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

EDITORS

John G. Bartlett, MD

Professor of Medicine, Chief, Division of Infectious Diseases, and 

Director, AIDS Service 

The Johns Hopkins University School of Medicine

Baltimore, Maryland

Laura W. Cheever, MD, ScM

Deputy Associate Administrator and Chief Medical Officer

HIV/AIDS Bureau

Health Resources and Services Administration

Rockville, Maryland

Michael P. Johnson, MD, MPH

Director, Office of Global AIDS

Office of Global Health Affairs, Office of the Secretary

Department of Health and Human Services

Washington, D.C.

Douglas S. Paauw, MD, FACP

Professor of Medicine and Rathmann Family Foundation 

Endowed Chair for Patient-Centered Clinical Education

University of Washington School of Medicine

Seattle, Washington

2004	Edition	

A	Guide	to	Primary	Care	of	People	with	HIV/AIDS
A Guide to Primary Care of People with HIV/AIDS

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

Department of Health and Human Services

Health Resources and Services Administration

HIV/AIDS Bureau

Parklawn Building, Room 7-05

5600 Fishers Lane

Rockville MD 20857

301-443-1993

Publication	date	2004

Dedication

A Guide to Primary Care of People with HIV/AIDS is dedicated to all 

the men and women working in the Ryan White CARE Act programs. Their 

commitment and dedication to serving people living 

with HIV and AIDS makes these programs possible.

Acknowledgments

Helen Schietinger managed the development and production 

of the guide. Joan Holloway oversaw its conception and execution. 

Cover design and layout was done by Laura Spofford. 

Design and layout of the book was done by Patrice Lincoln. 

Frances Porcher and Helen Schietinger copyedited the 

text, and Bill Todd created the index.
A Guide to Primary Care of People with HIV/AIDS

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

Table	of	Contents

Contributing Authors ................................................................................... v

Abbreviations .............................................................................................vii

Glossary of Antiretroviral Drugs.................................................................viii

Chapter 1. Primary Care as Chronic Care ..................................................................... 1

John G. Bartlett, MD, Laura W. Cheever, MD, ScM, 

Michael P. Johnson, MD, MPH, and Douglas S. Paauw, MD, FACP

Chapter 2. 

Approach to the Patient............................................................................... 5

John V. L. Sheffield, MD, and Gloria A. Casale, MD, MSPH 

Chapter 3. 

Core Elements of HIV Primary Care ......................................................... 13

John McNeil, MD, John V. L. Sheffield, MD, and John G. Bartlett, MD

Chapter 4. Prevention of HIV in the Clinical Care Setting............................................ 21

Michael P. Johnson, MD, MPH

Chapter 5. 

Antiretroviral Therapy ............................................................................... 29

John G. Bartlett, MD

Chapter 6. 

Metabolic Complications of Antiretroviral Therapy ................................... 39

David H. Spach, MD

Chapter 7. 

Adherence to HIV Therapies ...................................................................... 49

Laura W. Cheever, MD, ScM

Chapter 8. Symptom Management............................................................................. 55

Tara Evans Nysoe, MD, and Douglas S. Paauw, MD, FACP

Chapter 9. Management of Opportunistic Diseases .................................................... 67

Constance A. Benson, MD
A Guide to Primary Care of People with HIV/AIDS

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

Table	of	Contents			(continued)

Chapter 10. 

Abnormal Laboratory Values in HIV Disease.............................................. 77

David H. Spach, MD, and John G. Bartlett, MD

Chapter 11. 

Postexposure Prophylaxis.......................................................................... 85

Renslow Sherer, MD, Bruce D. Agins, MD, MPH, and Caroline J. Teter, PA-C, MPH

Chapter 12. 

Family Planning and Pregnancy ............................................................... 97

María del Carmen Ríos, MD, MPH, and José Rafael Morales, MD, FACOG

Chapter 13. 

Management of Substance Abuse............................................................ 105

Henry Francis, MD

Chapter 14. 

Mental Health Disorders ...........................................................................115

Linda Frank, PhD, MSN, ACRN, Glenn J. Treisman, MD, PhD, 

Niccolo D. Della Penna, MD

Chapter 15. 

Palliative and End-of-Life Care ................................................................. 123

Carla S. Alexander, MD, and Kennita R. Carter, MD

Chapter 16. 

Clinic Management ................................................................................. 133

Jonathan Allen Cohn, MD, MS, FACP

Chapter 17. 

Quality Improvement .............................................................................. 141

Bruce D. Agins, MD, MPH

Chapter 18. Keeping Up-To-Date: Sources of Information for the Provider.................. 149

Bruce D. Agins MD, MPH, Renslow Sherer, MD, and Caroline J. Teter, PA-C, MPH

Index of Topics ........................................................................................ 159

Index of Drugs......................................................................................... 165
U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau v

Bruce D. Agins, MD, MPH

Medical Director

New York State Department of Health AIDS Institute

New York, New York

Carla S. Alexander, MD

Assistant Professor of Medicine

Medical Director of Palliative Care

Institute of Human Virology

University of Maryland School of Medicine

Baltimore, Maryland 

John G. Bartlett, MD

Professor of Medicine 

Chief, Division of Infectious Diseases

Director, AIDS Service

The John Hopkins University School of Medicine

Baltimore, Maryland 

Constance A. Benson, MD

Professor of Medicine

Division of Infectious Diseases

University of Colorado Health Sciences Center

Denver, Colorado 

Kennita R. Carter, MD

Clinical Assistant Professor

Department of Hematology/Oncology

Veterans Administration Medical Center

Baltimore, Maryland

Gloria A. Casale, MD, MSPH

Adjunct Professor, University of St. Francis

Adjunct Professor, University of New Mexico 

School of Medicine

Albuquerque, New Mexico

Laura W. Cheever, MD, ScM

Deputy Associate Administrator

Chief Medical Officer

HIV/AIDS Bureau 

Health Resources and Services Administration

Rockville, Maryland

Jonathan Allen Cohn, MD, MS, FACP

Associate Professor of Medicine

Wayne State University School of Medicine

Detroit, Michigan 

Niccolo D. Della Penna, MD

Department of Psychiatry and Behavioral Sciences 

The Johns Hopkins University School of Medicine

Baltimore, Maryland

Henry Francis, MD

Director, Center on AIDS and Other Medical 

Consequences of Drug Abuse

National Institute on Drug Abuse

National Institutes of Health

Rockville, Maryland 

Linda Frank, PhD, MSN, ACRN

Assistant Professor

Graduate School of Public Health

University of Pittsburgh

Pittsburgh, Pennsylvania 

Michael P. Johnson, MD, MPH 

Director, Office of Global AIDS

Office of Global Health Affairs, Office of the Secretary

Department of Health and Human Services

Washington, DC

A Guide to Primary Care of People with HIV/AIDS

Contributing	Authors			
A Guide to Primary Care of People with HIV/AIDS

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

John McNeil, MD

Chief, Infectious Diseases

Howard University Hospital

Washington, DC 

José Rafael Morales, MD, FACOG

Associate Director for Clinical Affairs

Division of Community Based Programs

HIV/AIDS Bureau

Health Resources and Services Administration

Rockville, Maryland

Tara Evans Nysoe, MD

Department of Medicine 

University of Washington School of Medicine

Seattle, Washington

Douglas S. Paauw, MD, FACP

Professor of Medicine

Rathmann Family Foundation Endowed Chair for 

 Patient-Centered Clinical Education

Division of General Internal Medicine

University of Washington School of Medicine

Seattle, Washington 

María del Carmen Ríos, MD, MPH

Acting Chief, Northeastern Regional Branch

Division of Community Based Programs

HIV/AIDS Bureau

Health Resources and Services Administration

Rockville, Maryland

John V. L. Sheffield, MD

Associate Professor of Medicine

Division of General Internal Medicine

University of Washington School of Medicine

Seattle, Washington 

Renslow Sherer, MD

Director, Coordinated HIV Services 

The CORE Center 

Cook County Hospital

Chicago, Illinois 

David H. Spach, MD

Associate Professor of Medicine 

Division of Infectious Diseases

Department of Medicine

University of Washington Medical Center 

Seattle, Washington 

Caroline J. Teter, PA-C, MPH

Project Coordinator

AIDS Education and Training Center 

National Resource Center

Cook County Hospital

Chicago, Illinois 

Glenn J. Treisman, MD, PhD

Associate Professor

Department of Psychiatry

The Johns Hopkins University School of Medicine

Baltimore, Maryland 

Contributing	Authors			(continued)
A Guide to Primary Care of People with HIV/AIDS

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

Abbreviations

ALT: alanine aminotransferase 

anti-HBc: hepatitis B core antibody

ART: antiretroviral therapy, highly active 

antiretroviral therapy 

bid: twice a day

c/mL: copies of virus per mL

DSP: distal symmetrical polyneuropathy 

DRESS: drug rash with eosinophilia and 

systemic symptoms

FTA-ABS: fluorescent treponemal antibody 

absorption test for syphilis

HAART: highly active antiretroviral therapy (see ART)

INH: isoniazid

HCV: hepatitis C virus

IVIG: intravenous immune globulin

LDL: low-density lipoprotein 

LFT: liver function test

MAC: Mycobacterium avium complex

nPEP: nonoccupational postexposure prophylaxis

NRTI: nucleoside reverse transcriptase 

inhibitor, nucleoside

NNRTI: non-nucleoside reverse transcriptase inhibitor

OD: opportunistic disease

OI: opportunistic infection 

po: per os, by mouth 

PI: protease inhibitor

PPD: purified protein derivative of tuberculin 

qd: every day

qhs: every night

qam: every morning

RPR: rapid plasma regain test for syphilis

SSRI: selective serotonin reuptake inhibitor 

STD: sexually transmitted disease

STI: sexually transmitted infection

TB: tuberculosis 

VDRL: Venereal Disease Research Laboratory 

serologic test for syphilis

VL: viral load
A Guide to Primary Care of People with HIV/AIDS

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

Glossary	of	Antiretroviral	Drugs	

Generic name Abbreviation Trade name Class

abacavir ABC Ziagen nucleoside

amprenavir APV Agenerase PI

atazanavir ATV Reyataz PI

delavirdine DLV Rescriptor NNRTI

didanosine ddI Videx nucleoside

efavirenz EFV Sustiva NNRTI

emtricitabine FTC Emtriva nucleoside

enfuvirtide T-20 Fuzeon fusion inhibitor

fosamprenavir FPV Lexiva PI

indinavir IDV Crixivan PI

lamivudine 3TC Epivir nucleoside

lopinavir + ritonavir LPV/r Kaletra PIs

nelfinavir NFV Viracept PI

nevirapine NVP Viramine NNRTI

ritonavir RTV Norvir PI

saquinavir SQV soft gel cap Fortovase PI

saquinavir SQV hard gel cap Invirase PI

stavudine d4T Zerit nucleoside

tenofovir TDF Viread nucleotide

zalcitabine ddC Hivid nucleoside

zidovudine AZT, ZDV Retrovir nucleoside

zidovudine + lamivudine AZT + 3TC Combivir nucleosides

zidovudine + lamivudine + abacavir AZT + 3TC + ABC Trizivir nucleosides

PI: protease inhibitor

NNRTI: non-nucleoside reverse transcriptase inhibitor

nucleoside: nucleoside reverse transcriptase inhibitor 

(NRTI)
A Guide to Primary Care of People with HIV/AIDS

Chapter 1: Primary Care as Chronic Care

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 1

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What	is	a	primary	care	approach	to	the	

treatment	of	HIV/AIDS,	

and	why	is	it	important?

People with HIV/AIDS can live longer, healthier lives 

because of advances in treatment of HIV infection. 

However, longer lives are associated with increased 

prevalence of 1) adverse effects of HIV infection, 

2) adverse effects of the drugs used to treat HIV, and 

3) concurrent medical conditions that would occur in 

the absence of HIV. These long-term complications have 

put HIV infection in the realm of chronic diseases 

rather than of infectious diseases, which usually 

respond to short-term clinical interventions. 

Effective management of chronic diseases in the 

primary care setting requires the coordination of 

interventions that occur at the level of the clinical 

services, the community supports for those clinical 

services, and the individual patient. While clinical 

services begin in the primary care clinic, community 

supports are needed, and the patient must be engaged 

to enhance self-management. The coordinated 

interventions together contribute to the desired 

clinical outcomes. The Chronic Care Model, which is 

used in the design and quality improvement activities 

of clinical services, conceptualizes how these factors 

impact the clinical outcome of chronic disease 

management (see Figure 1-1).

What	is	the	purpose	of	this	guide?

This book addresses several important aspects of 

HIV/AIDS care and treatment in a concise, accessible 

format; it is not meant to be a comprehensive reference 

book. Recommended references and citations are 

provided for the reader to be able to access in-depth 

information on topics that are particularly important 

and/or controversial. Appropriate use of antiretroviral 

drugs, treatment of opportunistic infections, symptom 

management, treatment of concurrent medical 

conditions, and other specific interventions to treat HIV 

disease and its complications are addressed. 

The format of this guide is designed to provide practical 

information for the common questions that arise in 

the care of patients with HIV infection. Recognizing 

the broader array of best practices that contribute 

to effective clinical outcomes among patients with 

a complex array of service needs, the authors also 

address patient evaluation, adherence, mental health, 

substance abuse, overall clinic management, and 

other factors that lead to improved patient outcomes 

according to the Chronic Care Model. Last, because the 

authors recognize the challenges of maintaining clinical 

practices in the face of rapidly changing and ever 

more complex treatment interventions, a chapter on 

sources for updated and in-depth clinical information is 

provided. Pediatric HIV/AIDS treatment is not addressed 

in this book.

Chapter	1:	

Primary	Care	as	Chronic	Care

John G. Bartlett, MD

Laura W. Cheever, MD, ScM

Michael P. Johnson, MD, MPH

Douglas S. Paauw, MD, FACP
A Guide to Primary Care of People with HIV/AIDS

Chapter 1: Primary Care as Chronic Care

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

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Figure 1-1. The Chronic Care Model

Source: Adapted from Wagner EH. Chronic disease management: What will it take to improve care for chronic illness? Effective Clinical Practice. 

1998;1:2-4. Reprinted with permission. The Chronic Care Model was developed by Ed Wagner, MD, MPH, Director of the MacColl 

Institute for Healthcare Innovation, Group Health Cooperative of Puget Sound, and colleagues with support from The Robert Wood 

Johnson Foundation. Further details can be found at www.ihi.org.

Who	is	the	target	audience?

The target audience is providers of primary medical 

care, such as physicians, physician assistants, and nurse 

practitioners, who are taking care of a small but perhaps 

an increasing number of HIV-infected persons but 

who are not experts in HIV care. Parts of this book will 

also be useful for nurses, counselors, pharmacists, and 

others seeking specific, concise information about the 

treatment of HIV-infected persons. Last, specific chapters 

on clinic management and quality improvement are 

relevant for those responsible for the administration of 

clinical sites treating patients with HIV/AIDS. Clinicians 

with small numbers of patients with HIV/AIDS are 

encouraged to seek appropriate expert consultation 

when complex clinical situations arise. Provider 

expertise in HIV care is essential in many treatment 

decisions. In fact, patient outcome is correlated with the 

number of patients with HIV a provider has treated. 

For more information, see Suggested Resources 

in Chapter 18 on Keeping Up-to-Date: Sources of 

Information for the Practicing Clinician. 

What	is	the	purpose	of	the	pocket	guide	

contained	within	the	book?

The guide is a pocket-sized quick reference that 

provides a summary of all Federal guidelines 

dealing with HIV, including antiretroviral therapy 

(ART), prevention of opportunistic infections (OIs), 

management of class adverse reactions, treatment 

of tuberculosis (TB) and hepatitis C (HCV), laboratory 

testing, prevention after occupational exposure, and HIV 

management in pregnancy. It is presented in a format 

that is intended for point-of-care decision making: it 

can be carried in the clinic and at the bedside to rapidly 

access needed information for patient treatment. 

The pocket guide will be updated more frequently than 

the book to meet rapid changes in HIV medication 

options and recommendations. 

