problem in the United States, though it has been decreasing in recent years; 

in some parts of the country, methamphetamine is the third most common drug 

of abuse after alcohol and marijuana. Although limited data are available on 

methamphetamine use by HIV infected women, this drug is known to increase 

risky sexual behavior and has been associated with an increased proportion 

of drug-treatment admissions in pregnancy. (Methamphetamine Use and Risk for 

HIV/AIDS. CDC. 2007; http://www.cdc.gov/hiv/resources/factsheets/meth.

htm. Accessed 8/1/2012).

Greater vulnerability: At a more complex level, the intersection of HIV 

infection, poverty, and race/ethnicity in HIV infected women places them on 

the outer fringes of society and increases their vulnerability to substance use/

abuse. Substance abuse in women may begin because of childhood trauma, 

in an attempt to numb the pain and shame felt as a result of sexual abuse. If 

a woman left home in her teens because of abuse, she may resort to survival 

sex, and substance use may continue in order to counteract despair and 

shame. Women who are injection drug users (IDUs) are more likely than male 

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IDUs to adopt the drug-use patterns of and share needles with their partners. 

Although women often start using drugs and alcohol at older ages than men, 

some studies suggest that women become addicted more quickly, with a more 

“telescoped” course from use to abuse. Although the incidence of alcohol 

abuse or dependence is greater among men than women, women with alcohol 

abuse or dependence are more likely to seek medical help but less likely to 

be identified by their healthcare providers (J Gen Intern Med 2002;17:387). 

Drug-involved women often rely on their partners to procure the drugs they 

share and because women are often injected by their partners, they are 

“second on the needle,” which increases their risk for infection with HIV. For 

women who have a substance abuse problem, refusing to share needles and 

syringes can also increase the risk of physical and sexual violence, further 

potentiating risks for HIV infection and re-infection (Lancet 2010;376:312).

Whether HIV is acquired sexually or through IDU, ample evidence exists that 

substance abuse plays a significant role in the lives of women who abuse 

drugs or alcohol (J Assoc Nurses AIDS Care 2004;15(5):48). Sharing injection 

equipment, exchange of sex for drugs, and the likelihood of risky sexual 

behaviors (e.g., unprotected sex, multiple sexual partners), particularly when 

under the influence of drugs or alcohol, are all increased in the setting of 

substance abuse and all increase risk for HIV (HIV/AIDS among Women. CDC 

HIV/AIDS Fact Sheet). Although reports of substance abuse in HIV infected 

women often focus only on IDU, noninjection drugs also play a critical role in 

HIV transmission due to impaired decision making and disinhibition that leads 

to high-risk behaviors.

Substance abuse following HIV diagnosis: Women may exhibit three patterns 

of substance abuse upon learning of their HIV infection. Many accelerate 

their use/abuse out of despair and uncertainty and/or a belief that death is 

imminent (J Assoc Nurses AIDS Care 2004;15(5):48). Some decrease their use 

or stop altogether, realizing that they must be able to participate in a plan of 

medical care if they are to survive and understanding that continued use of 

drugs/alcohol would likely preclude optimal care. A few nonusers initiate use 

of drugs/alcohol, for many of the same reasons given by those who accelerate 

use (J Assoc Nurses AIDS Care 2004;15(5):48). Continued or accelerated 

substance use in the context of an HIV diagnosis also adds to the stigmatization 

women feel, particularly those who are mothers.

Substance Abuse Comorbidities

HIV infected women who abuse drugs and/or alcohol are at risk of developing 

other medical conditions (Table 9-8). These comorbidities can be difficult to 

treat with coexistent HIV infection and signs and symptoms of the various 

conditions may be difficult to distinguish. Comorbidities may also accelerate 

HIV progression and/or complicate HIV management (Guide to the Clinical 

Care of Women with HIV, 5th ed. 2005). Several factors, including lower body 

weight, lower total body water, and lower levels of alcohol dehydrogenase, 

may contribute to greater sensitivity to alcohol’s long-term effects among 

women compared with men.

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Table 9-8

Medical Conditions and Sequelae Associated with Drug and Alcohol 

Abuse

• Bacteremia

• Cancer

• Cellulitis

• Cirrhosis

• Cognitive dysfunction

• Cutaneous abscesses

• Endocarditis

• Hepatitis (A, B, C, D and GB virus C)

• HIV

• Pneumonia

• Poor nutrition

• Septic emboli

• Sexually transmitted infections

• Thrombophlebitis

• Trauma

• Tuberculosis

Source: Guide to the Clinical Care of Women with HIV, 5th ed. 2005;380

The conditions listed in Table 9-8 represent only a few of the many disease 

states that are either directly associated with or exacerbated by substance 

abuse. Excessive alcohol use also places women at risk for epilepsy, psychiatric 

disorders, cardiomyopathy, peptic ulcer disease, pancreatitis, and malignancies. 

Smoking tobacco is the most common cause of lung cancer and airway diseases 

and has been implicated in other malignancies such as cervical carcinoma 

(Guide to the Clinical Care of Women with HIV, 5th ed. 2005;380; Gynecol 

Oncol 1994;55(1):91). Methamphetamine use has been associated with 

neurologic deficits, severe dental problems, arrhythmias, hypertension, seizures, 

depression, suicidal ideation, and psychosis (Addiction 2010;105:991).

Liver disease: Both HIV and alcohol abuse appear to accelerate viral 

hepatitis–induced liver damage and are major risk factors for progression 

of liver disease and death from liver disease (Guide to the Clinical Care 

of Women with HIV, 5th ed. 2005;380); AIDS Res Hum Retroviruses

2002;18:757). End-stage liver disease has become the leading cause of death 

in specific patient populations with HIV infection.

Antiretroviral therapy: Treatment with ART is associated with improved 

outcomes in HIV infected patients with substance abuse and comorbidities such 

as hepatitis (Hepatology 2001;34:283). This underscores the importance of the 

timely identification and treatment of substance abuse and its sequelae as well 

as HIV. In both substance abuse treatment programs and primary care clinics, 

strategies are needed to identify and manage HIV and recognize comorbid 

conditions associated with HIV and/or substance abuse or have established 

linkages into appropriate care (Guide to the Clinical Care of Women with HIV, 

5th ed. 2005;381)

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Identification of Substance Abuse

Problems with substance and/or alcohol abuse can be identified in several 

ways. Table 9-9 provides clues that may be picked up when a woman’s clinical 

history is taken.

Table 9-9

Clues to Drug and Alcohol Abuse

Medical History Behavior Social History

• HIV infection

• Endocarditis

• Hepatitis B or C infection

• Septic emboli

• Septic thrombophlebitis

• Pancreatitis

• Cirrhosis

• Agitation

• Somnolence

• Disorientation

• Erratic behavior

• “Doctor hopping”

• Frequent unexplained 

accidents

• Inability to retain 

employment

• Child custody loss

• Seemingly unexplainable 

financial difficulties

• Relationship distress

Source: Guide to the Clinical Care of Women with HIV, 5th ed. 2005;383

Specific questions such as the following can assess for drug use or abuse:

• Have you ever used any street drugs such as heroin, methamphetamine, 

ecstasy, cocaine, crack, or marijuana?

• When was the last time? How often do you use?

• Are you interested now in any substance use services or treatment?

There are also screening tools that are effective in identifying drug use, such as 

the ASSIST and the DAST.

If the patient has a history of substance abuse or is currently using, proceed 

with further evaluation and referral to a treatment program or mental health 

specialist. Intervention is indicated when there is evidence of adverse affects 

owing to substance abuse on the woman’s physical and/or mental health, 

relationships, or job.

Assessing for alcohol abuse: Several tools are available to screen for alcohol 

abuse in women. One measure is the TWEAK questionnaire (Alcohol Clin Exp 

Res 1991;15(6):991):

• Tolerance: How many drinks can you hold (“hold” version; ≥ 6 

drinks indicates tolerance) or How many drinks does it take before 

you begin to feel the first effects of the alcohol? (“high” version; ≥ 

3 indicates tolerance).

• Worried: Have close friends or relatives worried or complained about 

your drinking in the past year?

• Eye openers: Do you sometimes take a drink in the morning when you 

first get up?

• Amnesia: Has a friend or family member ever told you about things you 

said or did while you were drinking that you could not remember?

• Kut down: Do you sometimes feel the need to cut down on your drinking?

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Score 2 points each for a positive response to Tolerance or Worried; 1 point 

each for a positive response to Eye opener, Amnesia or Kut down; the range 

of summed points is 0 to 7. A score of 3–7 indicates that the patient has an 

alcohol problem.

Another measure is the T-ACE (Am J Obstet Gynecol 1989;160(4):863):

• How many drinks does it take for you to feel high? (Tolerance)

• Have people Annoyed you by criticizing your drinking?

• Have you ever felt you ought to Cut down on your drinking?

• Have you ever had a drink first thing in the morning to steady your 

nerves or get rid of a hangover? (Eye opener)

Any woman who answers “more than two drinks” on the Tolerance question is 

scored 2 points. Each yes to the subsequent three questions scores 1 point. A 

score of 2 or more is considered a positive screen and the woman should be 

referred to a specialist for further assessment.

The care provider can also ask about quantity and frequency of alcohol use. 

For women, more than seven drinks per week or more than three drinks on any 

one occasion may put them at risk for developing alcohol dependence (Women 

and Alcohol. National Institute on Alcohol Abuse and Alcoholism [NIAAA]. 

2011; http://pubs.niaaa.nih.gov/publications/womensfact/womensfact.

htm. Accessed 8/1/2012). One standard drink is equivalent to 12 ounces 

(354.9 mL) of beer, 5 ounces (147.9 mL) of wine or 1.5 ounces (44.4 mL) of 

80-proof spirits (Women and Alcohol. NIAAA. 2011).

Physical symptoms or signs of long-term alcohol abuse include the following 

(Guide to the Clinical Care of Women with HIV, 5th ed. 2005):

• Loss of appetite, eating poorly, weight loss

• Spider angiomas on the skin

• Swelling or redness of the palms of the hands

• Redness on the face, especially the nose and cheeks

• Repeated skin sores or abscesses

• Numbness or tingling in feet and hands (this symptom could also 

indicate peripheral neuropathy related to HIV or ART)

• Unsteady gait

• Abnormal liver function tests, other liver problems such as cirrhosis

The physical signs of other substance abuse depend on which drug(s) are 

being abused. Physical examination findings are limited but may include 

injection marks, nasal lesions or recurrent epistaxis, poor dentition, or poor 

nutritional status. Signs or symptoms of intoxication or withdrawal are highly 

suggestive of substance use disorder. A toxicology screen or blood alcohol 

level may also be of use (Ferri’s Clinical Advisor. Philadelphia, PA: Elsevier; 

2011). Cocaine snorting can be suspected by observation of damaged nasal 

mucosa; hypodermic marks or “tracks” suggest IDU, although the absence of 

visible marks does not rule this out. The single most useful examination is of the 

eyes: nystagmus is often seen in abusers of sedatives/hypnotics or cannabis; 

dilated pupils are often seen in people under the influence of stimulants or 

hallucinogens or in withdrawal from opiates; pupillary constriction is a classic 

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hallmark of opioid effect. Evidence of multiple minor (or past major) injuries 

can also be a clue to possible substance abuse (Guide to the Clinical Care of 

Women with HIV, 5th ed. 2005;385).

Drug Testing

Drug testing for substances of abuse may be performed for clinical indications 

(e.g., need to exclude drugs as cause of acute change in mental status or 

behavior) or when required for legal indications. Drugs may be detected in 

almost any fluid or tissue in the body (false-positive screens for marijuana and 

the benzodiazepines have occurred in patients taking EFV). The most common 

samples used for drug tests are urine, blood, saliva, hair, sweat, and breath 

(Addiction 1999;94:1279).

Urine tests: Urine testing is the most available, useful, and reliable testing 

format for clinicians to use. Test kits are available for use in offices and 

at home that require the simple collection of a urine sample. Urine testing, 

however, has numerous limitations, including the ability to detect only recent 

drug or alcohol use. Adulterated urine samples and changes in urine acidity 

may prevent the quantification of illegal drugs in urine.

Other tests: Blood testing is available to many caregivers and is more 

accurate for the quantitative detection of drugs in the user; however, it is 

more expensive and more cumbersome than urine analysis. Saliva may be 

useful and correlates well with drug levels in the blood. Hair analysis has the 

advantage of detecting drug use over a 1- to 3-month period, depending on 

a person’s hair growth rate (Anal Bioanal Chem 2010;397(7):2987; J Forensic 

Leg Med 2010;17:254; Ther Drug Monit 2010;32:318). Sweat testing is 

another noninvasive test that is useful for monitoring drug relapse during drug 

treatment. It is designed to continuously monitor a person’s drug use over a 

period of time through a special absorbant pad placed on the skin. The pad 

collects microscopic amounts of sweat produced over time and is analyzed 

later for the presence of drugs. Breath testing is a reliable tool for measuring 

blood alcohol levels.

Interpretation: Drug test results may be difficult for the inexperienced care 

provider to interpret because they may be confounded by secondary drug 

exposures, chemical characteristics of the drugs to be detected, drug-level 

variations in different body tissues and fluids, and test-method variations. Drug 

testing properly used is a useful adjunct to clinical and behavioral drug-use 

assessment and is a useful but limited drug-use screening tool. Drug testing 

may also be helpful during substance abuse therapy and follow-up (Guide to 

the Clinical Care of Women with HIV, 5th ed. 2005;385).

Pregnancy: Drug screening in pregnancy should be performed only with 

consent; the pregnant woman must be informed of the potential ramifications 

of a positive test result, including any mandatory reporting requirements. 

Providers should be aware of laws and regulations in their jurisdictions 

regarding the reporting of maternal toxicology testing (ACOG Committee 

Opinion No. 473; Obstet Gynecol 2011;117:200).

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Treatment Readiness and Harm Reduction

Unmet treatment need: Combined data from the Substance Abuse and Mental 

Health Services Administration’s (SAMHSA’s) National Surveys on Drug Use 

and Health conducted from 2004 to 2006 indicate that, on average, 6.3 

million women annually (9.4% of women aged 18–49) needed treatment for 

a substance use (illicit drugs or alcohol) problem (The NSDUH Report: Substance 

Use Treatment among Women of Childrearing Age. SAMHSA. 2007; http://

www.samhsa.gov/data/2k7/womenTX/womenTX.htm. Accessed 7/17/2012). 

Of the women aged 18–49 who met the criteria for needing substance use 

treatment in the previous year, 84.2% neither received it nor perceived the 

need for it; 5.5% did not receive treatment even though they thought they 

needed it. The reasons for not receiving substance use treatment among women 

with an unmet treatment need were as follows: 36.1% were not ready to 

stop using alcohol or illicit drugs, 34.4% could not cover their treatment costs 

because of lack of or inadequate health insurance coverage, and 28.9% did 

not seek substance use treatment because of social stigma.

Treatment: For women who want treatment for substance abuse, drug/alcohol 

use treatment programs should be provided through community resources, 

along with education programs, social and work skills-building programs, 

health care, and programs to prevent sexually transmitted infections (Guide to 

the Clinical Care of Women with HIV, 5th ed. 2005;388). Table 9-10 describes 

the components of drug and alcohol treatment.

Table 9-10

Components of Drug and Alcohol Abuse Treatment

Personal Needs Treatment Needs

• Family services

• Housing and transport

• Financial services

• Legal services

• HIV/AIDS services

• Educational services

• Medical services

• Vocational services

• Child care services

• Mental health services

• Family planning services

• Behavioral therapy

• Clinical and case management

• Intake and processing

• Treatment plans

• Pharmacotherapy

• Continuity of care

• Substance use monitoring

• Self-help/peer support groups

• Substance education

Source: Guide to the Clinical Care of Women with HIV, 5th ed. 2005;388

The number of substance-abuse treatment programs is inadequate, especially 

for women with few or no resources and/or no insurance. Even when treatment 

is available, the patient may not be ready to go into treatment. Concern for 

children leads many women to seek treatment for substance abuse problems; 

however, many treatment programs do not accept women who are pregnant. 

Women with young children may have ongoing difficulty accessing outpatient 

day treatment and residential programs because of inadequate childcare 

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resources. Fear of the removal of children from the home by the welfare system 

and lack of emotional support from substance-abusing partners are other 

obstacles that may deter women from seeking substance abuse treatment.

Most patients do not seek treatment until symptoms and associated 

consequences are severe. Compared with men, women’s drug-use problems 

tend to occur at an older age and to develop more rapidly. Additionally, 

women often learn of their HIV infection and other comorbid conditions later 

than men. The late diagnosis of drug use and other conditions may result in 

shorter survival. The confluence of factors that complicate health care for 

female substance abusers underscores the importance of the early engagement 

and retention of women in care (Guide to the Clinical Care of Women with HIV, 

5th ed. 2005;388).

Harm reduction: Although barriers exist, harm reduction remains critical. Harm 

reduction refers to measures aimed at reducing the harm caused by substance 

abuse; these measures may be a first step in moving toward abstention. Harmreduction techniques for women who are IDUs include the following: (Cleaning 

Works. 2012; http://www.thewellproject.org/en_US/Living_Well/Health/

Cleaning_Works.jsp; Accessed 7/17/2012)

• Use clean sterile needles and syringes every time injection drugs are used.

• Do not share needles, syringes, cotton, or cookers with others when injecting.

• Participate in a needle exchange program if available and legal 

(these usually have other health promoting services [e.g., HIV/hepatitis 

screening, referral for treatment of substance abuse]).

• Purchase sterile equipment without a prescription from a pharmacy, 

if available.

• If these safer options are not adopted and needles and syringes are 

shared, reduce the risk of infection by always cleaning them in bleach 

and water immediately after use and just before reuse. Although not 

risk free, bleach cleaning is an important risk-reduction tool. (Hydrogen 

peroxide or rubbing alcohol may be substituted if bleach is not 

available; hard alcohol, not beer or wine, should be used if there are 

no other cleaning solutions available.)

• For greater cleaning effectiveness, take the set apart, remove the 

plunger from the barrel and soak both in bleach for at least 30 seconds.

• If the cooker (spoon) must be reused, soak it in bleach for at least 30 

seconds and then rinse it with clean water.

• Because bleach loses its effectiveness with exposure to light, store 

all bleach for cleaning needles and works in a container that blocks 

light from passing through it.

Pharmacologic Interventions for Addiction

Managing withdrawal symptoms: Today even the most severe physical 

withdrawal symptoms can be managed with appropriate pharmacologic 

treatments that control or prevent serious medical consequences of drug or 

alcohol withdrawal. Medications like methadone can help to stabilize an 

opiate-dependent patient and facilitate a return to productive functioning. 

Other important pharmacologic interventions include the treatment of 

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comorbid conditions common in drug- and alcohol-abusing populations, such 

as the treatment of depression. The use of antidepreirected at the effects 

of drugs of abuse. Pharmacologic treatments for drug use are well known 

but not well understood by many healthcare providers. Several classes of 

medications may be used to treat, modulate, or prevent ongoing drug use 

(Guide to the Clinical Care of Women with HIV, 5th ed. 2005; Basic Principles 

for Treatment and Psychosocial Support of Drug Dependent People Living with 

HIV/AIDS. WHO. 2006; http://www.who.int/substance_abuse/publications/

basic_principles_drug_hiv.pdf. Accessed 7/17/2012).

Opiate addiction: Opioid agonists such as methadone and buprenorphine 

are used to treat opiate-dependent persons. When used to treat addiction, 

these drugs block the ability of the illicit drugs to attach to opiate receptors, 

therefore thereby decreasing drug craving without causing euphoria.

The use of opioid agonists is the most misunderstood medical approach to 

addiction treatment. Although methadone and buprenorphine are addictive, 

they are successful in helping addicts stop the negative and harmful behaviors 

associated with drug use and begin to concentrate on developing the skills to 

discontinue drug use entirely. It is drug craving that is associated with drug-use 

relapse and criminal behavior and it is the prevention of drug craving that 

makes substitution medications work successfully as part of a drug treatment 

program (Guide to the Clinical Care of Women with HIV, 5th ed. 2005;389; 

Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid 

Dependence. WHO. 2009; http://www.who.int/substance_abuse/publications/

Opioid_dependence_guidelines.pdf. Accessed 7/17/2012).

• Methadone: Methadone suppresses withdrawal for 24 hours (four 

to six times the duration of the effects of heroin) and decreases or 

eliminates drug craving; it is not sedating, can be dosed once per 

day, and can be administered orally. Furthermore, it is medically 

safe even when used continuously for 10 years or more.

• Buprenorphine: Buprenorphine is a partial opioid agonist for officebased and program-based treatment of opioid addiction. Some of the 

advantages of using buprenorphine are milder withdrawal symptoms, 

a lower risk of overdose, and availability to patients in the offices 

of physicians trained and certified in the medication’s use. If used 

at the proper dosage, buprenorphine is as effective as methadone 

(Guide to the Clinical Care of Women with HIV, 5th ed. 2005;389). 

Recent reports show that buprenorphine/naloxone treatment can be 

successfully integrated into HIV clinical care in a variety of practice 

settings (J Acquir Defic Syndr 2011;56 (suppl 1):S68).

These medications are not a cure for drug dependence but are important 

adjuncts to care. It has been shown that while an opiate user is taking 

methadone, she is much less likely to commit a crime and is more likely to 

succeed in completing a drug treatment program. When combined with 

behavioral therapies or counseling and other supportive services, these 

pharmacologic approaches are highly effective for treating heroin addiction, 

particularly in those with long-term dependence and repeated prior treatment 

failures (Guide to the Clinical Care of Women with HIV, 5th ed. 2005; 

Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid 

Dependence. WHO. 2009).

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Opioid antagonist medications such as naloxone and naltrexone block the 

effects of morphine, heroin, and other opiates. As antagonists, they are 

especially useful as antidotes. Naltrexone, which has a duration of action 

ranging from 1 to 3 days depending on the dose, blocks the pleasurable 

effects of heroin and is useful in treating some highly motivated individuals, 

such as professionals who do not want to lose their jobs. It is also successful 

in preventing relapse by former opiate dependent individuals released from 

prison on probation (Guide to the Clinical Care of Women with HIV, 5th ed. 

2005). Naltrexone is now available as an extended-release formulation, given 

by IM injection once every 4 weeks.

Alcohol addiction: Disulfiram (Antabuse) is used in the context of alcohol 

abuse treatment to cause negative effects when the patient consumes alcohol. 

The drug interferes with alcohol metabolism, causing the production of 

acetaldehyde, a noxious chemical that causes severe flushing, nausea, and 

vomiting. The effectiveness of therapy depends on the patient’s adherence 

to a daily medication dose. Acamprosate is a newer drug currently used in 

Europe that increases alcohol abstinence and decreases craving by affecting 

g-aminobutyric acid and glutamate brain receptors. Naltrexone also has 

been found to decrease alcohol craving and relapse; it was approved by 

the U.S. Food and Drug Administration in 1994 for the treatment of alcohol 

dependence (Am J Psychiatry 1999;156:1758; Arch Gen Psych 1992;49:876; 

Guide to the Clinical Care of Women with HIV, 5th ed. 2005;390). Naltrexone 

is now available as an extended-release formulation, given by IM injection 

once every 4 weeks.

Cocaine addiction: Although no effective medications are available to 

treat cocaine addiction, the treatment of comorbid mental health problems 

may improve the likelihood that a patient will stop using cocaine or crack. 

Pharmacologic therapies have been specifically targeted at decreasing the 

dysphoric effects of cocaine withdrawal. Unfortunately, studies examining 

multiple generations of antidepressant medications such as fluoxetine, 

sertraline, maprotilene, phenelzine, trazodone, and lithium have not 

demonstrated the success of those drugs in assisting with the permanent 

cessation of cocaine or crack use (NIDA Res Monogr 1997;175:36). 

Dopaminergic agents such as bromocriptine, amantadine, haloperidol, 

bupropion, and others have also not been proven to be effective. In studies 

using desipramine, carbamazine, and bupropion, however, the mental-health 

effect of these drugs was clinically helpful for a patient’s successful drug 

cessation in drug treatment programs (Guide to the Clinical Care of Women 

with HIV, 5th ed. 2005;390); Psychiatr Clin North Am 1999;22:401).

Methamphetamine addiction: Evidence is limited on pharmacologic treatments 

for methamphetamine abuse; however, three double-blinded placebocontrolled trials using modafinil, bupropion and naltrexone have shown 

positive results in reducing amphetamine or methamphetamine use. The agonist 

replacement medications d-amphetamine and methylphenidate have shown 

promise in two studies (Br J Clin Pharmacol 2010;69(6):578).

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Nonpharmacologic Approaches

Behavioral and cognitive interventions: Behavioral and cognitive interventions 

are a vital part of drug and alcohol addiction treatment and prevention. 

Cognitive-behavioral therapies are based on the assumption that learning 

processes play an important role in the development of drug use and 

dependence and are therefore important to efforts to reduce use and 

dependence. Behavioral methods are employed to identify high-risk relapse 

situations, extinguish triggers to drug use, develop self-monitoring of use 

behavior, and establish competing coping responses. By learning to recognize 

situations conducive to substance use, patients can develop individual coping 

strategies to avoid circumstances that place them at risk for relapse. Perhaps 

the single most important factor for short- and long-term relapse prevention 

is the learning and application of individual coping skills. Avoidance of other 

drug users and drug-use environments are key tools for maintaining abstinence 

(Guide to the Clinical Care of Women with HIV, 5th ed. 2005).

At least 11 research-validated therapies use a variety of behavioral, social, 

and incentive-based systems to treat drug use. The objectives of these 

programs include

• removing patients from stressful environments to get care (short-term 

and long-term residential homes),

• providing alternatives to pharmacologic treatment (outpatient drug-free 

programs), and

• providing community-specific interventions (community-based 

programs for drug users and recently released criminals).

Several effective psychotherapy programs are based on a patient’s willingness 

to recognize drug use as a problem and to stay off drugs, with or without 

incentives (Guide to the Clinical Care of Women with HIV, 5th ed. 2005;392).

Twelve-step programs: Twelve-step self-help groups and meetings are 

important nonmedical, behavioral drug-use intervention and prevention 

activities used by millions of people. These meetings emphasize fellowship 

and provide support for maintaining abstinence from alcohol, other drugs, 

or addictive behaviors like overeating. These programs are not intended to 

replace medical and behavioral drug-use treatments but are meant to add 

to their effectiveness. The largest 12-step groups are Alcoholics Anonymous 

(AA); Narcotics Anonymous (for all drug users, including alcoholics); Al-Anon, 

to support family members and friends of alcoholics and drug users; and 

Overeaters Anonymous (Guide to the Clinical Care of Women with HIV, 5th ed. 

2005;392). Other self-help resources include Rational Recovery, which does not 

have the religious overtones of AA, and Moderation Management.

Pregnancy and Substance Abuse

Alcohol: Data from SAMHSA’s National Surveys on Drug Use and Health, 

conducted in 2002 through 2007, were used to compare alcohol-drinking 

rates, frequency, and quantity among women aged 15–44. Those surveyed 

were divided into three groups: 1) pregnant women; 2) recent mothers (i.e., 

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had a child within the previous 12 months); and 3) all other women in this age 

group. Pregnant women (11.6%) were significantly less likely to have used 

alcohol in the past month than recent mothers (42.1%) or all other women 

(54.0%). Among current alcohol drinkers, pregnant women drank alcohol on 

fewer days than other women. Pregnant women also had fewer drinks on their 

drinking days (The NSDUH Report: Substance Use Treatment among Women 

of Childrearing Age. SAMHSA, 2007; http://www.samhsa.gov/data/2k7/

womenTX/womenTX.htm; Accessed 7/17/2012).

Alcohol use in pregnancy is associated with the risk of fetal alcohol 

syndrome, a congenital syndrome characterized by growth retardation, 

facial abnormalities, and CNS dysfunction. Skeletal abnormalities and 

structural cardiac defects are also seen in the fetal alcohol syndrome, but it 

is the performance deficits that are most obvious. Decreased IQ, fine-motor 

dysfunction, and hyperactivity are all common findings (ACOG Technical 

Bulletin No. 195; Int J Gynaecol Obstet 1994;47(1):73; Guide to the Clinical 

Care of Women with HIV, 5th ed. 2005;395).

Illicit drugs: Combined 2004 and 2005 data showed that among pregnant 

women aged 15–44 years, 3.9% reported using illicit drugs in the previous 

month. This rate was significantly lower than that among women aged 15–44 

who were not pregnant (9.9 %) (The NSDUH Report: Substance Use Treatment 

among Women of Childrearing Age. SAMHSA. 2007).

Tobacco: Tobacco smoking during pregnancy is associated with increased 

perinatal mortality, bleeding complications in pregnancy, low-birth-weight 

infants and preterm delivery, and a possible increase in behavioral and 

learning problems among school-aged children whose mothers smoked 

during pregnancy (ACOG Committee Opinion #471; Obstet Gynecol

2010;166:1241; Am J Psychiatry 1996;153(9):1138). It is estimated that there 

could be as much as a 10% reduction in fetal and infant deaths if all pregnant 

women stopped smoking (Am J Epidemiol 1988;127(2):274).

Opiates: Opiate dependence in pregnancy is associated with a sixfold 

increase in maternal obstetric complications, including low birth weight, 

preeclampsia, 3rd-trimester bleeding, malpresentation, fetal distress, and 

meconium aspiration. Neonatal complications include narcotic withdrawal, which 

occurs in most newborns, poor postnatal growth, microcephaly, neurobehavioral 

problems, and increased neonatal mortality. A systematic review found a 

74-fold increase in sudden infant death syndrome among children born to 

women who used opiates during pregnancy (Cochrane Database Syst Rev

2008;(2):CD006318).

Methamphetamine: Methamphetamine use in pregnancy is associated with 

low birth weight, small-for-gestational-age babies, and neurodevelopmental 

abnormalities both in neonates and in childhood (ACOG Committee Opinion 

No. 479; Obstet Gynecol 2011;117(3):751).

Cocaine: Cocaine use in pregnancy poses both maternal and fetal hazards, 

some of which stem from the intense vasoconstriction associated with cocaine 

(malignant hypertension, cardiac arrhythmias, and cerebral infarction). Cocaine 

has been associated with premature rupture of membranes, preterm labor 

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and delivery, growth retardation, delays in cognitive development, and 

placental abruption. Cases of in utero fetal cerebral infarction have also been 

documented (Am J Obstet Gynecol 1987;157:686; Guide to the Clinical Care 

of Women with HIV, 5th ed. 2005;395).

HIV infection, substance use, and pregnancy: No data are available on rates 

of alcohol and/or substance abuse among HIV infected pregnant women. 

However, any substance abuse during pregnancy is of concern, especially in 

the setting of HIV. Substance use has been associated with an increased risk 

for perinatal HIV transmission (Adv Exp Med Biol 1993;335:211; N Engl J Med

1996;334:1617); although rates of perinatal transmission have decreased 

dramatically in developed countries, this problem has not been completely 

eradicated. Some residual transmission may be related to substance use 

among pregnant women. Exposure to drugs of abuse during pregnancy may 

increase mother-to-child transmission of HIV through a variety of mechanisms 

(J Neuroimmune Pharmacol 2010;5:507). A study of HIV infected mothers 

who were actively abusing substances found that most received inadequate 

or no prenatal care and that denial and substance use were the primary 

intrinsic barriers to disclosure and care. Substance-abusing pregnant women 

with HIV also may be less adherent to ART regimens during pregnancy. 

Attention to potent social and institutional barriers that impair the ability of 

the most marginalized women to disclose their HIV status and accept care is 

essential to maximizing the prevention of perinatal transmission (Soc Sci Med

2006;62(1):59). All pregnant women with a substance abuse problem should 

be offered treatment during pregnancy in consultation with maternal-fetal 

medicine and substance-abuse experts.

Treatment Retention and Relapse

Among clients discharged from substance-abuse outpatient care settings, 

treatment completion is highest among those who reported primary alcohol 

abuse and lowest among those who reported primary opiate or cocaine 

abuse. Both male gender and increased educational level were associated with 

a greater likelihood of completing outpatient treatment. Furthermore, patients 

who were referred to treatment by an employer, an employee assistance 

program, or the criminal justice system were more likely to complete outpatient 

treatment than patients referred by other sources (Treatment Outcomes among 

Clients Discharged from Outpatient Substance Abuse Treatment. SAMHSA. 2009; 

http://oas.samhsa.gov/2k9/outptTX/outptTX.pdf. Accessed 7/18/2012). 

Relapse is common and to be expected, and does not indicate failure or 

hopelessness. Indeed, women may make many attempts to stop substance 

abuse before succeeding; the clinician can play a major role in this journey by 

accepting the woman at whatever point she is in a recovery trajectory.

Antiretroviral Therapy and Substance Abuse

HIV infected women who are active substance abusers are less likely to be 

able to adhere to their ARV regimens than are women who are not abusing 

substances (AIDS Care 2009;21:168). A past or current history of substance 

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abuse, however, should not lead to automatic denial of ART; patient readiness 

should be assessed on an individual basis. Women previously treated for drug 

dependence may be more adherent that the general population or other 

groups. A strong patient-provider relationship, including trust and engagement 

with the provider, has been associated with improved ARV adherence (AIDS 

Patient Care STDS 2000;14:189).

Several ARV agents decrease methadone levels. When these agents are 

co-administered, the patient should be monitored for opiate withdrawal 

symptoms and the methadone dose increased if needed. Of note, when 

methadone is administered to a patient taking ZDV, the ZDV concentration 

is increased by >40%; the patient should be monitored for a potential 

increase in ZDV-related adverse effects. With newer ARV agents and dosing 

schedules that allow for once-daily ART regimens, directly observed therapy 

(DOT) in the setting of a methadone clinic may be an option for adherence 

support in some patients.

Tobacco

Most people with HIV infection also smoke cigarettes and are thus at high 

risk for tobacco-related disease and death (AIDS Educ Prev 2009;21(3 

suppl):14; Smoking Cessation in HIV Infected Patients. © New York State 

Department of Health AIDS Institute, 2000-2012; http://www.hivguidelines.

org/clinical-guidelines/adults/smoking-cessation-in-hiv-infected-patients/.

Accessed 8/1/2012). Information about the tailoring of smoking-cessation 

interventions to HIV infected people, and specifically to HIV infected women, 

is sparse. The U.S. Public Health Service guidelines recommend brief, individual 

smoking-cessation counseling sessions in which the following five components 

(the “5 As”) are addressed at each clinical encounter (AIDS Educ Prev

2009;21(3 suppl):14):

1. Ask about tobacco use at every encounter

2. Advise smokers to quit

3. Assess willingness to quit

4. Assist with quitting

5. Arrange follow-up

Smokers’ telephone quit lines, which offer free counseling and smoking 

cessation materials, are a cost-effective intervention with demonstrated 

efficacy. Other group and individual counseling interventions are available, 

with motivational interviewing and cognitive-behavioral interventions in 

particular being effective (AIDS Educ Prev 2009;21(3 suppl):14; Smoking 

Cessation in HIV Infected Patients. © New York State Department of Health 

AIDS Institute).

Pharmacological interventions, which include nicotine replacement therapy 

(gum, patches, lozenges, inhalers, and nasal spray), bupropion, and varenicline, 

have increased quit rates. Consideration of patient preferences, cost of the 

intervention, prior quit attempts, patient characteristics, and comorbidities 

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should help to determine the best intervention. A combination of nicotine 

replacement therapies usually works better than a single agent. Initial dosing 

depends on the number of cigarettes smoked per day; dosing should be 

tapered over the course of treatment. The usual course of treatment is 10–12 

weeks. Sustained-release bupropion, alone or in combination with nicotine 

replacement therapy, is effective. Varenicline, which relieves withdrawal 

symptoms and reduces the rewarding aspects of nicotine use, has been shown 

to be more efficacious than bupropion; however, adverse neuropsychiatric 

events have been reported with varenicline and the patient should be closely 

monitored (AIDS Educ Prev 2009;21(3 suppl):14; Smoking Cessation in HIV 

Infected Patients. © New York State Department of Health AIDS Institute).

Conclusion

HIV infection in women must be considered in the context of baseline 

psychosocial and cultural issues, as well as potential mental health and 

substance abuse conditions. The willingness and ability to address these 

concerns compassionately, directly and effectively will play a crucial role in the 

effective care and treatment of the medical manifestations of HIV and in the 

quality of life of the HIV infected woman.

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Chapter 10:

Adolescents

Donna Futterman, MD

Director, Adolescent AIDS Program

Montefiore Medical Center

Professor of Clinical Pediatrics

Einstein College of Medicine

Anita Radix, MD, MPH

Director of Research and Education

Callen-Lorde Community Health Center

Assistant Clinical Professor

Yale University School of Nursing

The authors declare no conflicts of interest

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Chapter 10: Adolescents

Chapter 10 at a Glance

HIV in Adolescents....................................................................................................................................379

Epidemiology...................................................................................................................................................379

Global Summary...................................................................................................................................379

U.S. Summary............................................................................................................................................379

Risk Factors ........................................................................................................................................................380

Sexual Behaviors...................................................................................................................................380

Substance Use..........................................................................................................................................381

Biological Risk...........................................................................................................................................381

Socioeconomic Risk and Access to Care.......................................................................382

Special Populations.............................................................................................................................382

Issues in HIV Care for Adolescents........................................................................................382

Confidentiality and Legal Issues...........................................................................................383

Counseling and Testing...................................................................................................................383

The ACTS Program..............................................................................................................................384

Prevention.....................................................................................................................................................387

Linking Youth to Care.......................................................................................................................388

HIV Clinical and Psychosocial Care......................................................................................389

Physical Exam, Laboratory Tests, and Immunizations.....................................390

HIV Treatment...........................................................................................................................................391

Psychosocial Issues...............................................................................................................................393

Mental Illness and Substance Use.......................................................................................395

Age Transitions..............................................................................................................................................395

Summary...............................................................................................................................................................396

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HIV in Adolescents

The HIV epidemic continues to evolve among adolescents, defined as youth 

aged 13–24 years. The prevalence of disease has been influenced by 

improved survival of perinatally infected youth after the introduction of 

effective antiretroviral therapy (ART) as well as changes in incidence rates. 

As youth explore intimacy and sexuality and develop autonomy, adolescence 

becomes a time of heightened vulnerability, including risk for HIV infection. 

This chapter focuses on young women as it reviews the epidemiology of 

HIV/AIDS in adolescents and provides guidelines for HIV counseling and 

testing, medical and psychosocial care, and strategies for linking HIV infected 

and at-risk youth to care.

Epidemiology

Global Summary

Adolescents are at high risk for HIV. In 2009, 33.3 million people worldwide 

were living with HIV, of whom 2.6 million were newly infected. More than 

40% of those new infections occurred in youths aged 15–24 years. A 

decline in HIV incidence among adolescents over the past decade has 

been attributed to improved knowledge of transmission and changes in risk 

behavior, including improved condom use, reduction in multiple partnerships, 

and delayed sexual debut (UNAIDS Global Report 2010, www.unaids.

org/globalreport/Global_report.htm). Despite these positive trends, the 

prevalence in young women continues to outpace prevalence in men; rates 

are almost 3 times higher among young women in Sub-Saharan Africa than 

among men (UNAIDS Global Report 2010).

U.S. Summary

In 2009, approximately 8,400 adolescents (1,670 women and 6,722 men) 

were newly diagnosed with HIV infection in 40 States and five U.S. dependent 

areas. These numbers are based on confidential name-based HIV infection 

reporting since at least January 2006, and they bring the cumulative total of 

HIV cases in this age group to 29,746 Significant racial and ethnic disparities 

exist: The majority of new infections occur among black/African-American 

and Latina youth. Most new infections in women (about 90%) occur through 

heterosexual contact, and 10% result from injection drug use (IDU). Of 

the 10,206 young women living with HIV at the end of 2008, 59% were 

exposed through heterosexual contact; 7%, through IDU; and the remainder, 

predominantly through perinatal transmission. The increase in heterosexual 

transmission in women has contributed to a decrease in the male-to-female 

ratio of AIDS cases. At the onset of the HIV/AIDS epidemic in the United 

States, diagnoses of AIDS were rare among adolescent women; however, 

in 2009 approximately one-quarter of AIDS diagnoses for this age group 

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occurred in women (CDC, HIV Surveillance in Adolescents and Young Adults, July 

2011. www.cdc.gov/hiv/topics/surveillance/resources/slides/adolescents/

index.htm)

Risk Factors

Adolescents are at increased risk for HIV and sexually transmitted 

infections (STIs) because of the interplay among behavioral, biological, and 

socioeconomic factors (Institute of Medicine 2011. The Science of Adolescent 

Risk-Taking: Workshop Report).

Sexual Behaviors

During adolescence, sexual activity is often initiated; risk-taking and 

experimentation are normative; and many sexually active adolescents fail 

to take appropriate prevention precautions, despite basic knowledge of 

HIV transmission and prevention. A majority of adolescent females with HIV 

are infected through heterosexual intercourse. This situation is consistent with 

widespread lack of awareness of the potential risk for HIV infection among 

sexually active adolescent and adult women. For example, among adolescents 

known to be HIV infected, 75% of young women are unable to identify their 

partners’ risk factors (Pediatrics 1993;91:730). Moreover, for many adolescents 

“having sex” means heterosexual vaginal intercourse, but some adolescent 

females may engage in receptive anal intercourse in the belief that doing so 

preserves their virginity and is safer (J Nurs Scholarsh 2003;35:231).

High risk for STIs: Youth and inexperience are no protection against STIs. 

Adolescents are at high risk for STIs and account for half of all new infections 

diagnosed in the United States. In 2006, 1 million youth and young adults 

aged 10–24 were diagnosed with chlamydia, gonorrhea, or syphilis. Evidence 

of HPV is detected in 25% of women aged 15–19 and in 45% of women 

aged 20–24. In 2006, 750,000 young women under age 20 became 

pregnant (Guttmacher Institute. U.S. Teenage Pregnancies, Births and Abortions: 

National and State Trends and Trends by Race and Ethnicity January 2010 

http://www.guttmacher.org/pubs/USTPtrends.pdf). The data on STIs and 

pregnancy are markers for unsafe sexual activity. In addition, ulcerative and 

inflammatory STIs increase susceptibility for HIV infection.

Youth risk behavior: According to the 2009 Youth Risk Behavior Survey 

(MMWR 2010;59 SS5:1), nearly half (46%) of all female high school students 

in the United States are sexually active, including 62.3% of 12th graders. 

African-American high school students were more likely to be sexually active 

than their Caucasian and Hispanic counterparts (58.3% vs. 44.7% and 45.4%, 

respectively). During their most recent sexual encounter, only 54% of female 

high school students reported using a condom. Many teens follow a pattern of 

sexual serial monogamy and may not consider themselves as having multiple 

partners. Of high school students surveyed, 11% of all females and 18% of 

African-American females reported four or more lifetime sexual partners.

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Younger teens, particularly females, are least likely to be considered at 

risk or to be screened for STIs, particularly if they are asymptomatic—and 

the majority of STIs in females are asymptomatic. For example, chlamydia 

is asymptomatic in 75% of infected women, and approximately 50% of 

women with gonorrhea infections have no symptoms. This pattern is especially 

concerning because adolescent females have the highest age-specific incidence 

rates for both gonorrhea and chlamydia. The REACH cohort of high-risk 

adolescents confirmed these findings (J Adolesc Health 2001;29 suppl 3:49).

Young women with HIV infection (either perinatally or behaviorally acquired) 

are also engaging in high-risk behaviors. A study of 166 HIV infected 

adolescents, ages 13-21, (53% female) found that 105 were sexually 

experienced and that 44% reported having unprotected sex. Eighty percent 

of the adolescents had not informed their partners of their HIV status, and 19 

females became pregnant (J Acquir Immune Defic Syndr 2010;55:380). These 

data stress the need for ongoing discussions about sexual risk behaviors.

Substance Use

More than 1 in 5 female high school students (20% to 24%) report episodic 

heavy drinking or current marijuana use; 12% report using inhalants, and 2% 

have injected illegal drugs (MMWR 2010;59 SS5:1). Substance use can impair 

judgment and increase potential for high-risk behaviors.

Biological Risk

Several biological factors also contribute to heightened risk in adolescent 

females. During puberty, as the cervix matures and the single-layer columnar 

epithelium of the cervix is replaced with thicker, multilayered squamous cells, 

the cellular lining becomes less susceptible to infection. Until this occurs, the 

cervix is much more vulnerable to STIs, particularly chlamydia and gonorrhea, 

which have an affinity for columnar cells and have been shown to facilitate 

other STI transmission. The same cervical anatomy is responsible for the 

increased risk of HPV infection in adolescent women. Moreover, HIV appears to 

increase the risk of progression of HPV disease. High-risk HPV DNA has been 

found in cervical samples of up to 77% of HIV infected adolescents; 70% 

of the adolescent women with high-risk HPV DNA had cytologic abnormality 

and 21% had high-grade dysplasia within 3 years of follow-up (Arch Peds 

Adolesc Med 2000;154:127). Moreover, male-to-female transmission of STIs is 

much more efficient than female-to-male transmission, given the larger surface 

area of the lower female genital tract and mechanics of sexual intercourse, 

which can result in mucosal trauma to women. In addition, STIs, which facilitate 

HIV transmission, are more likely to remain asymptomatic in women and, thus, 

unrecognized and untreated for a longer period.

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Socioeconomic Risk and Access to Care

Poverty, poor access to care, and lack of education and prevention skills 

further increase vulnerability to HIV. Additional barriers include mistrust of 

the healthcare system, fear of inappropriate disclosure, and providers’ lack 

of expertise in providing care for adolescents. In addition, adolescents are 

the most underinsured group in the United States and are the least likely 

to receive office-based medical care or to use primary care services (Bull 

NY Acad Med 1993;70:219). With less access to either employer-provided 

insurance benefits or public insurance options, 30% of youth aged 18–24 

have no health insurance (U.S. Census Bureau 2009, www.census.gov/

prod/2009pubs/p60-236.pdf). Even when they have insurance coverage 

through their parents, adolescents may be reluctant to use it out of fear 

of disclosure of sensitive medical issues. Moreover, many adolescents use 

emergency and walk-in facilities for acute care needs. As a result, they lack 

a primary care provider (or medical home) that can ensure ongoing care and 

address prevention and health promotion needs. Because adolescence is a 

time when help-seeking behaviors and attitudes about health and self-care 

are formed, the experiences adolescents have with healthcare providers are 

especially important. They form the basis for future provider–client interaction, 

communication patterns, and relationships.

Special Populations

Specific populations of teens, including those who are lesbian, bisexual, or 

transgender; homeless or runaway; injection drug users; or mentally ill, are 

at especially high risk of HIV exposure. Also at higher risk are youth who 

have been sexually or physically abused, incarcerated, or placed in foster 

care. These youth experience increased vulnerability and multiple health and 

social problems because of abuse and neglect and lack of services and care. 

Lesbian and bisexual females may view themselves at lower risk, but those 

who are sexually active with gay male peers are at risk for infection because 

of higher HIV prevalence among gay males (Lesbian and Gay Youth: Care and 

Counseling, Columbia University Press; 1998).

Issues in HIV Care for Adolescents

Cornerstones of adolescent care include consent policies, confidentiality, 

accessibility, outreach, testing, and linkage to care and prevention. Even though 

youth prefer healthcare settings that are geared to their needs, most teens will 

not receive care in adolescent programs. Although most facilities are unable 

to offer the ideal one-stop shopping for teens, quality care can be provided 

by identifying a staff member and/or provider team that wants to work with 

adolescents and by adapting adult and family programs to meet the needs 

of adolescents. For example, programs can accommodate walk-ins, because 

youth do not often plan ahead; address payment barriers; and provide 

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flexible appointments that will not conflict with school or work. In 2007, the 

Health Resources and Services Administration (HRSA) created a comprehensive 

website on HIV care for youth (www.hivcareforyouth.org).

Confidentiality and Legal Issues

All States have laws that allow minors to consent to treatment without parental 

consent for specific health services, including emergency care, treatment for 

STIs, reproductive healthcare, and substance abuse treatment services. In many 

States, the law includes the right to consent for HIV counseling and testing. 

However, not all providers are aware of these rights or understand their 

significance for adolescents, and rights vary by State and the medical service 

provided. The Compendium of State HIV Testing Laws is available at nccc.ucsf.

org and hivlawandpolicy.org. Providers should know that lack of confidentiality 

may cause adolescents to avoid or delay needed care. Even though parental 

consent may not be needed to provide an HIV test or HIV-related care, 

providers should carefully assess an adolescent’s cognitive capacity to 

understand the implications of having HIV disease and should encourage the 

involvement of a supportive adult in the adolescent’s care.

Counseling and Testing

Routine testing recommended: Since 2006, the CDC has recommended that 

medical providers routinely offer HIV testing to all patients aged 13–64. 

This recommendation is based on several factors, including the considerable 

number of HIV infected people who are unaware of their infection or not 

linked to care, advances in medical treatment that make early diagnosis and 

treatment life saving, and the prevention benefits of widespread knowledge 

of serostatus. Most youth and, often, their providers think they are not at risk 

of HIV infection (J School Nurs 2001;17:198). Most youth also prefer to have 

healthcare providers initiate discussions about HIV testing, prevention, and 

risk assessment (Pediatrics 2006;117:e468). All adolescents should receive 

HIV prevention education and should routinely be offered HIV testing. This 

process enables providers to identify HIV infected youth, provide ongoing 

medical care and support services, relieve their patients’ anxiety, and reinforce 

preventive behaviors for youth who are not HIV infected. For adolescents who 

are not sexually active, counseling provides an opportunity to talk about sexual 

readiness, delaying intercourse, and low-risk ways to explore intimacy. Routine 

testing also serves to identify the few perinatally infected adolescents who 

have not previously been tested, often because they were asymptomatic slow 

progressors (HIV Med 2009;10:253). Teens of HIV infected parents or whose 

parents died of unknown causes should certainly be tested, even if they are 

not sexually active.

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The ACTS Program

The Adolescent AIDS Program at Montefiore Medical Center, New York, 

has developed a streamlined approach that enables providers to routinely 

incorporate HIV screening into their clinical encounters with adolescents (and 

clients of any age). The program, called Advise–Consent–Test–Support (ACTS), 

teaches healthcare providers to do the following:

• Advise patients to get an HIV test, and ask if patients 

are ready to be tested today; if they are not, answer the 

patients’ concerns and then encourage testing.

• Consent patients according to applicable State law. As of 

2011, an increasing number of States are moving away 

from requirements for specific written consent to an opt-out 

approach, in which HIV testing is included under general 

consent for care, as encouraged by the CDC.

• Test with rapid or conventional HIV test.

• Support patients after testing.

For patients who are not infected, support consists of providing test results and 

informing patients about ways to take an active role in avoiding HIV infection. 

A care provider may help patients choose a prevention plan (e.g., abstinence; 

reduced number of partners; condom use for oral, vaginal, and anal sex). 

Patients should also be encouraged to get retested annually and advised 

about when more frequent testing is appropriate (i.e., following unprotected 

sex, sex with new partners, infection with an STI, or pregnancy or if there are 

any signs of acute HIV infection).

For HIV infected patients, support should focus on informing patients of test 

results, addressing immediate and short-term coping abilities, and providing 

links to appropriate medical care. Patients should be counseled about 

transmission prevention, which may entail informing sex partners personally 

or eliciting the help of the local health department to inform partners. Finally, 

patients should be encouraged to engage in safe sex.

The ACTS program is designed to facilitate practice change within the 

healthcare system through a four-step process:

• Obtain buy-in from clinic and administrative leadership.

• Implement planning, which includes identifying the role of all 

staff and process flow.

• Train care providers in the use of the ACTS approach.

• Utilize routine monitoring and evaluation to assess 

implementation efficacy.