Examples of Chronic 

Care Model Interventions

Self-Management Support: 

Emphasizing patient role, assessment, 

problem-solving, and interventions to 

enhance self-management

Delivery System Design: 

Defining care team, planning visits, 

follow-up reminders, continuity of 

care, and referral system

Decision Support: 

Use of clinical guidelines, provider 

education, and specialty support

Clinical Information Systems: 

Establishment and maintenance of patient 

registry, use of registry for patient followup, and quality improvement

Community

Resources and Policies

Health System

Organization of Health Care

Decision

Support

Delivery

System

Design

SelfManagement

Support

Clinical

Information

Systems

Prepared,

Proactive

Practice Team

Informed,

Activated

Patient

Productive

Interactions

Improved Outcomes
A Guide to Primary Care of People with HIV/AIDS

Chapter 1: Primary Care as Chronic Care

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 3

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How	will	the	book	keep	pace	with	the	rapidly	

changing	field	of	HIV/AIDS	treatment?

The book details principles and major recommendations 

for the treatment of persons with HIV/AIDS that will 

remain, for the most part, relevant for the coming 2 

or 3 years. However, the field of HIV treatment is very 

fluid, and specific drugs and drug combinations evolve 

rapidly. For this reason, such information has been 

consolidated in the pocket guide, which will be revised, 

with updates available in the on-line version on the 

HIV/AIDS Bureau (HAB) website. Revisions of the pocket 

guide will include new drugs, new treatment guidelines, 

and new side effects as well as new drug interactions. In 

addition to the pocket guide, information on other useful 

websites is provided to help with keeping up-to-date. 

KEY POINTS

HIV is now a chronic disease requiring 

ongoing primary care management.

The chronic care model uses coordinated 

interventions at the clinic, community, 

and individual levels.

A Guide to Primary Care of People with 

HIV/AIDS is for primary care providers 

who are taking care of a small number of 

patients with HIV but who are not experts 

in HIV care.

The Pocket Guide provides easy reference 

to rapidly changing treatment guidelines 

for point-of-care decision making.
A Guide to Primary Care of People with HIV/AIDS

Chapter 2: Approach to the Patient

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 5

2

BASIC ELEMENTS OF CARE

What	are	the	special	challenges	of	caring	

for	patients	with	HIV/AIDS?

Providers need to be mindful of several special issues: 

• Patients infected with HIV face a complex array of 

medical, psychological, and social challenges. A strong 

provider-patient relationship, the assistance of a 

multidisciplinary care team, and frequent office visits 

are usually required to provide excellent care. 

• The stigma associated with HIV/AIDS places a major 

psychological burden on patients. Confidentiality is 

critical, as is a careful assessment of each patient’s 

emotional support system. 

• Ethnic minorities are over-represented among people 

with HIV. Efforts to understand and acknowledge 

the beliefs of patients from a variety of cultural 

backgrounds are necessary to establish trust between 

providers and patients. 

• Providers play a key role in the public health system’s 

HIV prevention strategy. Disease reporting, partner 

notification, and risk assessment are important 

aspects of care.

• Many patients have inaccurate AIDS information that 

can heighten their anxiety, sabotaging treatment 

adherence and appropriate prevention behaviors. 

They need assurance that HIV is a treatable disease 

and that with successful treatment, patients may live 

indefinitely. They also need to hear explicitly that HIV 

is transmitted through sexual contact, intravenous 

drug use, and blood contact (perinatal or other) and 

how they can prevent transmission to others.

What	are	the	important	components	

of	good	HIV	care?

The elements that ensure good care for people with 

HIV/AIDS include mechanisms for coordination and 

communication of care: 

• Clinics must offer a nonjudgmental and supportive 

environment because of the sensitive nature of issues 

that must be discussed. 

• A multidisciplinary approach, utilizing the special 

skills of nurses, pharmacists, nutritionists, social 

workers, and case managers is highly desirable to help 

physicians address patients’ needs regarding housing, 

medical insurance, emotional support, financial 

benefits, substance abuse counseling, and legal issues.

• Providers and other clinic staff should be prepared to 

conduct appropriate interventions and make timely 

referrals to community resources and institutions. 

• The primary provider should coordinate care, with close 

communication among providers across disciplines. 

• Individual office visits should be long enough to allow 

a thorough evaluation. 

• Providers must be able to see patients frequently for 

good continuity of care, and clinic scheduling should 

be flexible so that patients with acute problems can 

be seen quickly. 

• A range of medical resources, including providers with 

subspecialties and laboratory expertise, must be in 

place (see Chapter 16: Clinic Management).

• Patient education is a vital aspect of care that begins 

during the initial evaluation and continues throughout the 

course of care (see section on Patient Education below).

What	steps	can	providers	take	to	

enhance	care?

Providing comprehensive care for patients infected 

with HIV requires a lot of time, attention to detail, and 

a strong patient-provider relationship. Specifically, the 

provider should do the following:

• Discuss issues in a straightforward fashion to foster 

trust and openness.

• Be realistic about the seriousness of HIV disease and 

yet, to instill hope, be optimistic about the potential to 

restore health and to provide comfort. Give accurate 

information regarding prognosis and the real hope 

that antiretrovirals provide.

• Encourage patients to learn all they can about 

their condition and take an active role in decisions 

regarding their care. 

Chapter	2:	

Approach	to	the	Patient John V. L. Sheffield, MD

Gloria A. Casale, MD, MSPH 

BASIC ELEMENTS OF CARE

STIGMA AND DISCRIMINATION

CONFIDENTIALITY AND DISCLOSURE

PATIENT EDUCATION

RISK ASSESSMENT AND COUNSELING

KEY POINTS

SUGGESTED RESOURCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 2: Approach to the Patient

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

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• Anticipate that significant time will be required for patient 

education (see section on Patient Education below).

• Explicitly outline clinic operations and expectations 

for provider-patient communication. 

• Plan to see patients often and communicate regularly 

between visits to answer questions, assess treatment 

effectiveness, and manage side effects. 

• Arrange to see patients with acute problems quickly. 

How	can	providers	help	patients	with	HIV/AIDS	

cope	with	the	emotional	issues	they	face?

Patients coming to terms with HIV infection often 

experience a range of emotions, including anger, fear, 

shock, disbelief, sadness, and depression. Loss is a 

major issue for patients with HIV disease because 

health, employment, income, relationships with friends, 

lovers, and family, and hope may all be threatened. 

Many patients feel overwhelmed, and providers need 

to recognize that a patient’s emotional state affects 

the ability to solve problems and attend to important 

medical or social issues. Even patients who seem to be 

adjusting reasonably well can find it difficult to keep all 

of the appointments that are scheduled as they initiate 

care. Providers can do the following:

• Assess each patient’s emotional state and the 

availability of friends and family for emotional 

support. Patients may feel hesitant about seeking 

emotional support, and some will need counseling to 

help them decide whether to disclose their diagnosis 

to friends, family, or employers. 

• Deliver important information in easily understood 

terms and in small amounts. Reassess patient 

understanding of crucial information at subsequent 

visits, and repeat important information as necessary.

• Screen for anxiety, depression (including suicidal 

ideation), and substance use. 

• Refer patients to community resources for crisis 

counseling, support groups, and, if appropriate, 

psychiatric treatment to help them achieve emotional 

stability (see also Chapter 14: Mental Health Disorders). 

• Assign a case manager who can help reduce anxiety 

about keeping life in order.

STIGMA AND

DISCRIMINATION

Why	is	stigma	associated	with	HIV/AIDS?

Stigma is founded on fear and misinformation. 

Theodore de Bruyn has observed that stigma is 

associated with HIV/AIDS because “it is a lifethreatening disease; people are afraid of contracting 

HIV; it is associated with behaviors that are considered 

deviant; a belief that HIV/AIDS has been contracted due 

to unacceptable lifestyle choices; and, some believe it is 

the result of a moral fault which deserves punishment” 

(de Bruyn, Theodore. Paper prepared for the Canadian 

HIV/AIDS Legal Network. 1999). 

Stigma can adversely affect how patients are perceived 

by others and how they view themselves. The stigma 

associated with HIV/AIDS is such that individuals 

known to be or suspected of being infected with HIV 

may be excluded from community activities and suffer 

isolation or abandonment. Some patients may feel 

ambivalent about seeking medical care if by doing so 

they risk disclosing their condition. Others may have 

learned from experience to expect rejection and are 

therefore untrusting of all care providers. It is essential 

for providers to be supportive of patients dealing with 

the burden of stigma. 

How	can	providers	support	patients	facing	the	

stigma	of	fear	of	contagion?

The clinic must be inviting, and all staff members must 

model behavior in this area. For example, gloves should 

be worn only as appropriate during physical exams and 

as consistent with universal precautions. There should 

not be separate facilities or procedures for HIV-infected 

patients. Patients and their families are often unaware 

that routine household contact with a person with HIV 

poses no risk of contagion. They should be educated 

about this but also taught what to do in situations that 

do pose risk, such as bleeding. 

How	can	providers	support	patients	who	face	

stigma	associated	with	being	gay,	lesbian,	

bisexual,	or	transgender?	

Demonstrating respect and providing excellent care to 

patients with various cultural backgrounds, beliefs, and 

sexual orientations define professionalism. Providers 

should approach patients in an open and nonjudgmental 

fashion and be familiar with medical management issues 

unique to these populations, such as STD screening 

for men who have sex with men (MSM) and high-dose 

hormonal treatment for transgender male-to-female 

patients. Clinic staff members must also be respectful 

and supportive; having staff who are familiar with 

gay and lesbian culture is a natural way to create a 

welcoming environment. Providers and social workers 

should be aware of community agencies with resources 

available to people who are gay, lesbian, or transgender. 

In addition, providers and clinic staff should be aware 

of special legal issues that affect these populations. For 
A Guide to Primary Care of People with HIV/AIDS

Chapter 2: Approach to the Patient

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 7

2

example, designating a durable power of attorney for 

medical decision making can be particularly important 

in states that do not recognize same-gender partners as 

legal next of kin. 

What	other	special	cultural	issues	affect	

patients	infected	with	HIV?

Minorities are disproportionately affected by HIV, 

and many people of color with HIV disease have 

major socioeconomic problems such as poverty, 

homelessness, lack of medical insurance, lack of 

acculturation, and undocumented immigration status. 

All of these can make accessing health care difficult 

and attending to health problems less of a priority. A 

patient’s cultural background influences health beliefs 

and behaviors, and the effectiveness of provider-patient 

communication may affect compliance with therapy. 

In addition, prior adverse experiences may make some 

patients distrustful of medical care. For all of these 

reasons, providers should do the following:

• Carefully explore what each patient believes about his 

or her health, what would be appropriate treatment, 

and who should be involved in medical decision 

making. 

• Use professional interpreters to help overcome 

language barriers.

• Use case managers to help overcome social barriers.

CONFIDENTIALITY AND

DISCLOSURE

Why	is	confidentiality	especially	important	for	

patients	with	HIV	disease?

Confidentiality of medical information is always 

mandatory, but the stakes are particularly high for 

patients infected with HIV, who risk losing medical 

insurance, employment, or the support of friends or 

family if the wrong individuals learn of their diagnosis. 

Unfortunately, fear and ignorance persist regarding 

HIV transmission; people with HIV disease may be 

shunned because of the incorrect belief that HIV can 

be transmitted via casual contact. Although people 

with HIV disease are protected against discrimination 

under provisions of the Americans with Disabilities Act, 

discrimination can be difficult to prove, and there are 

strict time limits after which charges of discrimination 

can no longer be made. 

What	steps	should	providers	take	to	protect	

patient	confidentiality?

By adhering to the newly implemented Health Insurance

Portability and Accountability Act (HIPAA) regulations, 

providers are protecting patient confidentiality. 

Personnel policies should reinforce measures such as 

requiring that papers and computer screens containing 

patient identifying information not be left unattended 

and documenting whether phone messages can be left 

for the patient, and if they can, with whom. 

How	can	providers	help	patients	decide	whom	

to	disclose	their	HIV	status	to?

Patients with a support network function better 

than those who are isolated. However, patients’ fear 

of disclosure is often well founded, and providers 

must find a balance between accepting patients’ 

unwillingness to disclose and the need to develop 

support networks. Patients may find support groups or 

individual psychotherapy sessions beneficial in deciding 

to whom and when to disclose. 

The sex and needle-sharing partners of people with 

HIV need to be informed about their possible exposure 

to HIV. The local health department should be able to 

either assist patients in making these disclosures or 

provide anonymous partner notification for them. 

What	public	health	role	do	providers	play	

in	the	HIV	epidemic?

Primary care providers must also consider their public 

health role in curbing the spread of HIV. The nationwide 

increase in the incidence of syphilis and gonorrhea, 

especially among MSM, suggests that the advent of 

potent antiretroviral therapy has resulted in relaxed 

adherence to safer sex recommendations. All patients 

with a diagnosis of AIDS and, in many states, those with 

a positive HIV test must be reported to the State health 

department. Laws vary by state regarding reporting 

requirements and subsequent notification of potentially 

exposed individuals, but the name of the source 

contact is never divulged to the person being notified. 

Providers should become familiar with the laws of their 

jurisdiction by contacting their health departments. 

(The Association of State and Territorial Health Officers 

provides links to all State health departments at: 

http://www.astho.org.) Providers are required to do 

the following:
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• Inform patients whose positive HIV or AIDS status 

must be reported to the State health department, 

tell them if partner notification is required, and 

explain what they should expect regarding efforts 

that must be made by the patient, provider, or health 

department to notify sex partners or individuals who 

may have been exposed to HIV through their needle 

sharing. Assure them that the patient’s name is always 

kept confidential, and is never given to potentially 

exposed individuals by the Health Department.

• Carefully assess patients’ risk-taking behaviors, 

educate them regarding HIV transmission, and 

perform STD screening (see question on STD 

screening in this chapter).

• Provide counseling to encourage safer sexual practices 

(see section on Risk Assessment and Counseling 

below) and make referrals to drug rehabilitation 

or needle exchange centers (see Chapter 13: 

Management of Substance Abuse). 

The recently released Federal guidelines on 

prevention for persons living with HIV, which contain 

recommendations for providers, are listed in the 

Suggested Resources below. (See also Chapter 4: 

Prevention of HIV in the Clinical Care Setting.) 

PATIENT EDUCATION

What	does	patient	education	involve?	

The provider should assess the patient’s understanding 

of HIV disease and begin patient education at the 

initial evaluation. To make sound decisions regarding 

treatment, the patient must understand certain medical 

information, including:

• The critical role of the patient in his or her own care

• Natural history of HIV disease and consequences of 

immune system destruction

• How HIV is transmitted

• The meaning of the viral load and CD4 count

• The beneficial impact of antiretroviral drugs

• Early signs and symptoms of opportunistic illnesses

• The role of prophylactic agents

What	should	patients	understand	before	

beginning	antiretroviral	therapy?

Before initiating antiretroviral therapy, patients must be 

fully aware of:

• The importance of adhering completely to the 

treatment regimen

• The possibility of drug resistance and loss of 

treatment options

• The proper timing of pills and coordinating pill-taking 

with meals

• Possible side effects and long-term drug toxicities

• The option to stop treatment at any time

In addition, patients should express a commitment to 

adhere to treatment before providers initiate any form 

of treatment. (For more on adherence, see Chapter 7: 

Adherence.)

How	should	providers	incorporate	patient	

education	into	care?	

Patient education is so important that entire clinic 

visits are often devoted to a discussion of key concepts. 

Providers should use easily understood language 

and confirm the patient’s understanding of medical 

terms and concepts. During these discussions, it is 

helpful for providers to be flexible, acknowledging 

that uncertainties exist regarding optimal medical 

management of HIV disease. 

Because patient education is time-consuming, 

many HIV specialty clinics utilize staff other than 

the primary care provider, such as nurses and nurse 

practitioners who specialize in HIV clinical care, 

physician’s assistants, pharmacists, and trained peer 

educators. This interdisciplinary team approach can 

supplement the limited time primary care providers 

often have with patients. 

What	information	resources	are	available	for	

patients?

Clinics can provide patient education materials 

and make referrals to social workers, nutritionists, 

pharmacists, and financial advisers who serve as 

first-line sources of information about medical issues 

and social services available in the community. At the 

regional level, community-based HIV/AIDS organizations 

and county and State public health departments 

offer information about medical care and facilitate 

access to legal aid, financial assistance, low-income 

housing, support groups, and other social services. 

At the national level, many organizations provide 

comprehensive information about HIV/AIDS. Table 2-1 

lists recommended resources to which providers can 

refer patients for information and support. 
A Guide to Primary Care of People with HIV/AIDS

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U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 9

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Table 2-1. Information Resources for Patients 

Internet Sites

Agency Topics Web address (accessed 4/04)

AIDS Education Global Information System Daily briefing; key topics; basics; fact sheets http://www.aegis.com

AIDS Gateway to the Internet Fact sheets; conferences; news; community http://www.aids.org

AIDS Info Resource for federally and privately 

funded clinical trials http://www.aidsinfo.nih.gov/

AIDSmeds.com Extensive treatment information http://www.aidsmeds.com

American Association of Family Practice Health topics http://familydoctor.org

Centers for Disease Control and Prevention Health topics; traveler’s health http://www.cdc.gov

Guides for Living Database of social service organizations http://www.guides4living.com

HIV InSite Comprehensive site for providers and patients http://hivinsite.ucsf.edu/

Johns Hopkins AIDS Service Comprehensive site for providers and 

patients; expert Q & A; resources http://www.hopkins-aids.edu/

New Mexico AIDS Info Fact sheets; internet bookmarks http://www.aidsinfonet.org

Project Inform Fact sheets; outreach and education; 

publications http://www.projectinform.org

San Francisco AIDS Foundation AIDS 101; treatment; prevention http://www.sfaf.org

The Body Comprehensive AIDS and HIV 

information resource http://www.thebody.com

The Well Project Resource for HIV positive women http://www.thewellproject.com

Phone Numbers

Agency Topics Phone number(s)

AIDS Clinical Trials Information Service Clinical trials information 1-800-874-2572

CDC National AIDS Hotline General AIDS information, local resources for 

HIV testing and services

English 1-800-342-2437 (24/7)

Spanish 1-800-344-7432 (8 am - 2 am EST)

TTY 1-800-243-7889

Guides for Living National resource directory 1-303-702-1254

Social Security Benefits How to apply for social security benefits 1-800-772-1213

Project Inform Treatment information 1-800-822-7422

AIDS Treatment Information Service Treatment information 1-800-448-0440

Direct Access Alternative Information 

Resources Alternative Treatments 1-888-951-5433

NYC: 1-212-725-6994
A Guide to Primary Care of People with HIV/AIDS

Chapter 2: Approach to the Patient

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RISK ASSESSMENT AND

COUNSELING

What	risk-taking	behaviors	should	be	reviewed	

with	patients?

Patients infected with HIV who practice unsafe sex or 

inject drugs can infect others, be reinfected themselves 

with new HIV strains, or contract STDs, viral hepatitis, 

or other infections. Abuse of alcohol or illicit drugs 

is directly harmful and may affect adherence to a 

complicated medical regimen. Accordingly, providers 

need a detailed understanding of their patients’ 

risk-taking behaviors to guide patient education and 

counseling efforts and to assess the advisability of 

initiating antiretroviral treatment.

Table 2-2 lists specific risk-taking behaviors to review 

with patients. See also Chapter 4: Prevention of HIV in 

the Clinical Care Setting and Chapter 13: Management 

of Substance Abuse.

Table 2-2. Risk-Taking Behaviors to 

Review with Patients Infected with HIV

Sexual Practices

Number and gender of partners

Specific sexual practices

Frequency

Condom use

HIV status of partners and disclosure 

of patient’s HIV status

Anonymous partners

Association with drug use

Prior STDs

Genital ulcer disease

Drugs

Substances used

Routes of administration

Tolerance and history of withdrawal

History of drug treatment 

How	should	one	ask	about	risk-taking	

behaviors?

Explaining the rationale for reviewing risk-taking 

behaviors, informing patients that such a review is 

routine, and asking for a patient’s permission to discuss 

these topics is a good way to initiate the conversation. 

Projecting comfort with the subject material and 

proceeding in a poised, professional, nonjudgmental, 

and supportive fashion will engender trust and help 

patients feel safe enough to discuss their behavior. With 

regard to sexual behavior, asking “Do you have sex 

with men, women, or both?” indicates the provider’s 

openness to all sexual orientations. Making a comment 

that many men who have sex with men, particularly 

in certain cultures, do not self-identify as gay assures 

patients that discussing their behavior will not cause 

the provider to categorize them without their consent. 

Providers should also explore factors associated with 

sexual abstinence.

At the same time, it is important for providers to be 

realistic. Wanting a satisfying sex life is a reasonable 

desire; the goal is to minimize risk associated with sex. 

Similarly, changing addictive behavior is extremely 

difficult and often requires several attempts. Discussing 

realistic goals will enhance a provider’s credibility and 

minimize a patient’s resistance to discussing these 

subjects. The goal of this initial survey is to learn what 

patients are doing, not to draw battle lines.

What	are	effective	counseling	strategies	to	

help	patients	decrease	their	risk	taking?

When discussing risk-taking behaviors, a key first goal 

is to assess a patient’s state of preparedness for change. 

Some patients with newly diagnosed HIV come to care 

motivated to make healthy lifestyle changes. For these 

individuals, an enhanced understanding of the risks 

associated with certain behaviors in conjunction with a 

provider’s strong recommendation to modify behavior 

may suffice. Providers should also be prepared to offer 

appropriate medications (e.g., to assist with smoking 

cessation) or referrals for drug and alcohol abuse 

counseling. For patients with complicating factors such 

as severe mental illness, substance abuse, domestic 

violence, or sexual abuse, referral and close linkages with 

specialty care are essential.

What	if	a	patient	is	not	prepared	to	make	

lifestyle	changes?

Providers should deliver a clear, unequivocal message 

regarding the risks to patients and others associated 

with unsafe sex and ongoing drug use and advise 

patients of ways, such as safer sexual practices 

and needle exchange programs, to reduce risk. 

It should be kept in mind, however, that pushing 

patients unprepared for behavioral change may lead 

to animosity and resistance and that direct advice 

alone is unlikely to result in immediate or sustained 

behavioral change. For example, advice to stop smoking 

generally results in 12-month success rates of 5%-
A Guide to Primary Care of People with HIV/AIDS

Chapter 2: Approach to the Patient

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2

10%. For patients unprepared to alter their risk-taking 

behavior, a longer-term strategy is required, and a 

nonconfrontational approach such as motivational 

interviewing is recommended (see Table 2-3).

When working with a patient over time to support 

behavioral change, it is crucial for the provider to be 

a consistent source of support, hope, and optimism. 

By acknowledging positive efforts even when initial 

attempts to modify behavior fail, by continuing to offer 

encouragement, and by supporting even small progress, 

the provider can help bolster a patient’s resolve and 

sense of control over his or her actions. 

Table 2-3. Motivational Interviewing

Basic Steps:

• Seek to understand the patient’s experience 

through careful and reflective listening.

• Help the patient voice his or her own reasons 

for change.

• Recognize and accept resistance to change.

• Affirm the patient’s ability to control his or her 

own actions.

In this patient-centered approach, the provider seeks an 

accurate understanding of the patient’s unique experience 

with certain behaviors. The interviewer listens carefully to 

the patient’s thoughts about his or her behavior, monitors 

readiness for change, clarifies what the patient believes to 

be obstacles to change, identifies the patient’s own selfmotivational statements, and selectively reinforces these 

expressions of desire, intent, and ability to change. In this 

manner, the provider yields the role of “expert” and offers 

affirmation and support for the patient’s ability to control his 

or her own behavior. 

Principles to Remember: 

• For most people, motivation for change must come 

from within. Direct persuasion does not often result 

in sustained behavioral change.

• It is the patient’s task to articulate resolve and 

ambivalence.

• When patients voice resistance to change, it is 

preferable to recognize and accept a lack of 

readiness than to press for immediate change. 

Timing is important.

• Patients must understand that resolutions to 

change often slip, and failure should not become a 

reason to avoid contact with the provider.

KEY POINTS

Caring for patients with HIV/AIDS 

requires a strong provider-patient 

relationship, a multidisciplinary care 

team, and frequent office visits.

Stigma and discrimination must be 

addressed through strong confidentiality 

protections, emotional support, and 

cultural sensitivity.

Patient education about the disease 

process, treatment, and community 

resources is a vital component of care. 

The primary care provider plays a key 

role in risk assessment and counseling 

for all patients with HIV.

SUGGESTED RESOURCES

Aranda-Naranjo B, Davis R. Psychosocial 

and cultural considerations. In: A Guide 

to the Clinical Care of Women with HIV/

AIDS, 1st ed. Washington: US Department 

of Health and Human Services, HRSA, 

HIV/AIDS Bureau; 2001. Available at 

http://www.hab.hrsa.gov.

Centers for Disease Control and 

Prevention. Incorporating HIV prevention 

into the medical care of persons living 

with HIV. MMWR Recommendations and 

Reports, (July 18, 2003; 52(RR12);1-24.

Hecht FM, Wilson IB, Wu AW, Cook RL, 

Turner BJ. Society of General Internal 

Medicine AIDS Task Force. Optimizing care 

for persons with HIV infection. 

Ann Intern Med. 1999;131:136-143.

Positive Living. A practical guide for people 

with HIV. Seattle: Public Health–Seattle & 

King County, HIV/AIDS Program; 1999. 

Rollnick S, Miller WR. What is motivational 

interviewing? Behavioral and Cognitive 

Psychotherapy. 1995;23:325-334.
A Guide to Primary Care of People with HIV/AIDS

Chapter 3: Core Elements of HIV Primary Care

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INITIAL EVALUATION

What	are	the	goals	of	the	initial	evaluation?

The goals will depend to a large extent on why the 

patient is being seen by the primary care provider, 

which may be because of symptoms, the need for 

evaluation after a positive HIV test, referral, for a 

consultation, etc. The initial evaluation should be 

tailored to the patient’s specific need, but the following 

are the usual goals of the initial evaluation:

• Evaluate HIV-related complaints that require 

immediate intervention

• Establish a strong patient-provider relationship with 

clear lines of communication

• Initiate a complete medical database (Table 3-1)

• Assess the patient’s understanding of HIV disease

• Identify health needs for current medical problems, 

including those associated with mental health, 

substance abuse, hepatitis, and hypertension 

• Assess the need for social and psychological 

intervention

• Assess the need for consultants for medical, social, or 

psychiatric care

• Describe HIV disease in lay terms, including natural 

history, laboratory tests (CD4 cell count and viral 

load), complications, treatment, and outcome

• Describe methods of transmission and of prevention

This is a large menu, and there may need to be several 

“first visits.”

What	are	the	important	aspects	of	the	initial	

evaluation	in	patients	with	symptoms?	

It is critical to learn quickly if the patient has any HIVrelated complications that indicate advanced disease 

and may require rapid intervention. The most common 

presentations related to earlier HIV disease are 

thrush, weight loss, skin lesions of Kaposi’s sarcoma, 

Pneumocystis carinii pneumonia (PCP), and fever. 

Patients with HIV can also have medical conditions 

that stem from other causes, such as headaches, 

upper respiratory infections (URI), gastroesophageal 

reflux disease (GERD), hypertension, diabetes, or heart 

disease. Distinction between these and conditions that 

are HIV-related may be obvious, but when not, the best 

laboratory test is a CD4 cell count, which represents 

the barometer of immune function with HIV infection. 

Nearly all HIV-related complications occur when the 

CD4 cell count is <200/mm3. It may take 2-3 days for 

the laboratory to report the CD4 cell count, but clues 

to late-stage disease include evidence of chronic illness 

with weight loss and/or fever, and/or a total lymphocyte 

count of <1,000 mL which is readily available from 

a stat complete blood count (WBC x % lymphocytes). 

Late-stage HIV also is an indication of some urgency 

to initiate antiretroviral therapy. Some patients present 

with late complications such as PCP, cryptococcal 

meningitis, toxoplasmosis, or cytomegalovirus (CMV) 

retinitis. When these are in the differential diagnosis, 

the workup may require hospitalization, consultation, 

extensive testing, and frequent followup by telephone 

or clinic visit. These are medical emergencies – all are 

ultimately lethal and all are treatable.

Chapter	3:	

Core	Elements	of	HIV	Primary	Care	

John McNeil, MD

John V. L. Sheffield, MD 

John G. Bartlett, MD INITIAL EVALUATION

ONGOING CARE

KEY POINTS

SUGGESTED RESOURCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 3: Core Elements of HIV Primary Care

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

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Table 3-1. Initial History and Physical Examination: Key Areas for Patients with HIV/AIDS

History

Emotional reaction to HIV diagnosis Availability of friends and family for support

HIV-specific information First known positive HIV test

Documentation of positive HIV test

Possible timing and risk factors for HIV infection

Opportunistic illnesses

Prior CD4 counts, viral load measurements, and resistance tests

Prior antiretroviral therapy and side effects

Understanding of HIV disease

Transmission, natural history of immune-response destruction and opportunistic

infections, significance of CD4 counts and viral load, and antiretroviral therapy

Risk assessment Risk category

Sexual behavior history (see Table 2-2)

Current sexual activity

History of syphilis and other STDs

Substance abuse history

Intravenous and other substance abuse

Rehabilitation and interest in rehabilitation

Past medical history Use of alternative medicine 

Mental health history

Reproductive history, including pregnancies since becoming HIV positive, and 

plans for pregnancy

Tuberculosis history

History of positive PPD test, TB disease, or treatment of latent TB infection

Concurrent medical conditions (diabetes, coronary artery disease, hypertension, etc.)

Hospitalizations

Social history Housing

Food sources, 3-day diet history

Income, employment, and insurance

Emergency contacts

Legal issues

Living will and durable power of attorney for medical decisions

Permanency planning for dependent children

Physical Examination

Vital signs, weight, height

Skin Dermatitis, folliculitis, fungal infections, molluscum, and Kaposis sarcoma

HEENT Retinal exam (with CD4 < 200/mm3)

Oropharynx: oral hairy leukoplakia, candidiasis, dentition

Lymph nodes Cervical, axillary, inguinal

Abdomen Liver and spleen

Neurologic status Special focus on mental status and sensation

Genital and rectal findings Discharges, ulcers, and warts
A Guide to Primary Care of People with HIV/AIDS

Chapter 3: Core Elements of HIV Primary Care

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What	are	important	aspects	of	the	initial	

history	in	asymptomatic	patients?	

The encounters should be tailored to the idiosyncrasies 

of the individual patient’s needs supplemented with 

the collection of some routine information about their 

HIV and general health status. The patient’s most 

pressing concern may require confirming the diagnosis, 

addressing denial, dealing with “HIV hysteria,” 

evaluating conditions unrelated to HIV, or evaluating 

for antiretroviral therapy (ART). For patients with prior 

medical treatment for HIV infection, the previous 

records are often critical for efficiency in time and cost. 

When possible, these should be brought by the patient 

or sent in advance of the visit. The type of information 

that is particularly useful is the record of CD4 cell 

counts and viral loads, HIV-related complications, 

current and prior medications, including information 

about tolerance, toxicity, and adherence (see Table 3-1).

What	information	do	patients	need	to	know	

about	HIV?	

HIV is a chronic infection, which will be lifelong, and its 

outcome will depend to a large extent on the patient’s 

understanding of the disease process and management. 

Parallels with type 1 diabetes are clear. With this in 

mind, it is very important that the patient have access 

to information to advance his or her understanding of 

the disease. Essential knowledge includes:

• Transmission Sex, injection drug use, and perinatal 

transmission are the “big 3” and have accounted for 

virtually all cases in the United States since blood 

began being screened in 1985. 

• Natural history Explain the 5 stages: 1) acute HIV, 

2) seroconversion, 3) long period with no symptoms 

and decreasing CD4 cell count, 4) complications 

when the CD4 cell count is <200/mm3, and 5) lethal 

outcome. Emphasize that without therapy the average 

untreated patient survives about 10 years from HIV 

acquisition to death, but there is a great deal of 

individual variation. 

• What does the CD4 cell count mean? This is the 

cell that becomes infected with HIV, it is also the 

quarterback of the immune system, and the count is 

a barometer of immunosuppression. Normal is >500/

mm3; a count of <200/mm3 is the definition of AIDS.

• What does the viral load mean? This indicates the 

amount of HIV in the blood. The average is about 

30,000 copies per ml (c/ml), but again there is a 

great deal of individual variation. When it is high, 

the CD4 cell count tends to decline rapidly (negative 

CD4 slope). The goal of therapy is to reduce the viral 

load to undetectable levels, and with this the CD4 cell 

count usually increases 100-150 cells/mm3 each year.