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ACTS has successfully increased routine counseling and testing in community 

health centers, school-based clinics, hospitals, cities throughout the United 

States, and in other countries in citywide and provincial scale-ups (see www.

adolescentaids.org).

Overcoming barriers: Testing options such as rapid testing for antibodies in 

oral fluids are helpful with youth who are afraid of needles. Those options 

also allow providers to offer testing in a variety of settings, including mobile 

vans, school-based clinics, and drug treatment programs. Meeting adolescents’ 

needs for flexibility, accessibility, and low- or no-fee HIV testing is important in 

overcoming primary barriers to accessing care and can serve as an entry point 

to care. Ensuring access to HIV counseling and testing is essential to enabling 

adolescents to receive ongoing treatment and care.

Risk assessment and counseling: HIV screening and testing can be streamlined 

and incorporated into the clinical visit, but prevention counseling and risk 

assessment takes more time. Because adolescents may have misconceptions 

about aspects of HIV transmission and prevention, providers should assess a 

youth’s baseline understanding and capacity to understand basic concepts of 

HIV disease and viral transmission. Effective HIV counseling for adolescents 

should be culturally sensitive and tailored to adolescents’ developmental 

needs, i.e. information provided at a level of comprehension consistent with 

the age of the client. In addition, providers should take special precautions 

to ensure confidentiality in institutional settings such as foster care, residential 

treatment, or detention centers. Elements of a youth-friendly risk assessment 

are summarized in Figure 10-1.

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Figure 10-1

HIV Risk Assessment for Adolescents

1. Engage and Assess

• Create a confidential atmosphere

- Assure youth that visit is confidential and explain ability to consent for 

testing per local laws.

- Assure youth that getting tested is his or her choice.

- Acknowledge that it can be embarrassing to discuss sexual behaviors.

- Help youth identify a supportive adult who is aware that he or she is 

being tested.

• Assess HIV/AIDS knowledge

- Allow youth to verbalize his or her understanding of HIV; clarify 

misconceptions, then fill gaps in knowledge.

- Assess youth’s feelings about testing and previous HIV testing experiences.

- Ask if youth knows anyone with HIV/AIDS (eg., sexual partner, family 

member).

• Assess sexual risk

- Assess sexual behaviors without making assumptions about sexual orientation: 

Not all youth are heterosexual, and not all youth who have engaged in samesex behavior self-identify as lesbian or gay.

- Assess number of youth’s partners, age differential, and partners’ known risks.

- Assess frequency of substance use in the context of sexual behavior.

- Assess consistency of condom use and obstacles to use such as lack of 

assertiveness, desire to become pregnant, fear of violence, and religiosity.

- Assess for history of sexual abuse or rape (coerced sex).

- Assess for history of sex work and transactional sex.

• Assess substance use and other risks

- Assess level of drug and alcohol use, context in which use occurs, and 

reasons for use.

- Review risk of impaired judgment that may lead to unsafe sex.

- Assess potential need for drug treatment.

- Assess violence and substance use in home and community.

2. Reduce Risk - Discuss abstinence.

- Discuss sexual activities that don’t involve exchange of body fluids (e.g., 

outercourse or frottage).

- Demonstrate proper use of male condom, female condom, and dental dam 

on anatomical model and provide opportunity for practice.

- Rehearse (role play) effective ways to communicate risk reduction with 

sexual partner(s).

- Discuss harm-reduction strategies, if youth is using drugs.

- Develop a personalized risk-reduction plan.

- Discuss postponing sex, if youth is not sexually active.

- Determine referral needs (e.g., medical, psychosocial, school/vocational, 

substance abuse, reproductive health, legal, housing, psychiatric).

Condom use: Several intrinsic and extrinsic factors, outlined in Figure 10-2, 

affect condom use among adolescents. Knowledge of appropriate condom 

use and widespread availability of condoms are especially important in 

promoting risk-reduction behaviors among youth. All facilities that provide 

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healthcare for adolescents should make condoms available, and providers 

should demonstrate condom use with anatomical models. Gender and power 

imbalances in relationships make condom use especially difficult for adolescent 

women, who may have older partners and who are just beginning to develop 

communication and negotiation skills. Helping youth identify their personal 

values may increase self-esteem and help them resist pressures to engage in 

sexual risk behaviors.

Figure 10-2

Factors That Encourage and Discourage Condom Use

Encourage Use

• Knowledge about condoms

• Belief in effectiveness

• Discussion with healthcare provider

• Self-esteem and self-efficacy

• Communication and negotiation skills

• Availability and accessibility

Discourage Use

• Drug and alcohol use

• Relationship power imbalances

• Peer pressure

• Lack of effective sex education

• Lack of media and cultural support

Prevention

Promoting abstinence and risk reduction among adolescents is especially 

challenging because developmental characteristics encourage concrete, 

short-term thinking and experimentation and increased reliance on peers. 

Thus, successful primary and secondary prevention programs for adolescents 

are those that provide interventions to increase self-esteem and selfefficacy, build social skills, and provide basic information geared to the 

adolescent’s developmental level, using a peer-support model (Psychosom 

Med 2008;70:598). For high-risk youth, the AIDS Risk Reduction Model (Health 

Educ Q 1990;17:53) has been widely used to foster primary and secondary 

prevention. The model is based on three stages of behavior change: (1) 

acknowledging that a behavior is risky (behavior labeling), (2) committing to 

change, and (3) taking action to reduce high-risk activity.

School-based programs: School-based programs that provide comprehensive 

health education in conjunction with school health clinics offer optimal 

opportunities to reinforce positive health behaviors and ensure routine 

screening for a range of health and mental health concerns. They are 

especially important to efforts to reduce risk and identify sexually active 

youth who are at risk for STIs and pregnancy. A comprehensive review of 

school-based programs designed to reduce risky behavior in teens found that 

adolescents who received AIDS education were less likely to engage in sexual 

activity and more likely to practice safer sex than peers who lacked AIDS 

education in school (Public Health Rep 1994;109:339). In particular, successful 

prevention programs focus on building skills, reinforcing age- and experiencebased values and norms that help prevent unprotected sex, and discussing 

social influence and pressure. School clinics also offer an important venue for 

access to condoms and appropriate instruction on condom use. Although not 

widely available, school clinics provide an important site for HIV counseling 

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and testing for in-school youth, given new rapid testing options. Ultimately, 

successful prevention must also involve society and the media—until youth see 

abstinence, condom use, and safer sex discussions incorporated into sex scenes 

in music videos and movies, they will not believe that these practices are the 

social norm.

Adolescents who are HIV infected are also in need of risk-reduction counseling 

to prevent transmission of HIV to uninfected sexual partners and to prevent 

acquisition of other STIs or reinfection with other HIV strains. Previous data 

show high prevalence of risky sexual behaviors and the attendant high risk 

of STIs among youth. (Perspect Sex Reprod Health 2004;36(1):6-10; MMWR

2010;59 SS5:1). Multiple studies of HIV infected youth reveal a significant 

unplanned pregnancy rate, which is further evidence of high-risk behaviors 

(HIV Med 2011;12:118).

Linking Youth to Care

Barriers to care: Linking HIV infected youth to care is essential in meeting their 

needs for risk-reduction education and appropriate ongoing HIV medical and 

psychosocial care. Barriers to care include stigma associated with HIV, lack 

of independent transportation, dependence on parents for health insurance 

or other financing for care, and feelings of vulnerability. Many HIV infected 

youth do not know they are infected, and many providers are not aware of 

available community service agencies that can address adolescents’ multiple 

mental health and social service needs. Community outreach is a primary 

component in ensuring access to care for youth with HIV disease. Programs 

often use peer-based outreach, because adolescents are more likely to listen 

to their peers.

Outreach: Unlike adult women, who have more opportunities to obtain 

HIV testing and to access care related to their reproductive health needs, 

adolescents who are not pregnant require proactive outreach efforts to 

promote HIV testing and engage them in care. These efforts include citywide 

campaigns to encourage testing and to make it more widely available with 

direct linkages to adolescent healthcare facilities. Another crucial element is 

social marketing, using the media (radio, TV, Internet, and mobile phones) that 

youth prefer for their communication and entertainment. To effectively reach 

adolescents, it is crucial that social marketing be continually updated and 

use the words and formats preferred by youth. Every 5 years brings a new 

generation, and marketing and outreach must be continually updated to reach 

these new generations.

Linkage to care is a crucial step in ensuring that newly identified HIV infected 

youth can access life-saving care. Knowing where youth are identified can also 

help guide expanded testing and collaboration programs. A survey conducted 

among 12 sites in the National Institutes of Health (NIH)-funded Adolescent 

Trials Network assessed the referral sources for 400 HIV infected youth who 

were identified and linked to care in 2009 (Futterman, unpublished data). 

Medical sites were the referral source for almost half the patients (48%); 

public health departments accounted for 21% of referrals; community-based 

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organizations, 16%; self, friend, or family, 10%; and other, 8%. This survey 

highlighted the importance of medical providers as referral agents as well as 

the full spectrum of sites involved in youth testing.

HIV Clinical and Psychosocial Care

Although the natural history of HIV infection in adolescence is still being 

defined, the course of disease among youth who acquire HIV sexually 

appears to follow that of adults. Descriptive studies of HIV infected 

adolescents in care consistently show that most youth enter care with significant 

immune dysfunction and that clinical status varies markedly by transmission 

category. Most HIV infected youth acquire their infection sexually and enter 

care while asymptomatic but with enough immune dysfunction to qualify for 

initiation of ART. In the NIH- and HRSA-funded REACH cohort (a national 

prospective study with sites in 13 cities to identify the course of disease in 

adolescents), 49% of HIV infected females and 66% of HIV infected males 

had CD4+ cell counts below 500/mm3 at study entry. Although a similar 

percentage of females and males had AIDS at study entry (16% of females 

and 18% of males), viral loads were higher in the males: 9% of females but 

23% of males had viral load above 50,000 copies/mL (J Adolesc Health

2001;29 suppl 3:8). The higher CD4+ cell count values and lower viral loads, 

yet similar percentage of AIDS among adolescents, provide a different 

perspective for the debate about whether females progress to AIDS at lower 

viral load and higher CD4+ cell counts.

In contrast, youth who are perinatally infected often have a much more 

serious course during adolescence, reflecting the effects of long-term infection. 

In many cases, the course of illness in adolescence also reflects the often 

complex patterns of resistance that result from treatment with serial mono or 

dual therapy that was based on earlier standards of care and medication 

availability. Of note, one study that predated the era of highly active 

antiretroviral therapy showed that among perinatally infected children, onefifth remained asymptomatic with CD4+ cell counts > 500/mm3. With the 

introduction of HAART, the subpopulation of perinatally infected youth will 

continue to grow as more survive and age into adolescence. Dramatic declines 

in mortality associated with HAART were demonstrated in the PACTG-219 

study (J Acquir Immune Defic Syndr 2010;53:86), but those gains are tempered 

by the fact that mortality rates still remain 30 times greater than in uninfected 

matched cohorts.

Perinatally infected youth are often confronted with their own physical 

disabilities, which may include multiorgan system disease, delayed puberty, 

body dysmorphisms, and developmental delay. Their difficulties may be 

compounded by isolation, stigma and, often, the death or illness of one or 

more parents. At the same time, HIV infected youth are challenged by the 

tasks of adolescence, including the emerging sense of self and the need for 

independence. Some youth are first told of their infection during adolescence 

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even after having taken medications for years. Clinicians also need to be 

aware that some slow-progressing perinatally infected youth might not even be 

diagnosed until adolescence.

Physical Exam, Laboratory Tests, and Immunizations

Privacy is an important consideration in the adolescent physical exam, because 

most adolescents have a high level of modesty that is often compounded 

by anxiety about physical changes and a lack of understanding about their 

anatomy. Physical examinations for adolescents should follow guidelines used 

for adults; however, when prescribing medications, providers should use the 

Tanner staging of puberty, presented in Table 10-1, which characterizes 

development of breasts, genitalia, and pubic hair (Comprehensive Adolescent 

Health Care, 2nd ed. St. Louis: Mosby; 1998).

Table 10-1

Classification of Sex Maturity Stages (Tanner Scale)

Stage Pubic Hair Breast Penis Testes

I Preadolescent Preadolescent Preadolescent Preadolescent

II Scanty, 

long, slightly 

pigmented, 

downy

Breast bud 

stage; elevated 

breast and 

papilla; 

increased 

areolar 

diameter

Slight 

enlargement

Enlarged scrotum 

and testes; pink; 

changed skin, 

texture

III Darker, coarser, 

curlier

Enlarged breast 

and areola 

with no contour 

separation

Increased length Increased size

IV Adult type, but 

less; no spread 

to medial 

surface thighs

Areola and 

papilla form 

secondary 

mound

Glans enlarged; 

increased 

breadth

Enlarged, skin 

darker in color

V Adult distribution 

with spread to 

medial thighs

Mature stage; 

projection of 

nipple

Adult size Adult size

Adapted from Growth at Adolescence, 2nd ed. Oxford, England: Blackwell Scientific 

Publications; 1962.

Routine screening: Because sexually active adolescents are at very high 

risk for STIs, providers should routinely screen with cervical cytology and for 

chlamydia, gonorrhea, syphilis, and hepatitis B and C; they also should follow 

TB screening guidelines for adults with HIV infection. Pregnancy testing should 

be performed when indicated by history or exam findings, and it should 

always be considered with missed menses, abnormal bleeding, or development 

of pelvic pain.

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Immunizations: Adolescents require more immunizations than adults; 

immunizations are listed in Figure 10-3. HIV infected adolescents can safely 

receive most childhood vaccines, although efficacy may vary. Those with severe 

immunosuppression (CD4+ cell count <200/mm3; CD% <15%) should not 

receive MMR or varicella vaccine. Oral polio and intranasal influenza vaccine 

are contraindicated in HIV infected patients. The CDC provides vaccination 

guidelines, including catch-up schedules, for patients older than 18 years of 

age (www.cdc.gov/mmwr/preview/mmwrhtml/mm5901a5.htm) and younger 

than 18 years of age (www.cdc.gov/vaccines/recs /schedules/default.htm).

Because immunizations may briefly boost viral load, they should be scheduled 

on the same day as or after viral load measurements. At present, CD4+ cell 

counts and viral load measurements are interpreted as for adults and used to 

guide treatment.

Figure 10-3

Immunizations for Adolescents

• Measles, mumps, and rubella (MMR) booster if CD4+ cell count is 

stable >200/mm3

• Diphtheria-tetanus toxoid (TdaP) booster

• Hepatitis B vaccine (3 in series)

• Hepatitis A vaccine (2 in series; not routine for females, but recommended 

for males who have sex with males)

• Influenza (yearly)

• Pneumococcal vaccine (PPSV-23) >age 2 years and booster 5 years after

• HPV (3 in series) age 9–26

• Varicella zoster vaccine for contacts (not currently approved for HIV infected people; can consider for those with CD4+ cell count >200/mm3)

• Meningococcal conjugate vaccine (MCV4; 2 in series) age 11–12, booster at age 16–18

Source: AIDS Clin Care 1999;11:17. Reprinted with permission.

HIV Treatment

Medication dosing: Adolescents have not been studied extensively in the 

clinical trial system; thus, few direct data about dosing regimens are available. 

The U.S. Department of Health and Human Services (HHS) has included the 

treatment recommendations (based on expert opinion) for postpubertal 

adolescents with adult treatment guidelines. Because pubertal changes may 

affect pharmacokinetics, dosage is based on Tanner staging rather than 

on age. For example, pediatric dosing should be used for adolescents who 

have entered or are in early puberty (Tanner stage I/II), whereas dosing for 

adolescents in midpuberty (Tanner III/IV) should be based on whether they 

have completed the growth spurt. Adolescents who have completed puberty 

(Tanner V) should receive adult dosages (www.aidsinfo.nih.gov). Factors that 

should be considered in choosing the initial treatment regimen for adolescents 

include results of viral resistance testing (genotype or phenotype), pill burden, 

potential side effects, and likelihood of adherence.

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ART and contraception: Note that several key medications commonly 

prescribed to adolescents have significant interactions with antiretroviral 

medications, including combined estrogen/progestin contraceptives, which 

may be less effective and/or cause more side effects when taken with 

antiretrovirals. Clinicians may consider switching to progestin-only methods, 

such as depot medroxyprogesterone acetate or the etonogestrel implant, both 

of which provide very effective and longer term contraception without the 

need to take daily pills. Concomitant use of a barrier method of contraception 

should be stressed. Efavirenz has been associated with risk of birth defects; 

since pregnancy is often unplanned in youth, this medication should generally 

be avoided in young women, unless other effective and well-tolerated options 

are not available. Currently, clinicians are advised to avoid tenofovir until 

patients reach Tanner IV/V. (For more information on drug–drug interactions, 

see the U.S. Public Health Service adult and adolescent guidelines at www.

aidsinfo.nih.gov).

Adherence: Treatment adherence, which is challenging for adults, can 

be especially challenging for adolescents, who struggle with a range of 

developmental tasks that require them to balance dependence with increasing 

autonomy. As with any successful work with adolescents, the first step in 

promoting adherence is to establish a solid therapeutic alliance. Providers must 

develop a systematic approach that facilitates adherence by addressing four 

areas of interaction: (1) building trust, (2) assessing and facilitating readiness, 

(3) helping teens initiate and practice a new treatment regimen, and (4) 

providing ongoing support for adherence. This approach is outlined in Figure 

10-4, which describes the EARS approach: Engage, Assess, Ready, Support. 

This approach addresses barriers to maintaining a complex medication 

schedule for adolescents, such as lack of privacy in school, home, or residential 

settings; the need to develop a reminder system; and the incongruity of 

having a serious illness while exhibiting few visible indicators of disease. In 

a Los Angeles adolescent HIV/AIDS program, the most common reasons for 

missing medication reported by youth include forgetfulness, side effects, the 

inconvenience of having to take so many pills, and the fact that taking the 

medication is a continual reminder of being HIV infected (J Adolesc Health

1998;22:160). Patients should be screened for depression, a known cause of 

nonadherence (Arch Pediatr Adolesc Med 2005;159:764).

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Figure 10-4

Adherence: Use Your EARS

Engage • Establish therapeutic alliance and build trust—the goal is to have 

youth participate actively in all aspects of treatment.

• Address immediate needs: health, housing, insurance, family, 

and partners.

• Educate about HIV infection—transmission, disease course, and benefits 

of medications.

Assess • Stage of HIV infection

• Mental and cognitive abilities

• Physical ability to take medicines

• Support systems and disclosure issues (family and friends)

• Readiness to begin medications

Ready • Decide with adolescent on a regimen that integrates clinical needs with 

lifestyle—show different pills and combinations.

• Solidify support systems: family, treatment buddy, or both.

• Practice chosen regimen with surrogate vitamins; distribute medications 

into a weekly medication planner and program 1-day pill timer with 

the adolescent.

• Address adherence barriers discovered in the practice run.

Support • Provide ongoing support with frequent clinic visits and phone contact.

• Acknowledge and address side effects.

• Develop strategies to ensure tolerability and regularity.

• Facilitate interactions with other youth who are taking medications.

Source: AIDS Clin Care 1999;11:17. Reprinted with permission.

Psychosocial Issues

An understanding of adolescent development is crucial to working effectively 

with adolescents as partners in their healthcare. In addition to the physical 

changes of puberty, adolescence consists of a series of cognitive and 

psychosocial phases that are key to successful maturation yet are greatly 

confounded in the setting of HIV infection. The Adolescent AIDS Program 

has identified five key issues that adolescents with HIV/AIDS must address 

in coping with their changing health status: (1) receiving an HIV diagnosis; 

(2) disclosing HIV status to parents, partners, and others; (3) coping with HIV 

disease; (4) becoming symptomatic; and (5) preparing for death (J Adolesc 

Health 1993;14 supp:S1). Family members can play a key role in the care of 

the HIV-infected adolescent if they are engaged and supportive.

Receiving an HIV diagnosis: Providers should instill a sense of hope and 

encouragement when giving adolescents an HIV diagnosis. Asymptomatic 

youth must learn to balance healthy denial and preoccupation with HIV 

infection. Concrete thinking makes it difficult for some youth to integrate the 

concept of disease latency and asymptomatic infection. Support is essential 

in helping youth integrate this life-changing information. Individual and 

peer-group interventions with psychologists and social workers can help 

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facilitate adjustment. Psychotropic medication may be needed to manage 

preexisting psychiatric problems or anxiety and depression that may 

accompany the diagnosis.

Disclosure of HIV status: After learning of an HIV diagnosis, adolescents face 

the hurdle of deciding whom to inform and when to disclose their HIV status. 

Although the involvement of a supportive adult is ideal, telling parents is 

difficult for many adolescents, who fear losing their parents’ love and support 

or worry about hurting them. The need to rely on adults because of illness 

sharply contrasts to the developmental need to establish independence and 

identify with one’s peer group. For gay or substance-using youth, disclosure 

to one’s parents may be especially threatening because they may have to 

reveal their HIV status, sexuality, and drug use all at once, which could lead 

to rejection, harassment, or violence. Disclosure becomes a particularly salient 

issue with advancing disease or initiation of ART because it is difficult to 

conceal medications from the people with whom one lives. Adolescence is one 

of the most observed times of life—young people often do not have space 

to call their own, and privacy is especially compromised for youth living in 

crowded homes or residential programs. In school, institutional bathrooms 

provide no seclusion for taking medications.

Disclosure to sexual partners is both ethically compelling and complicated. 

Of course, HIV infected adolescents should inform their sexual partners and 

engage in safer sex, but youth face several unique challenges in disclosing 

their HIV status. The adolescent social/sexual world is smaller, more intense, 

and often shorter lived than that of adults, so confidentiality is more easily 

compromised. Providers should be aware that adolescents in earlier stages 

of sexual development might have fewer partners, which could make 

an anonymous disclosure easier to figure out. If one person knows, then 

everyone in an adolescent’s group might easily find out. Fear of rejection 

and loss of confidentiality are thus major concerns in disclosing to sexual 

partners. Providers should offer to help with disclosure and offer guidance in 

determining when it is safe and appropriate for a youth to disclose her HIV 

status. Role-playing and working through scenarios ahead of time can help 

an adolescent manage potential fears and concerns. Collaboration with the 

local public health department can also facilitate partner notification and 

identification of sexual networks.

Coping with HIV disease: Given the prognostic significance of viral load and 

CD4+ cell count, adolescents need to understand how these markers relate to 

the course of their HIV disease. However, these concepts are often difficult to 

understand for youth, who may be concrete thinkers. Adolescents also need 

guidance in learning how to interpret changes, because fluctuation in results 

may cause some youth to panic. Providers can help by explaining that variation 

is common and that fluctuations in values will not prevent adolescents from 

leading satisfying and productive lives.

Becoming symptomatic: The appearance of HIV-related symptoms can 

be especially disturbing for adolescents, who may have only superficially 

acknowledged their HIV status. The onset of HIV symptoms may pierce their 

denial. For some youth, becoming symptomatic may encourage them to fight 

HIV and may enhance treatment adherence and self-care. Others, however, 

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may feel overwhelmed and lose their motivation to care for themselves. 

When symptoms occur, providers should explain their significance, correct 

misconceptions, and ensure that adequate services and support are available.

Preparing for death: Many adolescents have limited experience with death 

and have naïve perceptions about what to expect. Introducing the topic by 

talking about living wills and healthcare proxies before HIV becomes too 

advanced is a practical way to help youth begin to deal with issues related to 

death. When clinically appropriate, providers can help adolescents explore 

their feelings about dying by discussing options for dying in the hospital or at 

home, talking about funeral or memorial services, and exploring child custody 

or permanency planning with adolescent parents.

Mental Illness and Substance Use

Mental illness and substance abuse are significant comorbidities for HIV 

infected adolescents. Accurate screening, diagnosis, and treatment are essential 

to helping adolescents cope with their HIV disease and successfully maintain 

their ART regimen. Case studies of adolescents and young adults with HIV 

indicate a high prevalence of depression, bipolar disorder, and anxiety; these 

mental health issues often predate an HIV diagnosis (Arch Pediatr Adolesc Med

2000;154:240). Similarly, many HIV infected adolescents report alcohol and 

drug abuse. Of adolescents in the REACH study, 14% percent of females and 

more than 25% of males reported weekly use of alcohol in the prior 3 months. 

During the same period, 7% of females and 20% of males reported using 

hard drugs (J Adolesc Health 1998;22:300; J Adolesc Health 2001;29 suppl 

3:57). In addition, a high proportion of HIV infected youth report childhood 

sexual abuse, which has many psychological and behavioral sequelae, 

including depression, posttraumatic stress disorder, substance abuse, suicidality, 

and HIV risk behaviors.

Age Transitions

As medical care continues to improve, a considerable number of HIV infected 

adolescents will be healthy enough to graduate from pediatric to adolescent 

to adult programs. Emerging adults require programs and providers that can 

address their developmental needs. They face the concurrent challenges of 

healthcare maintenance, medication adherence, and chronic illness within the 

context of maturing sexuality and establishing an independent life. The issues 

of transition to adult care have been addressed in the literature for other 

chronic illnesses, but HIV infection has some unique features. Young people can 

be quite reluctant to leave their established and trusted providers and care 

teams. In response, many adolescent HIV programs have increased their upper 

age limit from 21 to 24 years. However, there comes a time when transfer to 

adult care is appropriate. Most successful programs begin the transition process 

months before it occurs. Patients and staff work together to develop skills 

such as dealing with the medical system (making and keeping appointments), 

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maintaining entitlements (health insurance and housing), learning to give a 

medical history and track symptoms, learning to take and be responsible for 

medications, and learning when to report emerging symptoms. Patients must 

also learn self-management skills, including setting and achieving life goals 

such as education and employment or careers.

Summary

The high risk of HIV in adolescent females underscores the need to develop 

realistic prevention programs that build prevention skills. It also highlights 

the need for routine HIV counseling and testing for all sexually active teens 

in all programs that provide care for adolescents. Youth at high risk for 

HIV should be identified and engaged in primary care as soon as possible. 

Outreach is an important component of programs that seek to link HIV 

infected youth to care. Although most HIV infected youth will not receive 

services in adolescent programs, services can be readily adapted to provide 

a youth-centered approach by making such basic accommodations as flexible 

hours, low or no payment for services and care, and engaging providers 

who are knowledgeable about adolescents. Information on relevant clinical 

trials should be made available to adolescents as well. Wide dissemination 

of information to healthcare providers about providing adolescent-related 

HIV care should take place, such as use of Tanner staging for determining 

appropriate medication dosages.

Adolescents with HIV need intensive individual and group support to maintain 

their health and reduce transmission to others. Healthcare providers in all 

settings that serve adolescents need to assist in making services visible, 

flexible, affordable, confidential, culturally appropriate, and available for 

all adolescents.

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Chapter 11:

Palliative and Supportive Care

Jessica S. Merlin, MD, MBA

Assistant Professor

Division of Infectious Diseases

Division of Gerontology, Geriatrics, and Palliative Care

University of Alabama at Birmingham

Rodney Tucker, MD, MMM

Associate Professor, Department of Medicine

Interim Director

Center for Palliative and Supportive Care

University of Alabama at Birmingham

The authors declare no conflicts of interest

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Chapter 11: Palliative and Supportive Care

Chapter 11 at a Glance

Therapy to Improve Quality of Life.......................................................................................399

Address Four Domains of Suffering..................................................................................399

Rapid Expansion in the United States.............................................................................400

Interdisciplinary Approach .........................................................................................................400

HIV as a Chronic Disease..................................................................................................................400

Alleviate Suffering of Chronic Disease .........................................................................400

HIV Disease Burden and the Role of Palliative Care.....................................401

Pain and Nonpain Symptoms.......................................................................................................402

Prevalence of Nonpain Symptoms.....................................................................................403

Assessment of Nonpain Symptoms.....................................................................................403

Management of Selected Symptoms...............................................................................404

Prevalence of Pain..............................................................................................................................407

Assessment of Pain ..............................................................................................................................407

Approach to Pain Management............................................................................................409

Principles for Use of WHO Pain Ladder.....................................................................409

Opioid Titration......................................................................................................................................413

Bowel Regimen ........................................................................................................................................413

Side Effects of Opioids..................................................................................................................414

Nonopioid Analgesics.......................................................................................................................414

Adjuvants.......................................................................................................................................................415

Peripheral Neuropathy...................................................................................................................416

Patients With Substance Abuse Comorbidities......................................................417

Advanced Illness..........................................................................................................................................417

Syndrome of Imminent Death ..................................................................................................417

Prognosis, Prognostication, and Hospice......................................................................418

Advance Care Planning.................................................................................................................421

Grief and Bereavement................................................................................................................422

Caring for the Caregiver.............................................................................................................422

Incorporating Principles of Palliative Care 

Into Everyday Practice...........................................................................................................................423

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Therapy to Improve Quality of Life

Address Four Domains of Suffering

Palliative care is defined as therapy intended to improve quality of life, 

irrespective of quantity (NEJM 2004;30:2582). The term palliative is 

derived from the Latin pallium (cloak) and means to protect (or “cloak”) from 

illness and suffering. Palliative care seeks to address the four domains of 

suffering—physical, psychological, social, and spiritual. Ideally, it involves 

an interdisciplinary team approach for pain and symptom management as 

well as for nonphysical needs that may arise during the course of illness. 

Those needs may be met with psychosocial support for marginalized patients, 

identification of substance abuse and mental health issues and provision of 

appropriate services, and advance care planning. When appropriate, care 

may also include facilitating transitions to end-of-life care, including hospice. 

High-quality palliative care begins at disease diagnosis and is delivered 

simultaneously with life-prolonging therapy throughout the course of illness 

(Figure 11-1). As a patient’s illness progresses, palliative care takes on an 

increasingly important role.

Palliative care encompasses end-of-life care, including hospice. In the United 

States, patients on Medicare may choose to disenroll from Medicare and 

enroll in the Medicare hospice benefit, which requires a physician to certify 

that the patient is in the last 6 months of his or her life. This separation 

between palliative care in general and hospice is artificial and applies only 

in the United States. In other countries, the terms palliative care and hospice

are often used synonymously (Cancer J 2010;16:423).

Supportive care is used in the literature and in practice to delineate a similar 

model of care. Supportive care is designed to support a patient and his or 

her family and caregivers during an illness that is not imminently terminal 

but is curable or has a good chance of recovery or survival. Supportive care 

describes many ambulatory programs, particularly in the areas of oncology 

and cardiac disease. Supportive care settings also include a focus on the four 

domains of suffering and an interdisciplinary model of care.

Figure 11-1

Palliative Care’s Place in the Course of Illness

Diagnosis 

of Serious 

Illness

Death

Life-Prolonging Therapy

Palliative Care

Medicare 

Hospice 

Benefit

Source: National Consensus Project for Quality Palliative Care. Clinical Practice Guidelines 

for Quality Palliative Care, 2nd ed. 2009. Copyright © 2009 by the National Consensus 

Project for Quality Palliative Care. Used with permission.

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Rapid Expansion in the United States

The number of hospital-based palliative care programs increased from 658 

in 2000 to more than 1151 in 2005 (J Palliat Med 2008;11:1094); in 2009, 

41.6%% of all deaths in the United States took place under the care of a 

hospice program (http://www.nhpco.org/files/public/Statistics_Research/

Hospice_Facts_Figures_Oct-2010.pdf). A recent high-profile study showed 

that an early outpatient palliative care intervention improved quality of 

life and extended survival as much as cisplatin-based chemotherapy for 

patients with metastatic non-small-cell lung cancer. Although this result is not 

necessarily generalizable to other patient populations, it is encouraging (NEJM

2010;363:733). Additionally, palliative care is an increasingly accepted part 

of care not only for patients with cancer but also for those with other chronic 

diseases, such as congestive heart failure (CHF), chronic lung disease, and HIV.

Interdisciplinary Approach

As noted above, the delivery of comprehensive palliative care should involve 

an interdisciplinary team consisting of physicians, nurses, social workers, 

pastoral care representatives, and mental health care providers. Highfunctioning teams also successfully incorporate midlevel care providers, such 

as nurse practitioners, physician assistants, pharmacists, pain management 

specialists, and integrative therapists (massage, music, and art) as well as 

volunteers. The National Quality Forum has produced a document of preferred 

practices that delineate the parameters or measures of quality for palliative 

care programs; it should be referenced when initiating or enhancing delivery 

of palliative and supportive care (National Quality Forum 2006. A national 

framework and Preferred practices for Palliative and Hospice Care Quality: A 

Consensus Report 2006).

HIV as a Chronic Disease

Alleviate Suffering of Chronic Disease

Before the introduction of effective ART in the mid-1990s, the trajectory 

of HIV/AIDS was a downward spiral, and all care was palliative. HAART 

transformed HIV from a disease with a uniformly poor prognosis into a chronic 

disease with a slowly progressive course and occasional exacerbations, 

much like chronic obstructive pulmonary disease (COPD), CHF, and chronic 

malignancies. Patients began to have the potential for normal or nearly normal 

life spans. In the post-HAART era, the focus understandably shifted toward 

optimal use of life-prolonging medications. Palliative care for HIV was seen as 

mostly of historical significance, appropriate only for patients facing imminent 

death from AIDS (JAMA 2003;290:806, Annals Int Med 1998;129:899). 

However, symptom burden remains high despite ART (Int J STD AIDS

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2006;17:400). Therefore, in the current treatment era, palliative care should 

be applied throughout the disease continuum to alleviate suffering associated 

with living for many years with a chronic disease.

HIV Disease Burden and the Role of Palliative Care

Today, HIV palliative care focuses on quality of life, maximized functional 

status, and treatment of complicated comorbidities (Figure 11-2). 

Unfortunately, the burden of HIV disease in the current treatment era remains 

high for several reasons.

Prevalence: Even though the number of new HIV diagnoses among US women 

has declined slightly from 2008–2011, HIV prevalence continues to increase 

as more infected individuals are living longer because of ART (http://www.cdc.

gov/hiv/surveillance/resources/reports/2010report/index.htm).

Pain and symptom burden: Patients living with HIV disease have significant 

pain and physical and psychological symptoms. Most studies of pain and 

symptoms in HIV come from the early treatment era, but emerging evidence 

indicates that pain and symptom burden remains high despite advances in 

therapy (J Pain Symptom Manage 2009;38:882).

Aging patients: As a result of effective ART, the population of patients 

with HIV is aging. In addition, a number of patients with HIV experience 

premature aging and are at increased risk for cardiovascular disease, 

metabolic complications, neurologic sequelae, frailty, osteoporosis, and 

malignancies, among other age-associated conditions (AIDS Patient Care STDS

2006;20:782, J Acquir Immune Defic Syndr 2008;49:S77, J Acquir Immune 

Defic Syndr 2009; 50:299, Top HIV Med 2010; 18:45, J Acquir Immune Defic 

Syndr 2003;33:281, J Acquir Immune Defic Syndr 2009; 52:203). Aging and 

comorbidities likely add to pain and symptom burden.

Death: People still die of HIV in the United States; 2010 data from the U.S. 

Centers for Disease Control and Prevention indicate that the death rate in 

women with HIV disease has leveled off at 4–5 deaths per 100,000 since 

1998. Increasingly, death is occurring among non-Hispanic blacks, residents of 

the South, and people aged 45 years and older (http://www.cdc.gov/hiv/

surveillance/resources/reports/2010report/index.htm). Death from HIV has 

shifted “from fate to tragedy” (Ann Intern Med 1998;129:899) and is often 

due to nonadherence to medical care and ART, psychiatric and substance 

abuse comorbidities, and marginalization from the medical system.

Non-AIDS-related death: HIV patients die more often of non-AIDS-related 

causes, such as cardiovascular, hepatic, and pulmonary disease; non-AIDS 

malignancies; and substance abuse. They are at greater risk for those diseases 

than is the general population (Ann Int Med 2006;145:397, J Acquir Immune 

Defic Syndr 2006;43:27, J Acquir Immune Defic Syndr 2009;52:203).

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Thus, the role of HIV care providers is to alleviate suffering while treating 

the primary disease. If for no other reason, HIV providers today must learn 

and use the principles of palliative care to address the burden of HIV as a 

chronic disease. Additionally, evidence increasingly shows that management 

of symptoms in patients with HIV improves quality of life (AIDS Behav

2004;8:151, CID 2008;46:941), adherence (J Acquir Immune Defic Syndr

2002;31:211, AIDS Beh 2003;7:109, Ann Behav Med 2007;34:46, AIDS Care

2009;21:244), and virologic outcomes (J Acquir Immune Defic Synd 2010; 

54:500). Palliative care for patients with HIV can be delivered by HIV primary 

care providers in addition to palliative care specialists when necessary.

Figure 11-2

Key Facts About Palliative Care in HIV

• Palliative care does not equate to end-of-life care and is not the same 

thing as hospice.

• Symptom burden in HIV patients, even in the current treatment era, 

remains high.

• Incorporating principles of palliative care, including pain and symptom 

management, early in the disease course can alleviate suffering and 

may improve quality of life, adherence, and virologic outcomes.

• Palliative care for patients with HIV can be delivered by HIV primary 

care providers in addition to palliative care specialists when necessary.

Pain and Nonpain Symptoms

This section focuses on pain and nonpain symptoms in ambulatory patients 

with HIV. As with other serious conditions prevalent in patients with HIV, such as 

syphilis and hyperlipidemia, pain must be assessed and treated, if present, in 

every patient.

Pain and other symptoms in patients with HIV are generally thought to result 

from several factors:

• Disease-related factors may include the acute effects 

and long-term sequelae of opportunistic infections (e.g., 

headache in cryptococcal meningitis, contractures resulting 

from a distant history of PML), AIDS-defining and non-AIDSdefining malignancies, and the effects of HIV itself or the 

body’s immune response to it (e.g., peripheral neuropathy).

• Treatment-related factors may include the medications 

used to treat HIV disease (e.g., dideoxynucleoside-related 

peripheral neuropathy and protease inhibitor–related 

gastrointestinal distress)

• Other factors may include the nonspecific effects of a 

chronic illness and other causes of pain and symptoms 

unrelated to HIV (e.g., shortness of breath in COPD or 

edema in CHF)

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Prevalence of Nonpain Symptoms

In the current treatment era, symptoms remain prevalent, and it is essential 

to pursue the cause of the symptom by searching for treatable underlying 

etiologies. Simultaneously, an effort should be made to relieve the symptoms. 

This approach does not detract in any way from the evaluation; in fact, 

attention to symptom management may increase the likelihood of the patient 

returning for regular followup and enhance overall quality of life.

Most data on nonpain symptoms in patients with HIV comes from the early 

treatment era. In 1996, a study of 434 ambulatory patients with HIV found an 

average of 17 symptoms on the Memorial Symptom Assessment Scale (MSAS), 

a 32-symptom instrument (Pain 1996;68:315). The most prevalent physical 

symptoms other than pain were lack of energy, difficulty sleeping, and dry 

mouth (86%, 74%, and 69% respectively). A recent study of 350 ambulatory 

HIV patients in the current treatment era found a median of 9 symptoms (J 

Pain Symptom Manage 2009;38:882). The most common symptoms were lack 

of energy (65%), drowsiness (57%), and difficulty sleeping (56%). Numbness 

and tingling (44%) were also common, as were psychiatric symptoms, such as 

feeling irritable (50%), worrying (48%), and feeling sad (45%).

Assessment of Nonpain Symptoms

As part of an overall systems review, it is important to ask patients specifically 

about the types of symptoms mentioned above—namely, lack of energy, 

difficulty sleeping, psychological problems, and neuropathic pain. A systematic 

approach to assessment is more important than the specific instrument used. 

The MSAS is often used for research, but it may be too cumbersome for 

routine use in the clinical setting. If that is the case, then a standard symptom 

assessment tool that meets the needs of an individual clinical practice setting 

is recommended. When assessing physical symptoms, a patient should be 

asked about the degree to which a symptom causes bother or distress—i.e., 

not at all, a little bit, somewhat, quite a bit, or very much, as illustrated in 

Figure 11-3. For psychological symptoms, a patient should be asked about the 

frequency with which a symptom occurs—i.e., rarely, occasionally, frequently, 

or almost constantly. If a patient reports a symptom that is particularly 

distressing, then the response to these questions may be followed over time.

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Figure 11-3

Key Questions in Assessing Nonpain Symptoms

How distressing 

is this symptom? Not at all A little Somewhat Quite a bit Very

How often do 

you experience 

this symptom?

Rarely Occasionally Frequently Almost 

constantly

Management of Selected Symptoms

Clinicians should always investigate the cause of symptoms, particularly 

for potentially curable etiologies. While investigating a symptom, it is also 

important to begin to manage the symptom.

In a patient with HIV infection, multiple factors should be taken into 

consideration, including the stage of illness, current ART and other medications, 

and total symptom burden. As noted above, patients may have multiple 

simultaneous symptoms that require a comprehensive, patient-centered 

approach that focuses on the effect on quality of life of each symptom. 

Symptom clustering also should be considered (e.g., inadequately treated 

pain that leads to depression, sleep disturbance, shortness of breath, anxiety, 

poor appetite, and fatigue), so as not to overlook appropriate medications 

that may successfully treat multiple symptoms simultaneously. Discontinuation 

of nonessential medications that may cause a disturbing symptom should be 

explored as well.

Table 11-1 lists common nonpain symptoms with appropriate medication 

classes. A comprehensive listing of all symptoms and medications with dosages 

is beyond the scope of this chapter. Treatment of psychiatric and psychological 

symptoms is addressed in Chapter 9. It is also important to keep in mind that 

symptoms certainly will change and evolve as a patient’s disease progresses. 

Therefore, use of medications may change over time as well.

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Table 11-1

Common Nonpain Symptoms in HIV Patients

Symptom Common Medications/

Classes Used in Treatment

Important Points/Notes

Fatigue • Psychostimulants 

(dextroamphetamine, 

methylphenidate)

• Steroids (dexamethasone, 

prednisone)

• Other agents, depending on 

comorbidities (testosterone, 

opioids, sleep agents)

• Determine whether etiology is 

reversible.

• Energy conservation counseling and/or an appropriate 

graduated exercise regimen 

may be helpful.

Weight loss/

anorexia • Steroids (dexamethasone, 

prednisone)

• Megestrol

• Mirtazapine

• Dronabinol 

• Evaluate for inadequately 

treated comorbidities

• Consider dietary or nutrition 

consultation.

• Likely not reversible near end 

of life. 

Insomnia • Benzodiazepines (lorazepam, 

temazepam)

• Antidepressants (trazodone, 

mirtazapine)

• Chloral hydrate

• GABA receptor 

nonbenzodiazepines (zolpidem, 

zaleplon)

• Melatonin receptor agonist 

(ramelteon)

• Emphasize nonpharmacologic 

sleep hygiene.

• Avoid chronic long-term use 

of meds.

Nausea/

vomiting • Dopamine agonists 

(haloperidol)

• Dopamine antagonists 

(prochlorperazine, 

chlorpromazine, promethazine)

• Gastric motility agents 

(meclizine, hydroxyzine)

• Antihistamines (meclizine, 

hydroxyzine)

• Anticholinergics (scopolamine, 

glycopyrrolate)

• Anxiolytics (lorazepam)

• Steroids (dexamethasone)

• 5-HT3 antagonists 

(ondansetron, granisetron)

• Thoroughly evaluate for 

mechanism and/or etiology.

• Remember bowel history and 

avoid constipation.

• Combinations of agents may 

be helpful.

• 5-HT3 antagonists may have 

limited utility near end of life.

• Sedation is a common limiting 

side effect.

Dysphagia/

odynophagia • Antifungals (fluconazole, 

nystatin)

• H2 antagonists (famotidine, 

ranitidine)

• Proton pump inhibitors 

(omeprazole)

• Steroids (dexamethasone)

• Anticholinergics (hyoscyamine, 

glycopyrrolate)

• Oral solutions (viscous lidocaine)

• Treatment of oropharyngeal 

comorbidities is crucial.

• Complicates many other 

symptoms.

• Very common near end of life.

• Combinations of agents in oral 

solution may be helpful.

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Table 11-1

Common Nonpain Symptoms in HIV Patients

Symptom Common Medications/

Classes Used in Treatment

Important Points/Notes

Cough • Guaifenesin (immediate or 

sustained release)

• Nebulized saline

• Guaifenesin with 

dextromethorphan

• Guaifenesin with codeine or other opioid

• Benzonatate

• Difficult to treat in many 

instances.

• Treat underlying comorbidities 

when possible.

• Provide smoking cessation 

counseling when appropriate.

• May be productive or 

nonproductive.

Hiccups • Chlorpromazine

• Baclofen

• Simethicone

• Haloperidol

• Anticonvulsants (gabapentin, 

valproic acid, carbamazepine)

• Search for reversible causes; 

usually self-limiting.

• Relation to meals is important.

• Nonpharmacologic measures may be beneficial.

• Holding breath, gastric 

distention, vagal maneuvers 

may be helpful.

Pruritus • Topical preparations 

(camphor–menthol lotion

• Lidocaine ointment, 

hydrocortisone

• Antihistamines 

(diphenhydramine, hydroxyzine)

• Steroids (dexamethasone, 

prednisone)

• Antidepressants (doxepin, 

mirtazapine, paroxetine)

• May have multiple etiologies.

• Soaps, detergents, and fabrics 

are common offenders.

• Cool environment is usually 

better than warm.

Dyspnea/

shortness of 

breath

• Immediate-release opioids 

(morphine, oxycodone, 

hydromorphone)

• Benzodiazepines (lorazepam, 

alprazolam)

• Nebulized medications 

(furosemide, fentanyl)

• Troublesome, common symptom 

near end of life.

• Nonpharmacologic treatment (fan, relaxation, etc.) may be 

most helpful.

• Opioids are a mainstay near 

end of life.

• Nebulized meds are somewhat 

controversial.

Xerostomia • Saliva substitutes

• Chemical stimulants

• Muscarinic agents (pilocarpine, 

cevimeline)

• Encourage ice, frozen fruits, etc.

• Sour candies may increase 

saliva production.

• Use humidified oxygen when 

appropriate.

• Use muscarinic agents only with 

caution.

continued

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Prevalence of Pain

Most studies of pain in patients with HIV were conducted in the early treatment 

era. The largest study surveyed 274 patients, 62.6% of whom reported 

frequent or persistent pain during the 2 weeks prior to the survey. The 

mean rating of pain intensity was 5.4 on a scale of 1 to 10, and the mean 

rating for interference with general activity was 5.7 on a scale of 1 to 10. 

Pain prevalence in women was similar to that in men, but women reported 

significantly higher pain intensity. Pain was associated with the presence of 

AIDS-defining conditions (Pain 1996;68:315). In a study of symptoms in HIV 

patients in the current treatment era, 55% had pain, 60% of whom reported 

the symptom frequently. Pain was associated with female gender, advanced 

disease, and absence of antiretroviral (ARV) medications (J Pain Symptom 

Manage 2009;38:882). In a recent study, muscle aches and joint paints were 

one of the two symptoms most associated with the physical component of 

health-related quality of life in patients with HIV (AIDS Behav 2011; 15:853). 

Another recent study found that up to 15% of HIV Outpatient Study patients 

used prolonged analgesic therapy each year; variables associated with the 

initiation of prolonged analgesia included both HIV and non-HIV related 

factors. (Clin J Pain 2011;27:699).

Although more research is needed to understand HIV patients’ pain in 

the current treatment era, the available data suggest that pain is widely 

prevalent in this population. Studies from the early treatment era suggest 

that pain is underrecognized and undertreated (BMJ 1997;314:23, J Pain 

Symptom Manage 1999;18:263, Pain 1996;65:243) and has a negative 

effect on quality of life (AIDS Behav 2004;8:151, CID 2008;46:941). 

Multisite pain syndromes are common as well–patients have musculoskeletal, 

neuropathic, and visceral pain syndromes simultaneously. Multisite syndromes 

may have distinct etiologies and require specific evaluations and treatments 

that can further complicate care plans, medical regimens, and patients’ 

emotional response to their illness. Although referral to a pain specialist may 

be useful for patients with a history of previous substance abuse, it behooves 

the primary care provider to attempt to clarify the types of pain present to 

ensure adequate follow-up.

Assessment of Pain

Brief Pain Inventory (BPI; Ann Acad Med Singapore 1994; 23 (2): 129): 

Many approaches to the assessment of pain in patients with chronic illness are 

available. Because no tool has been validated specifically in patients with HIV, 

having a systematic approach to assessing pain is more important than using 

a specific tool. A standard approach that is consistent with the intent of the BPI 

is generally recommended (Ann Acad Med Singapore 2004;23:129).The BPI 

has been validated in patients with chronic nonmalignant pain (J Pain 2004; 

5:133) and has been used in studies of patients with HIV (Pain 1996; 68: 315). 

In its entirety, the BPI may be too long for many clinical settings, but when 

appropriate, it should be incorporated into a patient’s ongoing pain assessment 

and treatment plan.

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Pain evaluations should begin by simply asking whether the patient has 

had pain that affects quality of life during the past week. If the patient 

answers yes, in addition to usual questions about pain (e.g., location, quality, 

exacerbating and alleviating factors, duration), a few brief follow-up 

questions, illustrated in Figure 11-4, may be asked:

• Severity: How severe is your pain right now on a scale of 

0 to 10, where 0 is no pain and 10 is pain as bad as you 

can imagine? On average? At its worst? At its least? (A pain 

scale, shown in Figure 11-5, may be used to help patients 

answer this question.)

• Relief: What current medications or therapies do you use 

to help alleviate your pain? How much relief do you get 

from these therapies, on a scale of 0% (no relief) to 100% 

(complete relief)? It is important to ask and document all 

medications or therapies that have been successful in the 

past; also emphasize reports of allergies or sensitivities to 

particular opioids or other pain medications.

• Interference: How much does the pain interfere with your 

general activity on a scale of 0 to 10, where 0 is no interference and 10 is complete interference? How does much 

does it interfere with your mood? Walking ability? Normal 

work? Relations with other people? Sleep? Enjoyment of life?

The answers to these questions can be followed over time.

Figure 11-4

Key Questions in Assessing Pain

How much 

does pain 

interfere 

with your

life?

On a 

scale of 

0 to 10

How much 

relief do you 

have with 

your current 

therapy?

On a 

scale of 

0% to 100%

How 

severe is 

your

pain?

On a 

scale of 

0 to 10

Several additional questions, noted below, may be especially helpful if 

patients have longstanding or multisite symptomatology. Discussing the 

questions below can build a therapeutic relationship that helps patients become 

more active in their care plan.

• Which of your pain locations is the worst today?

• When was the last time you remember being pain free?

• What are your goals, or what would be an acceptable pain 

score for you?

• If we meet these goals, what kinds of things would you like 

to do that you are not currently doing?

• What would be your time frame for acceptable pain relief?

• How do your emotions or stress affect your pain?

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Figure 11-5

Pain Scale

01 345678 9 10

Mild 

Pain

No 

Pain

Moderate 

Pain

Severe 

Pain

2

Approach to Pain Management

Initial medication selection: Although it has not been validated specifically in 

patients with HIV, the World Health Organization’s (WHO’s) pain ladder is a 

well-accepted approach to pain management (Figure 11-6).

Figure 11-6

WHO Pain Relief Ladder

Step 3: Severe Pain

Opioid (morphine, hydromorphone)

± Nonopioid analgesics

± Adjuvants

Step 2: Moderate Pain

Opioid (codeine, hydrocodone, oxycodone)

± Nonopioid analgesics

± Adjuvants

Step 1: Mild Pain

Nonopioid ± Adjuvants

Source: World Health Organization. WHO’s Pain Relief Ladder. Copyright © 2012. World 

Health Organization. Adapted with permission.

Principles for Use of WHO Pain Ladder

Initiation: Initiate pain medications according to the appropriate step on the 

WHO Pain Ladder. In the outpatient setting, this step may entail use of oral 

instead of intravenous medications, even for patients with moderate to severe 

pain. In the inpatient setting and in patients with severe pain, pain medications 

administered intravenously or subcutaneously may be needed for acute pain 

relief in opiate-naïve patients.

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Starting doses for opioid-naïve patients with normal renal and hepatic function 

are listed in Table 11-2. The medication should be given every 4 hours around 

the clock, not on an as-needed basis. In addition to the around-the-clock doses, 

prescribe a breakthrough dose that is 10% of the total daily opioid dose, 

given every hour if the pain is not controlled.

Long-acting pain medication: Once pain is fairly well controlled, if it is 

expected to continue and not improve (e.g., pain related to a fracture that is 

healing), then it is appropriate to change to a long-acting pain medication for 

ease of administration.

• Calculate the dose of a long-acting medication by adding 

all doses taken in 24 hours (including breakthrough doses). 

Oral long-acting medications are usually given 2 or 3 times 

per day, so the total daily dosage must be divided by this 

number to get the amount of each dose.

• Fentanyl patches and methadone are preferred in patients 

with renal and hepatic failure (when using methadone, 

consult with a palliative care or pain specialist). Provide a 

breakthrough dose every 1 hour as needed; the breakthrough 

dose should be 10% of the total daily dosage.

• Adjust for incomplete cross-tolerance; see below.

Adjusting for incomplete cross-tolerance: When exposed to a new opioid, a 

patient will not have had the opportunity to become tolerant to that opioid’s 

side effects. Therefore, as a rule of thumb, when converting between opioids or 

converting to long-acting medications, decrease the dosage by 25% to 50%. 

This adjustment is called “adjusting for incomplete cross-tolerance” to the new 

drug. Use an equianalgesic table, such as Table 11-2.

Fentanyl patches should never be used in opioid-naïve patients. To convert 

short-acting medications to fentanyl, see Table 11-3. To convert fentanyl back 

to short-acting medications, see Table 11-4. Note that liquid formulations, 

rectal suppositories, and sprinkles that can be mixed with food may be 

prescribed for patients who have with difficulty swallowing pills.

Most well-localized and acute pain can be controlled with the use of the 

pain ladder (JAMA 1995; 274:1870). Once a patient is on an appropriate 

dosage, side effects (except for slowed bowel motility) generally resolve 

within 7–10 days.

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Table 11-2

Oral Opioid Dosing

Drug Starting 

Doses 

for Naïve 

Patients

Equianalgesic 

Doses

Renal 

Impairment

Hepatic 

Impairment

Codeine 30-60 mg 200 mg Avoid Avoid

Oxycodone 5-10 mg 20 mg Adjust dose 

and frequency

Adjust dose 

and frequency

Hydrocodone 2-4 mg 30 mg Adjust dose 

and frequency

Adjust dose 

and frequency

Morphine 

(short-acting)

15-30 mg 30 mg Avoid Adjust 

dose and 

frequency; 

avoid in 

severe disease

Hydromorphone 2-4 mg 7.5 mg Preferred, but 

decrease dose 

and frequency

Adjust dose 

and frequency

Source: © Pain Management Guidelines. Hertzberg Palliative Care Institute. May 2008. 

Adapted with permission.

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Table 11-3

Converting the Current Opioid to a Fentanyl Patch*

Morphine, 

po mg/24 h

Oxycodone, 

po mg/24 h

Hydromorphone, 

po mg/24 h

Replace with 

Fentanyl Patch at 

Following Dose 

(mcg/hr q 72 h)

10–19 20–39 8–14 12

20–44 40–89 15–33 25

45–74 90–149 34–55 50

75–104 150–209 56–78 75

105–134 210–269 79–100 100

135–164 270–329 101–123 125

165–194 330–389 124–145 150

195–224 390–449 146–168 175

225–254 450–509 169–190 200

255–284 510–569 191–213 225

285–314 570–629 214–235 250

315–344 630–689 236–258 275

345–374 690–749 259–280 300

375–404 750–809 281–303 325

405–434 810–869 304–325 350

435–464 870–929 326–348 375

465–494 930–989 349–370 400

*PRN dosing for breakthrough pain: The breakthrough dose of oral morphine for a 

patient on a fentanyl patch is roughly 1/3 the fentanyl patch dose (e.g., if the patient is 

prescribed a fentanyl patch of 75 mcg/h q 72 h, the breakthrough dose is short-acting 

morphine 25 mg po q 1 h prn. If you want to use an opioid other than morphine, use 

the equianalgesic table to convert. As always, when starting a new opioid, adjust for 

incomplete cross-tolerance.

Source: © Pain Management Guidelines. Hertzberg Palliative Care Institute. May 2008. 

Adapted with permission.

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Table 11-4

Converting a Fentanyl Patch to Another Opioid*

Fentanyl 

patch dose 

(mcg/hr q 72 h)

Replace With One of the Following Opioids (Total mg/24 h)**

Morphine 

po mg/24 h

Oxycodone 

po mg/24 h

Hydromorphone 

po mg/24 h

12 45 30 11

25 90 60 22

50 180 120 45

75 270 180 67

100 360 240 90

*PRN dosing for breakthrough pain: The breakthrough dose of oral morphine for a 

patient on a fentanyl patch is roughly 1/3 the fentanyl-patch dose (e.g., if the patient 

is prescribed a fentanyl patch of 75 mcg/h q 72 h, the breakthrough dose is shortacting morphine 25 mg po q 1 h prn. If prescribing an opioid other than morphine, use 

the equianalgesic table to convert. As always, when starting a new opioid, adjust for 

incomplete cross-tolerance.

**Divide recommended doses (mg/24 h) into 6 equal doses given q 4 h.

Source: © Pain Management Guidelines. Hertzberg Palliative Care Institute. May 2008. 

Adapted with permission.

Opioid Titration

For many patients, pain is not adequately relieved by the initial low-dose 

opioid. When that is the case, the care provider must titrate the patient’s 

opioid dose to pain relief. Moderate pain requires titration every 24 hours, 

whereas severe pain may require more frequent titration. A patient may be 

instructed to alert the care provider if severe pain continues or if more than 

three to four doses of the breakthrough pain medication are taken, at which 

time the patient’s total daily dosage may be increased by 25% to 50% for 

mild to moderate pain and by 50% to 100% for severe pain. Patient or 

caregiver diaries of breakthrough pain medication dosing are helpful in opioid 

titration. Patients undergoing titration should be seen frequently, as often as 

every week, and called as often as is necessary between appointments to 

ensure adequate pain relief.

Bowel Regimen

Constipation is expected with opioids and will not resolve without 

pharmacologic intervention. Unlike other side effects, tolerance does not 

develop over time with long-term opioid therapy. Therefore, all patients 

receiving opioids must also be started on a bowel regimen at the time of 

opioid initiation. A combination of a stool softener and a mild stimulating agent 

(such as docusate, 100 mg orally twice daily, and senna, 2 tablets daily) may 

be an effective initial regimen. If this regimen is ineffective, then the doses of 

these agents can be increased or an osmotic agent (such as lactulose, sorbitol, 

or polyethylene glycol) can be added. If those measures do not work, then 

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a laxative suppository (e.g., Dulcolax) and enemas may be used. The newer 

agent methylnaltrexone can also be prescribed in severe refractory cases, but 

it is quite expensive, requires a subcutaneous injection, and can be used only 

once every 2 to 3 days.

Side Effects of Opioids

Table 11-5 outlines common side effects of opioids. Although respiratory 

depression is a much-feared side effect, it is unusual unless an opiate-naïve 

patient is given a large initial parenteral dose. Use of the Pain Ladder method 

and the starting doses described above is a safe approach. Patients should be 

counseled that side effects usually dissipate after a week of therapy.

Table 11-5

Common Side Effects of Opioid Analgesics

Constipation Requires prescription of bowel regimen at the Same Time opioids 

are prescribed.

Tolerance does Not develop.

Drowsiness Resolves after 24–36 h.

Extended sleeping can be from exhaustion; may need 

psychostimulant, such as methylphenidate.

Nausea Prescribe antiemetic with first opioid prescription.

Resolves in several days; may need around-the-clock 

dosing initially.

Urinary 

retention

Uncommon side effect.

Rotate opioids or adjuvants; may require catheter drainage 

of bladder.

Itching/

twitching

May indicate toxic levels due to impaired renal function.

Lengthen interval; rotate opioids.

Nonopioid Analgesics

The most commonly used nonopioid analgesics are

• acetaminophen (starting dose 650–1000 mg orally every 

6 hours, not to exceed 2-3 g/day in an adult with normal 

hepatic function or 2 g/day in patients with impaired 

hepatic function);

• ibuprofen (200-800 mg orally every 8 hours); and

• tramadol (50-100 mg orally every 4-6 hours, not to exceed 

400 mg orally daily).

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Prescribing opioids and nonopioids separately, as opposed to in 

combination pill form (e.g. oxycodone–acetaminophen) is better practice 

because it allows providers to titrate up opioids without exceeding the 

maximum dose of a nonopioid.

Adjuvants

Adjuvant medications are used to enhance the analgesic efficacy of opioids, to 

treat concurrent symptoms that exacerbate pain, and to provide independent 

analgesia. They may be used at all stages of the WHO Pain Ladder. 

Commonly used adjuvants include antidepressants, antipsychotics, anxiolytics, 

psychostimulants, anticonvulsants, and corticosteroids. Consider use of adjuvants 

for any patient with pain. In particular, it may be helpful to consider the 

mechanism of pain when selecting an adjuvant. For example, a patient with 

neuropathic pain may benefit from the anticonvulsant gabapentin, whereas 

a patient with colon cancer and liver metastases and right upper-quadrant 

pain may benefit from steroids for capsular pain. A complete discussion of 

initiation of adjuvant pain medications is beyond the scope of this chapter. 

However, care providers who are treating pain syndromes should be generally 

familiar with these medications and comfortable with the starting dosage while 

consulting with a pain management or palliative medicine specialist.

Adjuvants used in selected circumstances include:

• anticonvulsants (e.g., gabapentin, pregabalin, and 

carbamazepine) and GABA-receptor agonists (e.g., 

baclofen) for neuropathic pain;

• transdermal agents (e.g., the lidocaine patch) for 

postherpetic neuralgia and other localized pain syndromes;

• antidepressants, including tricyclic antidepressants (e.g., 

amitriptyline) and selective serotonin reuptake inhibitors 

(e.g., paroxetine, citalopram); and

• corticosteroids (e.g., dexamethasone) for pain due to 

increased intracranial pressure, pain due to bowel or 

bladder obstruction, bone pain, and spinal cord compression 

(Textbook of Palliative Medicine, 2006)

Adjuvant medications may be particularly helpful when patients have comorbid 

conditions such as depression, weight loss, or cachexia. Antidepressants may 

be beneficial for patients experiencing what has been described in the past as 

a “whole body” or more central-type chronic pain syndrome. As noted above, 

several adjuvant medications may be more helpful in patients who have a 

neuropathic component to their pain syndrome.

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Peripheral Neuropathy

Distal sensory polyneuropathy is the most common neurologic complication 

found in patients with HIV (Neurol Clin 2008;26:821). Prevalence estimates 

of clinically evident peripheral neuropathy in patients with well-controlled 

HIV in the current treatment era range from 13% to 49% (Clin Infect Dis

2005;40:148, Arch Neurol 2010;67:552, Neurology 2006;66:867).

Cause: Distal sensory polyneuropathy is thought to be caused by the direct 

effects of HIV on peripheral nerves. It is more common in patients with 

advanced disease and in those taking certain ARVs (i.e., DDI and d4T). It can 

occur at any CD4+ cell count. Risk factors include age greater than 40, CD4+ 

cell count nadir below 50/mm3, diabetes, and use of DDI and d4T (Clin Infect 

Dis 2005;1:148, Arch Neurol 2010;67:552, Clin Infect Dis 2005;40:148, 

Neurology 2006;66:867).

Clinical presentation: Typical clinical presentation is numbness and tingling in 

the feet, which may progress up the legs and, less commonly, to the hands and 

arms in a stocking–glove distribution. The neuropathy is usually only sensory, 

but in rare cases it may have a motor component.

Diagnosis: Diagnosis is clinical. Workup should include tests to exclude other 

causes of peripheral sensory neuropathy (e.g., B12 level, diabetes screening, 

hepatitis C virus (HCV) testing, thyroid function tests, renal/hepatic function, 

serum and urine protein electrophoresis, syphilis screening, and careful review 

of the medication list for neurotoxic medications).

Recommended approach to treatment: Remove neurotoxic drugs, such as 

implicated ARVs and isoniazid, and treat coexisting conditions found on initial 

evaluation.

• Antiepileptic drugs: Initiate gabapentin 100 mg p.o. 3x/

day with titration to a maximum dose of 3,600 mg daily 

(J Neurol 2004;251:1260) as tolerated.

• Antidepressants: Although studies in patients with HIV have 

not shown benefit over placebo (Neurol 1998;51:1682, 

JAMA 1998;280:1590), amitriptyline commonly continues to 

be used in this setting because of its efficacy in patients with 

diabetic neuropathy (Neurol 1987;37:589).

• Topical agents: Capsaicin has been shown to improve 

symptoms of peripheral neuropathy and may be used in 

combination with oral agents (J Pain Symptom Manage

2008;35:299, Neurology 2008;70:2305).

• Opioids: In recalcitrant cases, opioids may be added and 

have shown efficacy in many studies.

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Patients With Substance Abuse Comorbidities

Managing pain in patients with a history of substance use is a particularly 

challenging problem that HIV care providers often face. Basic principles for 

pain management in substance users are outlined below. (Also see Chapter 9, 

Psychosocial Issues, Mental Health, and Substance Abuse.)

Approach to Pain Management in Substance Users With HIV Disease

• Substance users with HIV disease deserve pain control; we 

have an obligation to treat pain and suffering in all of our 

patients.

• Accept and respect the report of pain.

• Be careful about the label substance abuse; distinguish 

between tolerance, physical dependence, and addiction

(psychological dependence or drug abuse) and 

pseudoaddiction (opioid-seeking behavior in a patient with 

undertreated pain).

• Not all substance users are the same; distinguish between 

active users, patients in methadone maintenance, and those 

in recovery.

• Individualize pain treatment.

• Utilize the principles of pain management outlined for all 

patients with HIV disease and pain (WHO Pain Ladder).

• Set clear goals and conditions for opioid therapy: Set limits, 

recognize drug abuse behaviors, make consequences clear, 

use written contracts, and establish a single prescriber.

• Use a multidimensional approach: pharmacologic and 

nonpharmacologic interventions, attention to psychosocial 

issues, team approach.

• Utilize pain diaries along with standard protocols for refills 

and periodic urine drug screens.

Advanced Illness

Syndrome of Imminent Death

It is important to recognize when a patient is actively dying. Several features 

characterize the syndrome of imminent death. Early on, patients may be 

bedbound, have delirium, and have decreased oral intake. As they progress, 

they may become increasingly obtunded; develop noisy secretions (i.e., the 

death rattle); and eventually become comatose and febrile, with periods of 

irregular breathing interrupted by long pauses (Syndrome of Imminent Death, 

2nd ed. Fast Facts and Concepts #3, July 2008; available at http://www.

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eperc.mcw.edu/EPERC/FastFactsIndex/ff_003.htm. Accessed 9/15/2012). 

Figure 11-7 describes key physical and emotional aspects of care at the end 

of life. This guide is formatted for use as a pocket guide for care providers.

Figure 11-7

Pocket Guide to End-of-Life Care

Pocket Guide to End-of-Life (EOL) Care [side 1]

Comfort Measures at LIFE’S END

L Lips, mouth, and eyes moistened—use ice chips and artificial saliva and tears

I Incontinence of bowel and bladder expected—use catheter, bed pads

F Fevers expected—use around-the-clock antipyretics, oral or suppository

E Eliminate all but essential meds

S Symptom management—be aggressive

E Eating—less is expected; diet as desired

N Nursing call orders—revise

D Decubitus—skin care and/or turning every 2 hours

Pocket Guide to EOL Care [side 2]

Provide RPC (see below): Once the difficult decision to write a Do Not Resuscitate 

(DNR) order has been made, more remains to be done for a dying patient and the 

family. After writing a DNR order, remember to reverse your thinking and write an 

order to Provide RPC.

R = Reassurance: Continue to care for the patient and family. • Control 

symptoms that interfere with quality of life. • Find effective ways to cope 

with stress and to grieve. • Let patient and family concerns direct how and 

where care is provided.

P = Presence: Be there to talk with the patient and the family. • Visit regularly. • Sit down and hold a hand. • Listen respectfully.

C = Caring: Provide comfort measures. • Honor the individual. • Share touch 

and laughter.

Life Review: Facilitate life review, important conversations, and the exchange of 

important words: Thank you • I love you • Please forgive me • I forgive you • Goodbye

Alexander, 1999. © Copyright Palliative Care Program, University of Maryland, Baltimore. 

Permission granted to reproduce for educational purposes.

Prognosis, Prognostication, and Hospice

The National Hospice and Palliative Care Organization has published 

guidelines hospice eligibility for patients with noncancer diagnoses, including 

HIV (Hosp J 1996;11(2):47). These widely used guidelines generally apply to 

patients who truly are at the end stage of their disease process and are no 

longer taking ART, although this is not always the case. The current guidelines 

were developed and published during a different era of HIV treatment, 

and they should be viewed as guidelines, not as absolute criteria. A brief 

summary and reference of hospice criteria for the diagnosis of advanced HIV 

is provided in Table 11-6.

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Table 11-6

Guidelines for Determination of Hospice Eligibility

Patient meets the following criteria:

CD4+ cell count <25 cells/mm3

or

persistent viral load >100,000 c/mL (2 or more assays at least 1 month apart)

and

Patient has at least one of the following conditions:

• CNS lymphoma

• Untreated or refractory wasting (loss of >33% lean body mass)

• Mycobacterium avium complex bacteremia, untreated, refractory, or treatment refused

• Progressive multifocal leukoencephalopathy

• Systemic lymphoma with advanced HIV and partial chemo response

• Refractory visceral Kaposi’s sarcoma

• Renal failure in the absence of dialysis

• Cryptosporidium infection

• Refractory toxoplasmosis

• Palliative Performance Scale of <60% (J Palliat Care 1996;12(1):5; 

J Pain Symp Manage 1999;18(1):2)

Supporting documentation:

• Chronic persistent diarrhea >1 y

• Persistent serum albumin <2.5 g/dL

• Concomitant active substance abuse

• Age >50 y

• Absence of ART and prophylactic meds

• Advanced AIDS dementia complex

• Toxoplasmosis

• CHF, Stage IV

• Rapid decline or other comorbidities

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Prognostication: Prognostication in patients with HIV is increasingly complex. 

Patients may present after a long history of inability to adhere to therapy, 

perhaps as a result of substance abuse or psychiatric comorbidities, and with 

low CD4+ cell counts, high viral loads, and opportunistic infections. These 

patients often have dramatic responses to initiation of ART. They initially may 

appear hospice appropriate, but if started on ART, they may improve quickly. 

Sadly, some patients have sought treatment too late or have difficulty with 

medication adherence and continue to need hospice services. Others are 

appropriate for hospice services on the basis of comorbid conditions such as 

cirrhosis secondary to HCV or malignancy. These patients will have a disease 

course and life expectancy more consistent with the comorbid condition rather 

than their HIV disease, despite remaining on ART.

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Goals of hospice: In the United States, hospice is an interdisciplinary program 

that delivers care for patients and families who have elected to live the final 

portion of their lives in nonhospital settings, such as home, skilled nursing 

facilities, or designated residential hospices. This choice allows patients to 

accomplish their personal goals and live life as fully as possible. In hospice, 

close attention is paid to management of pain and other symptoms and to 

relief of all suffering, whether physical, psychological, social, or spiritual. 

As noted earlier, criteria for hospice have been established, and all hospice 

admissions are certified by two physicians who verify that a patient’s life 

expectancy is likely to be 6 months or less if his or her disease follows its 

expected course.

No penalty exists for estimating someone’s life expectancy incorrectly. For 

instance, a patient with HIV infection who has a CD4+ cell count of 10/mm3

and recently received induction therapy with amphotericin for cryptococcal 

meningitis and is unable to adhere to ART would meet diagnostic criteria on 

the basis of her prognosis if her disease follows its expected course. If she 

outlives this estimate, the hospice medical director must determine whether the 

patient’s prognosis is still 6 months or less if the disease follows its usual course. 

For as long as this is the case, the patient may remain in hospice. Therefore, 

it is reasonable to consider hospice referral for patients hospitalized for 

opportunistic infections who are not improving on appropriate therapy or who 

do not wish to continue receiving life-prolonging treatments.

Limitations of hospice: Hospices receive capitated payments from Medicare 

at a low daily rate. They must pay for all of a patient’s care with that money; 

therefore, a hospice may have limited ability to provide expensive medications, 

whether or not those medications are considered palliative. These fiscal 

constraints limit the ability of many hospices to provide ART. The decision to 

provide expensive medications is made on a case-by-case basis. Medications 

that are relatively inexpensive and likely to prevent symptoms from occurring, 

such as maintenance fluconazole therapy, are more likely to be allowed.

It is possible that after receiving intensive symptom control and attention to 

social, spiritual, and psychological needs, a patient may decide to initiate ART. 

She may revoke the hospice benefit at any time and resume care under usual 

insurance coverage. The majority of hospice patients are those with end-stage 

malignancies. HIV was listed as a primary diagnosis for only 0.5% of all 2008 

hospice admissions in the United States (http://www.nhpco.org/files/public/

Statistics_Research/Hospice_Facts_Figures_Oct-2010.pdf. Accessed December 

28, 2011). The percentage of HIV-infected patients who die while enrolled 

in hospice is not known. Hospice care was the standard of care for many 

patients in the early HIV era. Now, it is just one aspect of what is available 

through palliative and supportive care referral and evaluation. Practitioners 

of palliative and supportive care may help patients and their families access 

hospice programs in their communities.

One common question is whether or when to discontinue ART for HIV-infected 

patients in hospice. ARV medications may cost thousands of dollars per 

month, and because hospice is paid at a relatively low capitated daily rate, 

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continuing those medications may be cost prohibitive to enrolling in hospice. 

Decisions about ART in such circumstances must be made on a case-by-case 

basis with careful consideration of the medications’ added benefit, if any.

Advance Care Planning

HIV practitioners play a particularly important role in facilitating patient and 

family (or caregiver) dialogues regarding patient wishes and advance care 

planning. At various points during the course of a disease, opportunities exist 

for patients to define important aspects of their care. Those decisions should be 

revisited periodically, especially when circumstances change (e.g., new partner, 

change in clinical condition). Attention should be paid to cultural or spiritual 

beliefs that may affect end-of-life decisions.

Key Decisions in Advance Planning

• Surrogate decision makers: Laws regarding default surrogate 

decision makers vary by State. In general, it is usually 

preferable for a patient to choose and document a surrogate 

decision maker who can speak for the patient in the event that 

the patient lacks the capacity to make decisions.

• Preferences for artificial nutrition and hydration, 

resuscitation, and life support

• Custody or guardianship of children

• Preferred location of care at the end of life, if appropriate 

(e.g., home vs. hospital)

• Discontinuation of ART therapy

Ideally, the patient will discuss these issues with her treating provider, who 

should document the patient’s preferences in an easily accessible place in the 

patient’s medical record. It is also important that the patient discuss these issues 

with her surrogate, who may be in the difficult position of making decisions for 

the patient when the patient can no longer speak for herself.

Palliative medicine practitioners who are specifically trained to discuss these 

difficult and complex issues can help HIV providers have these important 

discussions. In addition, as a patient’s illness advances and symptom burden 

increases, issues involving psychosocial conflict, spiritual distress, and cultural 

belief systems may become even more prominent and are amenable to 

palliative care attention.

The journey of many patients with HIV may be associated with loss of 

traditional family support systems. This loss can lead to complicated grief and 

caregiver burden, if not addressed. Once again, an interdisciplinary team 

facilitated by palliative and supportive care practitioners may be beneficial 

as a patient’s clinical condition worsens. One additional advantage of hospice 

care in the terminal phases of HIV illness is that hospice is required to provide 

follow-up bereavement care for the primary caregivers for 1 year following 

the death of a patient enrolled in hospice.

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Grief and Bereavement

Grief is a normal reaction to a major loss. Its manifestations vary but may 

include physical, cognitive, behavioral, and emotional elements, such as a 

feeling of numbness, loss and longing, restlessness, frequent crying, difficulty 

sleeping, loss of appetite, and somatic complaints. The expected duration of 

grief is 1 to 2 years, after which most people return to their previous level 

of functioning. Risk factors for complicated grief—grief of longer duration or 

greater intensity than expected—include protracted illness; difficult terminal 

symptoms; death from a stigmatizing disease; death of a spouse, child, or 

other close relative; lack of social or financial support; and the bereaved 

person’s own history of psychiatric or substance abuse (Textbook of Palliative 

Medicine, 2006). All of these factors are highly prevalent in patients with 

HIV. Many patients may also suffer from anticipatory grief as their condition 

worsens, and some have a variant of a grief response to loss at the time of 

their diagnosis (i.e., in sensing the loss of good health).

Physicians caring for patients with HIV need to be available to patients’ family 

and friends during the bereavement process. Health care providers can use 

five principles of bereavement support to care for patients and families during 

this difficult time:

• View patient and family as one unit of care.

• Enable open discussion of illness and death-related concerns.

• Provide emotional support.

• Facilitate practical assistance.

• Respect cultural, ethnic, and religious practices.

Caring for the Caregiver

Caregiver burden is the “physical, emotional, and financial toll of being a 

caregiver” (Gerontologist 1986;26:253, Am Fam Physician 2000;62:2613). 

Caregiver burden has most often been studied in spouses of patients with 

dementia; results indicate high rates of depression, worsening physical health, 

and increased mortality (Am Fam Physician 2000;62:2613). People caring 

for patients with HIV may have HIV themselves; therefore, it is important 

to recognize a patient’s caregiver(s) and assess for lack of social support 

and signs of caregiver burden, including stress, depression, and isolation 

(Gerontologist 1980;20;649).

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Incorporating Principles of Palliative Care Into Everyday 

Practice

The HIV care provider’s role is often that of a general internist for patients 

with HIV. To provide excellent primary care for this patient population, it 

is important to screen for common conditions. Providers routinely perform 

Pap smears; recommend mammography and colonoscopies; and screen for 

hyperlipidemia, syphilis, and many other conditions. Primary providers should 

also routinely screen for pain and symptoms, because these are just as common 

as other conditions, and are important to patients’ quality of life.

Providers should screen patients for pain and symptoms at every visit. This 

task can be done quickly, as outlined earlier. Management of pain and other 

symptoms can be handled by the HIV care provider, and if necessary, patients 

may be referred to a palliative care or pain specialist. In caring for patients 

and their caregivers, the primary HIV care provider and interdisciplinary team 

can incorporate purposeful dialogue with patients regarding advance care 

planning and preferences if they experience disease progression.

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Chapter 12:

Occupational Exposure and 

Postexposure Management

Mina Matin, MD

Assistant Clinical Professor

National HIV/AIDS Clinicians’ Consultation Center

Department of Family and Community Medicine

University of California, San Francisco

Ronald H. Goldschmidt, MD

Director, National HIV/AIDS Clinicians’ Consultation Center

Professor and Vice Chair

Department of Family and Community Medicine

University of California, San Francisco

The authors declare no conflicts of interest

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Chapter 12: Occupational Exposure and 

Postexposure Management

Chapter 12 at a Glance

HIV, HBV, and HCV Exposures Are Common.............................................................427

Postexposure Management Should Not Be Delayed......................................427

If Consultation Is Needed............................................................................................................427

Reporting.......................................................................................................................................................427

Universal Precautions to Prevent Exposure .................................................................428

Exposure and Transmission............................................................................................................429

Transmission Risks..................................................................................................................................429

Postexposure Assessment and Management.............................................................431

Baseline Laboratory Workup..................................................................................................431

Window Period.......................................................................................................................................431

U.S. Public Health Service Guidelines for PEP .....................................................431

Resistance ...........................................................................................................................................................435

Drug–Drug Interactions .................................................................................................................435

Adverse Drug Reactions and Symptom Management...................................437

Pregnancy.....................................................................................................................................................437

Breastfeeding...........................................................................................................................................438

Follow-Up Postexposure Laboratory Monitoring .................................................438

Hepatitis B and C Postexposure Management..........................................................439

Hepatitis B....................................................................................................................................................439

Hepatitis C...................................................................................................................................................441

HIV Infected Healthcare Providers...........................................................................................441

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HIV, HBV, and HCV Exposures Are Common

Exposures to HIV and hepatitis B and C (HBV and HCV) are common among 

healthcare workers, approximately 70% of whom are women (U.S. Bureau of 

Labor Statistics, 2007; Report 1002:30). Although universal precautions, safety 

devices, and other factors have reduced occupational exposures to bloodborne 

pathogens (BBPs), exposures continue to be a persistent problem in healthcare 

settings, and only a fraction of them are formally reported (National Institute 

for Occupational Safety and Health Pub. No. 2000-135). Safety measures, 

along with widely practiced HBV immunization and postexposure prophylaxis 

(PEP) for both HIV and HBV, have decreased the incidence of BBP transmission 

to healthcare workers over the past decade.

This chapter is designed to help the managing clinician decide whether PEP 

should be administered and to provide guidance for postexposure management.

Postexposure Management Should Not Be Delayed

Because HIV PEP efficacy depends on the timing of the first administered 

dose of antiretroviral (ARV) drugs, postexposure management is urgent and 

should not be delayed. The need for PEP is determined by assessing the risk 

and severity of the exposure and the source patient’s risk for HIV or hepatitis 

infection. Although time to initiation is critical to PEP efficacy, it is equally 

important to determine when PEP is not warranted.

If Consultation Is Needed

PEPline: Consultation is available 24 hours per day from the National HIV/

AIDS Clinicians’ Consultations Center’s Post-Exposure Prophylaxis Hotline 

(PEPline): 888-448-4911. PEPline provides expert guidance in managing 

healthcare worker exposures to HIV, HBV, and HCV. Callers receive immediate 

PEP recommendations.

Reporting

No nationwide central service exists for reporting healthcare worker exposures. 

All healthcare facilities must comply with Occupational Safety and Health 

Administration guidance in developing institutional policies for postexposure 

protocols, including institution-based reporting systems, systemwide prevention 

initiatives to minimize occurrence of work-related exposures, and incorporation 

of PEP into institutional occupational healthcare programs.

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Universal Precautions to Prevent Exposure

The phrase “universal precautions” is used to indicate that all patients should 

be considered potentially infectious and that safety measures should be 

applied universally, regardless of known risk factors, to prevent exposure to 

HIV, HBV, and other BBPs. Protective equipment and practices are used in the 

healthcare setting to protect healthcare workers and patients:

• Gloves are recommended for use in all procedures 

in which contact with infectious body fluid is likely 

(e.g., pelvic exam, phlebotomy, transfer of body fluid 

samples to a specimen cup).

• Masks are recommended for use when there is risk of blood 

or other infectious body fluid splash (e.g., during incision and 

drainage, insertion of chest tube, intubation, surgery).

• Goggles or other eye protection is recommended for 

use when there is risk of blood or other infectious 

body fluid splash.

• Gowns should be worn during surgery or with other 

procedures where there is significant risk of blood or other 

infectious body fluid splash or contamination of clothing.

• Puncture-proof containers should be available to dispose of 

used needles, scalpels, and other disposable sharp supplies. 

Needle and scalpel safety devices are also available in 

many higher resource settings.

• Operating room and emergency department precautions:

Avoid direct hand-to-hand transfer of sharp instruments in 

the operating room and emergency department; instead, 

pass sharps from hand to pan or emesis basin to allow for 

greater control in handling.

The need for safety precautions should be made on the basis of the risk of 

the medical procedure being performed. Gloves and other precautions are 

not needed when contact with infectious body fluid is unlikely, as when shaking 

hands with a patient or performing a routine examination.

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Exposure and Transmission

Transmission Risks

For BBP transmission to occur, an exposure must involve infectious body fluid 

from a source infected with a BBP, and it must involve a mechanism by which 

BBPs can be transmitted. If both factors are not present, then no risk of 

transmission exists and no further evaluation is required.

Figure 12-1

Body Fluids and BBP Transmission Risk

Body fluids that CAN transmit BBPs:

 Blood

 Semen

 Vaginal fluids

 Amniotic fluid

 Breast milk

 Cerebrospinal fluid

 Pericardial fluid

 Peritoneal fluid

 Pleural fluid

 Synovial fluid

Body fluids that DO NOT transmit BBPs (unless visibly bloody):

 Saliva

 Vomitus

 Urine

 Feces

Decreasing transmission: If an exposure occurs despite universal precautions, 

several steps can be taken immediately to decrease transmission risk:

• Mucous membrane exposure: Rinse area thoroughly with 

water or saline.

• Skin exposure: Wash thoroughly with soap and water.

• Needlestick: Wash area thoroughly with soap and water. Do 

not squeeze or pinch, because doing so may increase blood 

flow to the area and hypothetically facilitate transmission.

Risk and mechanism of exposure: Percutaneous exposures are of substantially 

higher risk for transmitting BBP than mucous membrane or cutaneous exposures. 

The risk associated with each mechanism of exposure is outlined in Table 12-1.

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Table 12-1

Associated Risk When Exposure Source Patient Is HIV Infected

Route of 

Exposure

Risk of 

Exposure 

Risk 

Determinants

Risk Qualifiers

Percutaneous* ~ 1/300 

episodes

 Larger 

gauge hollowbore needle

 Solid 

needle or 

instrument

• Risk of transmission from 

percutaneous exposures is 

increased with hollow-bore 

needles, visibly bloody devices, 

and deep injury.

• Solid devices, such as lancets 

or suture needles, have 

rarely been involved in HIV 

transmission.

• It is common for a discarded 

or found needle to cause 

percutaneous injury; however, in 

U.S. healthcare settings, found 

needles have been implicated 

in only 3 cases of transmission. 

Outside of the United States, 

no documented cases of 

transmission of HIV from a 

found needle have occurred.

Mucous†

membrane

~1/1000 

episodes

 Large 

volume

 Small 

volume

• Mucous membrane exposures 

usually involve infectious fluid 

contact with the eyes or mouth. 

The keratinized skin around the 

mouth that borders on mucous 

membrane is an effective 

protective barrier.

Cutaneous† <1/1000 

episodes

Compromised 

skin integrity • Cutaneous exposures can 

transmit virus, but risk is present 

only when skin integrity is 

compromised (e.g., chapping, 

abrasion, open wound or burn, 

dermatitis). Prolonged contact 

with nonintact skin may increase 

risk of transmission.

• Intact skin is an effective 

barrier that protects against 

transmission of BBPs.

Note:  = increased risk;  = decreased risk. Other abbreviations are defined in the list 

of Abbreviations and Acronyms, p. ix.

 * A substantial proportion of percutaneous exposures occur in dental offices; however, no 

transmissions from patient to provider have been reported in the dental setting. The lack 

of transmission is likely a result of the nature of dental instruments, most of which are solid, 

and the use of very small-bore needles for anesthetic injection. It is also plausible that 

neutralizing antibodies present in saliva may decrease chances of virus transmission.

 † Human bites expose both the biter (cutaneous exposure) and the bitten (mucous 

membrane exposure).

Source: MMWR Recomm Rep 2005;54(RR-9):1

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Postexposure Assessment and Management

Baseline Laboratory Workup

If the exposure is considered one that may transmit BBP, then baseline testing 

for HIV, HBV, and HCV should be performed on the exposed healthcare 

worker and the source, when possible. Recommended tests are summarized 

in Table 12-2.

PEP efficacy depends upon timing of first dose: Do not wait for baseline 

test results to proceed with the decision to administer PEP, unless the results 

of the source patient’s rapid HIV will be available within 1–2 hours. If 

the source patient’s baseline rapid HIV Ab test is positive, then assume 

it represents a true positive result, and proceed with PEP while awaiting 

confirmatory Western blot results. If the confirmatory Western blot test is 

negative, then PEP can be stopped.

Table 12-2

Recommended Postexposure Baseline Laboratory Tests

Baseline Tests Source Patient Exposed Person

HIV Ab or p24 

antigen-HIV antibody

(HIV Ag/Ab) 

Yes Yes

HIV Western blot or 

immunofluorescence 

antibody

Yes, if HIV rapid test 

positive

Yes, if HIV rapid test 

positive

HIV RNA PCR Yes, if status is known to 

be positive, but recent 

viral load is not known

No

HCV Ab Yes Yes

HCV RNA PCR* Yes No

HBsAg Yes Yes, if immune status 

is unclear

HBsAb No Yes, if immune status 

is unclear

Note: Test abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

* With CD4+ cell count <200 cells/mm3, a negative HCV Ab test may represent a false 

negative result, and HCV RNA can clarify HCV status of exposure source.

Source: MMWR Recomm Rep 2001;50(RR-11):1

Window Period

The window period for HIV Ab seroconversion—after infection has occurred 

but before antibodies develop—can cause anxiety for both the patient 

and the provider around postexposure management. However, if the source 

patient’s HIV test is negative at the time of the exposure, then PEP is not 

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recommended. Note that in the United States, no reports of HIV transmission to 

a healthcare worker from an exposure source who was in the window period 

have occurred (MMWR 2005;54(RR-9)).

Implications for postexposure management: The window period should be 

taken into consideration in postexposure management only when it is highly 

likely that a high-risk source patient is in a window period. This situation may 

occur when, in the 30 days prior to the exposure, the source patient shared 

needles with other drug users, was incarcerated, engaged in unprotected sex 

with multiple male partners (if male), could have been exposed through sex 

work (MMWR 2006;55:421), or had a potential exposure in a country with 

high HIV seroprevalence.

In assessing the likelihood of a source patient being in the window period, 

determine whether the patient has a history of recent illness consistent with 

possible acute HIV infection (see Chapter 4, Primary Medical Care). If acute 

HIV infection is suspected, then PEP should be started while confirmation of the 

source’s HIV RNA level is pending. In acute infection, HIV RNA level is usually 

very high and risk of transmission is great.

U.S. Public Health Service Guidelines for PEP

Time is of the essence in initiating PEP: If PEP is indicated or is being 

considered, then time is of the essence for efficacy: The optimal time to start 

PEP is within hours of exposure, not days. The first dose should be given as 

soon as possible. Seventy-two hours post-exposure is considered as the outer 

limit of opportunity to initiate PEP; however, a delay of that scale is believed 

to compromise PEP efficacy. The 72-hour outside limit recommendation is based 

on animal studies; no human data are available. Initiating PEP after a longer 

interval (e.g., 1 week) might still be considered for exposures that represent a 

very high risk of transmission. PEP should be administered for 4 weeks. 

Regimen: The USPHS no longer recommends that the severity of exposure 

be used to determine the number of drugs to be offered in a PEP regimen. 

A regimen containing 3 (or more) ARV drugs is now recommended routinely 

for all occupational exposures to HIV. These include newer ARV drugs that 

are better tolerated and have better toxicity profiles than agents previously 

recommended for PEP. Medications included in a PEP regimen should be 

selected to minimize side effects and toxicity, and optimize convenience in 

terms of dosing schedules to enhance likelihood of completion. Exposure to 

a source patient with an undetectable serum viral load does not eliminate 

the possibility of HIV transmission, and PEP should still be offered. Because 

of concerns about tenofovir effect on renal function, this regimen is not 

recommended to persons with renal problems, which should be assessed before 

prescribing this PEP regimen. The PEPline at 888-448-4911 is available for 

additional advice and recommendations. 

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Table 12-3

Recommendations for Postexposure Prophylaxis After Precutaneous 

Injury or Mucous Membrane and Nonintact** Skin Exposures

Exposure Source Recommendation

HIV-infected Three (or more) drug PEP

Unknown HIV status Generally no PEP is warranted. Consider PEP* for 

source with HIV risk factors; discontinue if source is 

found to be HIV-uninfected.

Unknown source (e.g., 

a needle from a sharps 

disposal container; splash 

from improperly disposed-of 

blood)

Generally no PEP is warranted. Consider PEP* in 

settings where exposure to HIV-infected persons is 

likely.

Not HIV infected No PEP is warranted.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix.

*“Consider PEP” indicates that PEP is optional and the decision to administer should be 

made case by case, on the basis of an individualized discussion between the provider 

and the exposed person. Higher risk source patients include injection drug users who 

have shared needles, sex workers, men who have unprotected sex with multiple male 

partners, and people who have been incarcerated.

*Followup is indicated only if there is evidence of compromised skin integrity (e.g., 

dermatitis, abrasion, open wound).

Source: Infect Control Hosp Epidemiol 2013;34(9):875–892

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PEP regimens: Current options for PEP, along with recommended toxicity 

monitoring, are listed in Table 12-4.

Table 12-4

Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis 

(PEP) Regimens (all given for one month)

Preferred HIV PEP Regimen

RAL 400 mg PO twice daily

Plus

TDF/FTC 300/200 mg (Truvada) once daily 

Alternative Regimens

(May combine 1 drug or drug pair from the left column with 1 pair of nucleoside/

nucleotide reverse-transcriptase inhibitors from the right column)

RAL TDF/FTC

DRV/r TDF + 3TC

ETR ZDV/3TC

RPV ZDV + FTC

ATV/r

LPV/r

The following alternative is a complete fixed-dose combination regimen, and no 

additional antiretrovirals are needed: EVG/COBI/TDF/FTC

Alternative Antiretroviral Agents for Use as PEP Only with Expert Consultation

ABC

EFV

T20

FPV

MVC

SQV

d4T

Antiretroviral Agents Generally Not Recommended for Use as PEP

ddI

NFV

TPV

Antiretroviral Agents Contraindicated as PEP

NVP

Note: Laboratory monitoring for drug toxicity should occur at baseline and 2 weeks after 

starting PEP and should minimally include CBC, renal and hepatic tests.

Source: Updated US Public Health Service Guidelines for the Management of 

Occupational Exposures to Human Immunodeficiency Virus and Recommendations for 

Postexposure Prophylaxis. Infect Control Hosp Epidemiol 2013;34(9):875.

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Resistances

Important factors that should increase suspicion of resistance include (1) history 

of problems with medication adherence, (2) failure to achieve undetectable 

viral load on ARV medications, (3) development of detectable viral load after 

previously undetectable levels while on ARV medications, and (4) previous 

genotypic or phenotypic test results demonstrating resistance to one or more 

ARV drugs. If resistance is suspected, consultation with an HIV expert is 

recommended, but this should not delay initiation of PEP. In instances of known 

or suspected exposure use of ARV agents to which the patient is unlikely to be 

resistant is recommended for PEP.

Drug–Drug Interactions

Interactions between drugs in the PEP regimen and the exposed person’s 

current medications may be a problem, and expert consultation may be 

indicated, especially when an expanded regimen is chosen. Most commonly, 

interactions involve the protease inhibitor component, such as LPV/r, DRV/r, and 

ATV/r. Table 12-5 lists several common drug–drug interactions. See also Tables 

13-8 to 13-9, pp. 500–512.

Table 12-5

Commonly Prescribed Drugs and Interactions With Concurrent 

Use of Protease Inhibitors

Medication Effects of Concurrent 

Use With PIs

Options and Recommendations

Acid reducers

Antacids ATV levels  Use another PI or d/c antacids.

H2 blocker(s) ATV levels  Use another PI if continuing 

H2 blocker treatment or d/c 

H2 blocker; may also space dosing 

of H2 blocker 12 h apart from PEP 

administration.

PPIs ATV levels  Use another PI if continuing PPI 

treatment or d/c PPIs.

Anticoagulants

Warfarin Warfarin levels  Monitor INR closely.

Anticonvulsants

Antiseizure medication 

levels may be 

altered to supra- or 

subtherapeutic levels

Use RAL as alternative to PIs.

Antidepressants

SSRIs SSRI levels  Titrate dose to clinical efficacy if 

needed.

Tricyclic 

antidepressants

Tricyclic levels  Toxicity monitoring is advised.

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Table 12-5

Commonly Prescribed Drugs and Interactions With Concurrent 

Use of Protease Inhibitors

Medication Effects of Concurrent 

Use With PIs

Options and Recommendations

Antipsychotics

Antipsychotics  to subtherapeutic levels

Titrate dose as needed; use RAL as 

alternative to PIs.

Antimycobacterials

Rifabutin RBT levels  Adjust RBT dose; consult expert.

Rifamycin PI  to subtherapeutic 

levels

Contraindicated with all PIs; use 

RAL as alternative to PIs. 

Benzodiazepines

Midazolam and 

triazolam levels 

Contraindicated with PIs; use RAL 

as alternative to PIs.

Cardiac medications

Calcium channel 

blockers

Calcium channel 

blocker levels 

Use RAL as alternative to PIs.

Corticosteroid

Fluticasone Fluticasone levels  Contraindicated with PIs; use RAL 

as alternative to PIs. 

Herbal remedy

St. John’s wort  PI to subtherapeutic 

levels.

Contraindicated with PIs.*

Hormonal contraceptives

Combined oral 

contraceptives

Ethinyl estradiol and 

progestin levels  with 

certain PIs

Use backup barrier method.

Lipid-lowering drugs

Statins Statin levels  Lovastatin and simvastatin 

are contraindicated; caution 

is advised with other statins. 

Consider time-limited d/c of 

statins for duration of PEP; use 

RAL as alternative to PIs.

Narcotics/Treatment for opioid dependence

Methadone Methadone levels  Monitor for opiate withdrawal; 

titrate methadone dose if 

necessary.

Note:  = increase;  = decrease. Other abbreviations are defined in the list of 

Abbreviations and Acronyms, p. ix.

continued

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Adverse Drug Reactions and Symptom Management

Potential for PEP interference: Side effects can be a limiting factor in PEP 

adherence. They generally decrease after the first few days but sometimes 

can last the duration of the 28-day PEP course. Gastrointestinal side effects 

(nausea, vomiting, diarrhea) are most common, especially with expanded 

regimens that include a PI. Zidovudine/lamivudine (Combivir) can cause 

headache, fatigue, and nausea. Tenofovir/emtricitabine (Truvada) is much 

better tolerated than Combivir and is given as once daily dosing. Antiemetic 

and antidiarrheal medications can be prescribed to help with PEP adherence. 

If side effects are severe, consider changing to a better tolerated regimen. 

With the current preferred PEP regimens, toxicities are rare, generally not life 

threatening, and reversible.

Pregnancy

Not a contraindication for PEP: Indications for PEP are the same for pregnant 

and nonpregnant women. Acute HIV infection during pregnancy carries a 

particularly high risk for perinatal transmission because of high viral loads in 

early infection. When deciding whether to administer PEP and choosing the 

specific drug regimen, the risk of ARV exposure to the fetus and the potential 

adverse effects for the pregnant woman should be weighed against the 

benefit of decreased risk of HIV transmission to the mother and the fetus.

PEP regimens for pregnant women: Information about the use of newer 

antiretroviral agents administered as PEP to HIV-uninfected pregnant women is 

limited. Expert consultation is recommended. EFV is not recommended as part 

of a PEP regimen in the first trimester. If EFV-based PEP is used in women, a 

pregnancy test should be done to rule out early pregnancy and nonpregnant 

women receiving EFV-based PEP should be counseled to avoid pregnancy until 

after PEP is completed. 

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Breastfeeding

Weigh risks and benefits: Both HIV itself and ARV medications can be found 

in breast milk. Some guidelines recommend that breastfeeding be avoided 

for 6 months postexposure. This recommendation is to prevent infant exposure 

to HIV should transmission occur and to avoid potential PEP drug toxicities in 

the infant. However, because breastfeeding offers significant benefits and 

because HIV is rarely transmitted to an exposed person (particularly when PEP 

is administered), the PEPline advises that mothers be informed of the potential 

risks and make their own decisions regarding breastfeeding. Because most 

transmissions are diagnosed by 6 weeks postexposure and almost all are 

detected by 3 months, a reasonable choice for some women may be to pump 

and discard breast milk initially and then reinitiate breastfeeding when they 

have reached a point at which no transmission can be safely assumed.

Follow-Up Postexposure Laboratory Monitoring

Following an exposure, laboratory followup is recommended for up to 

6 months. If HCV transmission has occurred or if the exposed person is 

already HCV positive, followup is extended to 12 months, because rare 

instances of HIV transmission have not been captured until then [MMWR

2005;54(No. RR-9)].

Recommended postexposure laboratory monitoring includes the following:

• 6 weeks: HIV Ab; HCV RNA PCR

• 3 months: HIV Ab; HCV Ab

• 6 months: HIV Ab; HCV Ab

• 12 months: HIV Ab when concurrent HCV infection is present 

in the exposed person

Use of 4th generation HIV Ag/Ab combination tests allows for earlier 

detection of HIV infection. If these tests are used, HIV follow-up testing may 

be concluded 4 mo after exposure.

HIV RNA PCR is not recommended for follow-up testing unless the exposed 

person presents within 4 to 6 weeks postexposure with symptoms consistent 

with acute HIV infection, because false positives (usually at low levels of 

virus, i.e., <10,000 copies/mL) occur and can cause diagnostic dilemmas and 

unnecessary anxiety.

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Hepatitis B and C Postexposure Management

Hepatitis B

Although widely utilized HIV PEP has been effective in decreasing HIV 

transmission to healthcare workers, the decrease in HBV transmission 

is attributed primarily to immunization of healthcare workers. Among 

nonimmunized healthcare workers, HBV confers a significant risk of 

transmission—as many as 2–3 infections per 5 needlestick exposures from 

HBV-infected individuals. As a result, HBV vaccination and documentation of 

immunity for healthcare workers has become a pre-employment requirement in 

most U.S healthcare settings. Immunization has helped to decrease transmission 

rates substantially and has virtually eliminated the need for HBV follow-up 

testing. However, some healthcare workers may not have received the full 

vaccination series or may not have responded adequately to vaccination.

Guidelines for HBV PEP: When a healthcare worker does not have 

documentation of adequate immunity (evidenced by HBsAb titer of >10 mIU/

mL at any point in the past), specific guidelines for HBV PEP and follow-up, 

specified in Table 12-6, should be followed.

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Table 12-6

Recommendations for Postexposure Prophylaxis 

After Exposure to HBV

Source 

Status

Unvaccinated 

Exposed Person

Previously Vaccinated Exposed Person*

Known 

Responder†

Known 

Nonresponder‡

Antibody Response 

Not Known

HBsAg 

positive

HBIG† x 1 and 

initiate HBV 

vaccine series 

immediately

No 

treatment HBIG† x 1 

and initiate 

revaccination

or

HBIG x 2 with 

second dose 

separated from 

first by 4 wk||

Test exposed 

person for HBsAb; 

if response is 

adequate,‡ no treatment is 

necessary.

If response is 

inadequate,§

administer HBIG†

x 1 and vaccine 

booster; recheck 

HBsAb titer in 

3–4 mo.

If titer is still 

inadequate§ for 

immunity, complete 

full second series 

of vaccinations.

HBsAg 

negative

Initiate HBV 

vaccine series

No 

treatment No treatment No treatment

Unknown 

or not 

available 

for 

testing

Initiate HBV 

vaccine series. If 

known high-risk 

source, may treat 

as if source were 

HBsAg positive.

No 

treatment If known highrisk source, treat 

as if source 

were HBsAg 

positive.

Test exposed 

person for HBsAb; 

if response is 

adequate,‡ no treatment is 

necessary.

If response is 

inadequate,§

administer vaccine 

booster and 

recheck HBsAb titer 

in 1–2 mo.

If titer is still 

inadequate§ for 

immunity, complete 

full second series 

of vaccinations.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

 * People who have previously been infected with HBV are not at risk of reinfection 

and do not require PEP.

 † HBIG (dose = 0.06 mL/kg intramuscularly).

 ‡ Responder = documented adequate levels of HBsAb (≥10 mIU/mL).