• Therapy Potent antiretroviral therapy (ART, also called 

highly active antiretroviral therapy, or HAART) has 

revolutionized the course of this disease. Although 

a miraculous development, HAART is also terribly 

demanding for the patient in terms of adherence, and 

some patients have big problems with side effects 

that are either short-term (eg, nausea, rash, asthenia) 

or long-term (eg, fat redistribution, hyperlipidemia, 

peripheral neuropathy). The benefits clearly 

outweigh the risks, and HIV is no longer an inevitably 

progressive disease, but is a chronic condition such 

as hypertension or diabetes that requires continual 

observation and care.

• Cure No cure yet and unlikely to be with any of the 

current medications.

• Prevention See discussion below.

For more information, see Chapter 2: Approach to the 

Patient (section on Patient Education, especially Table 

2-1, Information Resources for Patients).

How	should	prevention	be	addressed?	

Prevention needs to be addressed early and frequently, 

usually at every encounter. Nearly all adults who 

acquired HIV after 1985 did so by sexual exposure or 

needle sharing in the context of injection drug use. 

Patients in HIV clinics now constitute an important 

source for HIV transmission by the same mechanisms. 

Health care providers are now considered essential in 

risk reduction with a 3-part responsibility:

• Risk behavior screening Patients need to be screened 

for risk behaviors. The screening includes a history 

of sexual practices and a clinical assessment for 

evidence of sexually transmitted diseases (STDs). 

The history of sexual practices can be taken before 

patients are seen by the primary care provider, 

either by another staff member or by having patients 

complete questionnaires. A component of the 

assessment includes evaluation for STDs because 

having STDs is associated with a 5-fold increase 

in the risk of transmitting HIV and also indicates 

high-risk sexual activities. Women under 25 years 

old should be screened for cervical Chlamydia 

trachomatis, all symptomatic patients should be 

evaluated for gonococcal and chlamydia infection, 

and asymptomatic patients should be considered 

for screening for these pathogens. Screening is now 

facilitated by the use of urine specimens for nucleic 

acid amplification tests (NAAT) for both N. gonorrhoeae

and C. trachomatis.

• Risk reduction counseling The second component of 

prevention is risk reduction counseling, which may be 

done in the office or through referral. It is critical that 

patients be fully informed about how HIV is and is not 

transmitted and that they be counseled about how 

they can reduce the risk of transmitting HIV to others.
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• Partner referral The third component, partner 

referral, involves asking patients to identify persons 

whom they have placed at risk through sexual or drugusing behaviors. These persons are then referred to 

a “Partner Counseling and Referral Service” (PCRS) 

without identifying the source of the information. 

The PCRS provides public health resources for 

confidentially informing partners that they have been 

exposed to HIV and need HIV counseling and testing. 

For more information on prevention, see Chapter 2: 

Approach to the Patient (section on Risk Assessment 

and Counseling), Chapter 4: Prevention of HIV in the 

Clinical Care Setting, and Chapter 13: Management of 

Substance Abuse . 

What are common patient questions?

Patients have many questions when they are newly 

diagnosed with HIV. 

• What will happen to me? Patients need to know the 

facts of HIV regarding prognosis, but emphasis should 

be placed on the extraordinary benefits of therapy, 

which, for many, may mean a normal lifespan.

• Can HIV be cured? Not with current drugs (but it can 

be contained). 

• Will I need to take medicine forever? Patients 

who respond well to therapy will probably be able 

to discontinue treatment periodically, but regularly 

scheduled treatment interruptions generally result in 

poor long-term control of HIV.

• Would alternative medicine help me? Probably 

not, but some patients seem to think it does. Patients 

should be encouraged to report any alternative 

medicines they are taking because some of them are 

problematic in combination with ART.

• Will I give HIV to the people I live with? Patients 

can give HIV to anyone they have sex with or share 

needles with; however, they also need to understand 

that people who live in the same household without 

that kind of contact are not at risk. It is probably best 

for people with HIV to have their own toothbrushes 

and razors and not to share eating utensils that have 

not been washed, even though HIV is not generally 

transmitted that way.

• Are pets a problem for me? Pets don’t give or get 

HIV. Occasionally cats will become the source of 

Toxoplasma gondii or Bartonella, but this is rare; 

patients should wash their hands after handling pets 

and especially before eating, avoid contact with cat 

stool to prevent toxoplasmosis, and avoid cat bites and 

scratches and fleas to avoid bartonellosis. 

• Should I have a special diet? Nutrition is important, 

but there is nothing idiosyncratic about the needs 

of people with HIV (see Table 2-1 in Chapter 2 for 

nutrition resources). With late-stage disease, it might 

be smart to avoid ingesting lake water because of 

Cryptosporidium parvum, which is commonly present 

and can cause chronic disease. 

• Can I travel? Certain vaccines required for travel to 

developing countries are best avoided by people with 

suppressed immune systems, but vaccines rarely 

interfere with travel. The biggest problem may be 

access to good health care and the usual conditions 

such as traveler’s diarrhea that can affect any traveler.

• What will happen if I am around someone with a 

cold or some other common infection? This type 

of exposure would probably cause nothing more 

than an ordinary cold. People with HIV infection do 

not become susceptible to infectious complications 

until the CD4 cell count is low. Then they become 

vulnerable to a very specific menu of infectious 

disease complications that are extremely rare in the 

general public. The infections that are common, such 

as upper respiratory infections or gastroenteritis, are 

generally no worse in a person with advanced HIV 

disease than in a healthy person. 

• My cousin has a newborn infant that I want to visit. 

Is this a good idea? There should be no reservations 

here and no reason to talk about HIV infection. It’s 

okay to hold, kiss, and hug the child; patients should 

just obey the simple rules of hygiene that they would 

under ordinary circumstances. 

• Who should I tell? People who have been placed 

at risk either sexually or through drug use need to 

know, and either the patient can tell them or health 

department staff can do it. The reason is that they 

need to be tested so that if they are infected they do 

not transmit HIV to others, and they also need to gain 

access to care, which is critical. Beyond that, patients 

should be counseled to be very careful who they tell 

about the diagnosis.

• Do I need to tell people at work? Generally no. HIV 

is not transmitted by HIV-infected workers in the 

work place. A rare exception is some health care 

workers who could conceivably transmit HIV infection 

during surgery. Most institutions have policies about 

health care workers who perform invasive procedures, 

and these need to be followed. Otherwise, there are 

no other circumstances in which anyone needs to 

know unless the symptoms of HIV interfere with 

effective performance. 

What	should	be	covered	in	the	physical	exam?

Everything, but special attention should be paid to 

scrutiny of the vital signs, enlargement of lymph nodes, 

skin lesions, enlargement of liver or spleen, and mental 

status (see Table 3-1).

What	are	the	initial	laboratory	tests	to	order?

Standard laboratory testing should be done to stage the HIV 

disease, determine the general health status, and identify 

the presence of concurrent conditions, and baseline tests 

should be done on patients who are candidates for ART 

(see Table 3-2). In general, the CD4 cell count identifies the 

need to treat with antiretroviral drugs, and the viral load is 

the major indicator of therapeutic response. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 3: Core Elements of HIV Primary Care

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Table 3-2 Laboratory Testing in HIV Primary Care

(Revised 10/8)

Test Baseline Repeat Comment

Confirmation of Positive HIV Status

Standard HIV 

serologic test 

Either copy of 

prior lab results or 

new tests

Make sure there is a confirmed positive result with standard HIV 

serologic test

HIV Staging

CBC Yes Repeat at 3-6 month 

intervals

Repeat more often with some drugs or abnormalities

CD4 count Yes Repeat at 3-6 month 

intervals

Evaluates immune status 

HIV viral load Yes Repeat at 3-month 

intervals

Prognostic indicator

Repeat more frequently with initiation of ART

Health Status Evaluation

Chemistry panel Yes Repeat annually Repeat more frequently with abnormalities

Pap smear Yes Repeat at 6 months and 

then annually

PPD Yes if no history 

of TB or a prior 

positive test

Repeat if initial test was 

negative and patient was 

exposed, or if CD4 count 

increased to > 200/mm3

Hepatitis screen

HAV Optional Screen once to identify candidates for HAV vaccine 

HBsAg Test if abnormal liver function tests

anti-HBc or 

anti-HBs

Yes Identify candidates for HBV vaccine

HCV Yes Screen especially if liver disease present

STDs

VDRL or RPR Yes Repeat annually in 

sexually active patients

Syphilis screen

Urine 

nucleic acid 

amplification 

test (NAAT) 

for N. 

gonorrhoeae 

and C. 

trachomatis

Consider for 

sexually active 

patients

Consider annual testing 

or more frequently if at 

high risk

First-catch urine or urethral (male)/cervical (female) specimen

Chest x-ray Optional Must do if positive PPD or chest symptoms

Toxoplasma 

gondii IgG

Yes Consider repeating if there are typical symptoms and negative 

prior test

Baseline for HAART

Fasting glucose Yes

Fasting lipids Yes
A Guide to Primary Care of People with HIV/AIDS

Chapter 3: Core Elements of HIV Primary Care

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

3

ONGOING CARE

Af ter	the	initial	evaluation	is	completed,	how	

of ten	do	patients	need	to	be	seen?	

In general, patients with early-stage disease are seen 

at 3-month intervals to undergo routine medical 

evaluation and monitoring of CD4 cell count, viral 

load, and CBC. During the initial evaluation more 

frequent visits are common because there is so much 

information to transmit. Visits should also be more 

frequent when therapy is introduced and when the 

CD4 cell count is <200/mm3 because complications 

are more likely. It is very important for the primary 

care provider to thoroughly understand HIV and 

its complications. In general, the patients are in 4 

categories with some overlap: 1) those with a CD4 cell 

count of >200/mm3, whose complaints are rarely due 

to HIV or its complications, 2) patients with a CD4 cell 

count of <200/mm3, whose new complaints usually 

reflect an HIV-related complication which is usually 

both potentially serious and treatable, 3) patients 

from either group who are receiving ART and other 

medications, in which case the side effects of the drugs 

must be considered, and 4) patients with other medical 

problems, which is actually the rule rather than the 

exception because of the high frequency of concurrent 

conditions.

How	can	one	provider	take	care	of	all	of	

the	problems?	

HIV is generally a complex disease in patients 

with complicated lives, lifestyles, and concurrent 

conditions. They are best served by a multidisciplinary 

team with ancillary services for support regarding 

case management, mental health, substance abuse 

treatment, transportation, and housing assistance, using 

the chronic disease model of care. Another model of 

care emphasizes patient self-management, with the 

patient as the principal caregiver supported by a wellprepared practice team with a clear division of labor. 

The patient is linked not only to the provider unit (the 

clinic) but also to community-based resources and 

support from the larger health care organization.

What	needs	to	be	done	in	the	follow-up	

evaluations?	

Follow-up evaluations are important to document 

disease trends and response to therapy and to assess 

high-risk behavior. This includes history, physical exam, 

and lab tests (see Tables 3-1 and 3-2). In general, the 

review needs to be tailored to the specific needs of the 

patient. Sometimes the major issue is a concurrent 

condition such as hepatitis C, mental illness, or 

substance abuse requiring resources that are best 

achieved with a multidisciplinary approach. For 

patients who are receiving ART and prophylactic drugs 

to prevent opportunistic infections, heavy emphasis 

needs to be placed on adherence and drug-related 

toxicities as discussed in Chapter 7 or on symptoms 

related to HIV complications as discussed in Chapters 

8, 9, and 10. Under all circumstances, it is important to 

periodically assess the patient’s knowledge of HIV since 

misconceptions are common and patients are often 

reluctant to ask the questions that bother them most. 

In virtually all encounters, it is important to emphasize 

prevention.

In patients at highest risk for STDs (multiple or 

anonymous partners, sex in conjunction with illicit 

drug use, patients whose partners participate in these 

activities, high prevalence of STDs in the area or in the 

patient population), STD screening is recommended 

more frequently than annually (see Chapter 4).
A Guide to Primary Care of People with HIV/AIDS

Chapter 3: Core Elements of HIV Primary Care

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 19

3

KEY POINTS

The focus of the first visit is determined 

by the patient’s most immediate needs.

The initial evaluation is complex and 

usually requires several visits.

An important aspect of primary care 

is answering the patient’s questions to 

ensure that he or she understands the 

HIV disease process and treatment.

While patients with early-stage HIV 

disease can be seen at 3-month intervals 

for routine medical evaluation, those 

receiving ART or with more advanced 

disease must be seen more frequently.

A multidisciplinary team approach with 

the patient as primary caregiver is the 

best approach to care.

SUGGESTED RESOURCES

Bartlett JG, Gallant J. Medical Management 

of HIV Infection. Baltimore, MD: Johns 

Hopkins University; 2003.

Buckley RM, Gluckman SJ. HIV Infection 

in Primary Care. Philadelphia, PA: WB 

Saunders, 2002.

Centers for Disease Control and 

Prevention. Incorporating HIV Prevention 

into the Medical Care of Persons Living 

with HIV. MMWR. 52(RR12):1-24. July 18, 

2003. Available at: http://www.cdc.gov/hiv/

pubs/guidelines.htm#prevention.

Hecht FM, Wilson IB, Wu AW, et al. Society 

of General Internal Medicine AIDS Task 

Force. Optimizing care for persons with HIV 

infection. Ann Intern Med. 1999;131:136-143.

Nerad J, Romeyn M, Silverman E, et al. 

General nutrition management in patients 

infected with human immunodeficiency virus. 

Clinical Infect Dis. 2003;36(Suppl. 2):S52-62.

Sande MA, Volberding PA, Eds. The 

Medical Management of AIDS – 6th ed. 

Philadelphia, PA: WB Saunders; 1999. 

WEBSITES

AIDSInfo: http://www.aidsinfo.com

Accessed 9/03.

AIDS Education Global Information System: 

http:// www.aegis.com Accessed 9/03.

Centers for Disease Control and Prevention 

Division of HIV/AIDS Prevention: http://

www.cdc.gov/hiv/dhap.htm Accessed 10/03.

HIVInsite: http://www.hivinsite.ucsf.edu

Accessed 10/03.

Johns Hopkins AIDS Service: http://

www.hopkins-aids.edu Accessed 10/03.

STD/HIV Prevention Training Centers: http://

depts.washington.edu/nnptc/ Accessed 10/03.
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 21

4

RATIONALE FOR HIV 

PREVENTION IN

PRIMARY CARE

Why	is	HIV	prevention	important	in	the	

HIV	clinical	care	set ting?

Why rob banks?...

Because that is where the money is!

There is growing awareness that the majority of people 

living with HIV are having sex and that active substance 

abuse, often with needle-sharing behavior, remains 

common in the setting of HIV infection (see Chapter 13: 

Management of Substance Abuse). The HIV clinical care 

setting provides an opportunity to work with patients 

to reduce their risk of transmitting HIV to others. 

Studies are under way to measure the effectiveness of 

comprehensive clinical care in preventing the spread of 

HIV. Until those results are available, one should assume 

that interventions to reduce HIV concentrations in the 

body through antiretroviral therapy (ART) combined 

with behavioral counseling to reduce high-risk sexual 

behaviors and, when indicated, drug abuse treatment 

are important approaches to decreasing the incidence 

of HIV infection.

Do	most	primary	care	providers	incorporate	

HIV	prevention	into	their	care?

Experienced providers, and even HIV specialists, often 

do not conduct screening and assessment of behavioral 

risk or offer prevention counseling for their HIV-infected 

patients. The degree to which these are neglected is 

startling. Nationwide, approximately a third of HIVinfected patients report that their providers have never 

counseled them about HIV prevention; in some settings 

as many as three quarters of HIV medical care providers 

do not ask about sexual behavior and as many as half do 

not ask about drug use (Marks et al, 2002; Natter et al, 

2002). Results of an unpublished study suggest that HIV 

specialists are less likely than primary care physicians to 

engage clients in discussions about sexual and drug-using 

behaviors. Barriers of time, training, and comfort level 

contribute to this missed opportunity for HIV prevention. 

What	factors	are	associated	with	high-risk	

behaviors	of	people	living	with	HIV?

People living with HIV often practice high-risk sexual 

and drug-using behaviors in association with poor 

adherence to clinical care in general and to ART 

regimens in particular (Wilson et al, 2002). This is of 

particular concern given the risk of viral resistance with 

poor medication adherence, which may subsequently 

result in transmission of resistant viral strains to others. 

Also, both adherence to HIV prevention practices and 

adherence to medication regimens appear to be related 

to mental health problems, which are common among 

people with HIV (Kalichman et al, 2002). In particular, 

depression and anxiety disorders are common and 

should be assessed in patients who report continued 

high-risk sexual and drug-using behaviors. Any of 

these conditions should alert the provider to probe 

for problems in the other conditions or behaviors; 

addressing underlying issues can lead to improvements 

in several important behaviors.

What	behavioral	interventions	work	

to	prevent	people	living	with	HIV	from	

transmit ting	HIV?

The earliest behavioral interventions provided factual 

information and generated fear of AIDS to motivate 

people to reduce high-risk behavior. Most experts now 

agree that these interventions do not effectively reduce 

high-risk behaviors of persons at greatest risk for 

acquiring HIV, and that generating fear of AIDS most 

likely increases stigmatization of people living with 

HIV infection.

Chapter	4:	

Prevention	of	HIV	in	the	Clinical	Care	Setting

Michael P. Johnson, MD, MPH

RATIONALE FOR HIV PREVENTION IN PRIMARY CARE

INTERVENTIONS FOR HIV PREVENTION

KEY POINTS

SUGGESTED RESOURCES

REFERENCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

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

4

A number of counseling interventions have been 

found to be more effective than providing knowledge 

alone. Among these effective approaches are brief, 

provider-delivered counseling messages, which can 

be delivered within the context of a clinical encounter 

(Kamb et al, 1998; CDC, 2001). Several theoretical 

behavioral models have been used to guide counseling 

interventions. Some common elements of these theorybased counseling approaches include:

• Establishing dialogue and rapport with the client 

and providing ongoing services in an understanding 

and nonjudgmental manner, often with the support 

of trained peers to supplement the provider-based 

counseling

• Understanding and addressing client needs, situations, 

and pressures for sexual and drug-using behavior (eg, 

mental health needs), with emphasis on issues that 

might be perceived by the client as more pressing 

than HIV prevention (eg, food, housing, employment), 

and external barriers to the adoption of safer 

behaviors (eg, domestic violence)

• Addressing the client’s high-risk behavior in a 

step-wise manner, understanding the readiness 

and motivation for a change in each specific highrisk behavior, and building the client skills for 

implementing such changes

These elements are the basis for the assessment and 

counseling recommendations discussed below, which 

can be implemented in the clinical setting, along with 

planning and mobilization of supportive services. 

What	is	the	role	of	drug	abuse	treatment	in	

preventing	HIV	transmission?

Sharing of drug-injection paraphernalia is directly 

related to HIV transmission through the transmission 

of infected blood. Drug and/or alcohol abuse indirectly 

lead to HIV transmission through the exchange of sex 

for drugs and enhanced sexual risktaking under the 

influence of these substances. Drug abuse treatment is 

an important intervention in the setting of HIV clinical 

care (see Chapter 13) and should be considered as 

an important and effective means of HIV prevention 

among persons with HIV who abuse drugs and/or 

alcohol.

What	is	known	about	the	role	of	antiretroviral	

therapy	in	preventing	HIV	transmission?

Effective ART leads to a decline in plasma viral 

load, which reduces the risk of maternal-infant HIV 

transmission. The risk of sexual transmission of HIV 

is strongly correlated with plasma HIV levels (Quinn, 

2000) (see Figure 4-1). There is also a strong correlation 

between changes in plasma viral load and the HIV 

viral load in genital secretions (Ball et al, 1999); 

however, HIV can be present in genital secretions 

when plasma HIV is suppressed below the level of 

detection. While it is highly likely that effective ART 

leads to a significant reduction in HIV infectivity, from 

a behavioral standpoint an increase in high-risk sexual 

behavior because of a sense of lower risk to others 

has been observed in persons being treated with ART 

(Dukers, 2001; Scheer, 2001). For this reason, HIV 

prevention counseling remains important for those on 

effective ART, and it is particularly important when viral 

loads rise, eg, due to interruption of therapy and/or 

emergence of viral resistance.

Figure 4-1. Associations of HIV Plasma Viral 

Load and Sexual Transmission of HIV

Transmission Rate

per 100 person-years

HIV-1 RNA (copies/ml)

>50,000 10,000-49,999 3,500-9,999 400-3,499 <400

0

5

10

15

20

25

 Source: Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and 

heterosexual transmission of human immunodeficiency 

virus type 1. N Engl J Med. 2000;342:921-929. Copyright 

2000 Massachusetts Medical Society. All rights reserved. 

Reprinted with permission.

What	is	the	role	of	nonoccupational	

postexposure	prophylaxis	(nPEP)	in	the	

prevention	of	HIV	infection?

Nonoccupational postexposure prophylaxis (nPEP) 

refers to the use of ART to prevent HIV after a 

significant sexual exposure to HIV (eg, after sexual 

assault or condom breakage during intercourse 

between a discordant couple). A complete review 

of postexposure prophylaxis (PEP) can be found in 

Chapter 11: Postexposure Prophylaxis. In summary, a 

28-day course of ART may be considered for prevention 

of nonoccupational HIV transmission if therapy is 

initiated within 72 hours after a significant exposure 

from a person with known or suspected HIV infection. 

This approach will be addressed in upcoming US Public 

Health Service (PHS) guidelines for nPEP (watch the 

AIDSInfo website listed in Suggested Resources for 

these guidelines). 
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 23

4

INTERVENTIONS FOR HIV 

PREVENTION

What	can	the	provider	do	to	enhance	

prevention	practice	in	the	clinical	set ting?

Primary care interventions to assess and reduce the 

risk that HIV-infected persons will transmit the virus to 

others can be conducted at the level of 1) medical care, 

2) other care (eg, case management, social services), 

and 3) clinic structure. Ideally, interventions at all 3 

levels are combined to maximize the opportunities 

for HIV prevention, and each clinic will structure its 

interventions differently according to its configuration 

and resources. The following recommendations are 

directed primarily to the medical provider, although 

there are often other clinic staff members who support 

and reinforce these risk assessment and counseling 

interventions. Training can enhance the skills and 

motivation for providers to integrate these activities 

into their routine practice (see Suggested Resources and 

Chapter 18: Keeping Up-to-Date: Sources of Information 

for the Provider).

How	can	the	provider	identify	a	patient’s	risk	

behaviors?	

A brief history should be taken at each regularly 

scheduled clinic visit to identify knowledge of HIV 

transmission, sexual and drug-using behavior, and 

symptoms of an STD (eg, urethral or vaginal burning 

or discharge, dysuria, genital or anal ulcers, intermenstrual bleeding, or lower abdominal pain in 

women). History-taking methods include written, 

audio, and computerized questionnaires and face-toface interviews, using either structured or open-ended 

questions (see examples in Table 4-1). Studies suggest 

that patients may provide more honest and detailed 

responses to questionnaires not administered face-toface. Also, physicians trained in discussing sensitive 

sexual and drug-using issues are likely to perform 

better than those who are not. Providers should give 

positive reinforcement to patients when the screening 

questions indicate no high-risk sexual and drug-using 

behaviors. Conversely, indications of high-risk behavior 

should trigger a medical/laboratory evaluation for 

STDs, behavioral risk assessment and counseling 

interventions, and referral and contact notification, 

as indicated. For more detailed discussion, see the 

section on Risk Assessment and Counseling in Chapter 

2: Approach to the Patient as well as the screening 

questions for drug abuse in Chapter 13: Management of 

Substance Abuse. 

Table 4-1. Examples of Open- and 

Closed-ended Risk-screening Questions

Open-ended questions 

What do you know about HIV transmission?

What, if anything, are you doing that could 

result in transmitting HIV to another person?

Tell me about any sexual activity since your last 

clinic visit.

What do you know about the HIV status of each 

sex partner?

Tell me about condom use during any sexual 

activity.

Tell me about any drug use or needle sharing 

since your last clinic visit.

Closed-ended questions 

Do you know the facts about how HIV is and is 

not transmitted? 

Have you had sex (vaginal, anal, or oral) with 

any partner since your last clinic visit?

For each of your partners, do you know if 

he/she has HIV infection, doesn’t have HIV 

infection, or are you not sure?

Did you use a condom every time, from start to 

finish of each sexual encounter?

Have you shared drug injection equipment 

(including needle, syringe, cotton, cooker, 

water) with anyone?

Note: Symptoms of STDs (eg, urethral or vaginal 

burning or discharge, dysuria, genital or 

anal ulcers, inter-menstrual bleeding or 

lower abdominal pain among women) 

are asked in a closed-ended format, 

regardless of behavioral question format.

What	medical	and	laboratory	screening	should	

be	done?

Symptoms or signs of an STD or known exposure to 

STDs should prompt immediate physical and laboratory 

examinations. However, because STDs are often present 

without symptoms, every patient should be screened 

for laboratory evidence of syphilis, trichomonads 

(women only), gonorrhea, and chlyamdia at the initial 

visit and at least annually (see Table 4-2). Some experts 

also recommend type-specific testing for herpes 

simplex virus type 2 because of its association with 

a higher risk of HIV transmission and possible need 
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

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

4

for enhanced counseling. More frequent screening 

for STDs is appropriate with evidence or suspicion of 

high-risk sexual behavior (eg, sex with a new partner, 

sexual activity without consistent and correct condom 

use); however, there are no data to guide the precise 

frequency. More frequent screening might also be 

appropriate in asymptomatic men who have sex with 

men (MSM) and younger women because of a higher 

STD prevalence among these demographic groups. 

The local prevalence of these infections might guide 

frequency of screening. Laboratory screening for drug 

abuse is addressed in Chapter 13.

Table 4-2. Screening for Sexually 

Transmitted Diseases 

STD Recommended test

Syphilis Non-treponemal serologic test 

(RPR, VDRL)

Gonorrhea Nucleic acid amplification test 

(first-catch urine or urethral [male]/

cervical [female] specimen) or 

culture (urethral [male]/cervical 

[female] specimen)

Chlamydia Nucleic acid amplification test 

(first-catch urine or urethral [male]/

cervical [female] specimen)

Trichomonas Wet mount or culture 

(vaginal secretion)

Herpes simplex virus Type-specific HSV-2 

antibody testing

What	behavioral	assessment	and	counseling	

interventions	should	the	provider	implement?

Specific suggestions for assessment and counseling 

are presented in Table 4-3 and in Chapter 2. Each 

clinic must decide which aspects of HIV prevention 

assessment and counseling are best done by the 

primary provider, by other clinical providers with whom 

the patient interacts, or some combination of both. 

Brief interventions by physicians have been found to 

be effective with other conditions, including smoking 

cessation, improving dietary behavior, and reduction of 

alcohol consumption. Thus, while data are limited on 

the topic of HIV prevention, physicians should provide 

such counseling until studies suggest alternate and 

improved approaches.

How	can	clinic	staff	other	than	the	primary	

medical	provider	enhance	HIV	prevention	

practice?

In most medium-sized and larger clinics, staff 

members other than the primary medical provider 

are responsible for referral, contact notification, and 

quality improvement, which can all be used to enhance 

prevention practice, as discussed below. In addition, 

specific structural interventions (eg, arranging client 

flow to ensure interaction with clinic staff who conduct 

prevention counseling, use of video, written handouts 

or other educational media, and distribution of 

condoms) can strengthen the role of other clinic staff in 

prevention activities. 

What	role	does	referral	to	community	

resources	play	in	HIV	prevention?	

Some complex patient issues and conditions fall 

beyond the scope of a primary care clinic and must 

be addressed before risky behavior can be reduced or 

eliminated. These include drug abuse, mental health 

issues, domestic violence, and assistance with needs 

such as housing, food, and employment. Each clinic 

should have established relationships with community 

resources to address these issues, and staff members 

should have thorough knowledge of the available 

services as well as mechanisms in place to ensure that 

patients can access the services. Finally, followup should 

be done to be certain that the referrals are utilized 

and are effective for each patient. It is unlikely that 

persons at highest risk for transmitting HIV to others 

can effectively reduce such behavior without access to a 

comprehensive array of services and supports. 

What	are	key	elements	of	contact	notification?	

Contact notification is an effective way to identify 

additional HIV-infected persons through HIV counseling 

and testing, bring them into care, and provide support 

to help them avoid transmitting HIV to others. Health 

departments traditionally conduct contact notification; 

in some States providers are required by law to report 

to the health department known sexual or drugequipment-sharing contacts of persons infected with 

HIV. The standard method is to inform the patient’s 

contacts that they have been placed at risk and need 

HIV testing without identifying the source.
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 25

4

Table 4-3. Suggested Counseling Content for Behavioral Risk Reduction

Factual topics about 

HIV transmission Suggested content

Relative risk of HIV transmission during sex Most to least risky activities: receptive anal > receptive vaginal > insertive anal > 

insertive vaginal > receptive oral > insertive oral

Preventing HIV transmission during 

sexual activity

Abstinence (safest behavior)

Correct condom use (latex or polyurethane condoms, used with water-based, 

not oil-based, lubricants, used from start to finish of any sexual penetration)

Other means of reducing risk

Effect of drug use on sexual decisionmaking Potential increase in sexual risk behavior following drug and/or alcohol use

Risk of HIV transmission when 

sharing drug-injection equipment 

Highest risk for HIV transmission 

Risk of other disease transmission for either user

Entire works (drug paraphernalia), not only needles, need to be clean

Impact of viral load level on HIV 

transmission risk

Greatest risk of HIV transmission when viral load is elevated 

(eg, when antiretroviral therapy is stopped or is ineffective)

HIV transmission still possible during effective antiretroviral therapy (eg, there 

can be HIV in genital secretions even when plasma viral load is undetectable)

Components of assessment 

and counseling Suggested content

Motivation for HIV prevention Risk to self: acquiring non-HIV infectious agent and acquiring 

drug-resistant HIV strain

Risk to others: transmitting HIV

Readiness and capacity for HIV prevention Patient’s belief about his/her desire, intent, and sense of capacity 

to adopt behaviors that prevent HIV transmission

Barriers to adopting safer sexual and drug-using 

behaviors

Identification of barriers, such as mental health needs, substance 

abuse, domestic violence, and other social and economic pressures that might 

impede the adoption of behaviors to prevent the transmission of HIV

Willingness to accept in-depth counseling 

and/or referral to overcome barriers to 

adopting safer behaviors

Identification of history of past efforts to address the issue impeding 

the adoption of safer behavior

Encouragement and offering of assistance for more 

in-depth support through referral

Development of an HIV prevention plan Creation of a plan mutually agreeable to patient and provider, 

written for both the medical record and the client

Discussion of reproductive intentions Assessment of need for in-depth counseling with HIV-experienced 

obstetrician to address risks and benefits of conception
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

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

4

How	can	HIV	prevention	be	made	a	part	of	

routine	clinic	practice?

HIV prevention, often neglected as a component of 

HIV clinical care, is more likely to be a part of routine 

clinic practice if it is part of the clinical continuous 

quality improvement activities (see Chapter 17: Quality 

Improvement). While the most effective indicators for 

prevention practice in the clinical setting are not known, 

considerations include medical record documentation 

of risk assessment history, prevention counseling, 

medical/laboratory examination for STDs, establishment 

of a prevention plan, and completion of referrals. There 

should be regular assessment of whether such tasks 

are completed and regular feedback to staff members 

regarding the success rates of completing these 

interventions. Finally, training interventions should 

be guided by data from these quality improvement 

activities (see Chapter 18). 

KEY POINTS

The HIV clinical care setting offers 

an ongoing opportunity to work 

with patients to reduce their risk of 

transmitting HIV to others.

Common elements of behavioral 

interventions to reduce HIV risktaking 

include establishing rapport with the 

patient, addressing immediate patient 

needs (eg, mental health problems, 

substance abuse, housing), and working 

in small steps to build motivation and 

skills for change.

A brief history of patient risk behaviors 

and HIV prevention counseling should be 

parts of each patient visit.

Besides HIV prevention counseling, the 

following are important components of 

HIV prevention in the clinical setting: 

contact notification, drug abuse treatment, 

screening for STDs, decreasing the 

patient’s viral load through ART, and nPEP.

Structural interventions for HIV 

prevention include making available 

educational materials and condoms, 

establishing strong referral relationships 

with social service and substance abuse 

services, and incorporating prevention 

indicators into quality improvement 

activities.

SUGGESTED RESOURCES

Institute of Medicine/Committee on 

HIV Prevention Strategies in the United 

States. No time to lose: getting more 

from HIV prevention. Ruiz MS, Gable 

AR, Kaplan EH, Stoto MA, Fineberg HV, 

Trussell J, eds. Washington DC: National 

Academy Press. 2001. 