 § Nonresponder = inadequate levels of HBsAb (<10 mIU/mL).

|| The option of giving 1 dose of HBIG and reinitiating the vaccine series is preferred 

for nonresponders who have not completed a second 3-dose vaccine series. Two doses 

of HBIG are preferred for people who have completed a second vaccine series but 

have failed to respond.

Source: MMWR Recomm Rep 2001;50(RR-11):1

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Hepatitis C

Postexposure management: When a source patient is HCV infected, the risk 

of transmission following needlestick exposure is about 1 in 50. No PEP is 

available for HCV exposure, but early follow-up to identify transmitted 

infection and, when indicated, to offer early treatment is recommended. Direct 

viral testing with HCV RNA PCR at 6 weeks, before HCV Ab seroconversion has 

occurred, allows early identification of transmission and subsequent referral 

for evaluation and potential treatment. The rate of spontaneous clearance of 

HCV infection is about 25% in otherwise healthy people; however, with early 

diagnosis and treatment, HCV clearance can be increased to 90% or greater.

HIV Infected Healthcare Providers

No national standards limit clinical practice for HIV infected healthcare 

providers. The 1991 guidance (published before availability of effective 

combination ART) on prevention of HIV and HBV to patients during 

exposure-prone invasive procedures states that infected healthcare workers 

“should not perform exposure-prone procedures unless they have sought 

counsel from an expert panel and notify prospective patients of healthcare 

worker’s seropositivity prior to undergoing an exposure-prone procedure” 

(MMWR 1991;40(RR-8)). However, States vary in implementation of 

this guidance (JAMA 2000;284:1965). Mandatory testing of healthcare 

workers is not recommended. Other organizations have published safe 

practice guidance for healthcare professionals who are involved in invasive 

procedures (CID 2005;40:1665), but no universally accepted guidelines 

exist for specific limitations.

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Chapter 13:

Pharmacologic Considerations in HIV 

Infected Pregnant Patients

Paul Pham, PharmD

Research Associate, Division of Infectious Diseases

The Johns Hopkins University School of Medicine

Patricia Barditch-Crovo, MD

Clinical Associate, Division of Infectious Diseases

The Johns Hopkins University School of Medicine

The authors declare no conflicts of interest

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Chapter 13: Pharmacologic Considerations in HIV Infected 

Pregnant Patients

Chapter 13 at a Glance

Introduction.........................................................................................................................................................445

Pharmacokinetics of Drugs in Pregnancy......................................................................446

Sex-Based Differences in Response to HIV Treatment....................................447

U. S. Food and Drug Administration Categories for the 

Use of Prescription Drugs in Pregnancy..........................................................................448

Pregnancy Categories for Antiretroviral Agents ....................................................449

Use of Antimicrobial Agents in Pregnancy..................................................................450

Safety of Commonly Used Antimicrobials....................................................................475

Drug Choice in Management of Selected Medical 

Conditions in Pregnancy....................................................................................................................479

Alternative/Complementary Medication Concerns in Pregnancy.............488

Antiretroviral Dosing Recommendations in Patients with

Renal or Hepatic Insufficiency.....................................................................................................491

Drugs That Should Not Be Used with Antiretroviral Agents....................500

Recommended Dose Modifications with Boosted Protease 

Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, 

Integrase Inhibitors, and CCR5 Antagonists ...............................................................505

Clinically Pertinent Food-Drug Recommendations...............................................513

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Introduction

Information included in this chapter may include off-label recommendations for 

specific drugs or indications.

The information presented in this chapter includes detailed information about 

pharmacologic agents commonly used in the treatment of HIV infected women 

and drugs often used in pregnancy or as complementary therapies, with 

particular emphasis on issues related to their use in pregnancy.

Risk versus benefit: The decision to administer drugs to a pregnant woman 

depends on the potential therapeutic benefit versus the potential risk to the 

mother and/or the developing fetus. Clinicians are often advised to avoid 

prescribing drugs for pregnant patients because human safety data in 

pregnancy are lacking for many, if not most, medications; however, effective 

treatment for HIV, opportunistic infections, and other serious medical conditions 

should not be withheld in pregnancy. There are important considerations when 

selecting agents to treat women with HIV to prevent mother-to-child transmission 

and to prevent or treat opportunistic infections or other related or coexisting 

conditions. In general, when more than one effective treatment is available, the 

regimen with the best evidence for safety in pregnancy should be chosen. When 

animal studies suggest teratogenic or embryotoxic risk and human studies are 

lacking or also of concern, expert consultation is recommended.

Caveats: The literature on drug safety in pregnancy should be interpreted 

with caution and with the following caveats: animal studies (including studies 

of mutagenicity, carcinogenicity, and teratogenicity), which are the basis for 

most data on safety in pregnancy, are often inconsistent across species and 

may not accurately reflect risk in human pregnancy. For example, animals are 

often administered doses 5 to 20 times higher than those given to humans and 

the clinical applicability of such dosing to human treatment may not be clear. 

In humans, drug dose, intensity of exposure, placental transfer, and gestational 

age at exposure may all affect the presence or magnitude of risk. Teratogenic 

potential does not reflect the expected frequency of malformations; adequately 

controlled human studies are necessary to establish the degree of risk. A drug 

with teratogenic potential may be appropriate for use when there are no safer 

alternatives and when the benefits are expected to outweigh the risk.

It is now standard practice to treat HIV infected patients with a combination 

of antiretroviral (ARV) agents, which makes it difficult to assess the safety of 

a single agent, and information about the safety of newer ARVs in pregnancy 

is limited; additional prospective clinical data are needed. Clinicians are 

encouraged to report all in utero exposures to the Antiretroviral Pregnancy 

Registry (800-258-4263; fax: 800-800-1052; http://www.apregistry.com/). 

The registry is a collaborative effort of pharmaceutical manufacturers with an 

advisory committee of obstetric and pediatric practitioners; the group collects 

observational data on ARV exposure during pregnancy to assess the potential 

teratogenicity of these drugs.

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Pharmacokinetics of Drugs in Pregnancy

Although many physiologic changes occur during pregnancy, few trials have 

been conducted to evaluate the clinical significance of these changes to the 

pharmacokinetics of commonly used drugs. Physiologic changes that may affect 

drug pharmacokinetics include delayed gastric emptying, decreased intestinal 

motility, increased volume of distribution (average increase, 8 L), increased 

renal blood flow (25%–50%), and increased glomerular filtration rate (by 

50%) (Fundamentals of Gynecology and Obstetrics, Philadelphia: J.B. Lippincott 

Co; 1992; J Obstet Gynaecol 1974;81:588; J Obstet Gynaecol Br Commonw

1970;77:900).

Pharmacokinetic parameters of NVP given as a single dose of 200 mg at the 

onset of labor were similar to but more variable than those in nonpregnant 

adults, possibly because of incomplete absorption associated with altered 

gastrointestinal function during labor (J Infect Dis 1998;178:368). Data suggest 

that NVP levels may be detectable as long as 3 weeks after a single dose 

given at onset of labor (11th Conference on Retroviruses and Opportunistic 

Infections, February 8, 2004 [abstract 41LB]). Pregnancy does not change the 

pharmacokinetics of ABC, ZDV, 3TC, d4T, or ddI (J Infect Dis 1998;1778:1327; 

6th International Conference on AIDS, June 20, 1990 [abstract FB17]; J Infect 

Dis 1999;180:1536). On the other hand, FTC serum concentrations are slightly 

lower in the third trimester. Similarly, third-trimester TDF concentrations are 

lower, but trough concentrations are adequate. The clinical significance of these 

findings remains to be determined (see Table 8-7, pp. 285–298).

Serum concentrations of the protease inhibitors (PIs) that have been studied in 

pregnancy (ATV, IDV, RTV, and SQV) appear to be lower in pregnancy when 

the agents are given as single, unboosted PIs (Recommendations for Use of 

Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and 

Interventions to Reduce Perinatal HIV Transmission in the United States; http://

www.aidsinfo.nih.gov. Accessed 8/6/12). When boosted with RTV, SQV levels 

are adequate (HIV Clin Trials 2001;2:460), and adequate NFV levels are 

achieved when it is given at a dose of 1250 mg bid; in the third trimester, 

however, concentrations were lower and more variable (9th Conference on 

Retroviruses and Opportunistic Infections, February 2002 [abstract 795w]). 

When the old formulation of LPV/r capsules was administered to pregnant 

patients, LPV serum concentrations were lower during the third trimester. A 

pharmacokinetic study with the new LPV/r tablets is ongoing. Some experts 

recommend increasing the LPV/r dose to three tablets twice per day to 

compensate for the decreased LPV concentrations during the third trimester; 

other experts, however, recommend using the standard dose with close 

monitoring (Recommendations for Use of Antiretroviral Drugs in Pregnant HIV1-Infected Women for Maternal Health and Interventions to Reduce Perinatal 

HIV Transmission in the United States). In patients with PI mutations, a higher 

dose (e.g., three LPV/r tablets twice per day) should be considered in the third 

trimester. Use of newer ARVs (e.g., RAL, MVC, DRV, TPV, ETR) or older ARVs 

with limited clinical data in pregnancy (e.g., ENF, FPV) should be reserved for 

cases in which the benefit outweighs the risk to the pregnant woman and/or 

when better-studied agents are not options because of concerns for safety, 

tolerability, or effectiveness.

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Sex-Based Differences in Response to HIV Treatment

Clinical response: There are conflicting data on sex differences in clinical 

response to ARV treatment. Several studies have documented sex differences 

in CD4+ lymphocyte counts and HIV viral loads (VLs), indicating that women 

have higher CD4+ cell counts and lower HIV RNA levels early in the course of 

infection; however, differences in VL tend to dissipate several years after initial 

infection and rates of progression are similar in men and women (J Infect Dis

1999;180:666; N Engl J Med 2001;344:720; Clin Infect Dis 2002;35:315). 

Early studies suggested poorer outcomes for women, but when controlled for 

later presentation and lower rates of care and/or treatment with effective 

antiretroviral therapy (ART), these sex-based differences in HIV disease course 

generally disappeared (J Acquir Immune Defic Syndr 2000;24:475; AIDS

2001;15:1115). Several studies have shown sex differences in ART prescription 

and utilization, even with free access to ART and CD4+ cell counts <200 

cells/mm3 at baseline (J Acquir Immune Defic Syndr 2000;24:475; Women’s 

Health Issues 2006;16:104; J Acquir Immune Defic Syndr 2003;32:499; J 

Acquir Immune Defic Syndr 2005;38:96; South Med J 2007;100:775). A 

recent retrospective cohort study with 6,657 person-years follow-up found that 

women had an increased risk of death, even after adjustment for HAART use 

(hazard ratio, 1.62; p = .002) (J Infect Dis 2009;199:991); however, other 

large cohort studies found comparable or lower rates of clinical progression 

and death in women compared with men (J Women’s Health 2007;16:1052; 

AIDS 2007;21:835; HIV Med 2006;7:520). Virologic and clinical responses in 

clinical trials are comparable between men and women, although most trials 

have not been powered to detect gender differences. A recent open-label 

Phase 3b study specifically designed to enroll a high proportion of women 

examined treatment responses to DRV-RTV plus an investigator-selected 

optimized background regimen and found no significant difference in virologic 

response by sex, although women were more likely to discontinue therapy for 

reasons other than virologic failure (Ann Intern Med 2010;153:349).

Adverse drug events: A number of studies have shown a higher incidence, 

greater severity, or altered presentation of adverse drug events in women 

compared with men (Expert Rev Anti Infect Ther 2005;3:213). Women with 

higher CD4+ cell counts appear to be at the greatest risk for symptomatic, 

potentially fatal, and often rash-associated liver toxicity associated with NVP 

(J Acquir Immune Defic Syndr 2004;35:538; Clin Infect Dis 2004;38 Suppl 

2:S80). Lactic acidosis related to prolonged exposure to nucleoside reverse 

transcriptase inhibitors appears to occur more frequently in women (AIDS

2007;21:2455). Women also may be at greater risk for some metabolic 

complications of ART, such as central fat deposition, and they appear less 

likely to have triglyceride elevations (HIV Med 2001;2:84; J Acquir Immune 

Defic Syndr 2003;34:58). Women are at greater risk of osteopenia and/

or osteoporosis, especially after menopause, and this may be worsened in 

the setting of HIV and ART (AIDS 2006;20:2165). Although data are limited, 

women may metabolize and respond to specific ARV drugs differently from 

men, which may result in higher drug concentrations and a greater likelihood 

of adverse effects (Annu Rev Pharmacol Toxicol 2004;44:499; Pharmacol Res

2008;58:173; Gend Med 2007;4:106). Therefore, close monitoring for adverse 

drug events is recommended when initiating ARV therapy in women. It is also 

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important that clinicians recognize barriers to initiating and continuing ARV 

therapy in women because competing priorities, such as child and family care 

and issues related to stigma and disclosure, can interfere with ART adherence.

Table 13-1

U. S. Food and Drug Administration Categories for the Use of 

Prescription Drugs in Pregnancy

A Adequate and well-controlled studies of pregnant women fail to demonstrate 

a risk to the fetus during the first trimester of pregnancy (and there is no 

evidence of risk during later trimesters)

B Animal reproduction studies fail to demonstrate a risk to the fetus and adequate 

and well-controlled studies of pregnant women have not been conducted

C Safety in human pregnancy has not been determined, animal studies are either 

positive for fetal risk or have not been conducted, and the drug should not be 

used unless the potential benefit outweighs the potential risk to the fetus

D Positive evidence of human fetal risk based on adverse reaction data from 

investigational or marketing experiences, but the potential benefits from the use 

of the drug in pregnant women may be acceptable despite its potential risks

X Studies in animals or reports of adverse reactions have indicated that the risk 

associated with the use of the drug for pregnant women clearly outweighs 

any possible benefit

Note: At the time of publication of this guide, the FDA was preparing a revision of 

drug categories for pregnancy and lactation that will likely do away with the current 

letter categories

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Table 13-2

Pregnancy Categories for Antiretroviral Agents 

in ARV-Naïve Women

Preferred Drugs or drug combinations are designated as preferred for 

use in pregnant women when clinical trial data in adults have 

demonstrated optimal efficacy and durability with acceptable 

toxicity and ease of use; pregnancy-specific pharmacokinetic 

data are available to guide dosing; and no evidence of 

teratogenic effects on the fetus or established association with 

teratogenic or clinically significant adverse outcomes for the 

mother, fetus, or newborn are present

Alternative Drugs or drug combinations are designated as alternatives 

for initial therapy in pregnant women when clinical trial data 

in adults show efficacy but any one or more of the following 

conditions apply: there is limited experience in pregnancy; 

there is a lack of data on teratogenic effects on the fetus; or 

there are dosing, formulation, administration, or interaction 

issues for that drug or regimen

Not 

Recommended

Drugs and drug combinations listed in this category are not 

recommended for therapy in pregnant women because of 

inferior virologic response, potentially serious safety concerns 

for the mother or fetus, or pharmacologic antagonism. In 

addition, some drugs are listed in this category because 

they are not currently recommended in ARV-naïve adults and 

adolescents due to limited data. These agents may eventually 

move to a different category as more data becomes available.

Insufficient 

Data to 

Recommend

Although approved for use in adults, the drugs and drug 

combinations in this category do not have pregnancy-specific 

pharmacokinetic or safety data available or such data are too 

limited to make a recommendation for use for pregnancy

Source: Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women 

for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United 

States. 2013

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Note: At the time of publication of this guide, the FDA was preparing a revision of drug categories for pregnancy and lactation that will likely do away with the current letter categories

Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Acyclovir(Zovirax®)

FDA pregnancy category: B

• 5–10 mg/kg IV q 8 h• 200–800 mg po 3–5x qd

• Toxicities are infrequent• GI intolerance: nausea, vomiting, 

diarrhea

• Renal toxicity, esp. with rapid IV 

infusion

• Dizziness

• Transaminase elevation• Pruritus• Headache

Not teratogenic, but has potential 

to cause chromosomal damage at high dosesAntiviral drug with the most reported experience in pregnancy; appears to be safe—no increased risk of birth defects or patterns of defects (Birth Defects Res A Clin Mol Teratol 2004;70(4):201)

Can be used in pregnancy for treatment or suppression of HSV infections and treatment of uncomplicated chicken pox or shingles; however, valacyclovir can be considered for convenient dosing and better pharmacokineticsIV acyclovir recommended for severe HSV or VZV if parenteral therapy indicatedSuppressive therapy with either valacyclovir or acyclovir is recommended starting at 36 wk gestation for pregnant women with recurrences of genital herpes to reduce need for Cesarean delivery (Obstet Gynecol 2007;109:1489)No known benefit of suppressive therapy for women who are seropositive for HSV-2 without a history of genital lesions

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Albendazole(Albenza®)

FDA pregnancy category: C

Microsporidiosis: 400 mg po bid x 3 wk • Diarrhea

• Abdominal pain• Elevated transaminase• Hepatotoxicity• Reversible pancytopenia and 

neutropenia

Teratogenic (skeletal malformations) and embryotoxic in rodent and rabbit studies at exposure levels lower than those estimated with therapeutic human dosingNo adequate, well-controlled studies in early human pregnancyA recent randomized trial including albendazole for treatment of soiltransmitted helminth infections in 2nd trimester found no evidence of teratogenicity or other adverse pregnancy effects (Am J Trop Med Hyg 2008;79(6):856)

Not recommended for use in 1st trimester. Consider use 

later in pregnancy only if benefits outweigh potential risks.

Amphotericin B(Fungizone®)

FDA pregnancy category: B

Usual adult dose: 0.3–1.2 mg/kg IV qdFluconazole-resistant candida esophagitis: 0.3 mg/kg IV qdCryptococcal meningitis: 0.7 mg/kg (plus 5FC)

• Fever and chills (40%– 50%)• Renal tubular acidosis (30%–

40%); dose dependent and reversible in absence of prior renal damage and dose <3 g (reduced with hydration and sodium loading)

• Hypokalemia (20%)

• Hypomagnesemia• Anemia• Phlebitis and pain at infusion site

• Hypotension

• Nausea, vomiting

• Metallic taste

Animal studies demonstrated 

no evidence of teratogenicityExtensive clinical use has demonstrated no evidence of teratogenicity

Preferred initial regimen for treatment of serious fungal infections in pregnancyEvaluate neonates born to women on chronic amphotericin B for renal dysfunction and hypokalemia at delivery

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Artemisinin-based combination therapy(Artemether/lumefantrine)FDA pregnancy category: C

Artemether/lumefantrine (20 mg/120 mg tab) 4 tabs po as single initial dose; 4 tabs again after 8 h, and then 4 tabs bid (AM and PM) for next 2 d (total course of 24 tabs)

Generally well tolerated with occasional nausea, dizziness, headache, rash

Some preclinical studies found possible teratogenic effects and increased embryolethality with early 1st-trimester exposure to artemesinins in a variety of animal species, including at levels below equivalent human therapeutic doseSome data suggest pregnancy may lower levels of artemether/lumefantrine and dihydroartemisinin; optimal dosing strategies in pregnancy have not been determined

Considered first-line treatment during 2nd and 3rd trimesters for women with uncomplicated Plasmodium falciparum and severe malaria

ArtesunateFDA pregnancy category: C

U.S. IND protocol (available through CDC): 4 equal doses of 2.4 mg/kg over 3 d, followed by oral treatment with atovaquone-proguanil, doxycycline, clindamycin, or mefloquine to avoid emergence of resistanceWHO recommendations: IV artesunate 2.4 mg/kg IV or IM given on admission (time = 0), then 12 h and 24 h, qd in lowtransmission area or outside malaria endemic area

Generally well tolerated with bradycardia, nausea, and dizziness occasionally reported

No evidence of physical or neurological abnormalities during development observed with 1st trimester exposure in small studies (Malar J 2007;6:15)

Alternative treatment of P. falciparum in 2nd and 3rd trimesters along with clindamycinWHO recommends artesunate as a first-line agent in 2nd and 3rd trimestersIn 1st trimester, until more evidence becomes available, both artesunate and quinine may be considered

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Atovaquone(Mepron®)

FDA pregnancy category: C

PCP treatment or prophylaxis:750 mg po bidPCP prophylaxis: 1500 mg 

po qdToxoplasmosis treatment:

1500 mg po bid + pyrimethamine or sulfadiazine

• GI intolerance: nausea, 

vomiting, diarrhea

• Headache• Rash• 7%–9% require d/c because 

of side effects

Atovaquone did not increase 

malformations in rats and rabbits, although doses used were limited by toxicity to half the human doseHuman data are limitedNo adverse effects in mothers or newborns found with use of atovaquone in combination with other antimalarials in about 90 pregnant Thai women in 2nd or 3rd trimester (Trans R Soc Trop Med Hyg 2003;97(5):592; Eur J Clin Pharmacol 2003;59(7):545; J Infect Dis 2005;192(5):846)

Alternative regimen for PCP prophylaxis and treatmentThird-line treatment and prophylaxis for toxoplasmosis

Atovaquone–proguanil(Malarone®)

FDA pregnancy category: C

Malaria treatment: atovaquone 1000 mg/proguanil 400 mg (4 tabs, single dose) po qd x 3 dMalaria prevention:atovaquone 250 mg/proguanil 100 mg po (1 tab) qd, starting 1–2 d before travel and continuing for 1 wk after leaving endemic area

Generally well tolerated with occasional GI intolerance, headache, asthenia, dizziness, and rare cases of severe rash.

Preclinical studies have shown no increased risk of defectsLimited human dataPlasma levels appear lower in pregnancy

Can be used for malaria prophylaxis for travel to chloroquine-resistant regionsAlternative treatment for P. falciparum in 2nd and 3rd trimesters

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Azithromycin(Zithromax®)

FDA pregnancy category: B

MAC prophylaxis: 1200 mg po q wkMAC treatment: 500 mg or 600 mg po qd + ethambutol +/- rifabutin

• GI intolerance (4%): nausea, 

diarrhea, abdominal pain

• Vaginitis

• Reversible hearing loss (more 

common with 500 mg x 30–90 d)

• Elevated transaminase

Animal studies show no harm to fetusTwo studies including >300 

women found no increased risk of congenital anomalies with azithromycin exposure in pregnancy (Sex Transm Dis2006;33(2):106; BMC Pregnancy Childbirth 2006;6:18)

Recommended for MAC prophylaxis or treatment in pregnancy

Also used in treatment of Bartonellosis

Boceprevir(Victrelis®)

FDA pregnancy category: X

800 mg po tid (in combination with peginterferon + ribavirin)

• Headache

• Fatigue• Nausea• Elevated LFTs

No human data Not recommended for use 

in pregnancyBecause goal of HCV treatment is to prevent longterm sequelae, treatment in pregnancy is rarely indicated

Caspofungin(Cancidas®)

FDA pregnancy category: C

70 mg IV load on day 1, then 50 mg IV qd (infuse over 1 h)

• Generally well tolerated• Histamine-mediated symptoms 

including rash, facial swelling, 

pruritus and sensation of warmth have been reported

• Rare: fever, phlebitis, nausea, 

vomiting, headache, eosinophilia, proteinuria, increased alkaline phosphatase, hypokalemia

Embryotoxic: animal data with exposure comparable to human dosing resulted in incomplete ossification of skull, torso, and talus/calcaneusNo human data

Avoid in 1st trimester. Use later in pregnancy should be based on consideration of benefit versus potential risk.

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Chloroquine(Aralen®)

FDA pregnancy category: C

P. vivax, P. ovale, P. malariae, and chloroquine-sensitive P. falciparum: chloroquine phosphate 1 g salt (600 mg base) 1x; then 500 mg salt (300 mg base) 6 h later; then 500 mg at 24 h and 48 h poChloroquine HCl 160–200 mg (base) IM or IV q 6 h (IV n/a in U.S.)

• Visual disturbances

• Hemolysis with G6PD deficiency

• GI intolerance

• Pruritus• Alopecia• Headache• Confusion• Dizziness• Severe skin rash

• QTc prolongation

No evidence of increase in malformationsExtensive experience with use in pregnancy

Drug of choice for malaria prophylaxis and treatment of sensitive strains in pregnancy

Cidofovir(Vistide®)

FDA pregnancy category: C

CMV retinitis induction: 5 mg/kg q wk x 2 wk, then q 2 wk; give concurrently with probenecid and hydrationProbenecid regimen: 2 g given 3 h prior to cidofovir and 1 g given at 2 h and 8 h after infusion (total 4 g)>1 L normal saline 1 or 2 h immediately before cidofovir infusion

• Nephropathy (dose dependent); 

reduced with hydration and probenecid

• Probenecid side effects: chills, 

fever, headache, rash, nausea (30%–50%)

• Uveitis

• GI intolerance• Neutropenia• Metabolic acidosis

Embryotoxic and teratogenic 

(meningomyelocele, skeletal abnormalities) in rats and rabbitsNo experience with use of cidofovir in human pregnancy

Not recommended for use in pregnancy

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Clarithromycin(Biaxin®)

FDA pregnancy category: C

MAC prophylaxis: 500 mg po bidMAC treatment: 500 mg po bid + ethambutol +/- rifabutin

• GI intolerance: diarrhea (4%)• Headache• Reversible dose-related 

hearing loss

• Taste disturbances

Studies in monkeys show growth retardation, cleft palate, embryonic lossTwo studies, each with slightly >100 women with 1st-trimester exposure to clarithromycin, did not demonstrate an increase in or specific pattern of defects, although one study noted an increased risk for spontaneous abortion (Am J Perinatol 1998;15(9):523; Pharmacoepidemiol Drug Saf2000;9(7):549)

Not recommended in 1st trimester

Clotrimazole(Canesten®, 

Lotrimin®, 

Mycelex®)

FDA pregnancy category: C(troches)

Oral thrush: 10 mg troches 5 x/dCandida vaginitis:• 100 mg intravaginal tabs bid 

x 3 d or

• qd x 7 d or• 1 applicator (5 g) vaginal 

cream q hs x 7–14d

• GI intolerance: nausea, vomiting• Transaminase elevation• Topical treatment (rare): burning, 

erythema, pruritus

Embryotoxic in rats and mice. Not teratogenic in mice, rabbits, and rats.No adverse effects or congenital anomalies reported with use of vaginal or topical clotrimazole in pregnancy (Obstet Gynecol1987;69(5):751; Epidemiology1999;10(4):437)

Nystatin is preferred over clotrimazole in management of oral thrush during pregnancy because of minimal systemic absorptionClotrimazole is considered safe for treatment of vaginal candidiasis in pregnancy

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Cycloserine(Seromycin®)

FDA pregnancy category: C

TB: 10–15 mg/kg/d po (maximum daily dose = 1000 mg, but hard to tolerate)Usual dose 500–750 mg po qd, given in 2 divided doses

• Common CNS side effects: 

anxiety, confusion, somnolence, disorientation, headache, hallucinations, tremor, hyperreflexia, depression (with suicidal ideation), psychotic disturbances

• Occasional seizures

• Peripheral neuropathy

• Fever• Rash

No data available from 

animal studies

No data on use in human 

pregnancy

Avoid use in pregnancy unless other options not available

Dapsone(Aczone®)

FDA pregnancy category: C

PCP prophylaxis: 100 mg po qdTreatment of mild to moderate PCP: 100 mg po qd + trimethoprim x 3 wkPCP + toxoplasmosis prophylaxis: 50 mg po qd or 200 mg q wk + leucovorin and pyrimethamine

• Rash• Blood dyscrasias, including 

methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia (with or without G6PD deficiency)

• Nephrotic syndrome

• Fever• Nausea, anorexia• Blurred vision

• Photosensitivity• Tinnitus• Insomnia• Irritability• Headache (transient)

• Rare sulfone syndrome: 

fever, exfoliative dermatitis, jaundice

adenopathy

No animal teratogenicity studies conductedCarcinogenic risk in ratsHas been used safely for several decades to treat leprosy, malaria, and various dermatologic conditions during pregnancy (Trop Med Int Health 2003;8(6):488; Drug Saf 2004;27(9):633)Risk of mild maternal hemolysis with long-term therapy and potential risk, though extremely low, of hemolytic anemia in an exposed fetus with G6PD deficiency (South Med J1989;82(5):668)

Alternative for PCP prophylaxis and treatment of mild–moderate PCP (with TMP); also alternative to toxoplasmosis prophylaxisScreening of mother for G6PD deficiency is recommended before use

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Ethambutol(Myambutol®)

FDA pregnancy category: C

• 15–25 mg/kg po qd 

(1.6 g max)

• 35–50 mg/kg biw 

(4.0 g max)

• 25–30 mg/kg tiw 

(2.4 g max)

• Optic neuritis: decreased acuity, 

reduced color discrimination, constricted fields, scotomata (dose related and infrequent with 15 mg/kg)

• GI intolerance• Confusion• Precipitation of acute gout

Teratogenic among rodents and rabbits at doses much higher than those used in humansNo evidence of teratogenicity in humans

CDC considers ethambutol safe in pregnancy

Ethionamide(Trecator®)

FDA pregnancy category: X

15–20 mg/kg/d po (max 1 g/d); usually 500–750 mg divided q 24 h, q 12 h, or q 8 h administered w/food or hs

• Common, severe, and dosedependent GI intolerance: 

nausea, vomiting, metallic taste, anorexia, abdominal pain

• Occasional allergic reaction• Hepatitis• Neurotoxicity• Orthostatic hypotension

Associated with birth defects in multiple animal speciesNo increased risk for defects was noted with doses similar to those used in humansLimited experience In human pregnancy

Avoid use in pregnancy unless other options not available

Famciclovir(Famvir®)

FDA pregnancy category: B

Zoster: 500 mg po q 8 hRecurrent HSV and HSV suppression: 125–250 mg po q 12 h

• Headache

• Nausea• Fatigue

Carcinogenic but not embryotoxic or teratogenic in animal studiesHuman data limited

Acyclovir or valacyclovir preferred In pregnancy given limited information on famciclovir

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Fluconazole(Diflucan®)

FDA pregnancy category: C

Candida esophagitis: 200–800 mg po or IV qdCandida vaginitis: 150 mg po x 1; 150 mg po q wk for multiple recurrencesCryptococcal infection:• 1200 mg po or IV qd +5FC 

(alternative induction phase at least 2 wk)

• Then 400 mg po qd 

(consolidation phase x 8 wk);

• Then 200 mg po qd 

(maintenance)

• Dose-related GI intolerance: 

bloating, nausea, vomiting, pain, anorexia, weight loss (8%–11% with dose <400 mg/d; 30% with dose >400 mg/d)

• Reversible alopecia (10%–20% of patients receiving 400 mg/d 

for 3 mo)

• Transaminase elevation to 

>8 x normal

• Rare cases of fatal hepatitis 

and Stevens–Johnson syndrome

Teratogenic in animal studies, with limb and craniofacial abnormalities reportedCraniofacial, limb, and cardiac defects have been reported in 4 infants with 1st-trimester exposure to high-dose fluconazole (Clin Infect Dis 1996;22:336; Am J Med Genet 1997;72:253)Several cohort studies have shown no increased risk of birth defects with early pregnancy exposure, but most of these involved low doses and short-term exposure (J Antimicrob Chemother2008;62(1):172; Am J Obstet Gynecol 1996;75:1645)

Avoid in 1st trimester because of potential for teratogenicityUse topical agents in treatment of candida vaginitis in pregnancy

Flucytosine(Ancobon®)

FDA pregnancy category: C

25 mg/kg q 6 h (monitor levels; goal = 30–80 mcg/mL at steady state)

• GI intolerance: nausea, vomiting, 

diarrhea

• Marrow suppression with 

leukopenia or thrombocytopenia (dose related with renal failure, serum concentration >100 mg/mL or concurrent amphotericin)

• Confusion• Rash• Hepatitis (dose related)• Enterocolitis• Headache

Teratogenicity reported in animal studiesData limited to 3 case reports of 

2nd and 3rd trimester exposure that resulted in no defects in newborns

4% of administered dose biotransformed to 5FU, which has been associated with congenital malformationsUse in pregnancy only if benefits outweigh potential risks

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Foscarnet(Foscavir®)

FDA pregnancy category: C

CMV retinitis induction:• 60 mg/kg IV q 8 h or

• 90 mg/kg IV q 12 h x 14 d

Maintenance: 90–120 mg/kg IV qdAcyclovir-resistant HSV or VZV:• 40 mg/kg IV q 8 h or

• 60 mg/kg IV q 12 h x 3 wk

• Renal failure: usually reversible; 30% get Cr >2 mg/dL; monitor Cr 1–3 x/wk; d/c if Cr >2.9 mg/dL

• Mineral and electrolyte changes: 

reduced magnesium, phosphorus, ionized calcium, potassium; monitor serum electrolytes 1–2 x/wk and monitor for symptoms of paresthesias

• Seizures (10%)• Fever• GI intolerance• Anemia• Genital ulceration• Neuropathy

Skeletal malformation or variation in animal studiesNo experience with use in early pregnancyA single case report of use in 3rd trimester described normal infant outcome (Clin Infect Dis1999;29(4):937)

Use only if benefits outweigh risks and safer alternatives not availableAvoid in 1st trimester if possibleBecause foscarnet toxicity is primarily renal, monitor amniotic fluid volume by ultrasound weekly after 20 wk gestation to detect oligohydramniosIf therapy given near delivery, evaluate electrolyte and renal function in neonate

Fumagillin(Not commercially available in U.S.)FDA pregnancy category: N/A

20 mg po tid x 2 wk (not available in U.S.)

Systemic fumagillin associated with increased resorption and 

growth retardation in ratsNo data on systemic use in human pregnancyTopical fumagillin has not been associated with embryotoxic or teratogenic effects among pregnant women

Because of antiangiogenic effect of fumagillin, this drug should not be used systemically in pregnant womenTopical fumagillin may be considered when therapy with this agent is appropriate (ocular microsporidiosis)

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Furazolidone(No longer available in U.S.)FDA pregnancy category: C

100 mg po q 6 h x 7–10 d • GI intolerance

• Yellow to brown discoloration 

of urine

• Allergic reaction• Fever• Hemolysis• Headache

Not teratogenic in animal studiesHuman data limited to case series that found no association between 1st-trimester use and birth defects

Use in pregnancy only if benefit outweighs potential risk

Ganciclovir(Cytovene®)

FDA pregnancy category: C

CMV retinitis induction: 5 

mg/kg IV q 12 h x 2 wk, then maintenance: 5 mg/kg IV qd

• Neutropenia (ANC <500 in 

15%–20%); usually occurs early in treatment and responds within 3–7 d to drug holiday or to GCSF

• Thrombocytopenia (platelet 

count <20,000 in 10%); reversible; monitor CBC 2–3 x wk and d/c if ANC <500–750 or platelet count <25,000

• Anemia• Fever• Rash• CNS: headache, seizures, 

confusion, changes in mental status

• Abnormal LFTs (2%–3%).

Teratogenic (in concentrations comparable to those achieved in humans) and embryotoxic: cleft palate, anophthalmia, hydrocephalus, aplastic kidney and pancreas (rabbits); growth retardationSafe use in human pregnancy after organ transplantation has been reported (Transplantation1995;60(11):1353). Use in late pregnancy to treat fetal CMV infection in HIV uninfected women has also been reported (Semin Perinatol 2007;31(1):10).

For retinal disease, consider intraocular ganciclovir implants or intravitreous injections in 1st trimester to limit fetal exposure to systemically administered drugsStart systemic antiviral therapy after 1st trimester, generally with oral valganciclovir (see below)For patients with colitis or esophagitis, IV ganciclovir is recommended if symptoms are severe enough to interfere with oral absorptionMonitor fetus with fetal movement counts in 3rd trimester and after 20 wk gestation with periodic ultrasound for evidence of significant anemia, manifest as hydrops fetalisEvaluate newborn for bone marrow suppression

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Interferon(Roferon®, Intron®)

FDA pregnancy category: C

Treatment of hepatitis: 3 

million units IM or SC tiw + ribavirinAlso used at higher doses for treatment of hepatitis B and Kaposi’s sarcoma

• Flu-like syndrome

• GI intolerance: nausea, vomiting, 

diarrhea, anorexia

• CNS toxicity: delirium; 

obtundation, depression

• Neutropenia• Anemia• Thrombocytopenia

• Elevated transaminase• Rash

• Alopecia• Proteinuria

Abortifacient in rhesus monkeys 

when given at 20–500 x human doseLimited case reports of interferon exposure during pregnancy do not suggest an association with birth defects; however, data are too limited to draw conclusions

Not recommended for use in pregnancy because of direct antigrowth and antiproliferative effects (Neurology 2005;65(6):807)Because goal of HCV treatment is to prevent longterm sequelae, treatment in pregnancy is rarely indicated

Isoniazid(INH, Tubizid®, 

Nydrazid®)

FDA pregnancy category: C

300 mg po qd • Age-related hepatitis: <20 y 

(nil); 35 y (6%); 45 y (11%); 55 y (18%); d/c if transaminase levels are >3–5x normal limits

• Allergic reactions

• Fever

• Peripheral neuropathy 

(especially with preexisting alcoholism, diabetes, pregnancy, malnutrition)

• Glossitis

Animal studies show embryocidal 

effect, but not teratogenicRetrospective analysis of more than 4,900 exposures to INH did not show increased fetal malformations (Am Rev Respir Dis1980;122(1):65)

American Academy of Pediatrics and American Thoracic Society recommend that pregnant women with a positive PPD receive INH if they are HIV infected, have had recent TB contact, or have an X-ray showing old TB, once active disease is ruled out. Start after 1st trimester if possible.Hepatotoxicity caused by INH may occur more frequently in pregnancy and postpartum period; monthly monitoring of liver transaminases is recommended

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Itraconazole(Sporanox®)

FDA pregnancy category: C

100–400 mg po qd, depending on specific condition • Headache

• GI intolerance: nausea (10%) 

and vomiting

• Rash (8%)

• Hypokalemia reported with 

high doses (600 mg/d)

• Adrenal insufficiency

• Impotence

• Gynecomastia• Leg edema• Elevated transaminase• Rare cases of fatal hepatitis

Teratogenic in rats and mice (encephaloceles, macroglossia, skeletal malformation)FDA has received 14 case reports of malformations following use of itraconazole; 4 were limb defects. Prospective cohort studies of >300 women with 1st-trimester exposure, however, did not show an increased risk of malformation (Drug Saf 2009;32(3):239; Am J Obstet Gynecol 2000; 183(3): 617).

In general, avoid azole antifungals in 1st trimester because of potential for teratogenicity

Mefloquine(Lariam®)

FDA pregnancy category: C

Uncomplicated malaria treatment:• 1250 mg po x 1 or

• 750 mg 1x, then 500 mg 

12 h later

Malaria prophylaxis: 250 mg 

po q wk; start 1 wk prior to departure to an endemic area and continue for 4 wk after leaving endemic area

• Common CNS side effects: 

vertigo, light-headedness, nightmares, headache, decreased fine motor function

• Visual disturbances

• GI intolerance• Sinus bradycardia

Animal studies suggest potential teratogenicity and/or embryotoxicity, but clinical experience has not shown evidence of such effects in humansNo evidence of increase in defectsSeveral other large studies found mefloquine to be safe and effective in pregnancy (J Travel Med 1998;5(3):121)

Drug of choice for malaria prophylaxis with travel to chloroquine-resistant regions and for continuing prophylaxis after treatment

Nitazoxanide(Alinia®)

FDA pregnancy category: B

500 mg po q 6–12 h Generally well tolerated with 

occasional GI intolerance and headache

No evidence of teratogenicity in animal studiesNo data on use in human pregnancy

May be considered in pregnancy after 1st trimester in severely symptomatic women

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Nystatin(Bio-Statin®, 

Mycostatin®, etc.)

FDA pregnancy category: C

Oral thrush: 500,000 units; swish and swallow 5 x/d

GI intolerance: nausea, vomiting, diarrhea

No evidence of congenital defects in animal studiesNo evidence of congenital defects associated with use in pregnancy

May be used for management of thrush during pregnancy because of low systemic absorption

Paromomycin(Humatin®)

FDA pregnancy category: C

500–1000 mg po q 6 h Generally well tolerated with 

occasional nausea, vomiting, diarrhea, anorexia, cramps, epigastric burning pain

No evidence of teratogenicity in animal studiesLimited information in human pregnancyMinimal systemic absorption with oral administration, which may minimize potential risk

May be used in pregnancy after 1st trimester in severely symptomatic women

Peginterferon(PegIntron®

[alfa‐2B], Pegasys®

[alfa‐2A])FDA pregnancy category: C

PegIntron: 1 mcg/kg SC q wk + ribavirin; dose reduction to 0.5 mcg/kg recommended for ANC <750 or platelet count <50,000 and d/c if ANC <500 or platelet count <25,000Pegasys: 180 mcg SC q wk + ribavirin; reduce dose with hematologic toxicityPeginterferon alfa-2A or alfa‐2B + ribavirin is treatment 

of choice for HCV

• Common: flu-like symptoms, 

headache, dizziness, fatigue, fever, rigor, injection-site inflammation, depression (29%), insomnia, alopecia, GI intolerance (abdominal pain, anorexia, nausea, vomiting, diarrhea

• Occasional: thrombocytopenia, 

neutropenia, hypo- and hyperthyroidism, elevated LFTs

Abortifacient in rhesus monkeys when given 20–500 x human doseNo studies in human pregnancy

Not recommended for use in pregnancy because of direct antigrowth and antiproliferative effects (Neurology 2005;65(6):807)Because goal of HCV treatment is to prevent longterm sequelae, treatment in pregnancy is rarely indicated

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Pentamidine–aerosolized(NebuPent®)

FDA pregnancy category: C

PCP prophylaxis: 300 mg nebulized q mo • Asthma reaction (2%– 5%)

• Cough (30%)

Systemic pentamidine is embryotoxic but not teratogenic in rats and rabbits

Aerosolized pentamidine given to 15 women during the 2nd and 3rd trimesters did not alter pregnancy outcome or cause fetal harm (Am J Obstet Gynecol 1992;166:387)

Use for PCP prophylaxis only if alternatives not available. There are concerns about systemic absorption and about adequate drug distribution during pregnancy because of restrictive changes with an enlarged uterus.

Pentamidine–intravenous(Nebupent®, 

Pentacarinat®, 

Pentam 300®)

FDA pregnancy category: C

PCP treatment: 3–4 mg/kg IV qd • Nephrotoxicity (25%), usually reversible with d/c

• Hypotension (administer IV over 

60 min to decrease risk)

• Hypoglycemia (5%– 10%); 

usually occurs after 5 d of treatment including past treatment and may last days or weeks; may lead to insulindependent diabetes

• Marrow suppression (leukopenia; 

thrombocytopenia)

• GI intolerance: nausea, vomiting, 

abdominal pain, anorexia, bad taste

• Elevated transaminase

• Pancreatitis• Toxic epidermal necrolysis• Fever

Systemic pentamidine is embryotoxic but not teratogenic in rat and rabbit studies; however, it has been shown to be embryocidalPentamidine is concentrated in placental tissue, but the clinical significance of this is unknown(Am J Obstet Gynecol 1989; 160(3): 759-61)No human clinical data on use of IV pentamidine

Use in pregnancy only if 

benefits outweigh potential risks and recommended alternatives cannot be used

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Posaconazole(Noxafil®)

FDA pregnancy category: C

Treatment of invasive fungal infections:• 200 mg po q 6 h or• 400 mg po q 12 h• Some experts recommend 

increasing to 400 mg q 8 h for severe infection, lack of clinical response, and/or low posaconazole serum concentrations

Oropharyngeal and esophageal candidiasis refractory to itraconazole and/or fluconazole: 400 mg q 12 h, with duration of therapy based on clinical response

• Generally well tolerated• Occasional nausea, vomiting, 

diarrhea, abdominal pain; increased LFTs

• Rare cases of adrenal 

insufficiency, hypersensitivity reaction, QTc prolongation

Has been shown to cause skeletal malformations in rats, but not in rabbits, when given at 3–5 x human exposureNo adequate controlled studies

Avoid in pregnancy

PrimaquineFDA pregnancy category: C

PCP treatment: 15–30 mg 

(base) po qd + clindamycin

• Hemolytic anemia (G6PD 

deficiency)

• Methemoglobinemia• GI intolerance• Neutropenia

No animal studies availableNo human data available

Generally not used in pregnancy because of risk of maternal hemolysisPotential risk of hemolytic anemia in exposed G6PD‐deficient fetus; screen mother for G6PD deficiency before use

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

PyrazinamideFDA pregnancy category: C

Latent TB: 15 mg/kg/d (2.0 g max)

Active TB: 20–25 mg/kg/d 

(2.0 g max)Intermittent therapy:30–50 mg/kg 2–3 x wk 

(3.0–4.0 g max)

• Nongouty polyarthralgia• Asymptomatic hyperuricemia• Hepatitis (dose related; 

frequency not increased when given with INH or rifampin; rarely serious)

• GI intolerance• Gout

No evidence of increased congenital defects in rodent dataMinimal human data available

WHO and International Union Against Tuberculosis and Lung Diseases have recommended routine use of PZA in pregnant women; it has not been recommended for general use during pregnancy in the U.S. because of limited dataIf PZA not included in initial treatment regimen, minimum duration of TB therapy should be 9 moDecision to use PZA should take into account gestational age and susceptibility pattern of MTB strain

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Pyrimethamine(Daraprim®)

FDA pregnancy category: C

Acute treatment of toxoplasmosis: 100–200 mg loading dose, then 50–75 mg po qd + sulfadiazine 4–6 g po qd in 4 divided doses for at least 6 wk + leucovorin 10–20 mg po qdToxoplasmosis maintenance dose: After acute treatment, pyrimethamine 25–50 mg po qd + sulfadiazine 2–4 g po qd in 4 divided doses + leucovorin 10–25 mg po qdToxoplasmosis prophylaxis:50–75 mg po q wk + dapsone + leucovorin 25 mg po q wk

• Folic acid deficiency with 

megaloblastic anemia and pancytopenia (dose-related and reversed with leucovorin)

• Allergic reactions• GI intolerance: nausea, vomiting, 

anorexia

Teratogenic in animal studiesHuman data have not suggested an increased risk for defects (Curr Drug Saf 2006;1(1):1; Drug Saf2007;30(6):481; Clin Perinatol1994;21:675; Clin Infect Dis1994;18:853)

Recommended as part of treatment regimen for toxoplasmic encephalitis and prophylaxis for patients who cannot tolerate TMP-SMX

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Quinine(Qualaquin®)

FDA pregnancy category: C

Uncomplicated malaria: 650 mg q 8 h x 3–7 d, plus:• doxycycline 100 mg bid x 

7 d or

• clindamycin 450 mg q 8 h x 

7 d or

• pyrimethamine/sulfadoxine 3 

tabs on last day of quinine

• GI intolerance• Cinchonism (tinnitus, headache, 

nausea, abdominal pain, visual disturbances)

• Hemolytic anemia with G6PD 

deficiency

• QTc prolongation• Thrombocytopenia• Hepatitis

At high doses, associated with 

increased risk for birth defects (especially deafness) in some animal speciesAt high doses, associated with increased risk for birth defects (especially deafness) in humans

Use of therapeutic doses in pregnancy considered safeTreatment of choice with a diagnosis of chloroquineresistant P. vivax; with uncomplicated chloroquineresistant P. falciparum malaria, prompt treatment with quinine and clindamycin is recommended, particularly in 1st trimesterBecause of potential for hypoglycemia, monitor glucose levels of pregnant women treated with quinine and their neonates

Ribavirin(Rebetol®)

FDA pregnancy category: X

Treatment of hepatitis C:• <75 kg: 400 mg q AM and 

600 mg q PM + interferon

• >75 kg: 600 mg bid + 

interferon

• Hemolytic anemia (mean Hb decrease 3 g/dL)

• Leukopenia• Hyperbilirubinemia• Increased uric acid

Demonstrated to be teratogenic in low doses in multiple animal species (limb abnormalities, craniofacial defects, exencephaly, anophthalmia)No human data available. At this time, inadvertent pregnancy during paternal RBV exposure has not been associated with adverse events (Am J Gastroenterology2001;96:2286).

Use contraindicated during pregnancy and in male partners of pregnant womenWomen of childbearing potential and men receiving RBV should be counseled about risks and need for consistent contraception during and for 6 mo after use of RBVPregnancies that occur in women taking RBV should be reported to the Ribavirin Pregnancy Registry 

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Rifabutin(Mycobutin®)

FDA pregnancy category: B

• 300 mg po qd• With unboosted PIs (e.g., 

IDV, NFV): 150 mg qd or 300 mg tiw

• With boosted PIs (e.g., LPV/r, DRV/r, SQV/r, ATV/r) or ATV: 

150 mg qod

• With EFV: 450 mg qd or 600 

mg tiw

• With NVP: standard dose or 

300 mg tiw

Not recommended with DLVConsider therapeutic drug monitoring with PIs and NNRTI co-administration

• Orange discoloration of urine, 

tears, sweat

• Uveitis with eye pain, 

photophobia, redness, blurred vision; usually seen with high doses (600 mg/d) or concurrent use of fluconazole or clarithromycin

• Hepatitis

• GI intolerance• Allergic reactions

Animal data show no increase 

in birth defectsNo human data available

Limited experience in pregnancyMany drug interactions, for which dose modifications are recommended (see Table 13-8, p. 500 and Table 13-9, p. 505)

Rifampin

(Rifadin®)

FDA pregnancy category: C

For TB prophylaxis or active TB: 10 mg/kg/d (600 mg/d max, but up to 600 mg bid with CNS infections)With DOT: 600 mg 2–3 x/wk

• Orange discoloration of urine, 

tears, sweat

• Hepatitis (usually cholestatic 

changes during first month; frequency not increased when given with INH)

• Jaundice (usually reversible 

with dose reduction and/or continued use)

• GI intolerance

• Hypersensitivity reactions• Flu-like syndrome with intermittent 

use characterized by dyspnea, wheezing

Some but not all animal studies show increased risk of cleft palate, spina bifida, embryotoxicityNo evidence of human teratogenicity

American Thoracic Society recommends rifampin in combination with INH and ethambutol if treatment for drug-sensitive TB is needed during pregnancyMany drug interactions, including with ARVsAdminister prophylactic vitamin K 10 mg to neonate because of potential increased risk of hemorrhagic disease

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Sulfadiazine(Lantrisul®, 

Neotrizine®, etc.)