Centers for Disease Control and Prevention. 

Advancing HIV prevention: New strategies 

for a changing epidemic – U.S. 2003. 

MMWR. 2003;52:329-332. Available at 

http://www.cdc.gov/hiv/pubs/mmwr.htm.

Centers for Disease Control and 

Prevention. Incorporating HIV prevention 

into the medical care of persons living 

with HIV. MMWR. 52(RR12):1-24. July 18, 

2003. Available at: http://www.cdc.gov/hiv/

pubs/guidelines.htm#prevention.

WEBSITES

AIDSInfo: http://www.AIDSInfo.nih.gov

Accessed 11/03.

HIVInsite: http://www.hivinsite.org?InSite?p

age=Prevention Accessed 11/03.

STD/HIV Prevention Training Centers 

(PTCs): http://depts.washington.edu/nnptc

Accessed 10/03.
A Guide to Primary Care of People with HIV/AIDS

Chapter 4: Prevention of HIV in the Clinical Care Setting

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 27

4

REFERENCES

Ball JK, Curran R, Irving WL, Dearden 

AA. HIV-1 in semen: determination of 

proviral and viral titres compared to blood, 

and quantification of semen leukocyte 

populations. J Med Virol. 1999;59:356-363.

Centers for Disease Control and Prevention. 

Revised guidelines for HIV counseling, 

testing and referral. MMWR. 2001;50

(RR-19):1-57. 

Dukers NH, Goudsmit J, de Wit JB, Prins 

M, Weverling GJ, Coutinho RA. Sexual 

risk behavior relates to the virological 

and immunological improvements during 

highly active antiretroviral therapy in HIV-1 

infection. AIDS. 2001;15:369-378.

Kalichman SC, Rompa D, Luke W, Austin 

J. HIV transmission risk behaviors among 

HIV positive persons in serodiscordant 

relationships. Int J STD/AIDS. 2002;13:677-

682.

Kamb ML, Fishbein M, Douglas JM, et al. 

Efficacy of risk-reduction counseling to 

prevent human immunodeficiency virus and 

sexually transmitted diseases; a randomized, 

controlled trial. Project RESPECT Study 

Group. JAMA. 1998;280:1161-1167.

Marks G, Richardson JL, Crepaz N, et al. Are 

HIV care providers talking with patients 

about safer sex and disclosure?: A multiclinic assessment. AIDS. 2002;16:1953-1957.

Natter J, Fiano T, Gamble B, Wood RW. 

Integrating HIV prevention and care services: 

the Seattle “Collaboration Project.” J Public 

Health Manag Pract. 2002 Nov;8:15-23.

Quinn TC, Wawer MJ, Sewankambo N, et al. 

Viral load and heterosexual transmission of 

human immunodeficiency virus type 1. N 

Engl J Med. 2000;342:921-929.

Scheer S, Chu PL, Klausner JD, Katz MH, 

Schwarcz SK. Effect of highly active 

antiretroviral therapy on diagnoses of 

sexually transmitted diseases in people with 

AIDS. Lancet. 2001;357:432-435.

Wilson TE, Barron Y, Cohen M, et al. The 

Women’s Interagency HIV Study. Adherence 

to antiretroviral therapy and its association 

with sexual behavior in a national sample 

of women with human immunodeficiency 

virus. Clin Infect Dis. 2002;34:529-534.
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 29

5

THE PRINCIPLES OF

ANTIRETROVIRAL THERAPY

(ART)

What	are	the	goals	of	therapy?

The overall objective of treatment 

for HIV disease, as with treatment 

for many other infectious diseases, 

is to control the putative agent with 

antimicrobial agents while providing 

other appropriate therapies for HIV-related 

complications. The single most important 

goal of HIV antiretroviral therapy is to reduce 

the HIV viral load to as low as possible for as 

long as possible. The 5 other goals of antiretroviral 

therapy (ART) are to 

• Prevent HIV-associated complications

• Avoid the long-term and short-term adverse drug 

reactions associated with antiretroviral agents

• Prevent HIV transmission

• Avoid HIV resistance

• Preserve HIV treatment options 

Does	antiretroviral	therapy	work?	

Treatment recommendations have evolved greatly 

since zidovudine (AZT), a nucleoside, was first tested 

in 1986. The strategy was revolutionized in 1996-97 

with the introduction of protease inhibitors (PIs) and 

then subsequently non-nucleoside reverse transcriptase 

inhibitors (NNRTIs). Combined with AZT and other 

nucleosides (see Table 5-1), the result was potent 

combination ART (also referred to as highly active 

antiretroviral therapy, or HAART) that had an immediate 

and dramatic impact on the prognosis for HIV infection, 

in fact one of the most impressive changes in any 

disease since the introduction of penicillin in the 

1940s. Within 2 years there was a 60%-80% decrease 

in mortality, AIDS rates, and hospitalizations for HIVassociated complications. Nevertheless, this treatment 

was also associated with some disappointments: 

there is still no cure for HIV infection, many of the 

patients given ART develop serious side effects, and 

drug resistance causes many patients to 

eventually have virologic failure so that longterm benefit may be difficult to sustain. 

Also, adherence has been shown to be 

critical to treatment success, and the level of 

adherence required is among the stiffest for 

the treatment of any disease in medicine. 

WHEN TO START THERAPY

What	are	the	criteria	for	starting	therapy?	

The decision to start therapy, like most medical 

decisions, depends on the risk-to-benefit ratio of 

treatment. ART is given to control HIV replication and 

the consequent immune dysfunction, but therapy is also 

associated with the development of some substantial 

side effects and the risk of developing resistance that 

would limit future options. The reduction in CD4 cells is 

the pivotal event of HIV disease that renders the patient 

susceptible to the unique opportunistic infections (OIs) 

and tumors that have come to be known as AIDSdefining diagnoses (see Table 5-2). The patient becomes 

vulnerable to these diseases when the CD4 cell count 

decreases from normal levels (500-1500 cells/mm3) to 

<200 cells/mm3; the association with complications is 

the rationale for this CD4 cell threshold to be used by 

CDC to define AIDS. 

Virtually all guidelines in the world have reached a 

consensus that a CD4 cell count of <200/mm3 is an 

indication for ART. The only question is the CD4 level 

above which treatment should be started. According 

to the DHHS Guidelines for the Use of Antiretroviral 

Chapter	5:	

Antiretroviral	Therapy John G. Bartlett, MD

THE PRINCIPLES OF ANTIRETROVIRAL THERAPY (ART)

WHEN TO START THERAPY

WHAT TO START

WHEN TO CHANGE THERAPY

WHAT TO CHANGE TO

RESISTANCE TESTING

KEY POINTS

SUGGESTED RESOURCES

CASES

See	Glossary	of	

Antiretroviral

Drugs	on	

page	viii	and	the	

Pocket	Guide
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

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

5

Agents in HIV-Infected Adults and Adolescents (available 

at http://www.aidsinfo.nih.gov) the CD4 cell count range 

of 200-350/mm3 is also an indication for ART, but the 

decision is tempered by the viral load, the rapidity of 

the CD4 cell count decline (CD4 cell slope), and patient 

readiness. The role of viral load in this decision is based 

on 2 observations: 1) the viral load is an independent 

predictor of progression and 2) the CD4 decline slope 

is directly correlated with viral load. The implication 

is that a high viral load imparts a risk for more rapid 

progression to AIDS and a more rapid decline in the 

CD4 cell count. The threshold that appears important 

in the CD4 cell strata of 200-350 is ≥20,000 copies of 

virus/mL (c/mL). Some authorities also treat patients 

with a viral load of 50,000-100,000 c/mL even when the 

CD4 cell count is >350/mm3, but there is no consensus 

here. It should be emphasized that multiple cohort 

studies involving thousands of patients clearly indicate 

that therapy is necessary when the CD4 cell count is 

<200/mm3; some of these studies also show a benefit 

when the CD4 cell count is 200-350/mm3, but these 

findings are somewhat inconsistent from study to study.

What	patient	factors	influence	this	decision?	

Patient readiness may be the most important factor 

in the decision to treat most patients. ART is never an 

emergency, although the CD4 cell count clearly indicates 

the magnitude of risk from waiting. Most experienced 

HIV providers will never start ART on the first patient 

visit, which is designed for evaluation and the initiation 

of patient education. The patient must understand not 

only the risks and benefits of HIV treatment, but also the 

critical role of adherence to what may be one of the most 

complicated medical treatment regimens for any disease 

(see Chapter 7: Adherence to HIV Therapies).

WHAT TO START

How	do	you	suppress	HIV	replication?	

The goal of treatment is to suppress HIV as much as 

possible for as long as possible. This requires 3-4 drugs 

in combinations that have been proven to have merit in 

clinical trials (see Table 5-1).

Do	you	ever	start	with	1	or	2	drugs?	

No, with a rare exception; some providers treat 

pregnant women with a CD4 cell count of >350/mm3

and a viral load of <1,000 c/mL with zidovudine 

(AZT) alone. With this exception, all patients should be 

treated with 3-4 drugs combined in a fashion that has 

established merit. 

Table 5-1. Combination Antiretroviral Therapy

Standard initial regimens

• 2 nucleosides* and a protease inhibitor (PI)** or a 

ritonavir-boosted PI 

• 2 nucleosides* and a non-nucleoside reverse 

transcriptase inhibitor (NNRTI)***

Classes

* Nucleosides: zidovudine (AZT), didanosine (ddI), 

zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), 

emtricitabine (FTC), abacavir (ABC), tenofovir (TDF) 

(tenofovir is actually a nucleotide rather than a 

nucleoside)

** Protease inhibitors (PI): indinavir (IDV), ritonavir 

(RTV), nelfinavir (NFV), saquinavir (SQV; 2 formulations 

– Invirase and Fortovase), amprenavir (APV), 

fosamprenavir (FPV), lopinavir (LPV; co-formulated with 

ritonavir as LPV/r), and atazanavir (ATV)

*** Non-nucleoside reverse transcriptase inhibitor 

(NNRTI): efavirenz (EFV), nevirapine (NVP), and 

delavirdine (DLV)

Fusion inhibitors (used only for salvage): 

enfurvitide (T20) 

Table 5-2. When to Start Therapy

Patient 

status

Recommendation Comment

Symptomatic 

HIV/AIDS

Treat AIDS-defining 

diagnosis

Asymptomatic 

with CD4 

cell count of 

>350/mm3

Defer therapy Some authorities 

treat if viral load is 

>55,000 c/mL

CD4 cell 

count of 200-

350/mm3

Treat or defer therapy Influencing factors 

include

• Patient 

readiness

• CD4 slope 

(rate of 

decline)

• Viral load 

(<20,000 

c/mL = 

low risk of 

progression)

• Treatmentassociated 

risks: heart 

disease, drug 

interactions

CD4 cell 

count of 

<200/mm3

Treat Universally accepted 

CD4 threshold for 

initiating treatment in 

all guidelines
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 31

5

How	do	you	decide	on	a	specific	regimen?	

The selection of a regimen is based on the experience 

with completed trials and idiosyncrasies of the specific 

patients. No single regimen is appropriate for all 

patients, but virtually all experienced AIDS treaters have 

a few favorites. Most start with a 3- or 4-drug regimen 

that includes 1) an NNRTI combined with 2 nucleosides, 

2) a PI either alone or boosted with ritonavir (RTV) 

plus 2 nucleosides, or 3) a 3-nucleoside regimen 

that includes abacavir (ABC), lamivudine (3TC), and 

zidovudine (combined as Trizivir). This last regimen has 

been popular for patients who struggle with complicated 

medical regimens because it is only 1 pill twice a 

day; however, the regimen is considered suboptimal 

compared with the PI- or NNRTI-based regimens.

Is	once-a-day	therapy	possible?	

This is now feasible and clearly preferred by some 

patients. The following drugs may be given once a day: 

tenofovir (TDF), lamivudine (3TC), emtricitabine (FTC), 

didanosine (ddI), stavudine (d4T), efavirenz (EFV), 

atazanavir (ATV), and amprenavir plus ritonavir (APV/r).

WHEN TO CHANGE

THERAPY

When	do	you	change	therapy	because	of	

virologic	failure?	

The goal of therapy is to reduce the viral load to 

undetectable levels. The expectation is a reduction 

by 1 log10 c/mL within 1-4 weeks, a viral load of 

<500 c/mL at 16-24 weeks, and a viral load of 

<50 c/mL after 24 weeks. Viral load measurements 

are subsequently made at 3-month intervals and are 

expected to remain at <50 c/mL. Temporary increases 

above this level are sometimes called “blips.” Virologic 

failure is defined as 2 consecutive viral load counts 

of >500 c/mL (see Table 5-3). 

What	causes	virologic	failure?	

There are 2 causes: 1) resistance, meaning that the 

strain of HIV is resistant to one or more of the drugs 

in the regimen, and 2) failure of the drug to reach the 

virus, which may be due to failure of adherence, drug 

interactions, or drug malabsorption. The most common 

cause is lack of adequate adherence. 

 Table 5-3. Rationale for Changing Therapy

Problem Definition Intervention

Virologic 

failure

Failure to decrease viral load 

to <500 c/mL within 16-24 

weeks or achieving that goal 

with subsequent elevation to 

>500 c/mL with at least 2 

measurements

Causes: non-adherence, 

resistance or pharmacologic 

issues (poor bioavailability, 

drug interaction, etc.)

Consequences: viral 

replication with progression 

of immunodeficiency and 

accumulating resistance 

mutation

Change drugs, 

usually based 

on sensitivity 

tests

Drug 

toxicity

Side effects that may be 

1) annoying (GI intolerance, 

asthenia), 2) life-threatening 

(pancreatitis, lactic acidosis, 

hypersensitivity, hepatic 

necrosis), 3) cosmetic (fat 

redistribution), or 4) pose illdefined risks (hyperlipidemia)

Substitute a 

different drug 

What	do	you	do	when	the	patient	has	side	

effects	or	intolerance	to	the	regimen?	

Side effects of antiretroviral agents are common 

and highly variable in severity and implications. 

Nausea is particularly common and may become 

a huge impediment to adherence. Other side 

effects may be more serious in terms of specific 

medical consequences, including several that are 

potentially lethal: pancreatitis due to didanosine (ddI), 

hypersensitivity due to abacavir (ABC), Stevens-Johnson 

syndrome due to an NNRTI, nevirapine-associated 

hepatic necrosis, and lactic acidosis due to nucleosides, 

especially stavudine (d4T). If the side effect precludes 

adherence or is regarded as a serious consequence 

for adherence, the regimen must be changed. It is 

important to warn patients about common and serious 

side effects before treatment begins. 

Are	there	other	forms	of	treatment	failure?	

Immunologic failure, as opposed to virologic failure, 

is characterized by the failure of the CD4 count to 

rebound, and clinical failure is characterized by AIDSdefining events (see Table 5-4). Success in treatment is 

based on viral load response, and this dictates therapy 

decisions. No one knows what to do with immunologic 

or clinical failure if there is viral suppression.
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

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

5

Table 5-4. Definitions of Therapeutic 

Failure

Type Definition

Virologic 

failure

Initial therapy: failure to decrease viral 

load by 1 log10 c/mL by 1-4 weeks, to 

<500 c/mL by 8-16 weeks, or to <50 

c/mL by 16-24 weeks.

Chronic therapy: viral load >400 c/mL 

with 2 measurements after achieving viral 

suppression.

Immunologic 

failure

Failure to increase CD4 to >25-50/mm3/

year (this is an arbitrary definition; the 

average increase with viral suppression by 

the above definition is an increase of 100-

150 c/mm3/year).

Clinical 

failure

HIV-related complication, usually an 

AIDS-defining condition after antiretroviral 

therapy for ≥3 months.

WHAT TO CHANGE TO

How	do	you	address	intolerance	or	serious	side	

effects?	

Assuming virologic control has been achieved, the goal 

is to find a substitute for the offending agent. In most 

cases, this is simply a single drug substitution using an 

agent in the same class with comparable potency. For 

example, for zidovudine (AZT) intolerance, stavudine 

(d4T) is commonly substituted. For indinavir-associated 

nephrolithiasis, the usual tactic is to reduce the dose, 

increase fluid intake, or substitute another PI for 

indinavir (IDV). 

What	is	intensification?	