FDA pregnancy category: C

Acute treatment of toxoplasmosis: Sulfadiazine 4–6 g/d po in 4 divided doses + pyrimethamine 50–75 mg po qd for at least 6 wk + leucovorin 10–20 mg po qdToxoplasmosis maintenance dose: After acute treatment, sulfadiazine 2–4 g po qd in 4 divided doses + pyrimethamine 25–50 mg po qd + leucovorin 10–25 mg po qd

• Allergic reactions (rash, pruritus)• Crystalluria with renal damage, 

urolithiasis and oliguria

• GI intolerance• Photosensitivity• Hepatitis• Fever• Periarteritis nodosum• Stevens–Johnson syndrome• Serum sickness

At high doses, animals developed cleft palate and bone abnormalitiesExtensive use in humans without complications except one case of agranulocytosis that was possibly associated (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005)

Theoretical risk of kernicterus in neonate if administered near term

Telaprevir(Incivek®)

FDA pregnancy category: X

• 750 mg q 8 h• 1125 mg q 8 h (with EFV 

co-administration)

Co-administration recommended only with ATV/r or EFV; not recommended with LPV/r, DRV/r, or FPV/rMust be used in combination with peginterferon and ribavirin

• Rash

• Pruritus• Nausea, vomiting

• Fever

• Anorexia• Dizziness• Anemia• Elevated LFTs

No human data Not recommended in 

combination with interferon and ribavirin in pregnancyBecause goal of HCV treatment is to prevent longterm sequelae, treatment in pregnancy is rarely indicated

Thalidomide(Thalomid®)

FDA pregnancy category: X

Treatment of aphthous ulcers and/or wasting: 50–200 mg 

po qd

• Sedation• Rash• Neuropathy• Constipation• Neutropenia (up to 50%)

High potential for birth defects, including absent or abnormal limbs; cleft lip; absent ears; heart, renal, or genital abnormalitiesSingle dose can be associated 

Contraindicated in pregnancy and in women at risk for pregnancy (not using effective contraception or trying to conceive)

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Trimethoprim–sulfamethoxazole (TMP-SMX)(Bactrim®, 

Septra®, Cotrim®, 

Sulfatrim®)

FDA pregnancy category: C

PCP prophylaxis:• 1 DS po qd

• 1 SS po qd• 1 DS po tiwPCP treatment: 5 mg/kg (based on trimethoprim component) po or IV q 8 h

• Fever• Leukopenia

• Rash and/or GI intolerance 

(25%–50% of patients with HIV); most tolerate readministration of lower dose after 2 wk of d/c

• Megaloblastic anemia• Neutropenia

• Thrombocytopenia

• Hematologic toxicity increased 

with folate depletion and high doses; treat with leucovorin 3–15 mg q d x 3 d

• Reversible hyperkalemia (with 

high doses)

• Photosensitivity

• Renal failure

• Hemolytic anemia with G6PD 

deficiency

• Hepatitis including cholestatic 

jaundice

• Thrush

• Erythema multiforme

• Stevens–Johnson syndrome

Cleft palate has been observed in some animals

In case-control studies, TMP has been associated with an increased risk of neural tube defects and cardiovascular, urinary tract, and multiple anomalies after 1st-trimester exposure, but folic acid supplementation (up to 6 mg) decreased risk of birth defects (N Engl J Med 2000;343(22):1608; Reprod Toxicol 2001;15(6):637)In a surveillance study of Michigan Medicaid recipients, 2,296 exposures to TMP-SMX in 1st trimester resulted in a 5.5% incidence of birth defects. This suggests an association with congenital defects (cardiovascular); however, confounding factors such as maternal disease, concurrent drug use, etc., may be involved (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005)

Most authorities consider sulfonamides safe in pregnancy. Clinicians may consider use of supplemental folic acid (>0.4-mg/d routinely recommended) in 1st trimester for pregnant women on TMPSMX, but use should be limited to 1st trimester.Ultrasound at 18–20 wk recommended to assess fetal anatomy after 1st-trimester exposureTheoretical risk of kernicterus in neonate if administered near termTMP-SMX is recommended for treatment and prophylaxis of PCP and prophylaxis of toxoplasmosis in pregnancyAgent of choice for treatment and secondary prophylaxis for isosporiasis in pregnancy

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Valacyclovir(Valtrex®)

FDA pregnancy category: B

Treatment of zoster: 1000 mg po tidRecurrent HSV: 1000 mg po bidHSV suppression: 500 mg po bid 

• GI intolerance: nausea, vomiting, 

diarrhea

• Headache

• Constipation

Not teratogenic in animal studies

Use during pregnancy appears to be safe and well tolerated, though data are limited (JAMA2010;304:859)

Can be used for treatment and suppression of genital HSV infections and as treatment for uncomplicated chicken pox or shingles in pregnancyValacyclovir is converted to acyclovirSuppressive therapy with either valacyclovir or acyclovir is recommended starting at 36 wk gestation for pregnant women with recurrences of genital herpes to reduce need for Cesarean delivery (Obstet Gynecol 2007;109:1489)No known benefit of suppressive therapy for women who are seropositive for HSV-2 without a history of genital lesions

continued

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Table 13-3

Use of Antimicrobial Agents in PregnancyDrug Name Dosing Adverse Effects Animal Data and Human 

Experience in Pregnancy

Comments

Valganciclovir(Valcyte®)

FDA pregnancy category: C

Induction: 900 mg po bid w/

food x 3 wksMaintenance: 900 mg po qd

• Diarrhea

• Nausea• Fever

• Bone marrow suppression• Elevated LFTs

Embryotoxic in rabbits and mice; teratogenic in rabbits in concentrations comparable to those achieved in humans: 

cleft palate, anophthalmia, hydrocephalus, aplastic kidney and pancreas (rabbits); growth retardationNo experience reported with use in human pregnancy, but concerns are expected to be same as those for ganciclovir

On basis of limited data, toxicity reports and studies, and ease of use of various drugs, valganciclovir is recognized as treatment of choice during pregnancyMonitor fetus with fetal movement counts in 3rd trimester and periodic ultrasounds after 20 wk gestation for evidence of significant anemia, manifest as hydrops fetalis

Evaluate newborn for bone marrow suppression

Voriconazole(Vfend®)

FDA pregnancy category: D

• 6 mg/kg IV q 12 h x 2 doses (load), then 3–4 mg/kg IV q 

12 h infused over 1–2h

• >40 kg: 200 mg po tid x 1 

d (load), then 200–300 mg po bid

• <40 kg: 100 mg po q 12 h; 

may be increased to 150 mg po q 12 h

Administer on an empty stomach; avoid high-fat food

• Common: abnormal vision, 

described as blurriness, color changes, enhanced vision (20.6%, but <1% required d/c)

• Occasional: LFTs (13%), alkaline 

phosphatase (4%–8% of patients with hepatitis require d/c); hallucination (4.3%); rash (6%); nausea, vomiting

Teratogenic and embryotoxic in animal studies at doses lower than recommended human dosesNo adequate controlled studies

Avoid in pregnancyDo not use with RTV (400 mg bid)Check for potential drugdrug interactions (see Table 13-9, p. 505 for specific recommendations)Monitor trough concentrations for invasive fungal infections (goal >1–2 mcg/mL)

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixSource: Medical Management of HIV Infection, 16th ed. 2012. Durham, NC: Knowledge Source Solutions

continued

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Notes: 1. At the time of publication of this guide, the FDA was preparing a revision of drug categories for pregnancy and lactation that will likely do away with the current letter categories. 2. Unless otherwise noted, all data are taken from FDA labeling.

Table 13-4

Safety of Commonly Used AntimicrobialsDrug Name Animal Data Human Experience in Pregnancy CommentsAminoglycosidesFDA pregnancy category: D

Fetotoxicity reported in rodent studies

Toxicity to eighth cranial nerve in fetus is well documented with exposure to kanamycin and streptomycin and can potentially occur with other aminoglycosides

If possible, streptomycin should be avoided as part of TB treatment in pregnancyGentamicin is FDA pregnancy category C, although it has the same potential adverse effects. Use as preferred aminoglycoside if treatment is indicated.Amikacin or capreomycin might be alternatives when an aminoglycoside is required for treatment of MDR TB

AztreonamFDA pregnancy category: B

Animal studies indicate no harm to fetus

No clinical data in pregnancy Likely to be safe in pregnancy but, because of 

lack of data, use only if benefits are thought to outweigh potential risk

CephalosporinsFDA pregnancy category: B

Not teratogenic or fetotoxic Extensive pregnancy exposure not associated 

with birth defects

Usually considered safe to use in pregnancy

ChloramphenicolFDA pregnancy category: C

No animal data A collaborative perinatal project monitored 98 

1st- trimester exposures and 348 exposures anytime during pregnancy; no relationship was found between chloramphenicol and congenital malformations (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005)

Although there is no evidence of teratogenicity, chloramphenicol should not be used near term because of potential for development of “gray baby” syndrome and possible infant death due to cardiovascular collapse

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Table 13-4

Safety of Commonly Used AntimicrobialsDrug Name Animal Data Human Experience in Pregnancy CommentsClindamycinFDA pregnancy category: B

No fetal harm demonstrated in rat studiesCleft palate observed in one mouse strain

In a surveillance study of Michigan Medicaid recipients, 647 1st-trimester exposures to clindamycin resulted in a 4.8% incidence of birth defects. Patterns of anomalies do not support an association between clindamycin and congenital effects (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005).

Usually considered safe to use in pregnancy

ErythromycinFDA pregnancy category: B

No teratogenic effect in rat studies

In a surveillance study of Michigan Medicaid recipients, 6972 1st-trimester exposures to erythromycin resulted in a 4.6% incidence of birth defects. Patterns of anomalies do not support an association between erythromycin and congenital malformations (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005).

Avoid estolate salt due to hepatotoxicity in 10% of patients. Other forms of erythromycin are usually considered safe to use in pregnancy.

FluoroquinolonesFDA pregnancy category: C

Animal data indicate arthropathy that resulted in erosions in joint cartilage in immature animals

Congenital malformation rate was 4.8% in a prospective follow-up study of 666 cases of fluoroquinolone exposure (most during 1st trimester); this did not exceed previously reported background rate (Eur J Obstet Gynecol Reprod Biol 1996;69:83)A registry study of >1100 quinolone exposures during pregnancy found no increase in rate of birth defects (Pharmacoepidemiol Drug Saf2004;13(S1):S206)

Fluoroquinolones can be used in pregnancy as alternative antibiotics when indicated

continued

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Table 13-4

Safety of Commonly Used AntimicrobialsDrug Name Animal Data Human Experience in Pregnancy CommentsImipenemFDA pregnancy category: C

No evidence of teratogenicityIncreased embryologic loss has been observed in monkeys at 0.6 x maximal recommended human doseMaternal toxicity observed in pregnant rabbits and monkeys—weight loss, nausea, diarrhea, and death in some cases

Limited data in pregnancy have not shown an increased risk of malformations

Because of limited human data, use only for serious infections when potential benefits outweigh risk

MeropenemFDA pregnancy category: B

No evidence of teratogenicity No clinical data in pregnancy Because of limited human data, use only for 

serious infections when potential benefits outweigh risk

MetronidazoleFDA pregnancy category: B

Animal (rodents) data indicate risk of carcinogenicity

In 4 studies (2 meta-analyses, a populationbased case-control study, and a prospective controlled cohort study) no increased risk in birth defects was found (Teratology2001;63:186; Br J Obstet Gynecol1998;105:322; Br J Clin Pharmacol 1997; 44:179; Am J Obstet Gynecol 1995;172:525)

Most authorities consider use of metronidazole safe in 2nd and 3rd trimestersUse with caution in 1st trimester

NitrofurantoinFDA pregnancy category: B

Not teratogenic or fetotoxic in rat and rabbit studies

In a surveillance study of Michigan Medicaid recipients, 1292 exposures to nitrofurantoin resulted in a 4.0% incidence of birth defects. These data did not support an association between nitrofurantoin and congenital defects (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005).

Most authorities consider use of nitrofurantoin safe in pregnancy

continued

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Table 13-4

Safety of Commonly Used AntimicrobialsDrug Name Animal Data Human Experience in Pregnancy CommentsPenicillinsFDA pregnancy category: B

Carcinogenicity demonstrated in rats after prolonged subcutaneous administration of penicillin in peanut oil

Several collaborative perinatal project reports involving >12,000 exposures to penicillin derivatives during 1st trimester indicated no association between penicillin derivative drugs and birth defects (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005).

Usually considered safe to use in pregnancy

TetracyclinesFDA pregnancy category: D

Teratogenic in animal studies, resulting in retardation of skeletal development and embryotoxicity

Contraindicated in pregnancy due to retardation of skeletal development and bone growth, enamel hypoplasia, and discoloration of fetal teeth. Maternal liver toxicity also reported (Drugs in Pregnancy and Lactation, 7th ed. Baltimore: Williams & Wilkins. 2005).

Contraindicated in pregnancy

VancomycinFDA pregnancy category: C

No animal data Manufacturer has received reports of use 

during pregnancy without adverse fetal effects

Consider use only when benefit outweighs risk of drug administration

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixSource: Medical Management of HIV Infection, 16th ed. 2012. Durham, NC: Knowledge Source Solutions

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsAcne, severeRetinoids(isotretinoin, etretinate)FDA pregnancy category: X

Isotretinoin is associated with spontaneous abortion (incidence up to 40%; major malformations (up to 15%); defects in multiple organ systemsEtretinate, which is used for treatment of acne and psoriasis, is stored in adipose tissue and has an extremely long half-life. In 30 cases of pregnancy exposure, 30% had congenital defects (J Gynecol Obstet Biol Reprod1993; 22(1):43).

Contraindicated in women who are pregnant, trying to become pregnant, or not using effective contraception. FDA restricted distribution program requires monthly pregnancy tests and recommends two simultaneous forms of effective contraception.Patients taking etretinate are advised not to conceive for at least 2 y following cessation of treatment because of the drug’s long half-life: etretinate has been detected in serum up to 3 y after cessation of chronic treatment

Asthma: It is safer for pregnant women with asthma to be treated than to have asthma symptoms and exacerbations, with possible maternal and fetal hypoxiaRescue therapy Generally considered safe in pregnancy; no evidence of 

increased defects

Inhaled short-acting beta-2 agonist is therapy of choice; inhaled albuterol is preferred

Long-term control Theophylline has more side effects, a narrow therapeutic 

index, and requires serum monitoringFew data on use of leukotriene receptor antagonists in pregnancyLow- to moderate-dose inhaled steroids effective and considered safe in pregnancy (inhaled budesonide FDA category B)Systemic steroids may increase risk of cleft palate; may also be associated with increased risk of maternal hypertension, glucose intolerance, and infectionInhaled bronchodilators regarded as relatively safe in pregnancy

Treatment depends on severity and response to medications; stepwise approach to therapy is recommendedIn general, inhaled corticosteroids are first-line treatment, with budesonide preferred, followed by increasing doses of steroids and/or addition of long-acting beta-agonist (e.g., salmeterol)Severe asthma may require regular oral corticosteroid use to achieve adequate control

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsCancerAntimetabolites(e.g., 5-fluorouracil, methotrexate, cytarabine)FDA pregnancy category: X (most)

In general, antineoplastic agents given in 1st trimester may have teratogenic effects. In 2nd and 3rd trimesters, they may result in intrauterine growth restriction.

Management of cancer in pregnancy depends on type of malignancy, stage and expected rate of progression, specific treatment needed, and gestational ageSuccessful treatment of cancer while continuing with a pregnancy may be possible in individual cases with expert consultation. Other options include deferral of treatment until after delivery (with possible early delivery) and termination of pregnancy.

Alkylating agents(e.g., busulfan, chlorambucil, cyclophosphamide, mechlorethamine, cisplatin, bleomycin, vinblastine)FDA pregnancy category: D (most)

In general, antineoplastic agents given in 1st trimester may have teratogenic effects. In 2nd and 3rd trimesters, they may result in intrauterine growth restriction.

TamoxifenFDA pregnancy category: D

Little data in human pregnancy; some reports of defectsIncreased pregnancy loss in some animal studies. Results of animal studies suggest tamoxifen may cause developmental genital-tract abnormalities and that an interval of several years could exist between in utero exposure and clinical manifestations.Similar to DES in structure and activity in experimental systems

Avoid use in pregnancy and in women who are trying to conceive or are not using effective contraceptionLong-term follow-up recommended for exposed infants for adverse effects, including carcinogenicity

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsGlucose intolerance/diabetes: Pregnancy increases risk for glucose intolerance. No definite evidence that pregnant women on PIs are at increased risk 

for diabetes. Poorly controlled pregestational diabetes is associated with significant increased risk of adverse maternal and fetal outcomes, including worsening 

of end-organ damage, preeclampsia, congenital anomalies, intrauterine fetal death, excessive fetal growth, etc. Gestational diabetes is associated with increased risk for hypertensive disorders, macrosomia, newborn hyperbilirubinemia, shoulder dystocia and birth trauma, and need for cesarean delivery.Oral hypoglycemics Not well studied in pregnancy

Glyburide does not cross placenta; no evidence of adverse maternal and neonatal complications with use of this agentMetformin has been used in pregnancy, but long-term effects of in utero exposure are not well studied

Use of all oral agents for control of type 2 diabetes during pregnancy should be limited and individualizedGlyburide may be considered for treatment of gestational and type 2 diabetes mellitus

Insulin Insulin requirements increase throughout pregnancy Safe to use in pregnancyHypertension : Chronic HTN is associated with potentially significant maternal and fetal adverse outcomes: preterm delivery, intrauterine growth restriction, fetal death, placental abruption, as well as, when severe, maternal cardiac decompensation, renal deterioration, and CNS hemorrhage. HTN in pregnancy defined as SBP ≥140 and/or DBP ≥ 90. Pharmacologic treatment is generally indicated with SBP >150–160 and/or DBP >100–110 (treatment of milder HTN not recommended unless underlying cardiac or renal disease is present, due to concerns about interference with placental blood flow/fetal growth). Distinguish HTN from PEC, which typically appears at >20 wk gestation, is associated with proteinuria and, when severe, with seizures and hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). PEC alone is associated with normal BP prior to pregnancy and resolves after delivery; superimposed PEC is more common in setting of chronic HTN.Alpha-2 agonist(methyldopa)

Extensive experience in pregnancy and appears safe; limited effects on uteroplacental blood flow

Methyldopa safe to use in pregnancy and generally considered a first-line agent

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsAlpha and beta blockersAtenolol – FDA pregnancy category: DMetoprolol

Beta-blockers associated with small-for-gestationalage infants Labetalol (alpha and beta blocker) better tolerated and considered an alternative to methyldopa

IV labetalol considered safer than IV hydralazine and does not decrease placental perfusionAtenolol not recommended In pregnancy. Data on other beta blockers is limited, but they may be considered if benefit outweighs potential risk.Monitor fetal growth

Calcium channel blockers Limited experience in pregnancy but no evidence of 

increase in adverse effects or defects

Use if benefit considered to outweigh potential risk. Nifedipine is preferred agent, with most experience.

Diuretics Concerns have been raised about effects on normal blood 

volume expansion in pregnancy, but recent meta-analysis found no increase in adverse perinatal effects (Can Fam Physician 2009;55(1):44)

Considered safe and effective and not contraindicated in pregnancy, except when uteroplacental perfusion is decreased (e.g., PEC, intrauterine growth restriction)

ACE inhibitors(e.g., captopril, enalapril, lisinopril)FDA pregnancy category:C (1st trimester)D (2nd and 3rd trimesters)

Associated with oligohydramnios, pulmonary hypoplasia, skull hypoplasia, fetal and neonatal renal failure and deathUse in 1st trimester before development of renal tubular function not associated with defects

Contraindicated in pregnancy, particularly in 2nd and 3rd trimesters

If patient becomes pregnant while taking an ACE inhibitor, alternative treatment is recommended; if not possible, fetus should be monitored closely with ultrasound

Angiotensin II receptor blockersFDA pregnancy category:C (1st trimester)D (2nd and 3rd trimesters)

Concerns similar to those for ACE inhibitors Contraindicated in pregnancy, particularly in 2nd 

and 3rd trimesters

If patient becomes pregnant while taking an ARB, alternative treatment is recommended; if not possible, fetus should be monitored closely with ultrasound

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsLipid DisordersHMG-CoA reductase inhibitors(statins)FDA pregnancy category: X (all)

Possible increased risk for defects, particularly with atorvastatin, lovastatin, simvastatin, cerivastatin; also potential increased risk for other adverse neonatal outcomes

Contraindicated in pregnancy and should not be administered to women who are trying to become pregnant or not using effective contraceptionIf pregnancy occurs, discontinue statin use. Treatment can resume after delivery; this interruption is not believed to adversely effect overall outcomes.

N

ausea and vomiting: “Morning sickness” is very common, and generally resolves spontaneously toward end of 1st trimester. Hyperemesis gravidarum 

is at the extreme end of the spectrum and is a common indication for hospital admission during pregnancy; multiple gestation, molar pregnancy are risk factors. N/V first presenting after 9 wk gestation: rule out other conditions (e.g., gastroenteritis, pyelonephritis, hepatitis, pancreatitis, ulcer, drug toxicity/intolerance, acute fatty liver of pregnancy). Hyperemesis has been associated with Wernicke’s encephalopathy due to vitamin B1 deficiency, with resultant risk of permanent neurologic disability and low-birth-weight infants. There are concerns about adherence/absorption in women with hyperemesis on ARVs.Antihistamine H1 receptor 

antagonists(Pyridoxine +/-doxylamine)PhenothiazinesBenzamidesAnticholinergicsMetoclopramide5-hydroxytryptamine-3 inhibitors(ondansetron)Corticosteroids

Good safety data for vitamin B6, doxylamine, phenothiazines, trimethobenzamide; data more limited for other agents but benefits considered to outweigh risk in severe N/VDroperidol associated with prolonged QT interval and potentially fatal arrhythmiaAssociation between use of methylprednisolone use in 1st trimester and oral clefts, though risk is small

Treatment of N/V in pregnancy with ginger has shown beneficial effects and may be considered a nonpharmacologic optionStep-wise additive management is recommended: vitamin B6 (pyridoxine), doxylamine, promethazine or dimenhydrinate, metoclopramide or trimethobenzamide, methylprednisolone or ondansetronUse corticosteroids with caution and avoid if possible in 1st trimesterIV hydration as needed to prevent/treat dehydration; include dextrose and vitamins, especially thiamine, with prolonged vomitingFor severe and/or refractory hyperemesis, particularly with persistent weight loss, consider enteral or parenteral nutrition; enteral nutrition is preferred and may allow 

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsPainAcetaminophen No evidence of association with birth defects Considered safe for short-term use in all stages of 

pregnancyPreferred analgesic/antipyretic during pregnancy

Aspirin High-dose aspirin is FDA pregnancy category D in 3rd 

trimester; may increase risk for maternal or newborn hemorrhage, particularly at higher doses. Use of aspirin in 3rd trimester may result in premature closure of ductus arteriosus and may prolong gestation and labor.

Use of aspirin, especially of chronic or intermittent high doses, should generally be avoided in pregnancy; however, low-dose aspirin may be used for thromboprophylaxis in pregnancy in some high-risk conditions (e.g., antiphospholipid syndrome)

Nonsteroidal anti-inflammatory drugsFDA pregnancy category: CgD

≥30 wk gestation

3rd-trimester concerns include risk of premature closure of ductus arteriosus, oligohydramnios, possible increased risk of necrotizing enterocolitis or intraventricular hemorrhage, persistent pulmonary hypertension in neonate, and prolonged pregnancy

Generally avoid use of NSAIDs in pregnancy

Narcotics Narcotic analgesics can be used short term in pregnancy. 

Avoid use of high doses for prolonged periods near term as neonatal respiratory depression and withdrawal 

can occur.

Psychiatric illness: Inadequate treatment may result in adverse maternal and infant outcomes, including nonadherence to care, increased substance use, premature birth, low-birth-weight infants, etc. Multidisciplinary management recommended. A single medication at a higher dose is recommended over multiple medications. Use nonpharmacologic treatment when feasible (e.g., psychotherapy). Electroconvulsive therapy is safe to use in pregnancy if needed for severe depression. When medication is needed, drugs with fewer metabolites, higher protein binding (decreases placental transfer), and fewer drug interactions are preferred. Select drugs based on history of efficacy and available reproductive safety information.Benzodiazepines(Clonazepam, lorazepam, alprazolam)FDA pregnancy category: D

Possible small increased incidence of cleft lip/palate; possible neonatal withdrawal syndrome

Do not abruptly withdraw in pregnancy. In general, avoid in pregnancy; use based on risk vs benefit considerations.

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsNonbenzodiazepine anxiolytics and hypnotics(Buspirone, zolpidem)

Data limited in pregnancy but no increase in defects noted

Antidepressants (SSRIs, SNRIs, tricyclics, etc.)(Fluoxetine, sertraline, citalopram, nortriptyline, bupropion)

No confirmed increased incidence of birth defects, though some conflicting data for SSRIs; some studies have reported increased risk of cardiac defects, specifically with paroxetine, though absolute risk smallDecreased serum concentrations in pregnancy; possible neonatal withdrawal syndrome; unconfirmed association reported with SSRIs and newborn persistent pulmonary hypertensionLimited data for bupropion but no evidence of increase in defects

Individualize treatment based on risk vs benefits; avoid use of paroxetine if possible but also avoid abrupt discontinuation (associated with withdrawal symptoms)Consider fetal echocardiography with early-pregnancy exposure to paroxetine

LithiumFDA pregnancy category: D

Increased incidence of heart defects; decreased serum concentrations in pregnancy; potential increased risk for lithium toxicity in neonate

Use only if benefits thought to outweigh risksIf indicated, use sustained-release formulationMonitor lithium levelsConsider fetal echocardiography

Antipsychotics No confirmed increase in birth defects; possible risk for 

neuroleptic malignant syndrome and intestinal obstruction in neonate

Minimize doses to limit need to utilize medications for extrapyramidal side effectsAtypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone) generally better tolerated and may be more effective, but have very limited safety data in pregnancy; avoid routine useOptions for typical antipsychotics include haloperidol, 

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsSeizure disordersPhenytoinPhenobarbitalCarbamazepineValproateLamotrigineTopiramateAll FDA pregnancy category D (except lamotrigine: category C)

Increased incidence in both major and minor malformations associated with all anti-seizure medications; most common major malformations are NTDs, congenital heart and urinary-tract defects, skeletal abnormalities, and cleft palateValproate associated with higher rates of defects and may have increased placental transferLamotrigine may have lower risk of defectsIn-utero exposure to anti-seizure medications may be linked to impaired cognitive outcomes in childhoodLimited human information on fetal risks of newer drugs (gabapentin, felbamate, tiagabine, levetiracetam, pregabalin)Decreased serum concentrations in pregnancyOral hormonal contraceptive failure before or after pregnancy may be increased due to drug interaction with cytochrome P450-inducing anti-seizure medications (carbamazepine, phenytoin, phenobarbital, felbamate, oxcarbazepine, topiramate), resulting in decreased hormone levels

Several anticonvulsants also used in treatment of bipolar disorderIf anti-seizure medications cannot be withdrawn in pregnancy, administer most suitable medication for seizure type. No consensus exists as to which medication is most teratogenic; with exception of valproate, most effective agent for individual patient should be given.Use lowest effective dose; if possible avoid combination therapy to limit risk of teratogenicityMonitor drug levels in plasma throughout pregnancyIf possible avoid valproate in pregnant women and in women who are trying to conceive or are not using effective contraceptionConsider increased preconception folate supplementation (4 mg qd) for women on anti-seizure medications, particularly those on valproate or carbamazepine, to reduce risk of NTDsOral vitamin K (10mg/d) supplementation in last month of pregnancy recommended in patients on enzyme-inducing anti-epileptic drugs (e.g phenytoin, phenobarbital, carbamazepine)Prenatal surveillance for defects with serum alphafetoprotein; fetal echocardiography and detailed ultrasound of fetal anatomy

continued

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Table 13-5

Drug Choice in Management of Selected Medical Conditions in PregnancyDrug, Class, or Indication Concerns in Pregnancy RecommendationsThyroid diseaseThioamides(for hyperthyroidism; methimazole, propylthiouracil)FDA pregnancy category: D

Untreated hyperthyroidism associated with increased risk for preterm delivery, severe preeclampsia, heart failure, low birth weight, possible fetal loss. Neonates may be at risk of hyper- or hypothyroidism due to transplacental passage of antibodies in Graves disease or autoimmune thyroiditis.Recent data suggest no significant increase in defects with either PTU or methimazole

Either PTU or methimazole can be used to treat pregnant women with hyperthyroidism. Beta blockers may be used during pregnancy to ameliorate symptoms of thyrotoxicosis until thioamides decrease thyroid hormone levels.Iodine 131 contraindicated in pregnant women because of risk of fetal thyroid ablation

Levothyroxine(for hypothyroidism)

Untreated hypothyroidism associated with increased risk of preeclampsia and possible fetal growth restriction

Safe to use in pregnancyTreatment of hypothyroidism using levothyroxine in pregnant women is same as for nonpregnant women

Venous thromboembolism (treatment or prophylaxis )Low-molecular-weight heparin(enoxaparin, dalteparin, tinzaparin)Unfractionated heparinWarfarin – FDA pregnancy category: X

Warfarin has been associated with fetal hemorrhage and anomalies in all three trimesters

LMWH is preferredUFH is alternative; consider transition to UFH at 36 wk gestationProtamine sulfate can be used if rapid reversal of 

anticoagulant effect is neededAlso consider graduated compression stockings in pregnancy and pneumatic compression boots in intrapartum periodWarfarin contraindicated in pregnancy

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix. FDA pregnancy categories noted only for those drugs that are category D or XS

ACOG

continued

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Table 13-6

Alternative/Complementary Medication Concerns in PregnancySubstance Animal Data and Human Experience Use in Pregnancy, Possible Health Hazards, CommentsComfrey (herb) No animal data

No human experience in pregnancy

Avoid; possible obstruction of blood flow to liver; may lead to death

Chaparral (herb; used in traditional American Indian medicine)

No animal dataNo human experience in pregnancy

Avoid; liver disease; may be irreversible

Germander (herb) No animal data

No human experience in pregnancy

Avoid; liver disease; may lead to death

Germanium (mineral) No animal data

No human experience in pregnancy

Avoid; kidney damage; possibly death

L-tryptophan (amino acid) No animal data

No human experience in pregnancy

Avoid; eosinophilic myalgia syndrome, a potentially fatal blood dyscrasiaFDA has limited import of L-tryptophan into U.S.

Lobelia (herb; Indian tobacco) No animal data

No human experience in pregnancy

Avoid; respiratory distress, tachycardia, hypotension; possibly coma and death at higher doses

Ma-huang (Ephedra sinica) No animal data

No human experience in pregnancy

Avoid; FDA warns of possible health hazards, including high BP, irregular heartbeat, nerve damage, injury, insomnia, tremor, headache, seizure, heart attack, stroke, deathFDA has received >500 reports of adverse events, including 8 fatalities (MMWR 1996;45:689)

Magnolia-Stephania (herbs) No animal data

No human experience in pregnancy

Avoid; renal failure; possibly irreversible

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Table 13-6

Alternative/Complementary Medication Concerns in PregnancySubstance Animal Data and Human Experience Use in Pregnancy, Possible Health Hazards, CommentsNiacin (in doses >500 mg immediaterelease or >750 mg sustained-release) No animal data No human experience in pregnancy Avoid use of high doses in pregnancy GI symptoms (nausea, vomiting, diarrhea, abdominal cramps); 

liver disease

St. John’s wort (Hypericum perforatum) No animal data

No human experience in pregnancy

Meta-analysis suggests St. John’s wort more effective than placebo and as effective as low-dose tricyclic antidepressants for short-term management of mild to moderately severe depression (J Nerv Ment Dis 1999;187(9):532)Due to lack of data in pregnancy, routine use of St. John’s wort cannot be recommendedMajor drug interaction: indinavir trough concentration decreases by 81% when co-administered with St. John’s wort. This interacton applies to all PIs and NNRTIs.

Selenium (in doses >800–1000 mcg/d) No animal data

No human experience in pregnancy

Avoid high doses in pregnancy; possible tissue damage*

Slimming/dieter’s tea No animal data

No human experience in pregnancy

Avoid; nausea, diarrhea, vomiting, stomach cramps, chronic constipation, fainting; possibly death

continued

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Table 13-6

Alternative/Complementary Medication Concerns in PregnancySubstance Animal Data and Human Experience Use in Pregnancy, Possible Health Hazards, CommentsVitamin A Animal data: known teratogen at 

high doses

Human data: Double-blinded randomized trial of low-dose supplementation with vitamin A or beta-carotene (7000 mcg retinol equivalent) in malnourished pregnant women reported a 40% decrease in newborn mortality (BMJ1999;318(7183):570)In a prospective case-controlled study of 423 exposures to 10,000 IU vitamin A during first 9 wk of pregnancy, an increased risk of major malformations was not reported (Teratology 1999;59:7)

Until more data are available it is prudent to consume only RDA of 8000 IU, which can be obtained through a balanced diet

Vitamin B6 (in doses >100 mg/d) No animal data

No human experience in pregnancy

Avoid high doses in pregnancy; ataxia, peripheral neuropathy

Willow bark (herb) No animal data

No human experience in pregnancy

Avoid; allergic reactionAlthough marketed as aspirin-free, contains a precursor of aspirin, with subsequent conversion to aspirin

Wormwood (herb) No animal data

No human experience in pregnancy

Avoid; neurological symptoms, paresthesia, delirium, paralysis

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ixSource: Medical Management of HIV Infection, 16th ed. 2012. Durham, NC: Knowledge Source Solutions

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Nucleoside Reverse Transcriptase InhibitorsStribild should not be initiated in patients with CrCl <70 mL/min. Use of the following fixed-dose combinations is not recommended in patients with CrCl <50 mL/min: Atripla, Combivir, Stribild, Trizivir, or Epzicom. Use of Truvada is not recommended in patients with CrCL <30 mL/min.Abacavir(ABC)/Ziagen

300 mg PO BID No dosage adjustment necessary Child-Pugh Score Dose

5–6 200 mg PO BID

(use oral solution)

>6 Contraindicated

Didanosine EC

(ddl)/Videx EC

Body weight ≥60 kg: 400 mg PO once dailyBody weight <60 kg: 250 mg PO once daily

Dose (once daily)

CrCL (mL/min) ≥60 kg <60 kg

30–59 200 mg 125 mg10–29 125 mg 125 mg

<10, HD, CAPD 125 mg use ddl

oral solution

No dosage adjustment necessary

Didanosine oral solution(ddl)/Videx

Body weight ≥60 kg: 200 mg PO BID or 400 mg PO once dailyBody weight <60 kg: 250 mg PO once daily or 125 mg PO BID

Dose (once daily)

CrCL (mL/min) ≥60 kg <60 kg

30–59 200 mg 150 mg10–29 150 mg 100 mg

<10, HD, CAPD 100 mg 75 mg

No dosage adjustment necessary

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Nucleoside Reverse Transcriptase Inhibitors continued

Emtricitabine(FTC)/Emtriva

200 mg oral capsule once daily or

240 mg (24 mL) oral solution once daily

Dose

CrCL (mL/min) Capsule Solution

30–49 200 mg q48h 120 mg q24h

15–29 200 mg q72h 80 mg q24h

<15 or on HD* 200 mg q96h 60 mg q24h

*On dialysis days, take dose after HD session.

No dosage recommendation

Lamivudine(3TC)/Epivir

300 mg PO once daily or150 mg PO BID

CrCL (mL/min) Dose

30–49 150 mg q24h

15–29 1 × 150 mg,

then 100 mg q24h

5–14 1 × 150 mg,

then 50 mg q24h

<5 or on HD* 1 × 50 mg,

then 25 mg q24h

*On dialysis days, take dose after HD session.

No dosage adjustment necessary

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Nucleoside Reverse Transcriptase Inhibitors continued

Stavudine(d4T)/Zerit

Body weight ≥60 kg: 40 mg PO BID

Body weight <60 kg: 30 mg PO BID

Dose

CrCL (mL/min) ≥60 kg <60 kg

26–50 20 mg q12h 15 mg q12h

10–25 or 20 mg q24h 15 mg q24h

on HD*

*On dialysis days, take dose after HD session.

No dosage recommendation

Tenofovir(TDF)/Viread

300 mg PO once daily CrCL (mL/min) Dose

30–49 300 mg q48h

10–29 300 mg twice weekly

(every 72–96 hours)

<10 and Not recommended

not on HD

On HD* 300 mg q7d

*On dialysis days, take dose after HD session.

No dosage adjustment necessary

Emtricitabine (FTC)+Tenofovir (TDF)/Truvada

1 tablet PO once daily CrCL (mL/min) Dose

30–49 1 tablet q48h

<30 or on HD Not recommended

No dosage recommendation

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Nucleoside Reverse Transcriptase Inhibitors continued

Zidovudine(AZT, ZDV)/

Retrovir

300 mg PO BID CrCL (mL/min) Dose

<15 or HD* 100 mg TID or

300 mg once daily

*On dialysis days, take dose after HD session.

No dosage recommendation

Non-Nucleoside Reverse Transcriptase nhibitors I nhibitorsDelavirdine(DLV)/Rescriptor

400 mg PO TID No dosage adjustment necessary No dosage recommendation; use with 

caution in patients with hepatic impairment.

Efavirenz(EFV)/Sustiva

600 mg PO once daily, at or before bedtime

No dosage adjustment necessary No dosage recommendation; use with 

caution in patients with hepatic impairment.

Efavirenz (EFV)+Tenofovir (TDF)+Emtricitabine (FTC)/Atripla

1 tablet PO once daily Not recommended for use in patients 

with CrCl <50 mL/min. Instead use the individual drugs of the fixed-dose combination and adjust TDF and FTC doses according to CrCl level.

No dosage recommendation; use with caution in patients with hepatic impairment.

Etravirine(ETR)/Intelence

200 mg PO BID No dosage adjustment necessary Child-Pugh Class A or B: No dosage 

adjustmentChild-Pugh Class C: No dosage recommendation

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Non-Nucleoside Reverse Transcriptase Inhibitors continued

Nevirapine

(NVP)/Viramune or Viramune XR

200 mg PO BID or

400 mg PO once daily (using Viramune XR formulation)

Patients on HD: limited data; no dosage recommendation

Child-Pugh Class A: No dosage adjustmentChild-Pugh Class B or C: Contraindicated

Rilpivirine(RPV)/Edurant

25 mg PO once daily No dosage adjustment necessary Child-Pugh Class A or B: No dosage 

adjustmentChild-Pugh Class C: No dosage recommendation

Rilpivirine (RPV)+Tenofovir (TDF)+Emtricitabine(FTC)/Complera

1 tablet PO once daily Not recommended for use in patients 

with CrCl <50 mL/min. Instead use the individual drugs of the fixed-dose combination and adjust TDF and FTC doses levels according to CrCl level.

Child-Pugh Class A or B: No dosage adjustmentChild-Pugh Class C: No dosage recommendation

Protease InhibitorsAtazanavir(ATV)/Reyataz

400 mg PO once daily or(ATV 300 mg + RTV 100 mg) PO once daily

No dosage adjustment for patients with renal dysfunction not requiring HDARV-naïve patients on HD:(ATV 300 mg + RTV 100 mg) once dailyARV-experienced patients on HD:ATV or RTV

boosted ATV not recommended

Child-Pugh Class Dose

B 300 mg once daily

C Not recommended

RTV boosting is not recommended in 

patients with hepatic impairment (ChildPugh Class B or C)

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Protease Inhibitors continued

Darunavir(DRV)/Prezista

(DRV 800 mg + RTV 100 mg) PO 

once daily (ARV-naïve patients only)or(DRV 600 mg + RTV 100 mg) PO BID

No dosage adjustment necessary Mild-to-moderate hepatic impairment: No 

dosage adjustmentSevere hepatic impairment: Not recommended

Fosamprenavir(FPV)/Lexiva

1400 mg PO BIDor(FPV 1400 mg + RTV 100–200 mg) 

PO once daily or(FPV 700 mg + RTV 100 mg) PO BID

No dosage adjustment necessary PI-naïve patients only:

Child-Pugh Score Dose

5–9 700 mg BID

10–15 350 mg BID

PI-naïve or PI-experienced patients:Child-Pugh Score Dose

5–6 700 mg BID + 

RTV 100 mg once daily

7–9 450 mg BID + 

RTV 100 mg once daily

10–15 300 mg BID + 

RTV 100 mg once daily

Indinavir(IDV)/Crixivan

800 mg PO q8h No dosage adjustment necessary Mild-to-moderate hepatic insufficiency 

becasue of cirrhosis: 600 mg q8h

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Protease Inhibitors continued

Lopinavir/ritonavir(LPV/r) Kaletra

400/100 mg PO BIDor800/200 mg PO once daily

 Avoid once-daily dosing in patients on HD No dosage recommendation; use with 

caution in patients with hepatic impairment.

Nelfinavir(NFV)/Viracept

1250 mg PO BID No dosage adjustment necessary Mild hepatic impairment: No dosage 

adjustmentModerate-to-severe hepatic impairment: Do not use

Ritonavir(RTV)/Norvir

As a PI-boosting agent:100–400 mg per day

No dosage adjustment necessary Refer to recommendations for the primary 

PI.

Saquinavir(SQV)/Invirase

(SQV 1000 mg + RTV 100 mg) PO BID No dosage adjustment necessary Mild-to-moderate hepatic impairment: 

Use with cautionSevere hepatic impairment: Contraindicated

Tipranavir(TPV)/Aptivus

(TPV 500 mg + RTV 200 mg) PO BID No dosage adjustment necessary Child-Pugh Class A: Use with caution

Child-Pugh Class B or C: Contraindicated

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

Integrase InhibitorsRaltegravir(RAL)/Isentress

400 mg BID No dosage adjustment necessary Mild-to-moderate hepatic insufficiency:

No dosage adjustment necessarySevere hepatic insufficiency:No recommendation

Elvitegravir (EVG)/Cobicistat (COBI)/Tenofovir (TDF)/Emtricitabine (FTC)/Stribild (only availabe as a co-formulated product)

1 tablet once daily EVG/COBI/TDF/FTC should not be 

initiated in patients with CrCl <70 mL/min.Discontinue EVG/COBI/TDF/FTC if CrCl declines to <50 mL/min while patient is on therapy.

Mild-to-moderate hepatic insufficiency:No dosage adjustment necessarySevere hepatic insufficiency: Not recommended

Fusion nhibitor I nhibitorEnfuvirtide(T20)/Fuzeon

90 mg subcutaneous BID No dosage adjustment necessary No dosage adjustment necessary

continued

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Table 13-7

Table 13-7. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic Insufficiency Antiretrovirals Generic Name (Abbreviation)/ Trade Name

Usual Daily Dose Dosing in Renal Insufficiency 

(Including with chronic ambulatory peritoneal dialysis and hemodialysis)

Dosing in Hepatic Impairment

CCR5 AntagonistMaraviroc(MVC)/Selzentry

The recommended dose differs based on concomitant medications and potential for drug-drug interactions. 

CrCl <30 mL/min or on HDWithout potent CYP3A inhibitors or inducers:300 mg BID; reduce to 150 mg BID if postural hypotension occursWith potent CYP3A inducers or inhibitors:Not recommended

No dosage recommendations. Concentrations will likely be increased in patients with hepatic impairment.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix* Approved adult dose, but for most PIs lower doses are usually used with RTV boosting** Prediction based on PK principles. Drugs likely to be removed have a Vd <0.7 L/kg, protein binding <80%, and size <1500 DaltonSource: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

continued

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Table 13-8

Drugs That Should Not Be Used with Antiretroviral AgentsThis table only lists drugs that should not be co-administered at any dose and regardless of ritonavir (RTV) boosting.

Drug Categories

Antiretroviral Agentsa,b

Cardiac Agents

LipidLowering Agents

Antimycobacterials Gastro- intestinal 

Drugs

Neuroleptics Psycho- tropics Ergot Derivatives (vasoconstrictors) Herbs Anti- retroviral 

Agents

Others

ATV +/– RTV

amiodarone dronedarone

lovastatin simvastatin

rifampin rifapentinec

cisapride pimozide midazolame

triazolam

dihydroergotamine ergonovine ergotamine methylergonovine

St. John’s wort

ETR NVP alfuzosin 

irinotecan salmeterol sildenafil for PAH

DRV/r amiodarone 

dronedarone

lovastatin simvastatin

rifampin rifapentinec

cisapride pimozide midazolame

triazolam

dihydroergotamine ergonovine ergotamine methylergonovine

St. John’s wort

none alfuzosin 

salmeterol sildenafil for PAH

FPV +/– RTV

amiodarone dronedarone flecainide propafenone

lovastatin simvastatin

rifampin rifapentinec

cisapride pimozide midazolame

triazolam

dihydroergotamine ergonovine ergotamine methylergonovine

St. John’s wort

ETR alfuzosin 

salmeterol sildenafil for PAH

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Table 13-8

Drugs That Should Not Be Used with Antiretroviral AgentsThis table only lists drugs that should not be co-administered at any dose and regardless of ritonavir (RTV) boosting.

Drug Categories

Antiretroviral Agentsa,b

Cardiac Agents

LipidLowering Agents

Antimycobacterials Gastro- intestinal 

Drugs

Neuroleptics Psycho- tropics Ergot Derivatives (vasoconstrictors) Herbs Anti- retroviral 

Agents

Others

LPV/r amiodarone 

dronedarone

lovastatin simvastatin

rifampind

rifapentinec

cisapride pimozide midazolame

triazolam

dihydroergotamine ergonovine ergotamine methylergonovine

St. John’s wort

none alfuzosin 

salmeterol sildenafil for PAH

SQV/r amiodarone 

dronedarone dofetilide flecainide lidocaine propafenone quinidine

lovastatin simvastatin

rifampind

rifapentinec

cisapride pimozide midazolame

triazolam trazodone

dihydroergotamine ergonovine ergotamine methylergonovine

St. John’s wortgarlic supplements

none alfuzosin 

salmeterol sildenafil for PAH

TPV/r amiodarone 

dronedarone flecainide propafenone quinidine

lovastatin simvastatin

rifampin rifapentinec

cisapride pimozide midazolame

triazolam

dihydroergotamine ergonovine ergotamine methylergonovine

St. John’s wort

ETR alfuzosin 

salmeterol sildenafil for PAH

continued

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Table 13-8

Drugs That Should Not Be Used with Antiretroviral AgentsThis table only lists drugs that should not be co-administered at any dose and regardless of ritonavir (RTV) boosting.

Drug Categories

Antiretroviral Agentsa,b

Cardiac Agents

LipidLowering Agents

Antimycobacterials Gastro- intestinal 

Drugs

Neuroleptics Psycho- tropics Ergot Derivatives (vasoconstrictors) Herbs Anti- retroviral 

Agents

Others

EFV none none rifapentinec cisapride pimozide midazolame

triazolam

dihydroergotamine ergonovine ergotamine methylergonovine

St John’s wort

other NNRTIs

none

ETR none none rifampin 

rifapentinec

none none none none St 

John’s wort

unboosted PIs ATV/r, FPV/r, or TPV/r other NNRTIs

carbamazepine phenobarbitalphenytoinclopidogrel

NVP none none rifapentinec none none none none St. 

John’s wort

ATV +/– RTV other NNRTIs

ketoconazole

continued

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Table 13-8

Drugs That Should Not Be Used with Antiretroviral AgentsThis table only lists drugs that should not be co-administered at any dose and regardless of ritonavir (RTV) boosting.

Drug Categories

Antiretroviral Agentsa,b

Cardiac Agents

LipidLowering Agents

Antimycobacterials Gastro- intestinal 

Drugs

Neuroleptics Psycho- tropics Ergot Derivatives (vasoconstrictors) Herbs Anti- retroviral 

Agents

Others

RPV none none rifabutin 

rifampin rifapentinec

proton pump inhibitors

none none none St. 

John’s wort

other NNRTIs

carbamazepine oxcarbazepinephenobarbitalphenytoin

MVC none none rifapentinec none none none none St. 

John’s wort

none none

continued

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Table 13-8

Drugs That Should Not Be Used with Antiretroviral AgentsThis table only lists drugs that should not be co-administered at any dose and regardless of ritonavir (RTV) boosting.

Drug Categories

Antiretroviral Agentsa,b

Cardiac Agents

LipidLowering Agents

Antimycobacterials Gastro- intestinal 

Drugs

Neuroleptics Psycho- tropics Ergot Derivatives (vasoconstrictors) Herbs Anti- retroviral 

Agents

Others

EVG/COBI/ TDF/FTC

none lovastatin 

simvastatin

rifabutin rifampin rifapentinec

cisapride pimozide midazolame

triazolam

dihydroergotamine ergotamine methylergonovine

St. John’s wort

All otherARVs

alfuzosin sildenafil for PAH

aDLV, IDV, NFV, and RTV (as sole PI) are not included in this table. Refer to the appropriate FDA package insert for information regarding DLV-, IDV-, NFV-, and RTV (as 

sole PI)-related drug interactions.

bCertain listed drugs are contraindicated on the basis of theoretical considerations. Thus, drugs with narrow therapeutic indices and suspected metabolic involvement with 

CYP450 3A, 2D6, or unknown pathways are included in this table. Actual interactions may or may not occur in patients.

cHIV-infected patients treated with rifapentine have a higher rate of tuberculosis (TB) relapse than those treated with other rifamycin-based regimens. Therefore an 

alternative agent to rifapentine is recommended.

dA high rate of Grade 4 serum transaminase elevation was seen when a higher dose of RTV was added to LPV/r or SQV or when double-dose LPV/r was used with 

rifampin to compensate for rifampin’s induction effect and therefore, these dosing strategies should not be used.

eUse of oral midazolam is contraindicated. Parenteral midazolam can be used with caution as a single dose and can be given in a monitored situation for procedural 

sedation.Suggested alternatives to:• Lovastatin, simvastatin: Fluvastatin, pitavastatin, and pravastatin (except for pravastatin with DRV/r) have the least potential for drug-drug interactions (see Table 

15a). Use atorvastatin and rosuvastatin with caution; start with the lowest possible dose and titrate based on tolerance and lipid-lowering efficacy.

• Rifampin: Rifabutin (with dosage adjustment, see Tables 15a and 15b)• Midazolam, triazolam: temazepam, lorazepam, oxazepam

Source: Medical Management of HIV Infection, 16th ed., 2012. Durham, NC: Knowledge Source Solutions

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationAntifungal agents

Itraconazole

• All PIs: Monitor for toxicities• Itraconazole ≤200 mg/d• EFV, NVP, ETR:  itraconazole possible dose adjustments may be needed• EVG:  itraconazole: itraconazole ≤200 mg/d• MVC: 150 mg bid

Ketoconazole

• MVC: 150 mg bid• LPV/r, TPV/r, FPV/r, DRV/r, RTV: ketoconazole ≤200 mg/d• FPV: ≤400 mg/d• NVP: Consider fluconazole as an alternative• RPV AUC  49%; ketoconazole AUC  24%; monitor for breakthrough fungal infection

Voriconazole

• EFV: contraindicated at standard doses• NPV:  voriconazole possible,  NVP possible: monitor for toxicity and antifungal response

• All boosted PIs: significant  in voriconazole levels: do not co-administer unless benefit 

outweights risk

• EVG:  voriconazole: consider drug levels and adjust dose as needed• MVC: 150 mg bid

Fluconazole

• ETR: AUC  86%; use with caution• NVP: AUC ; monitor for ADR or use alternative• PI/r; EFV, RAL, MVC: Use standard dose• With TPV/r co-administration, do not exceed fluconazole 200 mg/d

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationAntifungal agents (continued) Posaconazole

• ATV: concentrations may be increased; monitor for adverse effects• Do not co-administer with unboosted FPV• EFV:  posaconazole level: avoid co-administration unless benefits outweigh risk• EVG:  posaconazole: monitor posaconazole drug levels if co-administered

Anticonvulsants

PhenobarbitalPhenytoinCarbamazepine

• Phenobarbital may decrease concentrations of all PIs: consider alternative anticonvulsant or 

monitor levels of both drugs and assess virologic response

• Carbamazepine: may decrease PI levels significantly (except for DRV): consider alternate 

anticonvulsant or monitor drug levels of both drugs and assess virologic response; DRV: monitor anticonvulsant level and adjust dose as needed

• MVC: 600 mg bid if used without strong CYP3A inhibitor• Phenobarbital, carbamazepine, phenytoin: do not co-administer with ETR, RPV; NVP or EFV: 

 anticonvulsant and ARV: monitor drug levels of both drugs, monitor virologic response and consider alternative anticonvulsant

• EVG:  carbamazepine possible: consider alternate anticonvulsant

• Phenytoin: all boosted PIs  phenytoin;  ARV level with ATV/r, DRV/r, SQV/r, TPV/r, LPV/r: 

consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response

Valproic acid • LPV/r: AUC  75%; monitor valproic acid levels and virologic response; monitor for LPV- related toxicity

Lamotrigine • LPV/r: lamotrigine AUC  50%; dose increase of lamotrigine may be needed

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationNarcotics/Treatment for Opioid Dependence

Methadone

• NVP, EFV: May significantly decrease methadone concentrations. Monitor for withdrawal 

symptoms.  methadone dose often needed

• RPV: Methadone  26%: monitor for withdrawal symptoms• TPV/r, LPV/r, SQV/r, DRV/r, ATV/r, SQV/r: May decrease methadone levels and require 

monitoring for withdrawal symptoms, but clinical significance is unclear

Oxycodone • LPV/r:  oxycodone AUC 2.6 fold: monitor for opioid-related adverse effects. Oxycodone dose reduction may be necessaryBuprenorphine

• ATV/r:  buprenorphine 66%: monitor for sedation. Buprenorphine dose reduction may be 

necessary

• TPV/r:  TPV: consider monitoring TPV level

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationAntimycobacterial agents

Rifabutin‡

• All PIs with RTV boosting: standard PI dose; Rifabutin dose 150 mg/dg or 300 mg 3x/wk. 

consider TDM

• EFV: RBT 450–600 mg/d or 600 mg 3x/wk• MVC: 300 mg bid; 150 mg bid with PI co-administration• EVG:  EVG: do not co-administer• ETR: rifabutin 300 mg qd, ETR SD; if ETR used with PI/r, rifabutin should not be co-administered• RPV: Contraindicated; do not co-administer

Rifampin

• All PIs and NNRTls contraindicated except EFV (600 mg/d) using SDs of rifampin. Monitor 

virologic response

• MVC: co-administration not recommended

• RAL: Avoid or use RAL 800 mg bid; monitor virologic response

• EVG:  EVG: do not co-administer

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationLipid-lowering agents

SimvastatinLovastatin

• EVG: do not co-administer• All boosted PIs: Contraindicated• EFV, NVP, ETR:  statin: adjust statin dose according to lipid response

Atorvastatin

• All PIs may substantially increase levels. Use lowest possible dose of atorvastatin.• TPV/r: do not co-administer• EFV, ETR: May reduce atorvastatin levels; adjust atorvastatin dose according to lipid responses• EVG: titrate statin dose slowly and use lowest dose possible

Pravastatin

• No dose change with most agents• DRV/r: May  statin AUC 81%: use lowest possible starting dose of pravastatin with careful 

monitoring

• EFV:  statin level: Adjust statin dose according to lipid response

Rosuvastatin

• ATV/r, LPV/r, DRV/r, SQV/r: titrate rosuvastatin dose carefully and use lowest necessary dose; 

monitor for toxicities

• EVG:  rosuvastatin level: titrate statin dose slowly and use lowest dose possible• RAL, MVC: Interaction unlikely

Calcium channel blockers (CCBs)

• All PIs:  CCB level: Use with caution, titrate CCB dose and monitor closely; ECG monitoring 

recommended when CCB used with ATV

• EFV, NVP:  CCB level possible: titrate CCB dose based on clinical response• EVG:  CCB level possible: co-administer with caution. Monitor for CCB efficacy and toxicity

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationContraceptives (See table 7-4)Corticosteroids

Budesonide (systemic)

• All PIs:  PI levels,  glucocorticoids: do not co-administer unless benefits outweigh risks: 

co-administration can result in adrenal insufficiency, including Cushing’s syndrome

Budesonide (inhaled or intranasal)

• All PI/r:  glucocorticoids (see above recommendation)

Dexamethasone

• All PIs:  PI levels: use systemic dexamethasone with caution or consider alternative 

corticosteroid for long-term use

• EFV, NVP, ETR:  ARV levels: consider alternate corticosteroid for long-term use. If 

dexamethasone used, monitor virologic response

• RPV:  significant RPV: contraindicated with >1 dose dexamethasone• EVG:  EVG possible: co-administer with caution, monitor HIV virologic response

Fluticasone (inhaled or intranasal)

• All PI/r: significant  steroid level; do not co-administer unless benefits outweigh risks of 

systemic corticosteroid adverse effects

• EVG: possible  fluticasone: use alternative inhaled steroid especially for long-term use

Prednisone • LPV/r:  prednisone  LPV; Monitor virologic response. Do not co-administer unless benefits outweigh risks of systemic corticosteroid adverse effects

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationAntidepressants

TCAs • Boosted PI, EVG may  TCA concentrations; use lowest possible TCA dose and titrate based on clinical assessment and/or drug levelsBupropion

• LPV/r, TPV/r:  bupropion: titrate dose based on clinical response• EFV:  bupropion: titrate dose based on clinical response

Trazodone

• ATV/r, LPV/r, DRV/r, TPV/r, FPV/r: use lowest dose of trazodone and monitor for CNS and 

cardiovascular adverse effects

• EVG: possible  trazodone: initiate with lowest dose and titrate carefully• SQV/r: Contraindicated

Sertraline

• DRV/r, EFV:  sertraline: titrate dose based on clinical response• EVG:  SSRI possible: initiate with lowest dose and titrate based on clinical response

continued

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Table 13-9

Recommended Dose Modifications with Boosted Protease Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Integrase Inhibitors, and CCR5 AntagonistsClass Agent ART/ModificationMiscellaneous

H2 blockers

• ATV/r: H2 blocker dose should not exceed a dose equivalent to famotidine 40 mg bid in ARTnaïve or 20 mg bid in ART-experienced

• Administer ATV/r 400/100 if used with H2 blocker and TDF

• RPV: Administer H2 blocker 12 h before or 4 h after RPV

Clopidogrel • ETR: May decrease efficacy of clopidogrel; avoid co-administration, if possible

Warfarin

• Monitor INR closely if given with any PI or NNRTI (or EVG); adjust warfarin dose as needed• PI/r and RTV may  INR at steady state

Antacid

• RPV:  RPV when given simultaneously; give antacids at least 2 hr. before or at least 4 hr. 

after RPV

• ATV/r, TPV/r: give ARV at least 2 hr. before or 1 hr. after antacids or buffered medications• EVG: separate EVG and antacid administration by more than 2 hr.

Proton Pump Inhibitors (PPIs)

• ATV/r: PPIs should not exceed a dose equivalent to omeprazole 20 mg/d in PI-naïve patients. PPIs should be administered at least 12 hrs. before ATV/r; PPIs are not recommended in 

PI-experienced patients

• DVR/r, TPV/r:  omeprazole; may need to  omeprazole dose• SQV/r:  SQV: monitor for toxicity• RPV:  RPV: contraindicated, do not co-administer

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix* RTV 100–200 mg/d may be given with voriconazole. May  voriconazole concentrations. Monitor voriconazole levels.† Do not coadminister ETR with DRV/r or SQV/r when combined with rifabutin‡ For treatment of TB, most experts recommend rifabutin 150 mg qd with PI/r. Consider rifabutin therapeutic dose management.§ Bepridil contraindicated with EFV; clinical significance unknownSource: Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents (http://aidsinfo.nih.gov). Accessed 5/22/2013

continued

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Table 13-10

Clinically Pertinent Food-Drug Recommendations

Atazanavir

Clarithromycin XL

Darunavir

Etravirine

Itraconazole capsule

Ribavirin

Rifapentine

Ritonavir

Tipranavir

Valganciclovir

Take with food or within 2 h of a meal

AZT Can be taken with food to decrease GI side effects

Atovaquone

Nelfinavir

Rilpivirine

Take with high-fat meal

Efavirenz Manufacturer recommends taking on empty stomach. Take 

on empty stomach to minimize risk of CNS side effects.

Didanosine* 

Indinavir 

(unboosted)† 

Isoniazid

Itraconazole solution 

Voriconazole

Take on empty stomach (1 h before or 2 h after a meal)

Grapefruit juice Increases saquinavir levels 40%–100%, but decreases 

indinavir AUC by 26%. Unlikely to be clinically significant 

with boosted PIs.

* No food restriction when ddI is co-administered with TDF, but this combination is 

generally not recommended due to potential for increased ddI toxicity and higher rates of 

virologic failure

† No food restriction when IDV is co-administered with RTV

Source: Medical Management of HIV Infection, 16th ed., 2012. Durham, NC: Knowledge 

Source Solutions

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Chapter 14:

Quality Management

Lori DeLorenzo, RN, MSN

Executive Director

Organizational Ideas

Robin Bidwell, RNC, BSN, CCRC

Performance Improvement Coordinator

HIV Community Program

Christiana Care Health Systems

The authors declare no conflicts of interest

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Chapter 14: Quality Management

Chapter 14 at a Glance

Quality Management..............................................................................................................................517

Improved Patient Care....................................................................................................................517

Elements of a Quality Management Program..........................................................518

Infrastructure..............................................................................................................................................518

Performance Measurement.........................................................................................................519

Quality Improvement........................................................................................................................524

Case Study: Quality Improvement In Action...............................................................527

Quality Management Infrastructure..................................................................................527

Performance Measurement.........................................................................................................528

Quality Management Phase 1...............................................................................................528

Quality Management Phase 2...............................................................................................529

End Results....................................................................................................................................................529

Sustaining Change and Spreading Ideas........................................................................530

No Improvement Without Change......................................................................................530

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Quality Management

Improved Patient Care

A structured approach: Improved patient outcomes are a goal toward which 

all clinicians strive. Without a formal process to measure and evaluate the 

effectiveness of care, however, a clinician cannot be certain that a goal 

is being met. Quality management (QM) is a process designed to identify 

meaningful goals, establish and implement a plan for achieving them, measure 

outcomes and, in the clinical setting, realize improved patient outcomes. For the 

purposes of this guide, QM refers to an overarching strategy encompassing 

quality improvement (QI) activities and a formalized structure for assessing 

the quality of care in any setting and with any patient population. Table 14-1 

provides a brief glossary of terms essential to any discussion of QM.

Table 14-1

Brief Glossary of Quality Management Terms

Term Definition

Indicator also known 

as process indicator, 

performance 

measure, or outcome 

measure

An operational definition of a specific quality characteristic 

that can be measured. Indicators typically conform to 

widely accepted guidelines or standards of care. Of note, 

“outcome” refers more specifically to benefits or results for 

patients that accrue as a result of QI activity. Results may 

be positive or negative, and outcome may be measured on 

the patient or system level. Regardless of the term used, 

all refer to a measureable indication of an organization’s 

performance in relation to a specified QI process.

Quality assurance QA refers to a formal set of activities to review and 

safeguard the quality of services provided. QA includes 

quality assessment and implementation of corrective actions 

to address deficiencies. It is focused on ensuring that 

standards are adhered to, problems are identified, and 

discrete quality issues are resolved. Resolution focuses most 

often on a responsible individual. QA is more commonly used 

in a regulatory environment.

Quality 

improvement also 

known as continuous 

quality improvement 

or performance 

improvement

QI is an organizational approach to improving quality of 

care and services that relies on established principles and 

methodologies. To be successful, QI requires committed 

leadership; resources; staff involvement; stakeholder 

involvement; and a patient-oriented, cross-functional team 

approach. QI is a continual process of improvement activities 

and performance measurements.

Quality 

management

QM refers to an overarching strategy that encompasses both 

QI activities and a formalized structure for assessing quality 

of care in any setting or with any patient population.

Table 14-1 continues on the next page

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Table 14-1

Brief Glossary of Quality Management Terms

Term Definition

Root cause analysis Root cause analysis is the first step toward developing 

permanent solutions to problems. It first entails identifying all 

the contributing or underlying causes of a problem; results of 

this analysis are often organized into a “fishbone diagram.” 

The results provide a way to approach solutions in the 

different domains identified.

Total quality 

management

TQM is a strategic approach to management that aims to 

embed awareness of quality in all organizational processes. 

TQM encompasses all QI activities as well as management of 

systems that foster QI, including communications, education, 

and resource allocation.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

QM can be applied to accomplish a wide variety of goals, such as enhancing 

clinical care for a specific population, assessing population-specific needs, 

understanding and correcting system inefficiencies, measuring outcomes, 

and identifying lessons learned. This chapter focuses on ways in which care 

of women with HIV can be improved in the face of everyday challenges 

confronting them and their HIV care providers.

Elements of a Quality Management Program

A QM program comprises all program-specific quality activities. To be 

successful, a QM program should have three key elements: (1) a quality 

infrastructure, (2) performance measurement, and (3) QI activities.

Infrastructure

The QM infrastructure, which provides the foundation and support for a QM 

program, has five essential components: (1) vision and planning, (2) oversight, 

(3) formalized structure, (4) resources, and (5) evaluation. These components 

are described in Table 14-2.

continued

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Table 14-2

Components of Quality Management Infrastructure

Component Key Tasks

Vision and 

planning • Quality vision is established and articulated.

• Annual planning process is implemented.

• Written QM plan is developed that includes defined 

responsibilities, accountability, performance measures, QI 

activities, and timetable.

Oversight • Performance data, findings, and accomplishments are 

shared frequently, both internally and externally.

• Progress on QM plan is reviewed routinely.

• QM infrastructure and planned activities are actively 

supported by senior leaders.

Formalized 

structure • QM committee with appropriate membership is established.

• Senior leaders, key providers, and stakeholders are 

actively involved in QM committee.

• Priorities are established, and recommendations for current 

and future QM activities are solicited by QM committee.

• Meetings are held regularly; reporting mechanisms are 

defined, and meeting minutes are maintained.

• Mechanisms for interface with QI project teams are 

clearly defined.

• Membership is reviewed and updated annually.

Resources • Key staff with QM activities are identified.

• Dedicated time is allocated for QM activities.

• Meeting space, training, materials, and other 

resources are provided.

• Mechanisms to collect, aggregate and synthesize 

data.

Evaluation • QM program effectiveness in meeting organizational needs 

is assessed annually.

• Stakeholders inform all intended results.

• Accomplishments are recognized.

• Areas for continued improvement are identified using 

performance data.

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Performance Measurement

Formalized performance measures are used to assess quality of care, 

determine progress over time, and confirm that changes made through the 

QI process actually have improved patient outcomes. Perceptions of care 

providers may be helpful in identifying areas for QI focus, but individual 

assumptions and perceptions may not align with documented clinical measures 

and trend data. Figure 14-1 illustrates such a discrepancy between a care 

provider’s assumption—that patients in her clinical practice were receiving 

regular Pap smears—and the reality made clear by clinical documentation.

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As part of QM activities, goals for each element of care should be established 

so that care providers are able to assess their performance. If the goals are 

not met in certain areas, these areas may be enhanced through a QI project. 

Regular review of data is critical, and additional analysis may be required for 

data that may indicate the existence of problems.

Figure 14-1

Provider Perception Versus Documented Reality

Assumption

Provider A believes that at least 

75% of women in her clinical 

practice received a Pap smear 

within the past 12 months.

Reality

Electronic medical records indicate 

that only 42% of patients received 

a Pap smear in the past year.

Creating a performance measurement plan: Establishing a performance 

measurement plan entails defining and selecting performance measures 

that are relevant to a specific program or population and then identifying 

appropriate data sources. The data that are collected must reflect the services 

and quality of care being provided. Finally, data must be collected at regular, 

defined intervals.

Standardized HIV care performance measures: Standardized performance 

measures for HIV care, including performance measures specific to OB-GYN 

care, have been established by several national entities: The Health Resources 

and Services Administration HIV/AIDS Bureau (HAB), the National Quality 

Forum (NQF), and the New York State Department of Health AIDS Institute 

National Quality Center (NQC) in partnership with HRSA HAB. The HAB 

performance measures have been developed specifically for use by programs 

funded by the Ryan White HIV/AIDS Treatment Extension Act of 2009. The 

performance measures endorsed by the NQF can be used across all service 

delivery systems, including private practices and large HMOs. Performance 

measures developed by the NQC were derived from established HIV clinical 

guideline panels to reflect the comprehensive package of services important 

to provide the best possible care to patients with HIV. The NQC performance 

measures include several specific to OB-GYN care.

Table 14-3 includes performance measures specific to care of women with 

HIV, sampled from the three resources noted in the previous paragraph. The 

measures are expressed in a standard format (i.e., a specific aspect of patient 

care accompanied by a quantitative measure designed to assess the quality of 

that care). Table 14-4 categorizes the same measures into three target groups: 

(1) pregnant women; (2) nonpregnant, sexually active women who want 

conception; and (3) all sexually active women.

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Table 14-3

Performance Measures Specific to Care of Women with HIV

Source Performance 

Measure

Numerator Denominator

HRSA/

HAB

% of women with 

HIV who have a 

Pap smear in MY

No. of HIV infected 

female patients 

who had Pap smear 

results documented 

in MY

No. of HIV-infected female 

patients who were >18 

yr old in MY or reported 

history of sexual activity 

and had a medical visit 

with a provider at least 

1x in MY

Exclusions: Patients 

who (1) were <18 yr 

old and denied history 

of sexual activity or 

(2) had hysterectomy 

for nondysplasia or 

nonmalignant indications

HRSA/

HAB

% of pregnant 

women with HIV 

infection prescribed 

ART

No. of HIV infected 

pregnant women who 

were prescribed ART 

during 2nd and 3rd 

trimester

No. of HIV infected 

pregnant women who 

had a medical visit with a 

provider with prescribing 

privileges at least once 

in MY

Exclusions: (1) Patients with 

terminated pregnancy; 

(2) pregnant patients in 

1st trimester and newly 

enrolled in care during last 

3 mo of MY

HRSA % of pregnant 

women who were 

screened for HIV 

infection during the 

1st or 2nd prenatal 

care visit

No. of pregnant 

women who were 

screened for HIV 

infection during the 

1st or 2nd prenatal 

care visit

No. of pregnant women 

seen for 2 prenatal visits 

during MY

NQC % of women with 

HIV who receive 

preconception care 

and counseling

No. of HIV infected 

women who received 

counseling about 

importance and use 

of male or female 

condoms

No. of sexually active HIV 

infected women

NQC % of women with 

HIV contemplating 

pregnancy 

who receive 

preconception care 

and counseling

No. of HIV infected 

women receiving 

preconception 

counseling

No. of sexually active 

HIV infected women 

contemplating pregnancy

NQC % of pregnant 

women with HIV 

who received CD4+ 

count and viral 

load each trimester 

of pregnancy

No. of HIV infected 

patients for whom 

CD4+ count and viral 

load were measured 

each trimester of 

pregnancy

No. of HIV infected 

pregnant women

Table 14-1 continues on the next page

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Table 14-3

Performance Measures Specific to Care of Women with HIV

Source Performance 

Measure

Numerator Denominator

NQC % of pregnant 

women with HIV 

who had HIV RNA 

measured at 34–36 

wk gestation

No. of patients 

who had HIV RNA 

measured at 34–36 

wk for mode of 

delivery assessment

No. of HIV infected 

patients for whom CD4+ 

count and viral load were 

measured each trimester 

of pregnancy

NQC % of pregnant 

women with HIV 

who received 

counseling to avoid 

breastfeeding

No. of HIV infected 

pregnant women 

who received 

counseling to avoid 

breastfeeding

No. of HIV infected 

pregnant women who 

delivered a live-born 

infant within the time 

period of study

NQC % of pregnant 

women with HIV 

who received 

intrapartum 

zidovudine

No. of HIV infected 

pregnant women 

who received 

administration of IV 

zidovudine during 

labor or prior to 

scheduled cesarean 

delivery alone or 

in combination with 

other ARV drugs

No. of HIV infected 

pregnant women within the 

time period of study who 

have delivered a live-born 

infant

NQC % of postpartum 

women who 

received maternal 

postpartum followup

No. of HIV infected 

women who received 

documented maternal 

postpartum follow-up 

including monitoring 

of HIV infection with 

CD4+ counts and 

viral load tests

No. of HIV infected 

postpartum women

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Performance measures are subject to ongoing change and revision. Readers are directed 

to the URLs below for the most up-to-date versions. Additional performance measures 

targeted for HIV infected patients, regardless of gender, can also be found at the 

following websites:

HRSA/HAB measures: http://hab.hrsa.gov/deliverhivaidscare/habperformmeasures.html

HRSA measures: http://www.hrsa.gov/healthit/coremeasures.html

NQC measures: http://www.nationalqualitycenter.org/index.cfm/5659

NQF measures: http://www.qualityforum.org

continued

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Table 14-4

Performance Measure by Target Population

Measure Population

Pregnant 

Women

Nonpregnant, 

Sexually Active, 

Wants Conception

All Sexually

Active Women

Pap smear X X X

Preconception 

counseling

X

HIV screening X X X

Prescribed ART X

CD4+ and viral load 

each trimester

X

HIV RNA 

@ 34–36 wk

X

Breastfeeding 

counseling

X

Intrapartum zidovudine

X

Maternal follow-up X

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Use of measures: Performance measurement data can be used to identify 

potential problems and areas in need of improvement; these areas can 

be examined further through the implementation of QI projects. Note that 

performance measurement is just one component of a QM strategy and is not 

an end in itself. Data analysis and subanalysis can be conducted to determine 

differences in clinical outcomes on the basis of any number of factors (e.g., 

gender, race, location, language, socioeconomic status, presence of children). 

Table 14-5 illustrates the results of subanalysis performed to determine gender 

differences in provision of CD4+ cell counts. In this example, 85.5% of all 

clients with HIV infection had 2 or more CD4+ cell counts performed during the 

measurement year. However, subpopulation analysis revealed that this level 

was reached for a lower percentage of female patients (71.4%), and further 

analysis revealed that among female patients, the standard was achieved 

most often for Latina patients and least often for African-American patients. 

Had this information been aggregated, resources used to address the actual 

observed disparity may not have had an appreciable impact because the 

largest gain would have been realized by focusing on the African-American 

women. When presenting data, program staff should keep in mind that data, 

charts, graphs, and other visual depictions of results can often relay messages 

or emphasize key points or trends more effectively than words.

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Table 14-5

Sample Performance Measure Subanalysis: Percentage of Patients with HIV 

Infection Who Had ≥2 CD4+ Cell Counts Performed in Measurement Year

Eligible Population

Patients With HIV Infection

Numerator

No. Who Had 

≥2 CD4+ 

Cell Counts 

Performed

Denominator

No. Who Had 

≥1 Medical Visit

Percentage

Numerator ÷ 

Denominator x 100

All patients (N = 425) 342 400 85.5

Male (n = 295) 257 281 91.5

Female (n = 130) 85 119 71.4

African-American female 

(n = 78)

44 70 62.9

Latina female (n = 14) 11 12 91.7

Caucasian female (n = 38) 30 37 81.1

Quality Improvement

Well-selected performance data can provide information about how well a 

system or program is functioning and identify potential problems. Table 14-6 

provides an example. Analysis of performance measure data indicate that 

Agency A appears to be doing well with ART for pregnant women, medical visits, 

and Pneumocystis carinii pneumonia (PCP) prophylaxis. For each measure, baseline 

rates have been maintained or have improved over time. Although hepatitis 

B (HBV) vaccination and cervical cancer screening rates remain low, notable 

improvement has been made in comparison to baseline data. However, rates of 

TB screening and CD4+ cell counts have declined. Of particular interest is the 

difference in rates of CD4+ cell count monitoring and medical visits: Although the 

majority of patients (94%) had ≥1 medical visit during the measurement period, 

only 76% had ≥2 CD4+ cell counts during the same time frame.

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Table 14-6

Example of Annual Quality Review Results (Agency A)

Indicator Performance (%) Indicator Performance (%)

Baseline Current Baseline Current

Medical visits 91 94 Cervical cancer 

screening

53 68

ART 78 82 Adherence 

counseling

73 78

CD4+ cell count 84 76 TB screening 66 62

PCP prophylaxis 

(if indicated)

90 91 Syphilis screening 59 77

ART for pregnant 

women 95 98 HBV vaccine completed

45 54

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Goals: Goals for each indicator should be set based on best practices. Any 

downward trend or measure that did not meet a defined goal can be further 

explored as a QI project. Once a process or issue is identified, a QI team 

should be convened. A QI team is a working group constituted to address one 

specific opportunity for improvement. The team should consist of the people 

who have regular involvement in the process and should have a leader, 

facilitator, or both. In this example, given the data presented above, the QI 

project could examine the rate of CD4+ cell count testing (Figure 14-2).

Figure 14-2

Quality Improvement Problem and Goal

Problem

In 2010, the percentage of 

CD4+ cell counts conducted 

at least every 6 months 

decreased to 76%.

Goal

Increase the percentage of 

CD4+ cell counts completed 

at least every 6 months for 

HIV infected patients to 90%.

For each QI project, the specific problem should be identified, baseline data 

should be collected, and a clearly defined goal should be established. Various 

strategies can be used to understand the issue at hand and identify potential 

change strategies that can be implemented to reach the goal. In these 

processes, such tools as fishbone diagrams, flowcharts, and force field analysis 

can be useful.

Another useful tool is the Model for Improvement (Figure 14-3), which poses 

three questions to help guide a QI project: (1) What are we trying accomplish? 

(2) How will we know that a change is an improvement? (3) What changes can 

we make that will result in improvement?

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Figure 14-3

Model for Improvement

ACT PLAN

STUDY DO

What are we trying 

to accomplish?

How will we know that a 

change is an improvement?

What changes can we make that will result in 

improvement?

Source: © The Improvement Guide: A Practical Approach to Enhancing Organizational 

Performance, 2nd ed. 2009. San Francisco, CA: Jossey-Bass. Reproduced with 

permission of John Wiley & Sons, Inc.

Plan–Do–Study–Act: By understanding a problem and implementing tests of 

change, performance rates can improve. However, not all change results in an 

improvement. To ensure that positive change is being made, performance must 

be measured. Plan–Do–Study–Act (PDSA) cycles (Figure 14-4) prompt a QI 

team to engage in continuous efforts to make change and measure its effect on 

patient outcomes. Multiple PDSA cycles are required to implement change that 

is sustainable over time. The most effective QI teams regularly communicate 

their progress with a QM committee. Senior leadership can be used to minimize 

or remove barriers, allocate resources, and provide guidance and support.

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Figure 14-4

Elements of Plan–Do–Study–Act Cycle

PLAN

• State cycle objectives 

• Make predictions

• Strategize: who, what, 

where, when

STUDY 

• Complete data analysis

• Compare data and predictions 

• Summarize lessons learned

DO

• Carry out test 

• Document problems and 

unexpected observations 

• Begin data analysis

ACT

• What changes are 

to be made? 

• What is to be the 

next cycle?

Case Study: Quality Improvement In Action

The case study that follows illustrates components of QM program as 

implemented in an urban, hospital-based HIV clinic.

Quality Management Infrastructure

The HIV program’s QM committee was established to support and guide all 

quality-related initiatives for the HIV program. The QM Committee, which met 

monthly, included the following members: medical director, nurse practitioner 

from each site, program director, site managers, QA manager, policy and 

procedure manager, pharmacist, and peer educator.

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Performance Measurement

The QM Committee was charged with identifying and monitoring performance 

measures that addressed a range of clinical issues. When the committee 

examined the measures, it was clear that systems needed to be enhanced 

to improve the clinic’s Pap smear rate. Patient data indicated the following 

information, which prompted initiation of a QI project:

• Visit adherence: 75%

• Patients on ART: 88%

• Viral load <48 c/mL: 57%

• Annual Rapid Plasma Reagin (RPR): 94%

• Women with annual Pap: 13%

Problem identified: Pap smear completion rate varied across clinic sites. Key 

baseline data indicated the following:

• 13% of women referred for routine OB-GYN care kept 

their appointments and had documented results.

• 35% of tests returned abnormal results.

• 100% of women with abnormal results were scheduled for 

further evaluation, but only 25% kept their appointments.

Goal: Within 12 months, improve the annual Pap smear rate for women 

infected with HIV to 75%. The overarching goal was for 100% of women to 

receive an annual Pap smear and 90% of the women with abnormal results to 

receive appropriate treatment.

Understanding the problem: Data indicated that, despite a clinician‘s vigilance 

in making referrals, female patients in the HIV clinics were not keeping 

appointments for yearly OB-GYN exams. In response, the team implemented a 

series of change strategies.

Quality Management Phase 1

Strategies: A series of change ideas were implemented to increase the Pap 

smear completion rate:

• Phone calls to remind HIV clinic patients of scheduled 

appointments in the OB-GYN clinic

• Assignment of HIV clinic staff members to meet patients 

in the OB-GYN clinic to help ease the transition to a new 

setting and new care providers and to address fears

• Provision of child care for patients who kept their 

OB-GYN clinic appointments

• Designation of the HIV clinic nurse as a single point of 

contact and the person with responsibility for scheduling 

appointments and making follow-up phone calls.

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Results: The rate of completion rose to only 42%. Of those patients with 

abnormal Pap smear results, only 36% received appropriate follow-up. Patient 

satisfaction surveys and information relayed from peer educators and the 

Patient Advisory Group indicated that the best way to meet this growing need 

was to provide onsite Pap smears during clinic visits and to build a women’s 

clinic nested within the HIV clinic.

Quality Management Phase 2

Strategies: On the basis of data collected after the first phase, several 

additional change ideas were tested:

• Patients were routed to a female nurse practitioner, who 

conducted Pap smears as part of routine HIV care.

• Reminder tags were placed on charts to indicate when 

patients were due for OB-GYN care.

• Performance data were reviewed more closely to 

ensure that every patient was assessed to identify 

need for OB-GYN care.

Results: Data monitoring provided evidence that the nested approach yielded 

a higher percentage (60%) of completed Pap smears. To build on these results, 

several additional services were established:

• On-site follow-up for women with abnormal Pap 

smear results

• On-site colposcopy, cervical biopsies, and loop 

electrosurgical excision procedure (LEEP), using equipment 

obtained from the women’s health clinic

• Training and certification in colposcopy for nurse 

practitioners in the HIV clinic

• One morning per week designated specifically for follow-up 

visits for women with abnormal results, with a primary care 

nurse assigned to coordinate appointments

End Results

The QI project was successful in providing patients with easy access to 

comprehensive care and follow-up. As a result, 57% of women had annual 

Pap (up from 13%), 84% of all abnormal Pap smears were followed up 

appropriately, and 100% of all pregnant women received ART prophylaxis 

for prevention of mother-to-child transmission. Another success was a reduction 

in missed appointments for onsite OB-GYN care, such that 88% of women 

adhered to scheduled appointments following completion of the QI initiative.

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Sustaining Change and Spreading Ideas

No Improvement Without Change

Clinicians and staff who initiate change must look at who and what the 

change will affect and select the changes that will bring about the best clinical 

outcomes for patients. Often, a needed change is obvious, but the resources 

or conditions are not readily available to support the effort needed to make 

change happen.

A dynamic process: Once changes have been made, progress must be 

monitored over time to ensure that improvements are sustained. Successful 

change ideas can be spread to other clinical sites and practices. Through 

the use of repeated PDSA cycles, ideas for change can be tested in new 

settings and modified as needed. As part of the change strategy, policies and 

procedures may have to be revised, and staff may have to be retrained or 

cross-trained to be able to implement new policies and practices.

Not all change = improvement: Improvement requires change, but not every 

change is an improvement. Purposeful change will alter an existing system 

in a positive way or create something new that is also improved. Only upon 

analysis of data and outcomes can it be determined whether a specific change 

led to a desired improvement.

Keys to QI success: The most important step in any QI project may be simply 

to get started (i.e., “just do it”; Figure 14-5). Also crucial is the selection of 

project: It’s best to begin with a project that has a good chance of success 

and that will interest and engage others. Start small and aim for incremental 

improvement in outcomes by making and testing small changes over short 

periods of time. Identify and engage or involve a champion for change early 

on to initiate rapid PDSA cycles that will produce data demonstrating early 

successes. Include all levels of the system to elicit diverse ideas and buy-in 

for improvement. Finally, ensure effective leadership, which is essential to the 

success of any QM program.

Figure 14-5

Secrets of Quality Improvement Success

“Just do it” Choice of 

project

Incremental 

change

Champion 

for change Leadership

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Chapter 15:

Resources

Lori DeLorenzo, RN, MSN

Executive Director, Organizational Ideas

with Skyler Tyne Sharp, RN, BSN

The authors declare no conflicts of interest

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Chapter 15: Resources

Chapter 15 at a Glance

How to Use this Chapter.....................................................................................................................533

Resources for Healthcare Professionals.........................................................................534

Resources for Patients.......................................................................................................................543

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How to Use this Chapter

A chapter devoted to additional resources is an essential part of this guide. 

First, HIV clinical care evolves so rapidly that some information in the guide will 

soon be out of date. Second, a wealth of information that supplements these 

chapters in specialized areas of care is available. We have included some of 

the most important resources for clinical care of women with HIV, but the list is 

by no means exhaustive. Readers can explore the websites for which we have 

provided URLs to find many other informative sites.

In this electronic information age, the term resources includes Internet sites and 

electronic documents as well as organizations and published documents, so the 

chapter includes a range of mechanisms for obtaining more information. We 

consider the Web-based resources to be primary because they are available 

from anywhere in the world and are usually updated on a periodic basis. 

Phone contact information is provided where available, so that readers without 

access to the Internet can still obtain information.

The resources are listed alphabetically in a grid that identifies major topics 

addressed by each resource as well as the type of information available. 

There is a brief description of the resource and website and phone contact 

information. The phone numbers with 800, 888, 877, and 866 prefixes are 

only toll-free in the United States.

Regarding special populations, many of the resources contain some information 

(e.g., fact sheets) about or for groups of people with special needs, such as 

people who are homeless, incarcerated, or transgender. Information for special 

populations is usually just one component of a resource, which makes the search 

function on most websites a useful tool for locating information on specific 

topics or special populations. In addition, providers caring for lesbians with HIV 

can find relevant information by searching The Body (www.thebody.com) and 

the website of the American Psychological Association Office on AIDS (www.

apa.org/pi/aids/index.aspx).

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

AIDS Clinical Trials Group (ACTG)*

https://actgnetwork.org/ NIH-funded AIDS Clinical Trial 

Groups • Website

• Print materials

• Tel/e-mail/Web consultation

• Research and clinical trials

AIDS Alliance for Children, Youth & Families (formerly the AIDS Policy Center for Children, Youth and Families)

www.aids-alliance.orgTel: 202-785-3564888-917-2437

Policy center that promotes advocacy, education, and support for children and families affected by HIV/AIDS

• Website• Print materials

• Tel/e-mail/Web consultation

• Meetings and conferences

• Patient education

• Treatment

• Peds/adolescents• Psychosocial support and 

quality of life

• Research and clinical trials

AIDS Education Global Information System (AEGIS)

www.aegis.comTel: 949-495-1952

Nonprofit group that assembles and archives information and resources from the mainstream press, professional journals, and legal and legislative sources

• Website

• Tel/e-mail/Web consultation

• Meetings and conferences

• Patient education

• Prevention

• Occupational exposure

AIDS Education and Training Centers (AETCs)

www.aidsetc.org Network of regional centers 

that provide HIV training and education for healthcare providers

• Website

• Guidelines• Print materials• Tel/e-mail/Web consultation

• Epidemiology

• Treatment• Prevention• Peds/adolescents• OB-GYN• Adherence• Psychosocial support and 

quality of life

• Substance abuse• Research and clinical trials

• Occupational exposure

• Quality improvement• Palliative care

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

AIDSInfo*(AIDS Clinical Trials Information Services and AIDS Treatment Information Services have been integrated into AIDSInfo)

www.aidsinfo.nih.govTel: 301-519-0459800-HIV-0440TTY: 888-480-3739Spanish speakers available M–F, 12 pm–5 pm, EST

HHS project that offers the latest federally approved information on HIV/AIDS clinical research, treatment, prevention, and medical practice guidelines

• Website• Guidelines

• Print materials• Tel/e-mail/Web consultation

• Meetings and conferences

• Treatment• Prevention• Peds/ adolescents

• OB-GYN

• Nutrition• Occupational exposure

American Academy of HIV Medicine (AAHIVM)*

www.aahivm.orgTel: 202-659-0699

Professional association for HIV specialists; promotes excellence in HIV/AIDS care and offers HIV credentialing for physicians, nurse practitioners, and physician assistants

• Website• Meetings and conferences

• Treatment

American Congress of Obstetricians and Gynecologists (ACOG)*

www.acog.orgTel: 202-638-5577

Professional association for specialists in OB-GYN; provides guidelines and information on reproductive care of women

• Website

• Meetings and conferences

• OB-GYN

Association of Nurses in AIDS Care (ANAC)*

www.anacnet.orgTel: 800-260-6780

Professional association for nurses; provides information and advises members about clinical and policy issues related to nursing and HIV care; offers the ACRN credential

• Website

• Print materials• Meetings and conferences

• Epidemiology• Nursing standards of practice• Nutrition• Adherence• Treatment• Psychosocial support

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

AIDSVU www.aidsvu.org Interactive online map of HIV 

prevalence in U.S. with national, state, and local map views

• Website • Epidemiology

• HIV testing center locations

• HIV treatment locations• NIH-funded HIV Prevention 

and Vaccine Trials Sites

The Body Pro* www.thebodypro.com HIV resource for healthcare 

professionals; goal is to use the Internet to “lower barriers between healthcare professionals and their HIVinfected patients”

• Website• Guidelines

• Tel/e-mail/Web consultation

• Meetings and conferences

• Epidemiology• Prevention• OB-GYN• Psychosocial support and 

quality of life

• Research and clinical trials

• Palliative care

CDC Division of HIV/AIDS Prevention (DHAP)

www.cdc.gov/hiv/resources/guidelines/index.htmTel: 800-232-4636TTY: 800-232-6348

Government site that details clinical guidelines and information on prevention of HIV and hepatitis

• Website

• Guidelines

• Epidemiology

• Prevention• Occupational Exposure• Research and clinical trials

CDC National Prevention Information Network (CDC NPIN)

www.cdcnpin.orgTel: 404-679-3860,

800-458-5231M–F, 9 am–6 pm, EST

Government site that provides comprehensive reference, referral, and distribution service for information on HIV/AIDS, STIs, and TB; information specialists can assist in identifying appropriate resource materials

• Website• Guidelines• Print materials• Tel/e-mail/Web consultation

• Patient education

• Prevention

• STIs and TB

• Patient education

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

CDC Prevention with Positives (PWP)

www.cdc.gov/hiv/pwp/

index.htm

Government site that provides basic information about scope of PWP and PWP recommendations

• Website• Guidelines

• Implementation resources

• Prevention with positives• Reproductive and pregnancy 

issues

Community Programs for Clinical Research on AIDS (CPCRA)*

http://cpcra.s-3.com Network of research sites 

comprising community-based healthcare providers who offer their patients the opportunity to participate in research where they receive their health care

• Website • Research and clinical trials

HIV and Hepatitis www.hivandhepatitis.com Nonprofit agency that provides 

clinical information and resources on hepatitis and HIV

• Website

• Tel/e-mail/Web consultation

• Meetings and conferences

• Patient education

• Treatment

HIVdent www.hivdent.org Nonprofit coalition focused on 

providing information on dental manifestations of HIV/AIDS

• Website

• Guidelines• Meetings and conferences• Articles• Patient education

• Oral health• Treatment

• Research and clinical trials

HIV InSite hivinsite.ucsf.edu Information on medical 

treatment, prevention, and policy from the University of California at San Francisco (UCSF)

• Website

• Patient education

• Epidemiology• Treatment• Prevention• Peds/adolescents• Psychosocial support and 

quality of life

• Nutrition• Palliative care

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

HIV Medication Guide www.hivmedicationguide.com Pharma-sponsored website that 

provides drug information and software to assess for potential drug interactions

• Website• Patient education

• Treatment

HIV Medicine Association (HIVMA)*

www.hivma.org Professional association within 

the IDSA; guidelines and information on HIV treatment and care

• Website• Guidelines

• Print• Meetings and conferences

• Treatment• Quality improvement• Care in resource-poor settings

HRSA HIV/AIDS Bureau (HAB)

hab.hrsa.gov Federal agency that administers 

Ryan White HIV/AIDS Program; provides information supporting care of people with HIV; HRSA/HAB’s Special Projects of National Significance grant program tests innovative approaches to the care of people with HIV/AIDS

• Website

• Print

• Meetings and conferences

• Epidemiology• Treatment• Prevention• Peds/adolescents• OB-GYN• Adherence• Nutrition• Quality improvement• Palliative care• Care in resource-poor settings

Institute of Medicine (IOM) www.iom.edu Nonprofit independent 

organization that works outside of government to provide unbiased and authoritative advice to decision makers and the public

• Reports • Broad range of topics related 

to health and health care

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

International HIV/AIDS Alliance

www.aidsalliance.org Nonprofit organization that 

helps communities in developing countries play an effective role in the global response to AIDS

• Website• Print materials

• Prevention• Care in resource-poor settings• Youth• Stigma

Johns Hopkins University AIDS Service

www.hopkins-aids.eduhttp://www.hopkinsmedicine.org/gim/fellowship/moore_clinic.html

Detailed information on medical treatment and prevention from Johns Hopkins University AIDS Service

• Website• Print

• Tel/e-mail/Web consultation

• Meetings and conferences

• Treatment• Adherence• Research and clinical trials

National Alliance of State and Territorial AIDS Directors (NASTAD)

www.nastad.org/default.aspx Represents chief state health 

agency staff who have programmatic responsibility for administering HIV/AIDS and viral hepatitis healthcare, prevention, education, and supportive service programs funded by state and federal governments

• Website

• Policies

• Technical assistance

• Print

• Policy and advocacy

• Health care access

• Prevention

• Viral hepatitis

• HIV counseling and testing

National HIV/AIDS Clinicians’ Consultation Center

www.nccc.ucsf.edu/home/Warmline: 800-933-3413M–F, 6 am–5 pm, PSTPEPline: 888-448-4911 (24/7)Perinatal HIV Hotline: 888-448-8765

National toll-free hotline to counsel healthcare workers with job-related exposure to HIV, hepatitis, and other bloodborne pathogens; offers treating clinicians up-to-theminute advice on managing occupational exposures and answers other questions on topics related to HIV care

• Website

• Guidelines• Tel/e-mail/Web consultation

• Meetings and conferences

• Treatment• Peds/adolescents• Occupational exposure

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

NIAID Database for AntiHIV Compounds www.niaid.nih.gov/daids/dtpdb Tel: 301-496-5717

866-284-4107TDD: 800-877-8339M–F, 8:30 am–5 pm, EST

Government site housing computerized databases of chemical structures and biologic data on ARVs

• Website• Tel/e-mail/Web consultation

• Epidemiology

• Treatment• Prevention• Research and clinical trials

Caring Connections www.caringinfo.org/

Tel: 800-658-8898Multilingual Line: 877-658-8896

Program of the National Hospice and Palliative Care Organization that provides resources, education, advocacy, and a hotline on palliative care and end-of-life issues such as living wills

• Website• Print materials

• Tel/e-mail/Web consultation

• Patient education

• Peds/adolescents

• Psychosocial support and 

quality of life

• Palliative care

PEPFAR www.pepfar.gov Government site for the U.S. 

President’s Emergency Plan for AIDS Relief which provides global support to limitedresource countries for HIV prevention, care, and treatment

• Website

• Guidance

• Country operational plans

• PEPFAR reports

Population Council www.popcouncil.org

Tel: 212-339-0500877-339-0500

International organization; research and policy on reproductive health and family planning

• Website• Guidelines• Print materials

• Treatment• Peds/adolescents• Research and clinical trials

• Care in resource-poor settings

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

Reproductive Health Online (Reproline)

www.reproline.jhu.edu Information and training tools 

on reproductive health in resource-poor settings provided by Johns Hopkins Program for International Education in Gynecology and Obstretrics; information available in Spanish, French, Portuguese, and Russian

• Website• Guidelines

• Print materials• Tel/e-mail/Web consultation

• Meetings and conferences

• Prevention• OB-GYN• Psychosocial support and 

quality of life

Resource Center for Prevention with Persons Living with HIV

http://hivpwp.org/ Government initiative focused on 

persons living with HIV/AIDS to improve their individual health and reduce risk of transmission to others

• Website

• Podcasts

• Slides• Online training

• Webinars

• Linkage to care

• Retention• Risk screening and reduction• Partner services

• ART as prevention

• Adherence• STDs• Reproductive health care

• PMTCT

UNAIDS: Joint United Nations Programme on HIV/AIDS

www.unaids.orgTel:+41 22 791 36 66 (Switzerland)

International program; provides technical assistance and HIV/AIDS information to countries and communities

• Website• Guidelines

• Print• Patient education

• Epidemiology• Treatment• Psychosocial support and 

quality of life

• Substance abuse• Nutrition• TB

continued

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Table 15-1

Resources for Healthcare ProfessionalsName URL and/or Telephone 

Number

Source Types of Resources 

Available

Topics Covered

The Well Project www.thewellproject.com

Tel: 888-616-9355

Nonprofit organization developed and administered by HIV-positive women; Web portal for women living with HIV; treatment information, groups, organizational tools, slide sets, searchable clinical trials listings, and resource information

• Website• Guidelines

• Print• Tel/e-mail/Web consultation

• Meetings and conferences

• Patient education

• Treatment

• Prevention• Peds/adolescents• OB-GYN• Adherence• Substance abuse• Nutrition• Care in resource-poor settings

Women, Children, and HIV www.womenchildrenhiv.org Project of UCSF Center for HIV 

Infection; Information on HIV and pregnancy, prevention of perinatal HIV transmission, and pediatric care; global focus

• Website• Guidelines

• Print materials

• Treatment• Prevention• Peds/adolescents• OB-GYN• Psychosocial support and 

quality of life

• Nutrition• Palliative care

WHO HIV/AIDS Department

www.who.int/hiv/en Technical support for HIV/AIDS 

treatment and prevention

• Website

• Guidelines

• Print materials• Tel/e-mail/Web consultation

• Epidemiology

• Treatment• Peds/adolescents• OB-GYN• Nutrition

Notes: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix. All URLs were active as of September 2012.

*Must be member to access select information

continued

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Table 15-2

Resources for PatientsName URL and/or Telephone 

Number

Brief Description Resources Topics Covered

American Social Health Association

www.ashastd.org/Tel: 919-361-8400STI Resource Center Hotline: 919-361-8488,M–F, 8 am–6 pm EST

Answers to confidential inquiries about HIV/AIDS prevention, risks, testing, treatment, and other concerns; referrals provided

• Website• Print materials

• Tel/e-mail/Web consultation

• Meetings and conferences

• Prevention• General HIV information• Common illnesses associated 

with HIV

• Risk reduction

AVERTing HIV and AIDS www.avert.org/women-hivaids.htm An international HIV and AIDS charity based in the United 

Kingdom that works to avert HIV/AIDS through education, treatment, and care

• Website• Tel/e-mail/Web consultation

• Epidemiology

• Treatment• Prevention• Peds/adolescents• OB-GYN• Adherence• Psychosocial support and 

quality of life

• Nutrition• Occupational exposure• Palliative care

The Body www.thebody.com Comprehensive HIV information 

and resources • Website

• Tel/e-mail/Web consultation

• Epidemiology

• Treatment• Prevention• Psychosocial support and 

quality of life

• Nutrition• Palliative care

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Table 15-2

Resources for PatientsName URL and/or Telephone 

Number

Brief Description Resources Topics Covered

Canadian AIDS Treatment Information Exchange (CATIE)

www.catie.caTel: 416-203-7122800-263-1638

Comprehensive HIV information and resources on drugs, other medical treatments, and complementary therapies, among other topics; available in English and French.

• Website• Print materials

• Tel/e-mail/Web consultation

• Meetings and conferences

• Epidemiology• Treatment• Prevention• Adherence

Gay Men’s Health Crisis Women and Family Services (New York, NY)

www.gmhc.orgTel: 800-243-7692

Information and services for people with HIV/AIDS, including the Lesbian AIDS Project

• Website• Print materials

• Psychosocial support and 

quality of life

• Nutrition

Healthy Women www.healthywomen.org/

condition/hivaidsTel: 877-986-9472

Health information to educate, inform, and empower women to make smart health choices

• Website

• Tel/e-mail/Web consultation

• Treatment

• Prevention

National Association of People With AIDS (NAPWA)

www.napwa.orgTel: 240-247-0880866-846-9366

Advocacy, information, and support for people living with HIV/AIDS

• Website

• Print materials• Meetings and conferences

• Treatment• Prevention

New Mexico AIDS Infonet www.aidsinfonet.org Nontechnical fact sheets on 

treatment

• Website• Print materials

• Treatment• Prevention• Peds/adolescents• OB-GYN• Nutrition

continued

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Table 15-2

Resources for PatientsName URL and/or Telephone 

Number

Brief Description Resources Topics Covered

The Office on Women’s Health

http://womenshealth.gov/hivaids/Tel: 202-690-7650

Aims to improve the health and sense of well-being of all U.S. women and girls through innovative programs that focus on health and education

• Website• Tel/e-mail/Web consultation

• Treatment

• Prevention• Adherence• Psychosocial support and 

quality of life

• Care in resource-poor settings

Project Inform www.projectinform.org

Treatment hotline: 415-558-9051 800-822-7422M–F, 9 am–5 pm; Sat 10 am–4 pm, PST

Treatment Information and tools for living with HIV, including confidential treatment information by phone and Project Wise, a program focused on HIV/AIDS treatment information and advocacy for women

• Website• Print materials

• Tel/e-mail/Web consultation

• Meetings and conferences

• Treatment• Prevention• OB-GYN• Adherence• Nutrition• Care in resource-poor settings

San Francisco AIDS Foundation

www.sfaf.orgTel: 415-487-3000866-245-3424

Information about prevention, care, and experimental treatments

• Website

• Print materials

• Epidemiology

• Treatment• Prevention• Psychosocial support and 

quality of life

Women Alive www.women-alive.org

Tel: 323-965-1564

Organization by and for women living with HIV that offers local services in Los Angeles as well as Internet services

• Website• Guidelines• Print materials• Tel/e-mail/Web consultation

• Meetings

• Peds/adolescents• Psychosocial support and 

quality of life

• Research and clinical trials

• Care in resource-poor settings

continued

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546 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

Table 15-2

Resources for PatientsName URL and/or Telephone 

Number

Brief Description Resources Topics Covered

Women Organized to Respond to Lifethreatening Disease (WORLD)

www.womenhiv.orgTel: 510-986-0340M–F, 10 am–6 pm, PST

Organization in Oakland, CA, for women with HIV that provides peer advocacy, treatment education training, and retreats

• Website• Tel/e-mail/Web consultation

• Meetings

• Adherence• Care in resource-poor settings

Notes: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix. All URLs were active as of September 2012.

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Chapter 16:

International Perspectives

Stacie C. Stender, MSN, MSc ID, FNP-BC

Africa Region Technical Advisor, TB/HIV/ID, Jhpiego

Associate, Department of International Health

Johns Hopkins Bloomberg School of Public Health

Kelly Curran

Director, HIV and Infectious Diseases, Jhpiego

Associate, Department of International Health

Johns Hopkins Bloomberg School of Public Health

The authors declare no conflicts of interest

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Chapter 16 International Perspectives

Chapter 16 at a Glance

International Perspectives..................................................................................................................549

Factors That Influence Approaches to HIV Care in 

Low- to Middle-Income Countries............................................................................................550

Burden of Disease................................................................................................................................550

Barriers to Care.....................................................................................................................................552

Comorbidities............................................................................................................................................553

Different Interventions for Different Settings..............................................................554

Public Health Approach.................................................................................................................554

Different Prevention Interventions.......................................................................................555

Testing and HIV Diagnosis...........................................................................................................557

HIV Care and Treatment in Lower-Resource Settings.......................................557

Prevention of Mother-to-Child Transmission..............................................................557

Comprehensive Care.........................................................................................................................558

Antiretroviral Treatment.................................................................................................................560

Targeted Laboratory Testing....................................................................................................565

Conclusion...........................................................................................................................................................568

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International Perspectives

The primary focus of this guide is to provide a resource for HIV providers in 

the United States and other high-resource settings. At the same time, though, 

the global perspective should be considered, because the overwhelming 

majority of women with HIV live in low- and middle-income countries (LMICs). 

LMIC is a World Bank classification for countries with gross national income 

(GNI) less than $12,196 per capita in 2009; it excludes the 69 high-income 

countries with per capita GNI above this level.