Intensification is the addition of a drug, usually a single 

drug, to enhance antiretroviral activity in a patient who 

has a good but suboptimal response to therapy. This 

needs to be done at a time when the viral load has 

not increased to too high a level; for example, most 

authorities consider a viral load of >5,000 c/mL to be 

an indication for a completely new regimen. Common 

ploys for intensification are the addition of tenofovir 

(TDF) or abacavir (ABC), or a boosting of a PI with 

ritonavir (RTV) if that was not done initially. 

How	do	you	deal	with	virologic	failure?	

The usual method is to measure HIV resistance. If the 

strain is sensitive, it is important to closely examine the 

adherence issue or look for drug interactions or some 

other reason that the antiretroviral agent does not reach 

the virus. If the virus is resistant, this information is 

used to select the next regimen as described below.

RESISTANCE TESTING

What	are	the	tests?	

There are 2 types of resistance tests: genotypic and 

phenotypic. Genotypic resistance measures mutations 

to the genes that are the target of antiretroviral 

drugs. These mutational changes predict resistance. 

Phenotypic resistance measures the activity of various 

drugs against the patient’s virus compared with 

“wild type” virus (untreated HIV strains). These tests 

are quite different in method of performance, but 

there is no consensus regarding their relative merit. 

Many people use genotypic resistance testing most 

frequently because it is faster and cheaper. Under 

any circumstances, interpreting both tests requires 

substantial expertise. It should be emphasized that the 

testing is valid only for the drugs that are being given 

at the time the test is done; drugs discontinued >2-6 

weeks earlier may not be reliably tested because the 

resistant strains often become “minority species” when 

drug pressure is removed. Thus, a history of prolonged 

ART and virologic failure in the past often indicates 

resistance even if this is not revealed with the current 

test. 

What	are	the	indications	and	requirements	for	

resistance	testing?	

The major indication for resistance testing is virologic 

failure, but testing is also sometimes done prior to 

initiation of therapy (see Table 5-5). The requirement for 

testing after virologic failure is an adequate viral load 

(usually >1,000 c/mL) to do the test. For patients who 

have failed therapy it is standard practice to sample 

while the drugs of interest are being given. Resistance 

to drugs discontinued >2-6 weeks before testing may 

not be expressed in the resistance testing, although this 

probably differs by individual patient and specific agent 

and has not been extensively studied. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 33

5

Table 5-5. Resistance Testing

Patient status Recommendation Comment

Primary HIV 

infection

Consider testing There are no studies to 

show use in this setting 

alters outcome of therapy, 

but the viral population is 

presumed to be relatively 

homogeneous, giving 

theoretical reliability to 

testing.

Chronic infection 

– treatment-naive

Consider testing The concern is that 

resistant HIV may be 

archived making the 

test less reliable. Testing 

at this stage is best for 

predicting which agent 

will not work.

Chronic infection 

– treatment 

failure on 

therapy

• First 

failure

• Multiple 

failures

 

Recommended if 

testing requirements are met

Recommended if 

testing requirements are met

Need viral load of 

>1000 c/mL to do 

the test. Patient may 

need to be receiving 

the antivirals that 

failed at the time of 

the test for resistance 

to be expressed.

Resistant strains from 

prior therapy may 

not be expressed in 

the majority of strains 

tested; it is important 

to select next a 

regimen based on 

the current resistance 

test results, prior 

resistance tests, and 

treatment history.

How	should	you	treat	someone	who	has	run	out	

of	options?	

Extensive use of ART over several years combined with 

virologic failure and resistance leads to limited options 

for many patients. However, it appears that antiretroviral 

drugs are still beneficial in these patients because of 

reduced “fitness” of the virus. The implication is that the 

antiretroviral drugs force development and persistence 

of resistant mutations, and these mutated strains have 

reduced replicative capacity in vitro and presumably in 

vivo as well. Several studies show that discontinuation 

of ART is often followed after 4-8 weeks by a significant 

increase in viral load and a very rapid decline in the CD4 

cell count. Thus, the goal of therapy for heavily treated 

patients who have few therapeutic options is often to 

continue these drugs despite virologic failure with the 

hope of maintaining the CD4 cell count and preventing 

HIV-related complications. Virologic control would be nice, 

but may be impossible or unrealistic.

What	is	therapeutic	drug	monitoring	(TDM)?	

TDM is the measurement of serum concentrations of 

antiretroviral drugs to determine if there are adequate 

levels to assure antiviral activity or to account for 

toxicity. Relatively few laboratories offer the test, and 

interpretation is confounded by limited experience and 

great variability among laboratories testing the same 

samples. Nucleosides are not tested because this would 

require measuring intracellular concentrations. It is 

usually PIs, which may have marginal levels, and to a 

lesser extent NNRTIs that are tested. Although TDM is not 

common in clinical practice at present, many experts feel 

it may become a standard component of treatment in the 

future with better standardization and more information 

about how to use the tests. The anticipated use is in 

situations in which levels are difficult to predict, as in 

renal failure, hepatic failure, pregnancy, concurrent use of 

drugs with possible drug interactions, use of once-a-day 

PIs with concerns about trough levels, and the monitoring 

of adherence.

When	is	structured	treatment	interruption	

(STI)	indicated?	

Although there are 4 reasons to suspend treatment 

temporarily, pulse therapy appears to be the most 

promising.

• Immunization One rationale for STI, when used with 

patients who have prolonged virologic control, is to stop 

therapy to let the virus come back and “immunize” the 

patient in a fashion analogous to a vaccine. The theory 

seemed good, but has not proven successful, and most 

have abandoned this tactic except with the rare patient 

who was treated very early in the course of the disease. 

• Treatment failure A rationale for discontinuing 

treatment when it has failed due to drug resistance is 

to allow growth of “wild type virus” that is sensitive to 

antiretroviral agents. The theory, that STI would permit 

a new round of therapy against sensitive virus, has not 

proven successful for possibly predictable reasons. In 

many or most patients, the resistant strains are minority 

species that quickly become the dominant strains under 

renewed antiviral pressure. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

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

5

• Intermittent therapy The plan with intermittent 

therapy is to periodically discontinue treatment on a 

prearranged schedule, such as 1 week on and 1 week 

off or 5 days of treatment followed by a weekend 

off. The theory is that when therapy is discontinued 

there is usually sustained viral suppression for 10-14 

days and treatment is restarted while the virus is still 

suppressed. This strategy could potentially reduce 

treatment-associated side effects and cost. Although 

the initial experience has been limited but promising, 

the strategy cannot be recommended until more 

substantial experience is gained.

• Pulse therapy With this strategy, therapy is 

discontinued when the CD4 cell count increases to a 

level that makes the patient and physician comfortable 

doing so and is restarted when the CD4 count declines 

to a worrisome level. Initial experience has generally 

been that the viral load returns within 2 weeks and 

the CD4 cell count declines rapidly and then plateaus. 

Most experts restart therapy when the CD4 cell count 

reaches 350/mm3, but this strategy has not been 

systematically studied. Nevertheless, it does appear 

that there is no penalty in terms of resistance and 

the period off therapy is often 1-2 years, depending 

to a large extent on the CD4 cell count at the time 

treatment is discontinued and on the pre-therapy 

CD4 nadir. The patient must be warned that viral 

loads will return to pre-therapy levels, with important 

implications for risk of HIV transmission to others.

KEY POINTS

The major indicator for the speed of 

progression in early stage disease is the 

viral load, which dictates the speed of 

CD4 cell decline. The major indicator for 

the risk of HIV-associated complications 

is the CD4 cell count.

ART is directed toward preventing 

HIV-associated complications and 

hospitalizations and improving quality of 

life and survival.

ART does not cure HIV infection, is 

expensive, is associated with substantial 

risks of short-term and long-term toxicity, 

and requires a level of adherence that is 

unmatched with any other antimicrobial 

therapy.

ART is recommended when there are HIVassociated symptoms or when the CD4 

count is <200-350/mm3.

The standard of practice for ART is 3 or 4 

drugs representing 2 classes.

The major objective of ART is to inhibit 

HIV as reflected by viral load. Successful 

antiviral therapy is defined as a viral load 

of <50 c/mL by 16-24 weeks, usually 

accompanied by an increase in the CD4 

cell count of 100-150/mm3/year.

Failed therapy is defined as virologic (viral 

load >400 c/mL twice after 24 weeks), 

immunologic (CD4 count fails to increase 

by >25-50/mm3 at 6-12 months), or 

clinical (new AIDS-defining OI after >3 

months of therapy).

Treatment is changed for drug intolerance 

(substitution) or virologic failure 

(selection by resistance tests).

The 3 factors that consistently predict 

outcome are CD4 cell count, patient 

adherence, and provider experience.
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 35

5

SUGGESTED RESOURCES

Deeks SG, Hirschel B. Supervised 

interruptions of antiretroviral therapy. 

AIDS. 2002;16:S157-169.

Hirsch MS, Brun-Vezinet F, Clotet B, et al. 

Antiretroviral drug resistance testing in 

adults with Human Immunodeficiency 

Virus type 1: 2003 recommendations 

of an International AIDS Society – USA 

panel. Clin Infect Dis. 2003;37:113-128.

Lawrence J, Mayers DL, Hullsiek KH, et 

al. Structured treatment interruption in 

patients with multidrug-resistant human 

immunodeficiency virus. New Engl J Med. 

2003;349:837-846.

Mellors JW, Munoz A, Giorgi JV, et al: 

Plasma viral load and CD4+ lymphocytes 

as prognostic markers of HIV-1 infection. 

Ann Intern Med. 1997;126:946-954.

Palella FJ, Delaney KM, Moorman AC, 

et al: Declining morbidity and mortality 

among patients with advanced human 

immunodeficiency virus infection. N Engl 

J Med. 1998;338:353-360.

Panel on Clinical Practices for Treatment 

of HIV Infection. Guidelines for the Use 

of Antiretroviral Agents in HIV-Infected 

Adults and Adolescents. Washington DC: 

U.S. Department of Health and Human 

Services. Nov 10, 2003. Available at 

http://www.aidsinfo.nih.gov.

Yeni PG, Hammer SM, Hirsch MS et al. 

Treatment for Adult HIV Infection: 2004 

recommendations of the International 

AIDS Society–USA Panel. JAMA. 2004; 

292:251-265.

Youle M. Strategies of HIV Management 

– When to start. AIDS. 2002;16:S145-149.

WEBSITES

AIDSInfo: http://www.aidsinfo.nih.gov

Accessed 11/03 (Several treatment 

guidelines are continuously updated 

at this U.S. Department of Health and 

Human Services website)

AIDS	information	–	

ht tp://www.aidsinfo.nih.gov

for	continuously	updated	

treatment	guidelines
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

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

5

CASES

1.

A 36-year-old woman is asymptomatic and has a CD4 cell count of 210/mm3 and a baseline viral load 

of >750,000 copies/mL. Other laboratory studies are unremarkable. She seeks your advice regarding 

management. 

Question:	What can you recommend?

a. zidovudine (AZT) plus stavudine (d4T) plus efavirenz (EFV)

b. lamivudine (3TC) plus zidovudine plus nelfinavir (NFV)

c. Trizivir (AZT + 3TC + ABC) plus lopinavir/ritonavir (LPV/r)

d. Trizivir 

e. lamivudine plus stavudine plus indinavir (IDV)

Answer:	

Virtually all of these are feasible except option a, which combines zidovudine and stavudine, a 

combination that shows pharmacologic antagonism. The worrisome part of her presentation is that the 

CD4 cell count is quite low and approaching the threshold of vulnerability to opportunistic infections, 

and the viral load is very high, which poses substantial challenge to virologic control. The best drugs for 

baseline high viral load according to currently available data are 2 nucleosides combined with efavirenz 

or lopinavir/ritonavir. Thus, option c would be the best choice.

2.

A 42-year-old truck driver has HIV infection that was treated in 1999 with efavirenz (EFV), stavudine (d4T), 

and lamivudine (3TC). He subsequently did well and maintained a viral load of <50 c/mL, and the CD4 

cell count increased from 250 to 450/mm3. He feels well, is fully adherent with his regimen by history, 

and has no complaints except that he is bothered by facial thinning (buccal cheek atrophy). 

Question:	Which of the following would you recommend?

a. Discontinue treatment

b. Change stavudine to abacavir (ABC)

c. Switch efavirenz to indinavir (IDV) plus ritonavir (RTV)

d. Switch stavudine to zidovudine

e. Give zidovudine, lamivudine, and abacavir

Answer:	

Discontinuing therapy is an option, although guidelines on when and how to do this are sparse because 

it has not been extensively studied. Anecdotal information suggests that this patient will have a sustained 

period with a CD4 cell count above the threshold for initiating treatment by current guidelines of 200-350/

mm3. The best predictor of a prolonged drug-free interval is the baseline CD4 cell count, which in his case 

is low, but not severely low. The main problem is that the CD4 cell count at 450/mm3 is high, but possibly 

not high enough. The most likely cause of his change in face appearance is stavudine, but methods to 

reverse the change are not necessarily clear. If we stop stavudine, face thinning will not progress and 

some studies suggest there may be reversal after a prolonged period. Since this is important to the patient 

and this kind of change is relatively easy to make, we should probably do it, so the best answers are to 

use a potent regimen without stavudine treatment (options a, b, and d). 
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 37

5

3.

A 36-year-old woman sees you for evaluation of HIV infection, which she has had since 1985. There have 

been multiple courses of treatment, including nucleosides in the period 1987 to 1996 and since then 

nucleosides combined with NNRTIs and PIs. The longest course of treatment was with zidovudine (AZT), 

lamivudine (3TC), and efavirenz (EFV), which produced a temporary period of virologic control but then 

failed. Currently she is receiving amprenavir (APV), lopinavir/ritonavir (LPV/r), and tenofovir (TDF). You 

perform a resistance test, which shows mutations on the reverse transcriptase gene at codons 41, 210, 

and 215 and mutations on the protease gene at 30 and 82. The conclusion is that HIV is resistant to most 

NRTIs and PIs. Her current numbers show a CD4 cell count of 87/mm3 and a viral load of 210,000 c/mL.

Question:	What would you recommend?

a. zidovudine plus lamivudine plus tenofovir plus efavirenz 

b. lopinavir/ritonavir plus efavirenz plus tenofovir 

c. AZT/3TC/ABC (Trizivir) plus lopinavir/ritonavir 

d. AZT/3TC/ABC plus tenofovir plus indinavir (IDV) plus ritonavir (RTV)

e. enfurvirtide (T-20) plus atazanavir plus lamivudine plus tenofovir 

Answer:	

The tricky part of this question is the need to assume resistance to efavirenz and lamivudine despite the 

failure to demonstrate the associated mutations: 103 and 184 on the RT gene. This reflects the fact that 

these drugs were not being given at the time the test was done, but history suggests that resistance to 

these drugs occurred at the time of failure. The point is that interpretation of resistance tests must take 

into account both the current pattern and the history of drug exposure in terms of specific agent, duration, 

and virologic outcome. This patient is running low on options and low on CD4 cells. She does have some 

PI options, but the most predictable response would probably be a regimen with the fusion inhibitor 

enfurvirtide (option e).

4.

A 50-year-old secretary has just learned that he has HIV infection with a CD4 cell count of 49/mm3 and 

viral load of 280,000 c/mm3. He is quite shaken by this information, claims that he has never been able 

to take pills for anything and wants treatment, but wants it to be as simple as possible.

Question:	What would you recommend?

a. Delay therapy until the patient is ready

b. AZT/3TC/ABC (Trizivir) plus efavirenz (EFV)

c. tenofovir (TDF), lamivudine (3TC), plus efavirenz 

d. zidovudine (AZT), lamivudine, amprenavir (APV), and ritonavir (RTV)

e. AZT/3TC/ABC (Trizivir) 

f. zidovudine plus efavirenz plus indinavir (IDV)

Answer:	

This patient needs to be treated rapidly because he is highly vulnerable to major opportunistic infections. 

We emphasize the need for patient readiness, but this patient does not have much time to get ready. 

Training will take substantial effort as described in Chapter 7: Adherence to HIV Therapies. We would 

like potency plus convenience to facilitate adherence. The combination of lamivudine plus tenofovir plus 

efavirenz (option c) means 4 pills once a day, which could be taken, for example, when he shaves. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 5: Antiretroviral Therapy

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

5

5.

A doctor telephones you about a patient who has read about structured treatment interruption for patients 

who have failed therapy. You are told this patient has extensive experience with antiretroviral treatment 

for over 10 years, a CD4 cell count of 80-100/mm3, and a viral load that is back to baseline at 420,000 

c/mL. 