Three-quarters of women and girls living with HIV are in sub-Saharan 

Africa, and half of them live in countries of southern Africa specifically. HIV 

prevalence among young women aged 15–24 years in sub-Saharan Africa 

(3.4%) is more than 5 times higher than the global average (0.6%) and more 

than 30 times higher than that of Western Europe (0.1%) (UNAIDS, Report on 

the Global AIDS Epidemic 2010, CDC, HIV/AIDS Surveillance Report 2009;19). 

Figure 16-1 illustrates the proportion of people living with HIV who are female 

and aged >15 years.

This chapter explores some of the factors unique to lower-resource settings 

and the consequent differences in the approach to HIV prevention, care, and 

treatment, many of which are driven by access or lack of access to human and 

financial resources.

Figure 16-1

Estimated Proportion of Women and Girls (>15 Years of Age) 

Living with HIV by Region

Source: Data from UNAIDS, Report on the Global AIDS Epidemic 2010. Available at http:// www.unaids.org/globalreport/global_report.htm. Accessed 9/9/2012.

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Factors That Influence Approaches to HIV Care in Low- to 

Middle-Income Countries

Factors that affect HIV care in a given country include the burden of disease, 

barriers to care, and prevalence and type of comorbidities.

Burden of Disease

HIV is a leading cause of death worldwide and the number one cause of death 

in Africa. The highest adult HIV prevalence worldwide is in Swaziland, where 

1 in 4 people between ages 15 and 49—and 42% of pregnant women—are 

living with HIV (UNAIDS, Report on the Global AIDS Epidemic 2010, p. 28). 

This extent of infection is in stark contrast to the United States, which has an 

estimated 0.6% adult prevalence. The global average prevalence is 0.8%, 

and many LMICs, including Indonesia, India, and Ecuador, have prevalence less 

than 0.5%. Even in sub-Saharan Africa, where the regional adult prevalence 

averages 5.0%, there is great variability among countries: Madagascar, Niger, 

and Senegal have rates similar to that of the United States, whereas Angola, 

Ghana, and Ethiopia have rates below 5%. Southern Africa is hardest hit by 

the epidemic: National adult prevalence rates there range from 12% to 26% 

(UNAIDS, Report on the Global AIDS Epidemic 2010).

Figure 16-2

Global Prevalence of HIV, 2009

Source: Data from UNAIDS, Report on the Global AIDS Epidemic 2010

Although most countries are on track to meet the 2015 UN Millennium 

Development Goal 5 target of reducing the maternal mortality ratio, defined 

as maternal death (the death of a woman while pregnant within 42 days of 

termination of pregnancy) per 100,000 live births, by 75% , five countries 

in southern Africa—where HIV prevalence is highest—have had increases in 

maternal deaths since 1990, largely attributable to HIV: Botswana (133%), 

Zimbabwe (102%), South Africa (80%), Swaziland (62%), and Lesotho (44%) 

(World Health Organization [WHO], Trends in Maternal Mortality 2010; Lancet

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2007;370:1311). Two countries, Botswana and South Africa, are upper/middle 

income countries, which mean they are in the same economic category as Brazil 

and the Russian Federation.

Epidemiology of transmission: The differences in HIV prevalence among 

countries and regions of the world reflect the differences in epidemiology 

of HIV transmission in those areas and the degree to which the epidemic 

is generalized or concentrated. In generalized epidemics, transmission is 

widespread in the heterosexual population, whereas in concentrated epidemics, 

transmission is confined mainly to people who engage in high-risk behaviors 

and general population prevalence is less than 1%. These differences 

in epidemiology have implications for prevention, care, and treatment 

interventions. Table 16-1 characterizes regional epidemics worldwide.

Table 16-1

Characteristics of Regional Epidemics

Region Description of Epidemic % of People With 

HIV >15 Years of

Age Who Are Women

Asia • No country has a generalized epidemic.

• HIV is concentrated among IDUs (16% 

are living with HIV), sex workers and 

their partners, and MSM.

34

Caribbean • Unprotected sex, especially paid sex, 

between men and women is driving 

transmission.

55

Central and 

South America • Main routes of transmission in this region 

are concentrated among MSM and IDUs.

• Brazil accounts for one-third of those 

infected.

35

Eastern 

Europe and 

Central Asia

• Epidemics continue to rise in this region, 

concentrated mainly among IDUs (25% 

are living with HIV) and sex workers and 

their partners.

49

Oceania • Papua New Guinea has the only 

generalized epidemic in the region.

• Unprotected sex is driving transmission.

46

Sub-Saharan 

Africa • The epidemic is stable or decreasing in 

most countries.

• The majority of transmission is due to 

unprotected heterosexual intercourse.

• Mother-to-child transmission during 

pregnancy, labor, or breastfeeding is 

also a major source of transmission.

60

Western 

and Central 

Europe 

and North 

America

• Unprotected sex between men and IDUs 

continues to dominate patterns of HIV 

transmission.

• Discrete geographic areas are affected, 

particularly urban coastal settings.

27

Note: All abbreviations are defined in the list of Abbreviations and Acronyms, p. ix

Sources: Adapted from UNAIDS, Report on the Global AIDS Epidemic 2010; CDC, HIV/

AIDS Surveillance Report 2009;19; and UN Millennium Development Goals Report 2010

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Barriers to Care

System factors: In many countries of the world, particularly LMICs, healthcare 

services are provided primarily by Ministries of Health or faith-based (mission) 

hospitals rather than by private-sector hospitals and clinicians (as in the United 

States). In those countries, various health system factors contribute to patients’ 

inability to access care:

• Political factors, which may include lack of government 

financial commitment to health, inadequate health facility 

coverage for the population, competing health priorities, 

and lack of universal health coverage or individual or group 

insurance schemes.

• Economic factors, such as poor or absent facility and 

transportation infrastructure, inadequate human resources, 

and poor pay for healthcare providers. In sub-Saharan 

Africa, healthcare workers must care for 2 of every 3 

people living with HIV globally, yet they represent only 3% 

of the world’s human resources for health (WHO, Global 

Tuberculosis Control 2010). Many healthcare workers in 

this region are themselves living with HIV, and most are in 

some way affected by the virus and have responsibilities to 

orphaned or ill family members.

• Geographic factors, such as physical barriers (e.g., 

impassable roads during rainy season).

• Organizational factors, such as lack of interpreters, negative 

attitudes among staff, inadequate staffing, and vertical and 

nonintegrated programs.

Patient factors: In countries that have functioning healthcare systems, access to 

services may be limited by patient factors that serve as barriers to care:

• Socioeconomic factors, such as extreme poverty with inability 

to pay for diagnostic tests, therapeutic interventions, or 

travel to clinic or hospital; and poor education and health 

literacy.

• Cultural factors, such as traditional practices, cultural and 

religious beliefs that influence health-seeking behavior, 

gender disparities, gender-based violence, and stigma 

related to HIV.

In adopting the 2001 Declaration of Commitment on HIV/AIDS (UN General 

Assembly Resolution S-26/2, 27 June 2001), UN member states agreed 

to systematically review and regularly report on their progress in realizing 

universal access to HIV prevention, treatment, care, and support by 2010. 

When widespread access to antiretroviral therapy (ART) began in 2004 

(UNAIDS, Report on the Global AIDS Epidemic 2010), it was considered a 

significant achievement given the health system challenges known to exist in 

most LMICs.

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Comorbidities

Comorbidities commonly associated with or affected by HIV in lower resource 

countries are often not the same as those seen in the United States, or they 

may have more significant implications for health because of inadequate 

resources for screening and treatment. In low-resource settings, common HIV 

co-infections include infections of significant public health consequence in the 

general population. This overlap may create competing health priorities and 

insufficiently coordinated resources where programs are not integrated. In the 

setting of HIV, increased rates of TB can result in greater risk of TB transmission 

to people who are not HIV infected. Where HPV infection is endemic, a lack of 

effective cervical cancer screening programs leads to increased risk of cervical 

cancer that may not be offset by adequate ART. Malaria and HIV have 

important interactions in both pregnant and nonpregnant women. All of these 

co-infections have significant implications for HIV prevention and care needs.

Tuberculosis: An estimated 380,000 HIV infected people died from TB 

in 2009. Among people living with HIV globally, TB is the leading cause 

of death. It is the third leading cause of death for HIV infected women of 

reproductive age. TB is the most common presenting opportunistic infection 

in the world, and it is the point of entry into HIV care for many patients, 

particularly in sub-Saharan Africa. South Africa alone accounts for 25% of 

all HIV-related TB infections globally (UNAIDS, Report on the Global AIDS 

Epidemic 2010; WHO/UNAIDS/UNICEF, Towards Universal Access Progress 

Report 2010).

HIV infection is the single greatest risk factor for the reactivation of latent 

mycobacterial infection (Tubercle Lung Dis 1992;73:311, Int J Tuberc Lung 

Dis 2000;4(2):9). Because of this relationship, there has been a dramatic 

increase in the incidence of TB in countries with a high prevalence of both 

TB and HIV (AIDS 1995;9:665). In the setting of HIV, TB is more likely to be 

smear negative or extrapulmonary, making diagnosis more challenging. HIV 

progression also appears to be increased in the setting of TB (J Acquir Immune 

Defic Syndr Hum Retrovirol 1998;19:361, AIDS 2001;15:143).

The rate of TB is approximately 10-fold higher in HIV infected pregnant 

women than in pregnant women who are not HIV infected, and TB–HIV 

co-infection increases maternal mortality. In some tertiary hospitals in South 

Africa, HIV–TB coinfection accounts for approximately 14% of all maternal 

mortality (AIDS 2001;15:1857). Results of a study from India indicate 

that HIV–TB coinfection in the mother was associated with a 3.4 increased 

probability of infant death with maternal HIV infection alone (Clin Infect Dis

2007;45:241).

Malaria: Malaria is a leading global cause of death and disability. Eightyfive percent of the 250 million cases and 91% of the 800,000 annual 

malaria deaths occur in Africa in areas where HIV prevalence is also elevated 

(Roll Back Malaria, Key facts, http://www.rollbackmalaria.org/keyfacts.

html; Wellcome Trust, Illustrated History of Tropical Diseases 1996;231). 

Moreover, the interaction of the two diseases may affect transmission, 

clinical manifestations, and treatment outcomes of both diseases. HIV impairs 

acquired immunity to malaria, and like other concomitant infections, malaria 

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can cause a transient increase in HIV viral load (Lancet 2000;356:1051, J 

Infect Dis 2005;192:984, Lancet 2005;365:233). In pregnancy, HIV infection 

increases malaria susceptibility and adverse outcomes; placental malaria is 

associated with increased risk of mother-to-child transmission of HIV (AIDS

2003;17:2539).

Human papillomavirus: HPV is the most common sexually transmitted 

pathogen worldwide and is the major etiologic agent of cervical cancer. 

In women in most developing countries, cervical cancer is the most common 

cancer and the most common cause of cancer death (Cervical Cancer Action, 

Progress in Cervical Cancer Prevention: The CCA Report Card 2011); it kills 

nearly 250,000 women per year. HIV is associated with higher incidence 

and prevalence and longer persistence of HPV; with a greater likelihood 

of oncogenic HPV subtypes; and with increased frequency and severity of 

cervical dysplasia, a precancerous condition. Invasive cervical cancer is an 

AIDS-defining illness, and rates of cervical cancer may be increased in the 

setting of HIV, especially if screening is not adequate.

Different Interventions for Different Settings

Public Health Approach

A public health approach to HIV prevention, care, and treatment is essential in 

LMICs, where financial constraints, competing health priorities, and shortages 

of healthcare providers are common. This requirement is particularly true for 

areas with generalized epidemics. In countries with concentrated epidemics, 

targeted approaches are essential for efficient use of scarce resources.

Decentralized services for universal access: The Declaration of AlmaAta, accepted by WHO member countries, emphasizes the importance of 

primary healthcare for equitable access to health (Declaration of Alma-Ata

1978). Universal access to HIV services requires decentralized services at the 

primary care and community levels. Essential to expansion of services for HIV 

prevention, care, and treatment in many LMICs is the allocation of clinical tasks 

to cadres of healthcare workers, who may include the following:

• Lay workers who are trained to provide HIV counseling 

and testing

• HIV infected women who have gone through prevention of 

mother-to-child transmission (PMTCT) programs themselves 

and are then trained to provide peer counseling to other 

HIV infected pregnant women

• Nurses and clinical officers who are trained to initiate and 

manage ART

• Nurses who perform voluntary medical male circumcision

• High school graduates who are trained to perform smear 

microscopy to diagnose TB.

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In LMICs, nongovernmental organizations (NGOs) are intimately involved in 

the provision of HIV prevention, care, and treatment services. By contrast, in 

well-resourced countries, HIV infected women receive care in a formal public or 

private healthcare system.

The United States is the largest donor to global AIDS response efforts. Through 

the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund 

to Fight AIDS, Tuberculosis and Malaria (in partnership with other high-income 

countries), the United States provides national governments and NGOs in LMICs 

with support to expand access to services, without which HIV incidence and 

mortality would continue to increase in many regions.

Different Prevention Interventions

For every two people who start ART each year, five are newly infected 

with HIV. In 2008, 72% of all new HIV infections occurred in sub-Saharan 

Africa (WHO, Guidance on provider-initiated HIV testing and counselling in 

health facilities 2007). Of the 1.4 million pregnant women in need of HIV 

care, treatment, and support, including options for PMTCT, 91% are in subSaharan Africa (WHO/UNAIDS/UNICEF, Towards Universal Access Progress 

Report 2010).

Targeted prevention: HIV prevention efforts should be evidence based and 

target the common drivers of transmission in different epidemic settings. 

In the words of UNAIDS, “know your epidemic and respond accordingly.” 

Knowing one’s epidemic often means knowing where the last 1,000 new HIV 

infections occurred, because the next 1,000 infections are likely to occur in 

similar populations. In concentrated epidemic settings, new HIV infections 

disproportionately affect “most-at-risk” populations, including sex workers, 

MSM, and IDUs. In hyperendemic settings such as southern Africa, the majority 

of new infections occur within the general population, often within stable 

partnerships (UNAIDS, HIV Prevention Toolkit, http://hivpreventiontoolkit.unaids.

org/Knowledge_Epidemic.aspx). In several African countries, 50% or more 

of HIV infected people may be in serodiscordant relationships (Reprod Health 

Matters 2008;16:151, Lancet Infect Dis 2010;10:770).

Combination prevention: Combination prevention uses a mixture of behavioral, 

biomedical, and structural interventions and targets the prevention needs of 

different populations on the basis of epidemiologic and demographic data 

(MMWR 2006;55 RR14:1). Successful prevention efforts effect change on 

multiple levels—individual, organizational, and societal—and provide mutually 

reinforcing messages and interventions (USAID/AIDSTAR-One, Combination 

Approaches: An Overview of Combination Prevention, http://www.aidstar-one.

com/focus_areas/prevention/pkb/combination_approaches/overview_

combination_prevention).

Behavioral prevention: Behavioral prevention includes the ABC approach—

Abstinence, Be faithful (partner reduction), and Condom use (and promotion). 

One challenge with behavioral approaches is that many women in LMICs find 

these prevention strategies difficult to use. For instance, in settings where a 

woman’s status in the family and the community is determined by the number 

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of children she bears, condom use may be prohibited because it prevents 

pregnancy. And in many cases, women have little or no control over the conduct 

of sexual relationships, particularly in the context of stable partnerships.

Biomedical prevention: Biomedical prevention includes medical approaches 

to block infection, decrease infectiousness, or reduce risk of infection. One 

such approach is voluntary male circumcision. Following issuance of WHO 

and UNAIDS recommendations, this approach is now being scaled up 

widely in Southern and Eastern Africa , where it has the potential to avert 

4.1 million new HIV infections by 2025 if coverage rapidly reaches 80% 

(USAID Health Policy Initiative, Potential Cost and Impact of Expanding 

Male Circumcision in 14 African Countries 2009). As described in Chapter 

3, Prevention, ARV-based vaginal microbicides are showing promise as a 

woman-directed method of prevention (Science 2010; 329 :1168). Data 

from HPTN 052, a randomized clinical trial designed to evaluate ART for 

prevention of sexual transmission among serodiscordant couples, indicates 

that earlier initiation of ART (at CD4+ cell counts of 350–550/mm3) 

reduced HIV transmission to the uninfected partner by 96% as compared 

with people who initiated ART at lower CD4+ cell counts (N Engl J Med

2011; 365:493).

Results of several PrEP clinical trials using either daily TDF or TDF/FTC in at 

risk HIV-uninfected individuals are now available and show mixed results (see 

Chapter 3: Prevention of HIV Infection). It is likely that adherence was a key 

factor in the discrepant results of these studies (AIDS 2012;26(7):F13). In July 

2012 the FDA approved a label indication for TDF/FTC for reduction of risk 

for sexual acquisition of HIV infection among adults, including heterosexual 

women. In August 2012 the CDC issued interim guidance for clinicians 

considering the use of PrEP for HIV prevention in heterosexually active 

adults, particularly those with known HIV-infected partners (MMWR 2012; 

61(31):586):1).

These studies and the HPTN 052 results have major implications for the use 

of antiretroviral agents for prevention, particularly among serodiscordant 

couples, and especially for those who wish to conceive or are unable 

or unwilling to use safer sexual practices. These results may also have 

implications for prevention in the setting of generalized epidemics or among 

high-risk groups in concentrated epidemic settings.

Structural prevention: Structural prevention takes into account social, 

political, and economic factors that contribute to individual risk and 

vulnerability. A recent study from Malawi found that paying school fees 

for adolescent girls and providing the girls and their families with a small 

amount of discretionary income (as little as $4 USD per month) reduced 

HIV acquisition by 50% and herpes simplex virus-2 (HSV-2) acquisition by 

75% among schoolgoing adolescent girls, who were less likely to engage 

in transactional sex (World Bank, A cash transfer program reduces HIV 

infections among adolescent girls, http://siteresources.worldbank.org/DEC/

Resources/HIVExeSummary(Malawi).pdf).

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Testing and HIV Diagnosis

Provider-initiated testing and counseling for HIV, also known as opt-out 

screening, in which a patient is notified that testing will be performed unless 

he or she declines, has been recommended by WHO since 2007 for countries 

with generalized epidemics (WHO, Guidance on Provider-Initiated HIV Testing 

and Counselling in Health Facilities 2007). However, implementation has been 

less than ideal in most settings. For example, in 2008, only 22% of TB patients 

globally knew their HIV status, despite the clear indication for HIV testing 

that TB provides in most settings, given high co-infection rates (WHO, Towards 

Universal Access Progress Report 2010).

Rapid tests: The use of rapid diagnostic tests for HIV, through either parallel or 

serial testing, is the mainstay of laboratory diagnosis of HIV in most resourcelimited settings, given limited laboratory capacity. Selection of tests in any 

setting depends on available resources and prevalence of HIV types 1 and 

2, which will have an effect on negative and positive predictive values. In 

addition to the FDA-approved rapid tests described in Chapter 3, several 

other rapid tests are available internationally.

Diagnosis in infants: With regard to diagnosis of HIV in infants, DNA PCR 

is used in resource-limited settings if laboratory capacity is sufficient. Where 

climate, transport of specimens, and laboratory capacity are especially 

challenging, dry blood spot samples are collected. Because breastfeeding 

is the primary infant feeding choice of women in most LMICs, HIV testing is 

conducted again 6 weeks after cessation of breastfeeding to avoid the risk of 

breast milk transmission.

HIV Care and Treatment in Lower-Resource Settings

The approach to HIV care and treatment in resource-limited settings is 

substantially different from the approach in the United States, which 

emphasizes use of state-of-the-art medications and laboratory testing. Care 

and treatment in lower resource settings, however, emphasize PMTCT and 

treatment of co-occurring infections such as malaria, TB, and cervical cancer 

(HPV). Availability of other types of care, including ART, varies from country to 

country. Laboratory tests for CD4+, viral load, and viral resistance often are 

not an option.

Prevention of Mother-to-Child Transmission

The international community has set a goal of virtual elimination of motherto-child transmission of HIV by 2015. However, in 2009, only half of HIV 

infected pregnant women in LMICs received any antiretrovirals (ARVs) for 

PMTCT (53%). One country, Nigeria, accounts for one-third of this gap 

between women in need of ARVs for PMTCT and those who actually receive 

any intervention, whether single-dose nevirapine, AZT + single dose nevirapine, 

or HAART. (UNAIDS, Report on the Global AIDS Epidemic 2010; WHO, Towards 

Universal Access Progress Report 2010; UN, Millennium Development Goals 

Report 2010).

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It is estimated that half of HIV infected pregnant women have CD4+ cell 

counts <350/mm3 and require ARVs for their own health. Yet, in 59 LMICs that 

reported in 2009, only 15% of women who received any ARVs received highly 

active antiretroviral therapy (HAART) as treatment (UNAIDS, Report on the 

Global AIDS Epidemic 2010; WHO, Towards Universal Access Progress Report

2010, AIDS 2010;24: 1374; J Acquir Immune Defic Syndr 2010;55:404; 

WHO Guidelines on HIV and Infant Feeding 2010).

Care and treatment of HIV infected women, irrespective of pregnancy status, 

must take priority if universal access to care and treatment is to be achieved. 

Although 80% of UN member states reported the percentage of adults and 

children receiving ART and 70% reported on percentage of HIV infected 

pregnant women who received ARVs to reduce the risk of mother-to-child 

transmission in 2009, few were able to report on whether pregnant women 

were receiving ARVs for treatment rather than prevention. Even fewer were 

able to report on the impact of PMTCT interventions.

In April 2012, WHO endorsed a new option for PMTCT known as Option 

B+. This involves use of a single universal regimen to both treat HIVinfected pregnant women and for PMTCT and to continue this therapy 

for life, regardless of CD4+ cell count. The strategic advantages of this 

approach include further simplification of regimen and service delivery 

and harmonization with ART programs; protection against MTCT in future 

pregnancies; prevention against sexual transmission to HIV serodiscordant 

partners; and avoidance of treatment interruption between pregnancies. 

Numerous countries are now adopting this approach, although systems and 

support requirements need careful assessment and outcomes after program 

implementation need evaluation. (WHO, Programmatic Update-Use of 

antiretroviral drugs for treating pregnant women and preventing HIV infection 

in infants. April 2012 (http://www.who.int/hiv/PMTCT_update.pdf)

With regard to choices for infant feeding, although replacement feeding 

undoubtedly prevents postnatal transmission, in LMICs it has been associated 

with increased risk of death from other causes. Therefore, in 2010, WHO 

infant feeding recommendations changed to include the key principle that 

infant feeding choices for HIV prevention must be balanced with protection 

from other causes of child mortality (WHO, Guidelines on HIV and Infant 

Feeding 2010). In most low-resource settings, breastfeeding has significant 

benefits that outweigh risk of HIV transmission: It provides ideal infant nutrition 

in the first 6 months of life; reduces infant morbidity and mortality; delays 

return of fertility with exclusive breastfeeding, promoting child spacing and 

maternal recovery from blood loss; and is low cost and culturally acceptable 

(Lancet 2000;355:451).

Comprehensive Care

Care and treatment of people living with HIV should address the needs of the 

patient as an individual and as a member of a family; however, the approach 

to care and treatment in resource-limited settings is substantially different 

from the approach in the U.S. Comprehensive packages of HIV care vary 

across countries and depend on resources available and prevalent diseases. 

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For example, in Africa, the package of care may include insecticide-treated 

nets for the prevention of transmission of malaria by mosquito vectors and 

safe water vessels and chlorine for the prevention of water-borne diseases, in 

addition to condoms and cotrimoxazole.

Tuberculosis: The dual epidemics of TB and HIV require specific interventions 

to reduce transmission of the bacilli and prevent progression from TB infection 

to disease. This approach is particularly the case in sub-Saharan Africa, where 

up to 80% of patients diagnosed with TB are co-infected with HIV. Essential 

components of care for people living with HIV in such areas include a high 

index of suspicion combined with isoniazid preventive therapy, respiratory 

infection prevention and control, and prompt diagnosis and treatment of 

TB (intensified case finding). TB symptom screening at each patient visit is 

becoming common in settings of co-epidemics, a situation not applicable to the 

United States, where incidence of TB is significantly lower.

Malaria: HIV infected people are at increased risk of severe or complicated 

malaria, depending on the malaria transmission setting, and therefore have an 

even greater need for malaria prevention and control measures. Insecticidetreated bed nets, confirmed diagnosis (particularly as rapid diagnostic tests 

are more readily available), and appropriate treatment should be afforded 

to everyone, regardless of HIV status, but are particularly important for those 

who are HIV infected. The recommended intermittent preventive therapy for 

malaria (i.e., 2 to 3 doses of sulfadoxine–pyrimethamine during pregnancy for 

women in malaria-endemic areas) is not given to HIV infected women taking 

cotrimoxazole, given the similar effects of the two sulfa drugs (WHO, Malaria 

and HIV Interactions and Their Implications for Public Health Policy 2004).

Cervical cancer: The most effective approach for cervical cancer control 

is cervical screening. Pap smear with adjunctive high-risk HPV testing is 

the standard of care in the United States and other high-income countries, 

but in LMICs, lack of adequate financing, healthcare infrastructure, human 

resources, and capacity to follow up often make such screening unavailable. 

Visual inspection with acetic acid (VIA) is considered safe and acceptable, is 

inexpensive, and provides results immediately, thereby allowing for prompt 

treatment with cryotherapy or loop electrosurgical excisional procedure (LEEP) 

or referral for more suspicious lesions. Implementation of this low-tech screening 

procedure is expanding across many LMICs in HIV care settings. Compared 

with Pap smear, VIA generally has higher sensitivity but lower specificity, and 

it has high negative predictive value but low positive predictive value (Gynecol 

Oncol 2010;1793, J Obstet Gynaecol 2008;28:638). Results of a cluster 

randomized trial in India comprising approximately 31,000 women receiving 

VIA and a similar number of controls indicated the following: VIA+ women 

received cryotherapy at the same visit, and VIA was associated with a 24% 

reduction in Stage 2 or higher invasive cervical cancer and a 35% reduction in 

cervical cancer mortality (Lancet 2007;370:398).

In general, HPV DNA testing appears to be more objective and reproducible 

and has higher sensitivity than VIA. In another cluster randomized trial in India, 

HPV testing was compared with VIA, cytology, and standard of care (no 

screening) in >31,000 women in each arm and with 8 years follow-up. HPV 

testing was associated with 50% reduction in detection of advanced cervical 

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cancer and cervical cancer deaths compared with women with no screening. 

No significant differences were found between women screened with VIA or 

cytology and standard-of-care participants (New Engl J Med 2009;360:1385).

More recently, an HPV DNA test has been adapted for low-resource settings 

and is being field tested; it can detect 14 high-risk HPV types, and results are 

available within 2 hours using basic laboratory facilities. However, cost may 

be a significant barrier. It is likely that more effective screening strategies 

will utilize both HPV testing and VIA, possibly using one technique as an 

initial screen with triage of positive results to the second technique. PEPFAR 

is providing funding to implement use of non-cytology-based screening 

techniques in HIV programs.

Antiretroviral Treatment

Unmet goals: The international community target of achieving at least 80% 

ART coverage for treatment-eligible patients by 2010 has not been met, and it 

is not likely to be met by the renewed goal of 2015. By 2009, of the people 

who needed HIV treatment, only 19% in Eastern Asia , 25% in Western and 

Central Africa, 41% in Eastern and Southern Africa, and 57% in Southeast 

Asia and Oceania had access to ART. However, these percentages represent 

significant progress, because only 2% of all eligible people were receiving 

therapy in 2002. Eight LMICs—Botswana, Cambodia, Croatia, Cuba, Guyana, 

Oman, Romania, and Rwanda—achieved universal access by December 2009, 

and currently, more than 5 million people are receiving these life-saving drugs 

(UNAIDS Global Report 2010, WHO Towards Universal Access Progress Report

2010, UN Millennium Development Goals Report 2010).

Eligibility: In 2010, the WHO HIV treatment guidelines were changed to 

recommend earlier initiation of ART (from CD4+ cell count <200/mm3 to 

CD4+ cell count <350/mm3) irrespective of clinical symptoms and WHO 

Clinical Stage 3 and 4, including TB, irrespective of CD4+ cell count. This 

change increases the estimated number of patients eligible for ART from 10 

million to 15 million (UNAIDS, Report on the Global AIDS Epidemic 2010; WHO, 

Towards Universal Access Progress Report 2010).

Challenges: Although six classes of drugs and more than 20 FDA-approved 

ARVs are available for use in the United States, only three classes of drugs 

are widely available for use in the developing world, and choices within those 

classes are limited, largely related to cost. Standardized first-line and secondline treatment regimens are generally recommended. Common challenges of 

ARV provision in many countries include the following:

• Limited availability or accessibility of drug alternatives 

when drug toxicity or failure occurs

• Refrigeration requirement for some formulations where 

electricity and refrigeration are not widely available

• Co-treatment with TB and the challenge of drug interactions 

between rifampicin and nevirapine and protease inhibitors

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• Limited ability to evaluate and manage adverse effects 

related to treatment (e.g., hyperlactatemia, lactic acidosis 

related to d4T)

• Stock-outs: More than one-third (38%) of countries reported 

at least one stock-out of ARVs (i.e., drug not available 

at the service delivery point) procured centrally in health 

facilities in 2009 (WHO, Towards Universal Access Progress 

Report 2010)

• Adherence concerns related to several factors:

- Stigma of HIV diagnosis, which is often greater in these 

settings and may affect willingness to take drugs on a 

regular schedule

- Sharing of drugs with other infected family members

- Improvement in symptoms, weight gain, etc., which may be 

interpreted as a signal that treatment is no longer needed

• Limited number of healthcare providers in general and, in 

particular, few who are able to prescribe ART

• Inadequate training and mentorship in prescribing ART

• Inadequate availability of referral and consultative services.

Cost: The cost of ART has dropped substantially in the past 10 years, in large 

part because of pressure from international groups and greater availability of 

generic formulations, including fixed-dose combinations.

WHO guidelines reserve protease inhibitors for second-line treatment, 

because of cost as well as other considerations (e.g., storage requirements, 

more extensive drug interactions). The weighted median costs of second-line 

regimens that include protease inhibitors are 10- to 40-fold greater than the 

least expensive first-line regimen, d4T/3TC/NVP (WHO/UNAIDS/UNICEF, 

Towards Universal Access Progress Report 2010).

In 2004, d4T was changed from a preferred to an alternative drug for 

treatment of HIV-1 by the U.S. Department of Health and Human Services 

(HHS) because of increasing reports of associated toxicities (HHS, Guidelines 

for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, 

2004), yet in LMICs, it has been the backbone of ART in combination with 

3TC since the introduction of ARVs. The most common first-line regimen in the 

59 LMIC countries evaluated in 2009 (excluding the Americas region) were 

d4T/3TC/NVP (38.1%), d4T/3TC/EFV (21.5%), AZT/3TC/NVP (18.9%) and 

AZT/3TC/EFV (12.6%). However, as of 2010, WHO no longer recommends 

d4T in the first-line regimen as a result of drug toxicity (hyperlactatemia 

affects up to 5% of those taking d4T), and many governments are currently 

phasing out the use of the drug entirely (WHO, Antiretroviral Therapy for HIV 

Infection in Adults and Adolescents 2010). Table 2 presents a comparison of 

HIV prevention, care, and treatment in the United States and LMICs.

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Table 16-2

Comparison of Recommended HIV Prevention, Care, and Treatment 

in the United States and in Low- and Middle-Income Countries

Intervention United States International (LMICs)

Primary HIV 

prevention • Condoms (male and female)

• Reduced number of partners

• STI prevention/screening/

treatment

• Harm reduction for IDUs

• Drug abuse treatment

• PEP

• ART as prevention

• Condoms (male and female)

• Voluntary male medical 

circumcision

• Reduced number of partners

• STI prevention/screening/

treatment

• PEP

• ART as prevention

HIV testing • Opt-out testing recommended

• Reactive rapid or conventional 

screening test, with confirmation 

by supplemental antibody test 

(e.g., Western blot)

• Opt-out testing recommended 

in regions with generalized 

epidemics

• Serial or parallel rapid tests 

for screening and confirmation

STI screening 

in pregnancy • HIV, syphilis, HbsAg, C. 

trachomatis, N. gonorrhoea, 

and trichomoniasis

• HCV in high-risk women

• HIV and syphilis

Cervical cancer 

screening 

and 

prevention

• Year 1, cytology x2; annually 

thereafter if normal

• Colposcopy if any abnormal 

Pap smear

• Excisional treatment with LEEP 

or cervical conization for highgrade lesions

• HPV vaccine recommended for 

primary prevention

• Pap smear where available, 

but access is extremely limited 

Alternatives include VIA; 

cryotherapy or LEEP can be 

performed at same visit if VIA 

is abnormal

• HPV testing an option if rapid 

test available and affordable

• HPV vaccine largely 

unavailable due to cost

Vaccinations 

for primary 

prevention

• HPV recommended for 

children and adolescents 

irrespective of HIV status

• HBV, HAV, pneumococcal, 

and influenza vaccines 

recommended

• HBV recommended if 

serological testing is available

• Influenza vaccination where 

available and feasible

Other 

prevention • Primary prevention of several 

opportunistic infections, on the 

basis of CD4+ cell count:

- PCP (CD4+ cell count 

<200/mm3): TMP–SMX

- Toxoplasmosis (CD4+ cell 

count <100/mm3):TMP–SMX

- Disseminated MAC disease 

(CD4+ cell count<50/mm3): 

azithromycin

- TB (test for (+) latent TB and/or close contact with 

active TB, if active TB ruled 

out): isoniazid + pyridoxine

• TMP–SMX decreases clinical 

malaria in areas of stable 

malaria transmission

• Isoniazid for HIV-infected 

persons with unknown or (+) 

TB skin test, once active TB 

excluded

• Sulfadoxine–pyrimethamine 

during pregnancy for women 

in malaria-endemic areas 

(this is not needed of woman 

already on cotrimoxazole)

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Table 16-2

Comparison of Recommended HIV Prevention, Care, and Treatment 

in the United States and in Low- and Middle-Income Countries

Intervention United States International (LMICs)

STI screening 

and 

treatment

• Annual screening for HIV, 

syphilis, chlamydia, gonorrhea, 

and trichomoniasis

• Treatment widely available 

and based on etiologic 

diagnosis

• Passive case finding, with 

syndromic management.

• Antivirals for HSV not widely 

available

HIV 

assessment 

at diagnosis

• CDC clinical staging

• CD4+ cell count

• HIV viral load

• HIV drug-resistance testing 

• WHO clinical staging

• CD4+ cell count if available

Initiation of 

ART • ART recommended for all 

with HIV

- Strong recommendation: 

CD4+ cell count <200–500 

cells/μl

- Moderate recommendation: 

CD4+ cell count >500 

cells/μl

• ARV resistance testing prior to 

initiation

• Screen for HLA-B5701 before 

starting ABC

• Co-receptor tropism assay 

before starting CCR5 inhibitor

• CD4+ cell count <350/mm3

• WHO Clinical Stage 3 or 4 

irrespective of CD4+ cell count 

PMTCT: 

maternal 

interventions

• HAART for all, irrespective of CD4+ cell count or signs/

symptoms

• Cesarean delivery if viral load >1,000 c/mL at 36 weeks

• Monitor viral load and CD4+ 

cell count in pregnancy

• HAART if CD4+ cell count 

≤350/mm3 or WHO Clinical 

Stage 3 or 4

• If CD4+ cell count >350/mm3, then choose option A or B:

- Option A: AZT beginning at 

14 weeks + single dose NVP 

at onset of labor + AZT/3TC 

in labor and for 7 days 

postpartum or

- Option B: triple ARV prophylaxis with AZT/3TC/

LPV/r or AZT/3TC/

ABC or AZT/3TC/EFV 

or TDF/3TC(FTC)/EFV 

beginning at 14 weeks and 

continuing until delivery or, if 

breastfeeding, until 1 week 

after complete cessation

- Option B+: triple ARVs with TDF/3TC/FTC/EFV, starting 

as soon as diagnosed and 

continued for life

PMTCT: ART 

preferred/

alternative 

drugs/

regimen

• NRTIs: AZT, 3TC, ABC, FTC, 

TDF

• NNRTIs: NVP; EFV

• PIs: LPV/r, ATV, SQV/r; DRV/r

• INSTI: RAL

• AZT/3TC/NVP or AZT/3TC/ EFV or TDF/3TC(FTC)/NVP or 

TDF/3TC(FTC)/EFV

continued

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564 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

Table 16-2

Comparison of Recommended HIV Prevention, Care, and Treatment 

in the United States and in Low- and Middle-Income Countries

Intervention United States International (LMICs)

PMTCT: infant 

interventions • Avoid breastfeeding

• Infant prophylaxis with AZT for 

6 weeks

• When the mother has not 

received antepartum ARV 

drugs: add 3 doses of NVP in 

the first week of life

• DNA–PCR or RNA assay at 

14–21 days, 2–3 months and 

4–6 months; confirm positive 

test on separate sample to 

diagnose HIV

• Exclusive breastfeeding for 6 

months

• Infant prophylaxis if mother 

is on HAART: AZT or NVP for 

4-6 weeks

• If mother is on ARV 

prophylaxis only:

Option A:

- Breastfeeding: daily NVP 

until 1 week after all 

exposure to breast milk 

(minimum 4–6 weeks if 

breastfeeding stops before 

6 weeks)

- Nonbreastfeeding: daily 

NVP or sd-NVP at birth and 

twice daily AZT for 4–6 

weeks

• Mother on ARV prophylaxis 

only: Maternal Option B:

breastfeeding or replacement 

feeding:

- Daily NVP or twice-daily AZT 

for 4–6 weeks

• DNA–PCR at 6 weeks (if 

available); otherwise, antibody 

testing at 18 months

Preferred 

first-line ART 

regimens

• EFV/TDF/FTC or ATV/r/TDF/

FTC or DRV/r/TDF/FTC or RAL/TDF/FTC

• AZT or TDF +3TC (or FTC) + 

EFV or NVP

• Move toward AZT or TDFbased regimens from d4T, 

when d4T regimens have been 

used as principal option

TB/HIV 

co-infection • Preferred: rifampin plus EFVbased ART

• Rifabutin is preferred 

rifamycin in PI-based regimen 

needed, dose reduction of 

rifabutin indicated

• EFV-based regimen 

(alternatives if EFV not 

tolerated: NVP or triple NRTI)

• Rifampicin is in first-line TB 

regimen: co-administration 

with PI-based regimen not 

recommended because of 

drug interactions

Notes: If an intervention is included in the U.S. column but not in the international guidelines 

column, then that intervention is not recommended by WHO. All abbreviations are defined 

in the list of Abbreviations and Acronyms, p. ix.

Sources: WHO, Antiretroviral Therapy for HIV Infection in Adults and Adolescents 2010; 

ACOG, Practice Bulletin: Clinical Management Guidelines for Obstetrician–Gynecologists

2010;117; MMWR 2010;59 RR12 ;1; WHO, Guidelines for the Management of Sexually 

Transmitted Infections 2003; WHO, Essential Prevention and Care Interventions for Adults 

and Adolescents Living With HIV in Resource-Limited Settings 2008; WHO, Antiretroviral 

Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants 2010; WHO, 

Cervical Cancer Screening in Developing Countries 2002

continued

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Targeted Laboratory Testing

Country-level guidelines: In most LMICs, the WHO guidelines are adapted at 

the country level to guide provision of HIV services; in the United States and 

other high-resource countries, guidelines for care are developed nationally 

and updated regularly. Guidelines vary from country to country, largely as a 

result of differential resources. Access to resistance testing in LMICs is virtually 

nonexistent, in stark contrast to the United States, where HIV resistance testing 

is widely available and implemented at patient entry into care and with 

treatment failure. Even viral load testing is not widely available in LMICs, 

where one test may cost more than the country’s per capita health expenditure 

(WHO, Patterns of Global Health Expenditures: Results for 191 Countries 2002).

Efficient use of resources: In the United States, laboratory tests are considered 

essential elements of HIV care because they assist clinicians in determining the 

optimal treatment regimen. However, in LMICs, considerations of cost, efficient 

use of resources, and inadequate laboratory infrastructure have precluded 

their widespread use. In addition to a country-level HIV drug resistance and 

assessment strategy, WHO recommends targeted use of viral load testing to 

reduce the risk of resistance (WHO, Antiretroviral Therapy for HIV Infection in 

Adults and Adolescents 2010)

It has been established that routine laboratory monitoring for toxic effects, such 

as hematology and liver function tests, are not necessary for safe delivery of 

ART; however, CD4+ cell count monitoring is important in determining eligibility 

for treatment and deciding when a switch to second-line treatment might be 

necessary (Lancet 2010; 375: 123). Now that eligibility includes anyone with 

CD4+ cell count <350/mm3, a lack of access to CD4+ testing will exclude 

many patients who may need HAART but do not have WHO Clinical Stage 3 

or 4 disease.

Managing ART: The WHO guiding principles for ART management include 

the following:

• Laboratory monitoring is not a prerequisite for initiation 

of ART.

• CD4+ cell count and viral load testing are not essential 

for monitoring.

• Laboratory monitoring should be symptom directed.

• If resources allow, viral load should be used to confirm 

treatment failure suspected on the basis of immunological or 

clinical criteria.

• If resources allow, viral load should be measured every 6 

months to detect failure earlier (WHO, Antiretroviral Therapy 

for HIV Infection in Adults and Adolescents 2010).

Table 16-3 shows the divergence between U.S. and WHO 

recommendations for laboratory monitoring. In many LMICs, even 

CD4+ cell count, the only recommended test (all others are considered 

desirable), is not widely available.

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Table 16-3

Minimum Recommended Laboratory Monitoring Schedules

Time U.S. Guidelines: HHS 2011 International Guidelines: 

WHO 2010

At diagnosis 

or entry into 

care

• CD4+ cell count

• HIV viral load

• Resistance testing

• HBV and HCV serology

• Basic chemistry

• ALT, AST, total and direct 

bilirubin

• CBC with differential

• Fasting lipid profile

• Fasting glucose or hemoglobin 

A1C

• Urinalysis

• CD4+ cell count

• HBsAg

Routine care when not on 

ART

• CD4+ cell count every 3–6 mo.

• HIV viral load every 3–6 mo.

• Basic chemistry every 6–12 mo.

• ALT, AST, total and total 

bilirubin every 6–12 mo.

• CBC with differential every 

3–6 mo.

• Fasting lipid profile v 12 mo.

• Fasting glucose or hemoglobin 

A1C every 12 mo.

• CD4+ cell count every 6 

months

At initiation of 

ART or switch • CD4+ cell count

• HIV viral load

• Resistance testing

• HLA–B*5701 testing if 

considering ABC

• Tropism testing if considering 

CCR5 antagonist

• HBV serology repeated if not 

immune at baseline

• Basic chemistry

• ALT, AST, total and total 

bilirubin

• CBC with differential

• Fasting lipid profile

• Fasting glucose or hemoglobin 

A1C

• Urinalysis

• Pregnancy test if starting EFV

• CD4+ cell count

• Creatinine clearance if starting 

TDF and high risk1

• ALT if starting NVP and high 

risk2

• Hb if starting AZT and low 

CD4+ cell count or BMI

2-8 weeks 

after ART 

initiation or 

switch

• HIV viral load

• Basic chemistry

• ALT, AST, total and direct 

bilirubin

• CBC with differential if on AZT

• Fasting lipid profile

• ALT and AST at 2 and 4 weeks 

for women with CD4+ cell 

count >250/mm3 and NVP

• ALT and AST at 4 weeks if 

HCV or HBV co-infection

• Hb if on AZT at 4 weeks and 

low CD4+ cell count or BMI

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Table 16-3

Minimum Recommended Laboratory Monitoring Schedules

Time U.S. Guidelines: DHHS 2 International Guidelines: 

WHO 2010

Every 3-6 

months after 

ART initiation 

or switch

• CD4+ cell count

• HIV viral load

• Basic chemistry

• ALT, AST, total and direct 

bilirubin

• CBC with differential

• Fasting glucose or hemoglobin 

A1C, if abnormal at last 

measurement

• ALT and AST at 12 weeks for 

women with CD4+ cell count 

>250/mm3 and NVP

• Hb if on AZT and low CD4+ 

or BMI

Every 6 

months after 

ART initiation 

or switch

• Fasting glucose

• Urinalysis if on TDF

• Fasting lipid profile if 

abnormal at last measurement

• CD4+ cell count

• Creatinine clearance if on TDF

At 12 months 

after ART 

initiation or 

switch

• Fasting lipid profile

• Urinalysis

• CD4+ cell count (in clinically 

stable patients with 

suppressed viral load, monitor 

every 6–12 mo.)

Treatment 

failure3

• CD4+ cell count

• HIV viral load

• Resistance testing

• Tropism testing if considering a 

CCR5 antagonist

• CD4+ cell count

• HIV viral load to confirm 

treatment failure

• HIV viral load if immunological 

failure

Notes: “Desirable” tests are in italics. All abbreviations are defined in the list of 

Abbreviations and Acronyms, p. ix.

1 Defined as underlying renal disease, older age group, low BMI, diabetes, hypertension, 

and concomitant use of boosted PI or nephrotoxic drugs.

2 Defined as ART-naïve HIV infected women with CD4+ cell count >250/mm3 or HCV coinfection.

3 Treatment failure in resource-limited settings is diagnosed differently from in the 

United States, because viral load monitoring is not readily available. If it is available, 

virological failure is only diagnosed when the viral load remains >5,000 copies/

mL. Alternatively, clinical failure is the diagnosis of new or recurrent WHO Stage 

4 condition on HAART (not immune reconstitution and inflammatory syndrome), and 

immunological failure is a fall of CD4+ cell count to below baseline, 50% from peak 

value, or failure to rise above 100/mm3.

continued

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568 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

Conclusion

Scientific knowledge and advances, translated into effective clinical 

interventions, are the fundamental underpinnings of HIV prevention, care, and 

treatment; however, for most of the world, social and economic factors are the 

prime determinants of the approach to HIV/AIDS care. Healthcare structure 

and social support systems must be strengthened if global HIV control is to be 

achieved. Gender equity in society, including reproductive choice, economic 

independence, and freedom from gender-based violence, is essential for 

optimal HIV prevention and care in women.

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Index of Topics

See p. 581 for Index of Drugs. Page numbers in boldface type indicate figures and tables.

A

abdomen, 80

abscesses

Bartholin’s, 201, 218

breast lumps, 207

access to care

for adolescents, 382, 388–389

international perspective, 552

sex differences, 29

acne, 479

ACTS program, 384

adenomyosis, 159

adherence

among adolescents, 392, 393

to ART, 103

assessment, 143–145, 145

defined, 136

factors affecting, 136, 136–137

improvement methods, 146

interventions for support, 148–149

in lower-income countries, 561

non-, magnitude of, 138–140

to postexposure prophylaxis, 435

and pre-exposure prophylaxis, 63, 556

during pregnancy, 325

study results, 238–239

viral load increase, 92

in women, 141–143

adjustment disorders

vs. anxiety, 354 vs. depression, 352

adolescents

biological risk, 381

epidemiology, 379–380

issues in care, 382–385

risk factors, 380

Adult AIDS Clinical Trials Group, 534

advance care planning, 421

advance directives, 325

adverse effects

of ART, 104–106, 107

postexposure prophylaxis adherence, 

437

sex differences in, 447–448

aging

natural history of infection, 16

and palliative care, 401

patient demographics, 4–5

AIDS, as cause of death, 10

AIDS Alliance for Children, Youth, and 

Families, 534

AIDS dementia complex. see HIVassociated dementia

AIDS Education and Training Centers, 

534

AIDS Education Global Information 

System, 534

AIDS-indicator conditions, 13

AIDS Policy Center for Children, Youth, 

and Families, 534

AIDSInfo, 535

AIDSVAX trial, 58

AIDSVU, 536

albumin, 86

alcohol use

during pregnancy, 372–373

medication treatment, 357, 371

screening, 89, 347

alcohol withdrawal, 357

alfa-fetoprotein, 307

alkaline phosphatase, 87

allergic reactions, 204

ALT (alanine transaminase), 86

amenorrhea, 156

American Academy of HIV Medicine, 

535

American Congress of Obstetricians and 

Gynecologists, 535

American Social Health Association, 

543

amniocentesis, 311

anemia

ART side effect during pregnancy, 

303

review, 131

anorexia, 405

anovulation, 159

antibody tests, 82

antigen/antibody test, 82

antiretroviral therapy (ART)

adherence, 103

adverse events, 104–106, 107

agents categories for pregnancy, 449

agents summary, 101–103

choosing a regimen, 100–101

continuing after delivery, 335–336

and contraception, 392

disease progression, 15–16

drug interactions, 502–503

effects on mortality, 10–11

goals, 98

for HIV prevention, 61–70, 67–68

and HPV disease, 163–164

initiating, 98–100

initiation recommendations, US vs. lowerincome countries, 563–564

interactions with drugs, 502–503

interactions with food, 514

intrapartum use, 325–326

in lower-income countries, 560–561

menstrual disorders, 156

and opportunistic disease, 132

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antiretroviral therapy (ART) (continued)

in patients who abuse substances, 364

performance measures, 521

and pregnancy, considerations, 280–

284, 281, 299–303

pregnancy categories, 449

resource limitations, 70

scenarios for experienced pregnant 

patients, 313, 314–315

scenarios for naïve pregnant patients, 

299, 312–313

stopping during pregnancy, 314–315

and substance use, 374–375

suppression failure during pregnancy, 

315–316

WHO guiding principles, 565

anxiety

medication treatment, 357

over gynecological examination, 22

screening for, 347, 352–354, 354

aphthous ulcers

genital, 179

oral, 225

thalidomide use in pregnancy, 471

ASCUS (atypical squamous cells of 

undetermined significance), 165

Asia, HIV in, 551

assessment

for alcohol use, 365–366

of HIV risk, 40, 41

initial evaluation, 28

of menstrual bleeding, 157–160

non-pain symptoms, 403, 404

of occupational exposure, 431

of pain, 407–408, 408–409

of psychosocial status, 346

of retention in care, 145

of risk for adolescents, 385, 386

of treatment adherence, 143–145, 145

of treatment failure, 109

assisted reproductive technology

right to care, 240

safe conception, 238

Association of Nurses in AIDS Care, 535

AST (aspartate transaminase), 86

asthma, 479

atrophic vaginitis, 189

autonomy, 18

AVERTing HIV and AIDS, 543

B

bacterial vaginosis

during pregnancy, 269

screening recommendation during 

pregnancy, 306

vaginal discharge, 181–182

Bartholin’s abscess

genital masses, 201

image, 218

behavior, 49

behavioral interventions

for STI risk, 49–50

for substance use, 372

Behçet’s syndrome, 179

bereavement, 422

beta-hCG testing, 307

bilirubin testing, 86

bipolar disorders

medication treatment, 358 vs. depression, 352

birth and delivery, 325–328

bleeding, 104

The Body, 543

The Body Pro, 536

body fluids, 429

bone densitometry, 90

bone marrow suppression, 104

bowel regimen, 413–414

breast cancer, 208

breast lumps, 206

breastfeeding

benefits, 334

HIV transmission risk, 279, 280

and postexposure prophylaxis, 438

Brief Pain Inventory, 407

BUN (blood urea nitrogen)

recommendation during pregnancy, 

305

testing indications, 86

C

Canadian AIDS Treatment Information 

Exchange, 544

cancer. see also specific sites, such as

breast cancer; cervical cancer

differential diagnosis, 159

neoplasia, 179

neoplasms, 196

review, 131

treatment in pregnancy, 480

candidiasis

diagnosis and treatment, 120–121

image, 216, 217

during pregnancy, 268

vaginal discharge, 182–185, 183–184

CAPRISA 004 trial, 56, 67, 238

cardiovascular disease

as ART side effect, 104

review, 130

caregivers, 422

caretaking, 342

Caribbean basin, HIV in, 551

Caring Connections, 540

CBC (complete blood count), 85, 93, 305

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CD4+ cell count

correlation with opportunistic disease, 

113–114, 113–115

example performance measures, 524

HIV staging criteria, 12

natural course, 91, 91–92

recommendation during pregnancy, 305

testing indications, 85

CDC Division of HIV/AIDS Prevention, 

536

CDC HIV classification system, 12, 12–13

CDC National Prevention Information 

Network, 536

CDC Prevention with Positives (PWP), 

537

Central America, HIV in, 551

Central Asia, HIV in, 551

Central Europe, HIV in, 551

central nervous system symptoms, 104

cervical cancer

HPV infection, 162

in lower-income countries, 559–560

screening, US vs. lower-income country 

recommendations, 562

cervical cap, 249

cervical dysplasia

HPV infection, 161

management, 169–170

cervicitis

image, 222

management, 205

cesarean section

considerations, 327–328

and viral load, 316

chancre, 219

chancroid, 177–178

change, sustaining, 530

childcare, 342

chlamydia

testing during pregnancy, 307

vaginal discharge, 188–189

chorionic villus sampling, 311

chronic care model, 30–34, 31

circumcision (male), 54–55

“clap.” see gonorrhea

CMV retinitis. see also cytomegalovirus

cidofovir use in pregnancy, 455

foscarnet use in pregnancy, 460

ganciclovir use in pregnancy, 461

cocaine use, 371, 373–374

coccidioidomycosis, 117

cognitive impairment, 347

colonoscopy, 90

colorectal cancer screening, 212

colposcopy

indications, 167–168, 170–171, 271

screening recommendation, 165, 199

commercial sex, 8

communication, with patients, 21–22

Community Programs for Clinical 

Research in AIDS, 537

compliance. see adherence

conception safety, 236–239

condom use

after delivery, 335–336

among adolescents, 386–387, 387

effectiveness, 253

guidance, 50–51, 51–53, 53–54

during pregnancy, 325

condoms (female)

guidance, 50–51, 51–52

method comparison, 249

condoms (male), 248

condylomata acuminata, 220, 223

confidentiality

for adolescents, 383

with patients, 23

constipation, 413–414, 414

contraception

considerations in choice, 242–245

considerations of use, 242

counseling, 243

counseling for, postpartum, 324

methods compared, 246–252

use after delivery, 335–336

contraction stress test, 309

cordocentesis, 311

corticosteroids

for pain relief, 415

use in pregnancy, 483

cough, 406

counseling

for adolescents, 383

and behavior changes, 50

contraception, 243

patient needs, 27–28

post-testing, goals, 47

postexposure prophylaxis, 67

for preconception, 235

provider sensitivity, 78

and rapid HIV testing, 49

recommendations, 46

for risk reduction, 40, 42–43, 45

“crabs,” 205, 222

creatinine testing

indications, 86

during pregnancy, 305

primary care, 93, 97

Crohn’s disease, 179

cryptococcal meningitis

amphotericin B use in pregnancy, 

451

diagnosis and treatment, 121–122

fluconazole use in pregnancy, 459

cultural sensitivity, of providers, 25

cystitis, 197

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cytomegalovirus. see also CMV retinitis

diagnosis and treatment, 124–125

genital ulcers, 178

during pregnancy, 272–274

screening recommendation during 

pregnancy, 306

testing, 88, 94

D

death. see also mortality

approaching, 417–420

in era of ART, 401

decentralization of services, 554–555

decison-making, 32

delirium, 352

delivery modes, 327–328

dementia, 126, 352

demographics, 5–6

depression

diagnosis, 349, 350, 351, 352

medication treatment, 359

screening, 89, 347

diabetes

as ART side effect, 104

PIs as risk factor, 301

testing during pregnancy, 307

treatment in pregnancy, 481

diaphragms, 249

digital rectal examination, 89

disclosure

considerations, 343

and HIV spread, 342

issues for adolescents, 394

patient needs, 26–27

domestic violence

and HIV spread, 343–344

screening indications, 89

donovanosis, 178–179, 221

douching, 60

drowsiness, 414

drug holiday

not recommended, 108, 112

during pregnancy, 314–315

drug reactions, 179

drug resistance

development during pregnancy, 

282–283

nevirapine, postpartum, 283, 315, 336

patient management consideration, 435

testing, 92–93, 110–111

treatment non-adherence, 138

drug-resistant HSV, 175

dry mouth, 406

dysmenorrhea, 194

dysphagia, 405

dysplasia, 171

dyspnea, 406

E

Eastern Europe, HIV in, 4, 551

economic problems, 342

education, 27–28

electrolytes

recommendation during pregnancy, 

305

testing indications, 86

emergency contraception, 252, 259–260

empowerment. see autonomy

encephalopathy, 126

end-of-life care, 418

endometrioma, 196

endometriosis, 194

enzyme immunoassay, 82

epidemiology

adolescents, 379–380

HIV rates by region, 549, 549

key trends among women, 6

esophagitis

amphotericin B use in pregnancy, 451

fluconazole use in pregnancy, 459

ethnicity, 342

eye examination

elements, 80

indications, 89

F

fall risk, 90

family involvement, 28–29

fat maldistribution syndrome

as ART side effect, 106, 107

breast lumps, 207

fatigue, 405

FEM-PrEP trial, 63, 67, 239

fertility, 239–240

fetal monitoring

for CMV infection, 273

during syphilis treatment, 272

tests, 308–311

fibroadenomas, 207

fibrocystitis, 207

fibroids

differential diagnosis, 159

pelvic mass, 196

pelvic pain, 194

folliculitis, 202

food-drug recommendations, 513

frailty, 90

fungal infections

clotrimazole use in pregnancy, 456

genital irritation, 203–204

images, 216, 217

nystatin use in pregnancy, 464

posaconazole use in pregnancy, 466

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

G

gallstones, 105

gastrointestinal symptoms, 105

Gay Men’s Health Crisis Women and 

Family Services, 544

gender inequality, 341

gender norms, 341

genital irritation, 202–203

genital masses, 201–202

genital tract infections

differential diagnosis, 159

HIV transmission risk, 9

and safe conception, 237

genotypic assays

described, 110–111

for hepatitis C infection, 129

geographic differences, 3, 4

glucose-6-phosphate hydrogenase 

(G6PD) deficiency, 97, 306

glucose testing, 86, 97

gonorrhea, 187–188

granuloma inguinale

genital ulcers, 178–179

image, 221

grapefruit juice, 513

grief

considerations, 422

vs. depression, 352

gynecologic examination

communication for, 22

health maintenance, 211

referral guidelines, 214

H

HAART. see antiretroviral therapy

hair analysis, 367

health maintenance

screening and prevention, 211–214

screening indications, 88–90

Healthy Women, 544

heart examination, 80

hemorrhage, postpartum, 329

hepatitis

diagnosis and treatment, 128–130

interferon use in pregnancy, 462

occupational exposure, 427

ribavirin use in pregnancy, 469

screening recommendation during 

pregnancy, 306

testing, 94–96, 95

testing indications, 87

vaccination, 118, 322

hepatitis A, 95

hepatitis B

postexposure management, 439, 440

during pregnancy, 275, 317–318

recommendations, 95–96

hepatitis C

postexposure management, 441

during pregnancy, 276, 318–319

recommendations, 96

hepatotoxicity. see liver function

herpes simplex virus type 2 (HSV-2)

famciclovir use in pregnancy, 458

foscarnet use in pregnancy, 460

genital ulcers, 173–175

and HIV transmission, 9, 60–61

images, 222, 224

during pregnancy, 269–270

valacyclovir use in pregnancy, 473

herpes zoster infection

famciclovir use in pregnancy, 458

valacyclovir use in pregnancy, 473

hiccups, 406

hidradenitis suppurativa, 179

histoplasmosis, 117

history

elements of, 76–77

of pregnant women, 303–304

HIV-2 infection, 319–320

HIV and Hepatitis, 537

HIV-associated dementia (HAD), 126

HIV infection

acute, treatment of, 112

acute presentation during pregnancy, 

316–317

adolescent care issues, 389–395

as chronic disease, 400–402

effects on pregnancy, 267, 268

natural history, 11–12, 12–14, 15–16

pregnancy effects on, 266–267

prevalence, 401

and substance use during pregnancy, 

374

HIV InSite, 537

HIV Medication Guide, 538

HIV Medicine Association, 538

HIV testing, 562

HIV therapy goals, 135

HIVAN. see nephropathy

HIVdent, 537

HLA-B*5701

testing during pregnancy, 308

testing indications, 87

homelessness, 344

hospice

described, 399

use, 418–421, 419

host immune response, 15

HPTN 043 trial, 49

HPTN 052 trial, 8, 27, 62, 68

HPV. see human papillomavirus

HRSA HIV/AIDS Bureau, 538

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574 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

human papillomavirus (HPV)

anal infection, 163

and HIV infection, 160–163

infection prevention, 172

in lower-income countries, 554

oral infection, 163

during pregnancy, 270–271

screening in lower-income countries, 

559–560

screening, 165–166

vaccination recommendations, 118

hyperemesis, 299

hyperglycemia. see diabetes

hyperlipidemia, 104

hypersensitivity reactions, 105

hypertension, 481–482

hysterectomy, 169

I

iatrogenic transmission, 8

incarceration, 345

incidence of HIV infection, as unknown, 

5

indicators, of quality, 517

infants. see also neonates

diagnosing in lower-income countries, 

557

feeding, 333–334

infertility, 239–240

information systems, 33–34

infrastructure

case study, 527–529

for quality management, 518, 519

injection drug use

as risk factor, 4

risk reduction, 54

transmission epidemiology, 7

insomnia

management, 405

medication treatment, 358

Institute of Medicine, 538

instructions, for patients, 21

insulin resistance, 104. see also diabetes

intake information, 78–79, 78–79

International HIV/AIDS Alliance, 539

interstitial cystitis, 197

intraepithelial neoplasia, 162

iPrEX trial, 63, 238

itching, 414

IUDs (intrauterine devices)

as emergency contraception, 260

HIV transmission, 258–259

J

Johns Hopkins University AIDS Service, 

539

K

kidney function

ART dosing in presence of insufficiency, 

491–501

recommendation during pregnancy, 305

testing, 86, 93

kidney stones

as ART side effect, 106

symptoms, 197

L

laboratory tests

efficient use, 565

for postexposure prophylaxis, 431

for postexposure prophylaxis followup, 

439

for pre-exposure prophylaxis, 69–70

for pregnant women, 305–308

US vs. WHO guidelines, 566–567

lactic acidosis, 106, 107

leiomyomas. see fibroids

lice

genital irritation, 205

image, 222

limited-resource settings

ART in, 560–561, 562–564

disease care, 558–559

issues in, 29–30

laboratory testing guidelines, 565, 

566–567

mother-to-child transmission, 557–558

lipid levels

and ART side effects, 104

screening, 213

testing, 86, 97

treatment in pregnancy, 483

lipodystrophy. see fat maldistribution 

syndrome

liver disease

as cause of death, 11

and substance use, 364

liver function

ART dosing in presence of insufficiency, 

491–501

and ART side effects, 105, 107

recommendation during pregnancy, 

305

testing, 86, 93

lung examination, 80

lymph node examination, 80

lymphadenopathy, 196

lymphogranuloma vereneum, 178

lymphoma, 127, 128

M

MAC. see Mycobacterium avium complex

malaria

artesunate use in pregnancy, 452

in lower-income countries, 553–554, 559

mefloquine use in pregnancy, 462

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

malaria (continued)

proguanil use in pregnancy, 453

prophylaxis guidelines, 117

quinine use in pregnancy, 469

malignancies. see cancer

mammography

health maintenance, 212

testing indications, 90

mastitis, 207

maternal death, 550

meningitis, 121–122

menometrorrhagia, 155

menopause

differential diagnosis, 159

history, examination, and evaluation, 

209

and HIV infection, 5, 209–210

management, 210–211

menorrhagia, 155

menstrual bleeding

abnormalities, 155–156

assessment, 157–160

and HIV infection, 156–157

mental health. see also specific conditions, 

such as anxiety; depression

general considerations, 345–346

pharmacology guidelines, 355–356

screening, 347–348

and substance use in adolescents, 395

treatment in pregnancy, 484–485

triggering events, 348–349

methamphetamine use

addiction treatment, 371

during pregnancy, 373

prevalence, 362

metrorrhagia, 155

microsporidiosis, 451

mitochondrial toxicity, 301

mittelschmerz, 194

Model for Improvement, 525, 526

Molluscum contagiosum, 202, 223

mortality. see also death

and ART, 10–11

HIV as cause, by region, 550

leading causes, 10

predictors, 11

sex differences, 11

mother-to-child transmission

clinical factors, 278–279

epidemiology, 7

interventions, US vs. lower-income 

countries, 563–564

in lower-income countries, 557–558

rate, 276–277

risk factors, 277, 277

zidovudine for prevention, 330, 331

Mycobacterium avium complex (MAC)

azithromycin use in pregnancy, 454

clarithromycin use in pregnancy, 456

diagnosis and treatment, 125

prevention during pregnancy, 321

prophylaxis guidelines, 117

myopathy, 106

N

narcotic use, 484

National Alliance of State and Territorial 

AIDS Directors, 539

National Association of People With 

AIDS, 544

National HIV/AIDS Clinicians’ 

Consultation Center, 539

nausea and vomiting

management, 405

opioid side effect, 414

during pregnancy, 299, 483

needlesticks, 429

neonates. see also infants

assessment, 332

HIV diagnosis, 333

HIV prophylaxis, 329–332

HSV-2 infection, 269

neoplasia, 179

neoplasms, 196

nephropathy, 130. see also kidney 

function

neurological system examination, 81

neuropathy, 106

New Mexico AIDS Infonet, 544

NIAID Database for Anti-HIV 

Compounds, 540

non-pain symptoms, 402

nonoccupational exposure, 65–66

nonstress test, 309

North America, HIV in, 551

nuchal translucency testing, 307

O

obsessive-compulsive disorder, 354

occupational transmission, 7

Oceania, HIV in, 551

odynophagia, 405

The Office on Women’s Health, 545

oligomenorrhea, 156

opiate use

medication treatment, 359, 370

during pregnancy, 373

opiate withdrawal, 360

opportunistic disease. see also specific 

conditions, such as candidiasis; CMV 

retinitis

and ART, 132

correlation with CD4+ cell counts, 113–

114, 113–115

during pregnancy, 319–320, 320

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576 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

organic mood disorder, 352

oropharynx examination, 80

osteoporosis

as ART side effect, 106

prevention, 213

outreach programs

to adolescents, 388–389

school-based, 387–388

ovarian cysts

pelvic mass, 196

pelvic pain, 194

ovarian torsion, 194

P

pain

assessment, 407–408, 408–409

causes, 402

management protocols, 409, 409–410

prevalence, 407

pain relief, 484. see also pain relievers 

in drug index

palliative care

expansion of use, 400

place for, 399

role of, 400–402, 402

panic disorder

medication treatment, 357 vs. anxiety, 354

Pap smears

abnormalities in, 160–162

Bethesda system, 166

evaluation of results, 167–168

health maintenance, 212

liquid-based method, 165

management of abnormal results, 

170–171

performance measures, 521

rate improvement case study, 528–529

screening, 164–165, 306

testing, 88, 97

papillomavirus. see human 

papillomavirus

PAPP-A testing, 307

Partners PrEP trial, 67, 238

Pediculosis pubis (lice)

genital irritation, 205

image, 222

pelvic examination, 80

pelvic inflammatory disease, 191–196, 

193

pelvic masses, 195–196

pelvic pain, 190–191

PEPFAR, 540

PEPline, 427

performance measurement

case study, 527–529

use, 519–520, 520–524, 523

perinatal transmission. see mother-tochild transmission

peripheral neuropathy

as ART side effect, 106

diagnosis and treatment, 416

Phambili trial, 59

pharmacokinetics

during pregnancy, 299

in pregnant patients, 446

phenotypic assays, 111

phobias, 354

physical examination

elements of, 80–81

of pregnant women, 303–304

Plan-Do-Study-Act cycles, 526, 527

Pneumocystis jirovecii (PCP) pneumonia

atovaquone use in pregnancy, 453

dapsone use in pregnancy, 457

diagnosis and treatment, 120

in neonates, 333

pentamidine use in pregnancy, 465

prevention during pregnancy, 320

primaquine use in pregnancy, 466

prophylaxis guidelines, 116

TMP-SMX use in pregnancy, 472

polymenorrhea, 156

Population Council, 540

postexposure prophylaxis

followup monitoring, 439

laboratory tests, 431

recommendations, 432, 433

regimen options, 434

and symptom management, 437

post-traumatic stress disorder (PTSD)

medication treatment, 357

screening for, 348, 353 vs. anxiety, 354

postcoital bleeding, 156

poverty, 342

pre-exposure prophylaxis (PrEP)

guidance for prevention, 69–70

in lower-income countries, 556

for prevention, 62–66

safe conception, 238–239

trial results, 67–68

preconception. see also pregnancy

counseling for, 235

evaluation, 233–234

interventions, 235

pregnancy

decision aids, 231–232

differential diagnosis, 159

discussion timing, 230

drug screening considerations, 367

effects on HIV infection, 266–267

HIV effects on, 267, 268

HIV transmission risk, 9–10

natural history of infection, 16

pelvic mass, 196

pelvic pain, 191

pharmacokinetic changes, 446

and postexposure prophylaxis, 437

prescription drug risk categories, 448,

449

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

pregnancy (continued)

and substance use, 372–374

testing for, 265, 266

testing indications, 87

and treatment adherence, 142

treatment considerations, 445

unintended, 240–241

preterm birth, 300

prevalence, 5

prevention

challenges, 39

combination strategies, 71

failed strategies, 56–57, 57–58, 59–61

interventions in lower-income countries, 

555–556

postexposure prophylaxis, as not 

substitute for risk reduction, 68

programs for adolescents, 387–388

risk reduction plans, 44

US vs. lower-income country 

recommendations, 562

prognostication, 419

progressive multifocal leukoencepha­ lopathy (PML), 127

Project Inform, 545

providers

experience level, 75

HIV-infected, 441

and patient counseling, 40

requirements for success, 23–25

pruritus, 406

psychosis

medication treatment, 360

screening for, 348

psychosocial issues, 393–395

puberty, 390, 391

pyelonephritis, 197

Q

quality assurance, 517

quality improvement

case study, 527–529

defined, 517

quality management

defined, 517

program elements, 518–526, 519–526

terms defined, 517–518

quality review, 525

questioning, of patients, 21

R

race

and HIV prevalence in US, 5

and HIV spread, 342

rapid HIV testing

described, 83

in lower-income countries, 557

screening, 47–49, 48

rash, 106, 302–303

reporting

of occupational exposure, 427

requirements for, 23

Reproductive Health Online, 541

Resource Center for Prevention with 

Persons Living with HIV, 541

respect, 22

retention in care

assessment, 145

influences, 140, 140–141

interventions for support, 148–149

right to care, 240

risk factors, unidentified, 16–17

risk reduction, postexposure prophylaxis 

as not substitute for, 66

RNA. see viral load

root cause analysis, 518

rubella screening, 306

Russia, HIV in, 4

RV144 trial, 58, 59

S

saline, 406

San Francisco AIDS Foundation, 545

scabies, 204–205

schizophrenia, 360

school-based programs, 387–388

screening

of adolescents, 383

anal examination, 169

for colorectal cancer, 212

for depression, 349, 350, 351

for HIV, 40, 45–46

HPV testing, 165–166

for lipid levels, 213

mental health, 347–348

Pap smears, 164–165

rapid HIV testing, 47–49, 48

for sexually transmitted infections, 

212

test types, 82–83

for toxoplasmosis during pregnancy, 

274–275

transmission prevention, 18

US guidelines, 5

vaginal and vulvar examination, 

168–169

seizure disorders

treatment in pregnancy, 486

self-management, 32–33, 33

semen analysis, 237–238

sensitivity, 22–23

serodiscordant couples

in lower-income countries, 556

and safe conception, 237

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578 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

sex differences

access to care, 29

mortality, 11

natural history of infection, 15

in response to treatment, 447–448

treatment adherence, 141

sexual activity

among adolescents, 380–381

assessment at intake, 28

number of partners, 8

partner’s infectivity, 8

partner’s risk factors, 16

rates among older women, 5

risk per event, 7

and safe conception, 236–239

sexual dysfunction, 208

sexually transmitted infections (STIs). 

see also specific conditions, such as

chlamydia; gonorrhea

among adolescents, 380–381

screening, 212, 390–391

screening, US vs. lower-income countries, 

562–563

testing, 88, 97

treatment, as HIV prevention failure, 

59–61

shortness of breath, 406

skin examination, 81

“slim disease.” see wasting syndrome

South America, HIV in, 551

special populations

adolescents, 382

treatment adherence, 143

spermicides

effectiveness, 253

HIV transmission risk, 9

method comparison, 250

spirituality, 25–26

squamous intraepithelial lesions, 165

STDs/STIs. see sexually transmitted 

infections (STIs)

STEP trial, 58, 59

sterilization, 251

Stevens-Johnson syndrome, 106

stigma, 342–343

sub-Saharan Africa, maternal death 

rates in, 550

substance use

among adolescents, 381

comorbidities, 363–364, 364

considerations in pain relief, 417

counseling during pregnancy, 325

diagnosis criteria, 361–362

following HIV diagnosis, 363

harm reduction, 369

identification of, 365, 365–367

nonpharmacological interventions, 372

and patient vulnerability, 362–363

and pregnancy, 372–374

prevalence, 362

testing, 367

treatment needs, 368, 368–369

treatment retention, 374

vs. depression, 352

suffering, domains of, 399

suicidal ideation, 348

support systems

patient history, 77

patient needs, 26–27

for pregnant patients, 324

treatment adherence, 146, 147

supportive care, 399

swallowing difficulty, 405

sweat testing, 367

syndrome of imminent death, 417

syphilis

genital ulcers, 175–176, 177

images, 219, 223

during pregnancy, 271–272

screening recommendation during 

pregnancy, 305, 307

testing, 87, 93

T

T-ACE questionnaire, 366

task shifting, 29

Tay-Sachs disease screening, 306

TDF2 trial, 63, 67

team approach, 23–24

teratogenicity, 299–300

testing. see also screening; and specific 

tests, such as genotypic assay

fetal monitoring, 308–311

for pregnancy, 265, 266

therapeutic drug monitoring (TDM), 110, 

111

thromboembolism, 487

thrush. see fungal infections

thyroid disease, 487

tobacco use, 89, 373, 375–376

tolerance, of substances, 361

total quality management, 518

toxic epidermal necrolysis, 106

toxoplasmosis

atovaquone use in pregnancy, 453

dapsone use in pregnancy, 457

diagnosis and treatment, 122

during pregnancy, 274–275

prevention during pregnancy, 320

prophylaxis guidelines, 116

pyrimethamine use in pregnancy, 468

screening recommendation during 

pregnancy, 306

sulfadiazine use in pregnancy, 471

testing, 88, 94

transgender persons, 345

transitions, age-related, 395–396

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transmission. see also mother-to-child 

transmission

ART for prevention, 61–62

epidemiology, 551, 551

factors influencing, 8–10

hormonal contraceptives, 258

and HSV-2, 60–61

local declines in, 4

patterns, 6, 7–8

risks from specific exposures, 429, 

429–430

treatment failure

adherence, 139

defined, 135

patient management, 107–110

treatment success, 147

trichomoniasis

image, 215

vaginal discharge, 185–187, 186

tropism testing, 85

tuberculosis

cycloserine use in pregnancy, 457

diagnosis and treatment, 123

genital ulcers, 179

in lower-income countries, 553, 559

prevention during pregnancy, 321

prophylaxis guidelines, 116

pyrazinamide use in pregnancy, 467

rifampin use in pregnancy, 470

screening recommendation during 

pregnancy, 306

testing, 87, 96

treatment, US vs. lower-income countries, 

564

TWEAK questionnaire, 365–366

twelve-step programs, 372

twitching, 414

U

ulcers (genital)

history, examination, evaluation, and 

diferential diagnosis, 172–173

HIV transmission risk, 9

image, 225

ulcers (oral), 225

ultrasound

indications for, 310–311

testing during pregnancy, 306

umbilical artery Doppler velocimetry, 

309

UNAIDS Joint United Nations 

Programme on HIV/AIDS, 541

universal precautions

described, 428

intrapartum, 325

urinalysis

described, 83

recommendation during pregnancy, 

305

substance use, 367

testing indications, 86

urinary retention, 414

urinary symptoms, 196–198

urinary tract infection, 197

V

vaccination

in adolescents, 391–391

for hepatitis, 95

during pregnancy, 321–322, 322–323

recommendations, 118–119

US vs. lower-income country 

recommendations, 562

vaccines, 57, 58, 59

vaginal discharge, 180–181

vaginal ring, 247

vaginitis

clotrimazole use in pregnancy, 456

fluconazole use in pregnancy, 459

image, 215

management, 205

varicella vaccine, 119, 323

varicella zoster

screening recommendation during 

pregnancy, 306

testing, 94

venous thromboembolism, 487

violence, 343–344

viral load

performance measures, 522

recommendation during pregnancy, 

305

sex differences, 15

suppression failure during pregnancy, 

315–316

testing, 85, 92, 307

virologic tests, 83

vision. see eye examination

visual inspection with acetic acid, 559

VOICE trial, 63, 67, 238, 239

vulvar changes, 205

vulvovaginal candidiasis, 182–185, 

183–184

W

warts (genital), 198–200, 200

wasting syndrome, 126

weight loss, 405

The Well Project, 542

Western Europe, HIV in, 551

WHO HIV/AIDS Department, 542

WHO HIV classification system, 13–14

WHO Pain Ladder, 409, 409–410

WIHS cohort, 10–11

window period, for PEP, 431–432

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580 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

withdrawal

described, 361–362

symptom managment, 369–370

Women, Children, and HIV, 542

Women Alive, 545

Women Organized to Respond to Lifethreatening Disease, 546

women who have sex with women

considerations, 54

and HIV spread, 345

X

xerostomia, 406

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

Index of Drugs

See p. 569 for Index of Topics. Page numbers in boldface type indicate figures and tables.

A

abacavir (ABC)

dosing in presence of renal/hepatic 

insufficiency, 491

side effects, 104, 105

use in pregnancy, 286

ABC. see abacavir

acamprosate, 357, 371

acetaminophen

dosing, 414

use in pregnancy, 484

acyclovir

HSV treatment, 175

resistance in HSV, 175

use during pregnancy, 270, 450

adjuvant pain relievers, 415

albendazole, 451

Albenza. see albendazole

alfuzosin, 500–501, 504

alkylating agents, 480

alpha-2 agonists, 481

alpha blockers, 482

alprazolam

alcohol withdrawal treatment, 357

anxiety treatment, 357

dyspnea treatment, 406

aminoglycosides, 475

amiodarone, 500–501

amitryptyline, 416

amphotericin B, 451

amprenavir. see fosamprenavir

Ancobon. see flucytosine

angiotensin-converting enzyme (ACE) 

inhibitors, 482

angiotensin II receptor blockers, 482

Antabuse. see disulfiram

antacids, 435, 512

anticholinergics, 483

anticonvulsants

interaction with ART, 435, 506

interaction with hormonal contraceptives, 

256

for pain relief, 415

antidepressants. see also SSRIs; tricyclic 

antidepressants

interaction with ART, 435, 511

interaction with hormonal contraceptives, 

256

menopause management, 211

for pain relief, 415

use in pregnancy, 485

antifungal agents, 505–506

antihistamine H1 receptor antagonists, 

483

antimetabolites, 480

antimicrobial agents

safety in pregnancy, 475–478

use in pregnancy, 450–474

antimycobacterial agents, 500–504

antipsychotics

interaction with protease inhibitors, 436

overview, 356

use in pregnancy, 485

anxiolytics, 485

aqueous crystalline penicillin, 177

aripiprazole

bipolar disorder treatment, 358

schizophrenia treatment, 360

artemisinin-based therapy, 452

artesunate, 452

aspirin, 484

atazanavir (ATV)

dosing in presence of renal/hepatic 

insufficiency, 495

food recommendations, 513

interaction with hormonal contraceptives, 

255

side effects, 104, 105

use in pregnancy, 291

atenolol, 482

atorvastatin, 509

atovaquone

food recommendations, 513

Pneumocystis jirovecii prophylaxis, 116

use in pregnancy, 453

ATV. see atazanavir

azithromycin

chancroid treatment, 178

chlamydia treatment, 189

MAC prophylaxis, 117

use in pregnancy, 454

azoles

candidiasis treatment during pregnancy, 

268

resistant fungal strains, 184

AZT. see zidovudine

aztreonam, 475

B

baclofen, 406

Bactrim. see TMP-SMX

BCA. see bichloroacetic acid

benzamides, 483

benzathine penicillin, 177

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582 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

benzodiazepines

interaction with protease inhibitors, 436

use in pregnancy, 484

benzonatate, 406

beta blockers, 482

Biaxin. see clarithromycin

bichloroacetic acid (BCA), 200

bleomycin, 480

bocepravir, 454

boric acid, 184, 185

budesonide, 510

Buffergel, 57

buprenorphine

interaction with ART, 507

opiate addiction treatment, 370

opiate dependence treatment, 359

bupropion

depression treatment, 359

interaction with ART, 511

overview, 356

buspirone, 357

busulfan, 480

butoconazole, 183

C

calcium channel blockers

interaction with ART, 436, 509

use in pregnancy, 482

capsaicin, 416

carbamazepine

bipolar disorder treatment, 358

contraindication with ART, 502–503

hiccups treatment, 406

interaction with ART, 506

use in pregnancy, 486

Carraguard gel, 57

caspofungin, 454

CCR5 antagonists. see also maraviroc

described, 103

interaction with hormonal contraceptive, 

255

cefixime, 188

cefotetan, 193

cefoxitin, 193

ceftriaxone

chancroid treatment, 178

gonorrhea treatment, 187, 188

pelvic inflammatory disease treatment, 

193

cellulose sulfate gel, 57

cephalosporins

gonorrhea treatment, 187, 188

safety in pregnancy, 475

cevimeline, 406

chaparral, 488

chloral hydrate, 405

chlorambucil, 480

chloramphenicol, 475

chlordiazepoxide, 357

chloroquine, 455

chlorpromazine

hiccups treatment, 406

nausea and vomiting treatment, 405

cidofovir

HSV treatment, 175

use in pregnancy, 455

ciprofloxacin, 178

cisapride, 500–502, 504

cisplatin, 480

citalopram

anxiety treatment, 357

depression treatment, 359

clarithromycin

food recommendations, 513

MAC prophylaxis, 117

MAC treatment, 125

use in pregnancy, 456

clindamycin

bacterial vaginosis treatment, 182, 

269

pelvic inflammatory disease treatment, 

193

safety in pregnancy, 476

clonazepam, 357

clonidine, 360

clopidogrel

contraindication with ART, 502

interaction with ART, 512

clorazepate, 357

clotrimazole

candidiasis treatment, 183, 185

use in pregnancy, 456

COBI. see cobicistat

cobicistat (COBI)

dosing in presence of renal/hepatic 

insufficiency, 498

side effects, 106

codeine

cough treatment, 406

oral dosing, 411

comfrey, 488

complementary therapies

considerations, 112

respect toward, 22

use in pregnancy, 488–490

contraceptives (hormonal)

effectiveness, 253, 254

HIV progression, 257–258

HIV transmission risk, 9, 258

interaction with ART, 253–254, 254–

255

contraceptives (oral)

interaction with ART, 257, 436

method comparison, 246, 248

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

corticosteroids

interaction with ART, 510

for pain relief, 415

use in pregnancy, 483

Cotrim. see TMP-SMX

Crixivan. see indinavir

cyclophosphamide, 480

cycloserine, 457

cytarabine, 480

Cytovene. see ganciclovir

D

dapsone

Pneumocystis jirovecii prophylaxis, 116

toxoplasmosis prophylaxis, 117

use in pregnancy, 457

Daraprim. see pyrimethamine

darunavir (DRV)

dosing in presence of renal/hepatic 

insufficiency, 496

food recommendations, 513

use in pregnancy, 293

ddI. see didanosine

delavirdine (DLV), 494

depot medroxyprogesterone acetate 

(DMPA) contraceptives

and bone loss, 257

HIV transmission risk, 9

method comparison, 247

dexamethasone

dysphagia treatment, 405

interaction with ART, 510

nausea and vomiting treatment, 405

pruritus treatment, 406

dextroamphetamine, 405

dextromethorphan, 406

didanosine (ddI)

dosing in presence of renal/hepatic 

insufficiency, 491

food recommendations, 513

side effects, 104, 105

use in pregnancy, 287

dideoxycytidine. see zalcitabine

dieter’s tea, 489

Diflucan. see fluconazole

diphenhydramine

insomnia treatment, 358

pruritus treatment, 406

diphenoxylate, 125

disulfiram, 357, 371

diuretics, 482

DLV. see delavirdine

dofetilide, 501

dolutegravir, 337–338

doxepin, 406

doxycycline

chlamydia treatment, 189

pelvic inflammatory disease treatment, 

193

dronabinol, 405

dronedarone, 500–501

DRV. see darunavir

d4T. see stavudine

duloxetine

anxiety treatment, 357

depression treatment, 359

E

efavirenz (EFV)

contraindication in pregnancy, 244–245

dosing in presence of renal/hepatic 

insufficiency, 494

food recommendations, 513

hormonal contraceptive interaction, 255

side effects, 104

use in pregnancy, 288

EFV. see efavirenz

elvitegravir (EVG)

dosing in presence of renal/hepatic 

insufficiency, 498

use in pregnancy, 297

EMB. see ethambutol

emtricitabine (FTC)

dosing in presence of renal/hepatic 

insufficiency, 492

hepatitis B treatment, 129

for pre-exposure prophylaxis, 67

for postexposure prophylaxis, 434

for prevention, 63–66

side effects, 105

use in pregnancy, 286

Emtriva. see emtricitabine

enfuvirtide (T-20)

dosing in presence of renal/hepatic 

insufficiency, 498

use in pregnancy, 297

Epivir. see lamivudine

ergot alkaloids, 500–502, 504

erythromycin

chlamydia treatment, 189

safety in pregnancy, 476

erythromycin base, 178

escitalopram

anxiety treatment, 357

depression treatment, 359

estrogen-progestin contraceptives, 9

eszopiclone, 358

ethambutol (EMB)

MAC treatment, 125

tuberculosis treatment, 123

use in pregnancy, 458

ethinyl estradiol, 252

ethionamide, 458

etonorgestrel, 248

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584 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

etravirine (ETR)

dosing in presence of renal/hepatic 

insufficiency, 494

food recommendations, 513

hormonal contraceptive interaction, 

255

use in pregnancy, 290

etretinate, 479

EVG. see elvitegravir

F

famciclovir

HSV treatment, 175

use in pregnancy, 458

famotidine, 405

Famvir. see famciclovir

fentanyl

conversion from oral opioids, 412

conversion to oral opioids, 413

dyspnea treatment, 406

flecainide, 500–501

fluconazole

candidiasis treatment, 121, 183, 185

coccidioidomycosis prophylaxis, 117

cryptococcal meningitis treatment, 122

dysphagia treatment, 405

interaction with ART, 505

use in pregnancy, 459

flucytosine

cryptococcal meningitis treatment, 

122

use in pregnancy, 459

fluoroquinolones

interaction with hormonal contraceptives, 

256

safety in pregnancy, 476

5-fluorouracil (5-FU)

use in pregnancy, 480

vulvar lesions treatment, 171

fluoxetine

anxiety treatment, 357

depression treatment, 359

fluticasone

interaction with ART, 510

interaction with protease inhibitors, 

436

Fortovase. see saquinavir

fosamprenivir (FPV, fosAPV)

dosing in presence of renal/hepatic 

insufficiency, 496

hormonal contraceptive interaction, 

255

interactions with HRT, 254

use in pregnancy, 296

fosAPV. see fosamprenivir

foscarnet

cytomegalovirus treatment, 124

HSV treatment, 175

use in pregnancy, 460

Foscavir. see foscarnet

FPV. see fosamprenivir

FTC. see emtricitabine

FTV. see saquinavir

fumagillin, 460

Fungizone. see amphotericin B

furazolidone, 461

furosemide, 406

fusion inhibitors, 103. see also

enfuvirtide

Fuzeon. see enfuvirtide

G

gabapentin

hiccups treatment, 406

peripheral neuropathy treatment, 

416

ganciclovir

CMV retinitis treatment, 124

cytomegalovirus treatment, 178

use in pregnancy, 461

garlic supplements, 501

gentamicin, 193

gentian violet, 184, 185

germander, 488

glycopyrrolate, 405

granisetron, 405

guaifenesin, 406

H

H2 blockers, 435, 512

haloperidol

hiccups treatment, 406

nause and vomiting treatment, 405

heparin, 487

HMG-CoA reductase inhibitors. see statins

hormone replacement therapy (HRT), 

210–211

hydrocodone, 411

hydrocortisone, 406

hydromorphone

conversion from fentanyl patch, 413

conversion to fentanyl patch, 412

dyspnea treatment, 406

oral dosing, 411

5-hydroxytryptamine-3 inhibitors, 

483

hydroxyzine

nausea and vomiting treatment, 405

pruritus treatment, 406

hyoscyamine, 405

hypnotics, 485

hypoglycemics, 481

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

I

ibuprofen, 414

IDV. see indinavir

imipenem, 477

imiquimod

genital warts treatment, 200

HSV treatment, 175

implant contraception, 248

Incivek. see telaprevir

indinavir (IDV)

dosing in presence of renal/hepatic 

insufficiency, 496

food recommendations, 513

side effects, 105

use in pregnancy, 294

influenza vaccine

during pregnancy, 322

recommendations, 118

INH. see isoniazid

insulin, 481

integrase strand transfer inhibitors. see also raltegravir

described, 103

hormonal contraceptive interaction, 255

interferon, 462

Intron. see interferon

Invirase. see saquinavir

irinotecan, 500

isoniazid (INH)

food recommendations, 513

tuberculosis prophylaxis, 116

tuberculosis treatment, 123

use in pregnancy, 462

isotretinoin, 479

itraconazole

candidiasis treatment, 121

food recommendations, 513

histoplasmosis prophylaxis, 117

interaction with ART, 505

use in pregnancy, 463

IUDs (intrauterine devices)

for emergency contraception, 260

method comparison, 250

K

Kaletra. see lopinavir

ketoconazole

contraindication with ART, 502

interaction with ART, 505

L

lamivudine (3TC)

dosing in presence of renal/hepatic 

insufficiency, 492

side effects, 105

use in neonates, 332

use in pregnancy, 285

lamotrigine

bipolar disorder treatment, 358

interaction with ART, 506

interaction with hormonal contraceptives, 

256

use in pregnancy, 486

leucovorin, 122

levofloxacin, 189

levonorgestrel

for emergency contraception, 259

method comparison, 250, 252

levothyroxine, 487

Lexiva. see fosamprenivir

lidocaine

contraindication with ART, 501

dysphagia treatment, 405

for pain relief, 415

pruritus treatment, 406

lindane, 204

lipid-lowering agents. see statins

lithium

bipolar disorder treatment, 358

use in pregnancy, 485

lobelia, 488

loperamide, 125

lopinavir (LPV)

dosing in presence of renal/hepatic 

insufficiency, 497

pharmacokinetics in pregnant patients, 

446

side effects, 104

use in pregnancy, 292

lorazepam

alcohol withdrawal treatment, 357

anxiety treatment, 357

dyspnea treatment, 406

insomnia treatment, 358, 405

nausea and vomiting treatment, 405

lovastatin, 500–501, 504, 509

LPV. see lopinavir

M

magnolia, 488

ma-huang, 488

maraviroc (MVC)

dosing in presence of renal/hepatic 

insufficiency, 499

interaction with hormonal contraceptives, 

255

side effects, 105

use in pregnancy, 298

mechlorethamine, 480

meclizine, 405

medroxyprogesterone acetate

DMPA contraceptive as HIV transmission 

risk, 9

menopause management, 211

CCGW.indb 585 11/7
586 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

mefloquine, 463

megestrol, 405

Mepron. see atovaquone

meropenem, 477

methadone

interaction with ART, 436, 507

opiate use treatment, 359, 370

opiate withdrawal treatment, 360

methotrexate, 480

methylphenidate, 405

metoclopramide, 483

metoprolol, 482

metronidazole

bacterial vaginosis treatment, 182, 269

pelvic inflammatory disease treatment, 

193

safety in pregnancy, 477

trichomoniasis treatment, 186

miconazole, 183

microbicides, 56, 57

midazolam, 500–502, 504

mirtazapine

anorexia treatment, 405

depression treatment, 359

insomnia treatment, 405

pruritus treatment, 406

morphine

conversion from fentanyl patch, 413

conversion to fentanyl patch, 412

dyspnea treatment, 406

oral dosing, 411

MVC. see maraviroc

Myambutol. see ethambutol

Mycobutin. see rifabutin

N

naltrexone

alcohol dependence treatment, 357, 371

opiate dependence treatment, 359

nelfinavir (NFV)

dosing in presence of renal/hepatic 

insufficiency, 497

food recommendations, 513

use in pregnancy, 294

nevirapine (NVP)

dosing in presence of renal/hepatic 

insufficiency, 495

drug-resistance postpartum, 283, 315, 

336

interaction with hormonal contraceptives, 

255

pharmacokinetics in pregnant patients, 

446

side effects, 105

use in pregnancy, 289

NFV. see nelfinavir

niacin, 489

nitazoxanide, 463

nitrofurantoin, 477

non-nucleoside reverse transcriptase 

inhibitors (NNRTIs). see also

delavirdine; efavirenz; nevirapine

described, 102

interaction with hormonal contraceptives, 

255

side effects, 105

nonoxynol-9

for HIV prevention, 57

HIV transmission risk, 9, 253

nonsteroidal anti-inflammatory drugs 

(NSAIDs), 484

Norvir. see ritonavir

nucleoside reverse transcriptase 

inhibitors (NRTIs). see also specific 

agents, such as abacavir; stavudine

described, 102

side effects, 105

NVP. see nevirapine

Nydrazid. see isoniazid

nystatin

candidiasis treatment, 184

dysphagia treatment, 405

use in pregnancy, 464

O

ofloxacin, 189

olanzapine

bipolar disorder treatment, 358

schizophrenia treatment, 360

omeprazole

contraindication with ART, 503

dysphagia treatment, 405

ondansetron

nausea and vomiting treatment, 405

use in pregnancy, 483

opioids

conversion from fentanyl patch, 413

conversion to fentanyl patch, 412

dose titration, 413

oral dosing, 411

peripheral neuropathy treatment, 416

side effects, 414

opium, tincture of, 125

oxcarbazepine, 503

oxycodone

conversion from fentanyl patch, 413

conversion to fentanyl patch, 412

dyspnea treatment, 406

interaction with ART, 507

oral dosing, 411

P

pain relievers. see also specific agents, 

such as aspirin; oxycodone

non-opioids, 414–415

opioids, 410–414

paliperidone, 360

paramomycin, 464

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

paregoric, 125

paroxetine

anxiety treatment, 357

depression treatment, 359

pruritus treatment, 406

patch contraception, 247

Pegasys. see peginterferon

peginterferon (pegIFN)

hepatitis C treatment, 129

use in pregnancy, 464

Peg-Intron. see peginterferon

penicillins

syphilis treatment, 177

use during pregnancy, 272, 478

pentamidine

Pneumocystis jirovecii prophylaxis, 116

use in pregnancy, 465

permethrin, 204

phenobarbital

contraindication with ART, 502–503

interaction with ART, 506

use in pregnancy, 486

phenothiazines, 483

phenytoin

contraindication with ART, 502–503

interaction with ART, 506

use in pregnancy, 486

pilocarpine, 406

pimozide, 500–502, 504

PIs. see protease inhibitors

pneumococcal vaccine

during pregnancy, 322

recommendations, 118

podofilox

genital warts treatment, 200

not recommended during pregnancy, 

271

podophyllin resin

genital warts treatment, 200

not recommended during pregnancy, 

271

polio vaccine

during pregnancy, 322

recommendations, 118

posaconazole

interaction with ART, 506

use in pregnancy, 466

pravastatin, 509

prednisone

interaction with ART, 510

pruritus treatment, 406

prescription drugs, pregnancy risk 

categories, 448

primaquine, 466

PRO 2000 gel, 57

probenecid, 193

prochlorperazine, 405

progesterone antagonists, 260

progestins

for emergency contraception, 259–260

interaction with ART, 257

proguanil, 453

promethazine, 405

propafenone, 500–501

protease inhibitors (PIs). see also specific 

agents, such as darunavir; saquinavir

described, 102–103

drug interactions, 435–436

interaction with hormonal contraceptives, 

255

pharmacokinetics in pregnant patients, 

446

side effects, 104, 105

proton pump inhibitors

contraindication with ART, 502

interaction with ART, 436, 512

psychotropic agents, 500–502, 504

pyrazinamide (PZA)

tuberculosis treatment, 123

use in pregnancy, 467

pyrimethamine

toxoplasmosis treatment, 122

use in pregnancy, 468

PZA. see pyrazinamide

Q

quetiapine

bipolar disorder treatment, 358

schizophrenia treatment, 360

quinidine, 501

quinine, 469

quinolones, not recommended 

for gonorrhea, 187. see also

fluoroquinolones

R

RAL. see raltegravir

raltegravir (RAL)

dosing in presence of renal/hepatic 

insufficiency, 498

interaction with hormonal contraceptives, 

255

for postexposure prophylaxis, 434

use during pregnancy, 316

use in pregnancy, 296

ramelteon, 405

ranitidine, 405

RBV. see ribavirin

Rebetrol. see ribavirin

Rescriptor. see delavirdine

retinoids, 479

Retrovir. see zidovudine

Reyataz. see atazanavir

ribavirin (RBV)

food recommendations, 513

hepatitis C treatment, 129

use in pregnancy, 469

CCGW.indb 587 11/7
588 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

rifabutin

contraindication with ART, 503–504

interaction with ART, 436, 508

interaction with hormonal contraceptives, 

256

MAC prophylaxis, 117

tuberculosis prophylaxis, 116

tuberculosis treatment, 123

use in pregnancy, 470

Rifadin. see rifampin

rifampin

contraindication with ART, 500–504

interaction with ART, 508

interaction with hormonal contraceptives, 

256

tuberculosis prophylaxis, 116

use in pregnancy, 470

rifamycins, 436, 564

rifapentine

food recommendations, 513

interaction with ART, 500–504

rilpivirine (RPV)

dosing in presence of renal/hepatic 

insufficiency, 495

food recommendations, 513

interaction with hormonal contraceptives, 

255

use in pregnancy, 290

risperidone

bipolar disorder treatment, 358

schizophrenia treatment, 360

ritonavir (RTV)

dosing in presence of renal/hepatic 

insufficiency, 497

food recommendations, 513

side effects, 104

use in pregnancy, 292, 295

Roferon. see interferon

rosuvastatin, 509

RPV. see rilpivirine

RTV. see ritonavir

RV144 vaccine, 58, 59

S

salmeterol, 500–501

saquinavir (SQV)

dosing in presence of renal/hepatic 

insufficiency, 497

side effects, 104

use in pregnancy, 293

Savvy gel, 57

scopolamine, 405

selenium, 489

Septra. see TMP-SMX

sertraline

anxiety treatment, 357

depression treatment, 359

interaction with ART, 511

sildenafil, 500–501, 504

simethicone, 406

simvastatin, 500–501, 504, 509

sinecatechins, 200

slimming tea, 489

Sporanox. see itraconazole

SQV. see saquinavir

SSRIs (selective serotonin reuptake 

inhibitors)

depression treatment, 359

interaction with protease inhibitors, 435

menopause management, 211

overview, 355

use in pregnancy, 485

St. John’s wort

contraindication with ART, 500–504

interaction with ART, 436

interaction with hormonal contraceptives, 

256

use in pregnancy, 489

statins

contraindication with ART, 500–501, 504

interaction with ART, 436, 509

use in pregnancy, 483

stavudine (d4T)

dosing in presence of renal/hepatic 

insufficiency, 493

side effects, 104, 105

use in lower-income countries, 561

use in pregnancy, 288

STEP vaccine trial, 58, 59

steroids

fatigue treatment, 405

natural history of infection, 16

sulfadiazine

toxoplasmosis treatment, 122

use in pregnancy, 471

Sulfatrim. see TMP-SMX

Sustiva. see efavirenz

T

T-20. see enfuvirtide

tamoxifen, 480

3TC. see lamivudine

TCA. see trichloroacetic acid; tricyclic 

antidepressants

TDF. see tenofovir

telaprevir, 471

temazepam, 358, 405

tenofovir (TDF)

dosing in presence of renal/hepatic 

insufficiency, 493

hepatitis B treatment, 129

for pre-exposure prophylaxis, 67

for postexposure prophylaxis, 434

for prevention, 56, 63–66

side effects, 105

use in pregnancy, 287

terconazole, 183

CCGW.indb 588 11/7
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure

tetanus toxoid vaccine

during pregnancy, 322

recommendations, 119

tetracyclines, 478

thalidomide

aphthous genital ulcer treatment, 180

use in pregnancy, 471

Thalomid. see thalidomide

theophylline, 479

thioamides, 487

tincture of opium, 125

tinidazole

bacterial vaginosis treatment, 182

trichomoniasis treatment, 186

tioconazole, 183

tipranavir (TPV)

dosing in presence of renal/hepatic 

insufficiency, 497

food recommendations, 513

interaction with hormonal contraceptives, 

255

side effects, 104, 105

use in pregnancy, 295

TMP-SMX (trimethoprimsulfamethoxazole)

Pneumocystis jirovecii prophylaxis, 116

Pneumocystis jirovecii treatment, 120

toxoplasmosis prophylaxis, 117

use in pregnancy, 472

topiramate, 486

TPV. see tipranavir

tramadol, 414

trazodone

insomnia treatment, 358, 405

interaction with ART, 511

triazolam, 500–502, 504

trichloroacetic acid (TCA), 200

tricyclic antidepressants (TCAs)

interaction with ART, 435, 511

use in pregnancy, 485

Truvada, 434

L-tryptophan, 488

Tubizid. see isoniazid

U

ulipristal acetate

for emergency contraception, 260

method comparison, 252

V

valacyclovir

HSV treatment, 175

use during pregnancy, 270, 473

Valcyte. see valganciclovir

valganciclovir

CMV treatment, 124

food recommendations, 513

use during pregnancy, 273, 474

valproate, 486

valproic acid

hiccups treatment, 406

interaction with ART, 506

Valtrex. see valacyclovir

vancomycin, 478

venlafaxine

anxiety treatment, 357

depression treatment, 359

Vfend. see voriconazole

Videx. see didanosine

vinblastine, 480

Viracept. see nelfinavir

Viramune. see nevirapine

Viread. see tenofovir

Vistide. see cidofovir

vitamin A, 490

vitamin B3. see niacin

vitamin B6, 490

voriconazole

interaction with ART, 505

use in pregnancy, 474

W

warfarin

interaction with ART, 436, 512

use in pregnancy, 487

white willow bark, 490

wormwood, 490

Z

zaleplon, 405

ZDV. see zidovudine

Zerit. see stavudine

Ziagen. see abacavir

zidovudine (AZT, ZDV)

dosing in presence of renal/hepatic 

insufficiency, 494

food recommendations, 513

intrapartum use, 325–326

side effects, 104, 105

use in neonates, 332

use in pregnancy, 285

ziprasidone

bipolar disorder treatment, 358

schizophrenia treatment, 360

Zithromax. see azithromycin

zolpidem, 358, 405

Zovirax. see acyclovir

CCGW.indb 589 11/7
CCGW.indb 590 11/7
CCGW.indb 591 11/7
CCGW.indb 592 11/7