Question:		What would you recommend to the physician?

a. Test resistance while receiving antiretroviral drugs and select the drugs 

based on the ART history and resistance tests

b. Discontinue treatment, test the HIV strain at 12 weeks, and treat 

accordingly

c. Continue therapy with same drugs

d. Treat with lopinavir/ritonavir (LPV/r), Trizivir (AZT/3TC/ABC), tenofovir 

(TDF), and either efavirenz (EFV) or nevirapine (NVP)

Answer:	

The experience with STI for virologic failure is that wild-type virus that is less resistant replaces the 

predominant strain after about 6-11 weeks, but the CD4 cell count drops rapidly during the period off 

treatment; after new treatment, the more completely resistant pre-STI strain returns. The largest experience 

indicates only about 10%-15% of these attempts have been judged successful. Therefore, STI for virologic 

failure has fallen into disfavor. Nevertheless, if you wanted to play long odds, the right time to do the 

testing is after there has been a sufficient interval for ingrowth of a new, more sensitive strain of HIV 

making option b the correct option. However, most would prefer option a with expert interpretation of 

the test results. 

6.

Question:	Which of the following patients is the best candidate for genotype resistance testing?

a. A previously untreated pregnant woman with HIV

b. A chronically infected, previously untreated man with a partner who is 

currently taking triple therapy with poor control

c. A woman who has failed her initial treatment with a viral load of 7,000 

c/mL after 1 year on indinavir (IDV), ritonavir (RTV), lamivudine (3TC), and 

stavudine (d4T)

d. A 40-year-old man with good virologic control, but a need to change 

therapy because of AZT-induced anemia

Answer:	

Recommendations for the use of resistance testing are somewhat arbitrary, but the highest priority 

according to virtually all guidelines is for patients who have failed treatment for the purpose of identifying 

the next regimen; therefore, option c is the best answer.
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 39

OVERVIEW 6

What	is	meant	by	metabolic	complications	of	

antiretroviral	therapy	(ART)?

Metabolic complications refers to a group of adverse 

drug reactions that have been associated with long-term 

use of antiretroviral drugs, 

which include:

• Lipid abnormalities

• Lipodystrophy

• Lactic acidosis

• Hyperglycemia

• Decreased bone mineral density

Each adverse reaction is more commonly associated 

with a specific class of antiretroviral drugs, and the 

agents within the class that cause the reactions do 

so with variable frequencies. In most cases, the 

pathophysiologic mechanism of the changes is 

unknown. The classes of drugs associated with each 

major adverse reaction are listed in Table 6-1.

What	metabolic	toxicities	should	you	monitor	

for	in	patients	taking	ART?

Recommendations for monitoring patients for ARTrelated metabolic complications, listed in Table 6-2, 

are discussed in detail in the sections below. 

Chapter	6:	

Metabolic	Complications	of	

Antiretroviral	Therapy David H. Spach, MD

OVERVIEW

LIPID ABNORMALITIES

LIPODYSTROPHY

LACTIC ACIDOSIS

OTHER METABOLIC COMPLICATIONS

KEY POINTS

SUGGESTED RESOURCES 

REFERENCES

CASES

Table 6-1. Adverse Reactions of Classes of Antiretroviral Drugs

Adverse Reaction Cause

NRTIs* NNRTIs** PI***

Lactic acidosis ++ - -

Lipid changes

 Elevated triglycerides - (+) ++

 Elevated LDL cholesterol - + ++

Insulin resistance - - ++

Fat redistribution

 Fat atrophy + - -

 Fat accumulation - - ++

* NRTIs = Nucleoside and nucleotide reverse transcriptase inhibitors

** NNRTIs = Non-nucleoside reverse transcriptase inhibitors

*** PIs = Protease inhibitors

(+) = possibly causes adverse reaction

+ = sometimes causes adverse reaction

++ = frequently causes adverse reaction

See	Glossary	of	

Antiretroviral

Drugs	on	

page	viii	and	the	

Pocket	Guide
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

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

6

LIPID ABNORMALITIES

What	antiretroviral	medications	adversely	

affect	lipid	levels?

Available data suggest that drugs in the protease 

inhibitor (PI) class have the greatest adverse effect 

on triglycerides, total cholesterol, and low-density 

lipoprotein (LDL) cholesterol levels. The mechanism 

remains unclear. Among the PIs, ritonavir (RTV) and 

ritonavir-boosted regimens appear to have the greatest 

impact on triglycerides and total cholesterol levels. 

Because some patients who receive ritonavir had no 

significant changes whereas others have dramatic 

increases, genetic predisposition may play a major role. 

The PI atazanavir (ATV) does not significantly affect lipid 

levels. The impact of nucleoside reverse transcriptase 

inhibitors (NRTIs) and non-nucleoside reverse 

transcriptase inhibitors (NNRTIs) on lipid levels has not 

been well defined, but the impact appears much less 

than changes associated with PIs. In 96-week data from 

a trial that compared stavudine (d4T) plus lamivudine 

(3TC) plus efavirenz (EFV) with tenofovir (TDF) plus 

lamivudine plus efavirenz, those patients in the 

stavudine arm had significantly higher cholesterol and 

triglyceride levels. The NNRTI nevirapine (NVP) has no 

adverse affect on lipids, and the changes with efavirenz 

are variable. Patients receiving PIs should undergo 

regular monitoring of lipid levels (see Table 6-2).

Do	antiretroviral	drugs	cause	an	increase	in	

cardiovascular	disease?

Several isolated case reports initially suggested ART 

could lead to cardiovascular disease, including death 

from myocardial infarction, in HIV-infected patients. 

More recent aggregate data from over 20,000 patients 

in cohort studies indicate the risk related to ART is 

low and substantially lower than the risk of smoking 

(Friss-Moller, et al, 2003). In addition, in a large study 

that involved more than 36,000 veterans, investigators 

found the benefit of these drugs far outweighed the 

risks. Because cardiovascular disease may take 10-15 

years to manifest, investigators will need long-term 

followup of individuals who have received ART to 

determine the long-term impact. 

Table 6-2. Recommendations for Assessment and Monitoring of Metabolic Complications 

of Antiretroviral Therapy for HIV Infection

Glucose 

and lipid 

abnormalities

• The following assessments are recommended before initiation of potent ART, at the time of a switch of 

therapy, 3 to 6 months after starting or switching therapy, and at least annually during stable therapy:

 - Fasting glucose (if therapy includes a PI)

 - Fasting lipid panel (total cholesterol, HDL, and LDL cholesterol [calculated or direct], and 

triglyceride levels)

• A blood glucose level after oral administration of 75 g of glucose may be used to identify impaired glucose 

tolerance in patients with risk factors for type 2 diabetes mellitus or those with severe body fat changes.

Body fat 

distribution 

abnormalities

• No specific technique can be recommended at the present time for routine assessment and monitoring of body 

fat distribution changes.

Lactic acidemia • Routine measurement of lactic acid levels is not recommended.

• Lactic acid levels should be monitored in those receiving NRTIs who have clinical signs or symptoms of lactic 

acidemia, and in pregnant women receiving NRTIs.

• If alternative NRTIs are resumed in those who have interrupted antiretroviral therapy for lactic acidemia, lactate 

levels should be monitored every 4 weeks for at least 3 months.

Osteopenia, 

osteoporosis, and 

osteonecrosis

• Routine screening for osteoporosis or osteonecrosis is not recommended.

• Radiographic examination of involved bone is recommended for those with symptoms of bone or joint pain; the 

contralateral joint should also be assessed.

DEXA = dual-energy x-ray absorptiometry

HDL = high-density lipoprotein

LDL = low-density lipoprotein

NCEP = National Cholesterol Education Program

NNRTI = non-nucleoside reverse transcriptase inhibitor

NRTI = nucleoside reverse transcriptase inhibitor

Source: Schambelan M, Benson CA, Andrew Carr A, et al. Management of metabolic complications associated with antiretroviral therapy for 

HIV-1 infection: Recommendations of an International AIDS Society-USA Panel. J Acquir Immune defic Syndr. 2002;31:269. Reprinted with 

permission of Lippincott Williams and Wilkins, http://lww.com. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 41

6

Should	you	treat	abnormal	lipid	levels	in	HIVinfected	persons?

Although prospective studies have not clearly defined 

the long-term adverse cardiovascular effects associated 

with hyperlipidemia in HIV-infected persons, abnormal 

lipid levels appear to pose the same long-term risks 

as have been well established in persons who do not 

have HIV infection and thus need to be managed 

appropriately (see Table 6-3). Accordingly, clinicians 

should address abnormal lipid levels and the individual 

patient risks, including prior cardiovascular events, 

smoking, hypertension, diabetes, family history, obesity, 

and baseline lipid levels. The potential interventions 

include 1) switching to a regimen less likely to 

cause abnormal lipids (if possible without sacrificing 

antiviral effectiveness), 2) implementing dietary 

changes, 3) using a lipid-lowering agent according to 

recommendations in Table 6-4, and 4) addressing other 

lifestyle habits that affect cardiovascular risk, such as 

smoking and exercise. 

What	statins	are	recommended	for	treating	

patients	on	PIs?

Significant drug interactions may occur with PIs and 

lipid-lowering statins; for patients on PI-based ART, 

most experts consider pravastatin and atorvastatin 

as preferred statins and avoid using lovastatin or 

simvastatin. Initial therapy should consist of a low dose 

of either pravastatin (20 mg po qd) or atorvastatin (10 

mg po qd), with monitoring of response to therapy 

and, if required, gradual and cautious increases in 

doses of the statin. Triglyceride levels in excess of 

1000 mg/dL place the patient at risk for developing 

pancreatitis. Most experts recommend intervening 

Table 6-3. Recommendations for Treatment of Metabolic Complications of 

Antiretroviral Therapy for HIV Infection

Glucose 

intolerance 

and diabetes 

mellitus

• Weight loss for overweight subjects is recommended.

• Follow established guidelines for treating diabetes in the general population, with preference given to insulin 

sensitizing agents such as metformin (except for those with renal disease or history of lactic acidemia) or 

thiazolidinediones (except for those with prexisting liver disease).

• Avoid use of a PI as initial therapy in patients with preexisting glucose intolerance or diabetes mellitus.

Lipid and 

lipoprotein 

abnormalities

• Follow NCEP III guidelines for assessment of risk factors for cardiovascular disease, and dietary and lifestyle 

alterations for lowering cholesterol and triglyceride levels.

• Avoid use of PIs, if possible, in those with preexisting cardiovascular risk factors, family history of 

hyperlipidemia, or elevated lipid levels.

• Follow NCEP guideline thresholds for lipid-lowering therapy.

• Fibrates are recommended as initial therapy for those with isolated fasting hypertriglyceridemia.

• Pravastatin or atorvastatin are preferred statin agents for those with isolated fasting hypercholesterolemia 

requiring treatment in the setting of PI or other CYP 3A4 inhibitor therapy.

• If combination therapy for hypercholesterolemia and hypertriglyceridemia is indicated, therapy should begin 

with a statin, followed by the addition of a fibrate if there is insufficient response after 3 to 4 months of 

treatment.

Body fat 

distribution 

abnormalities

• No therapies for fat distribution abnormalities in the absence of other metabolic complications can be routinely 

recommended.

Lactic acidemia • ART should be withheld for all patients with confirmed lactate levels >10 mmol/L (90 mg/dL) or those with 

confirmed lactate levels >5 mmol/L (45 mg/dL) who are symptomatic.

• No intervention apart from NRTI cessation is recommended.

• Restart combination NNRTI and PI therapy after lactate levels return to normal and symptoms resolve.

Osteopenia, 

osteoporosis, 

and 

osteonecrosis

• Surgical resection of involved bone is the only effective therapy for symptomatic osteonecrosis.

• If osteoporosis is demonstrated by radiography or regional DEXA scanning, or if a pathological fracture occurs 

in the setting of osteoporosis, therapy with a bisphosphonate should be considered. 

DEXA = dual-energy x-ray absorptiometry

HDL = high-density lipoprotein

LDL = low-density lipoprotein

NCEP = National Cholesterol Education Program

NNRTI = non-nucleoside reverse transcriptase inhibitor

NRTI = nucleoside reverse transcriptase inhibitor

Source: Schambelan M, Benson CA, Andrew Carr A, et al. Management of metabolic complications associated with antiretroviral therapy for 

HIV-1 infection: Recommendations of an International AIDS Society-USA Panel. J Acquir Immune defic Syndr. 2002;31:269. Reprinted with 

permission of Lippincott Williams and Wilkins, http://lww.com. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

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

6

when triglyceride levels exceed 500 mg/dL. Although 

dietary changes can improve triglyceride levels, most 

patients with PI-associated hypertriglyceridemia will 

require pharmacologic intervention. Patients with 

isolated hypertriglyceridemia should receive a fibric 

acid derivative, either gemfibrozil (600 mg po bid) or 

fenofibrate (200 mg po qd). For those who have high 

triglyceride and LDL cholesterol levels, a statin drug 

should be used first with the plan of adding a fibric 

acid derivative after 4 months if the response to the 

statin is suboptimal. Because both the statin drugs and 

the fibric acid derivatives can cause rhabdomyolysis, 

caution should be used if these medications 

are given concurrently. In patients with severe 

hypertriglyceridemia refractory to a fibric acid derivative, 

some experts would recommend a trial of adding fish oil 

supplements to the lipid-lowering regimen. 

Does	switching	ART	improve	lipid	

abnormalities?

Although some antiretroviral medications clearly have a 

greater adverse impact than others on lipids, modifying 

the regimen in an attempt to improve the lipid profile 

is sometimes difficult, mainly because of the need to 

maintain antiretroviral efficacy. Examples of possible 

changes likely to improve lipid abnormalities include 

switching a PI to either nevirapine (NVP) or using the 

alternative PI atazanavir (ATV). Changing from a PI to 

efavirenz (EFV) has not produced consistent results. 

Preliminary data from one study has shown that 

patients who switched from stavudine (d4T) to tenofovir 

(TDF) had a significant improvement in cholesterol and 

triglyceride levels. Future work will better determine 

whether changes from one nucleoside to another will 

affect lipid levels. 

Table 6-4. Summary of National Cholesterol Education Program Treatment 

Recommendations Based on LDL Cholesterol* 

Risk Category Initiate therapeutic 

lifestyle changes†

Consider drug 

therapy

LDL** cholesterol 

goal

Non-HDL** 

cholesterol goal

With CHD or CHD** 

risk equivalent (10-year 

risk >20%, noncoronary 

atheroslerotic vascular 

disease, or type 2 

diabetes mellitus)

≥100 mg/dL 

(≥2.6 mmol/L)

≥130 mg/dL 

(≥3.4 mmol/L)

100–129 mg/dL (2.6–

3.3 mmol/L):

therapy optional

<100 mg/dL

(<2.6 mmol/L)

<130 mg/dL

(<3.4 mmol/L)

2 or more risk factors 

(10-year risk <20%)‡

≥130 mg/dL

(≥3.4 mmol/L)

10-year risk of 

10%–20%:

≥130 mg/dL

(≥3.4 mmol/L)

10-year risk of <10%:

(≥160 mg/dL

(≥4.1 mmol/L)

<130 mg/dL

(<3.4 mmol/L)

<160 mg/dL

(<4.1 mmol/L)

0 or 1 risk factor‡ ≥160 mg/dL

(≥4.1 mmol/L)

≥190 mg/dL

(≥4.9 mmol/L)

160–189 mg/dL

(4.1–4.9 mmol/L):

therapy optional

<160 mg/dL

(<4.1 mmol/L)

<190 mg/dL

(<4.9 mmol/L)

* For patients with high triglyceride levels in whom LDL cholesterol cannot be measured, non-HDL cholesterol level (total cholesterol 

– HDL cholesterol) may be used as an approximation if 30 mg/dL (0.8 mmol/L) is added to the LDL cholesterol threshold. For those with 

triglyceride levels >200 mg/dL (2.3 mmol/L), the non-HDL cholesterol level is considered a secondary target of therapy and the goals of 

therapy are as indicated under the heading of non-HDL cholesterol goal.

‡ Risk factors include cigarette smoking; hypertension (blood pressure ≥140/90 mm Hg or taking antihypertension drugs); HDL cholesterol 

level below 40 mg/dL (1.0 mmol/L); family history of premature CHD (in first-degree male relatives <55 years and first-degree female 

relatives <65 years); age (>45 years for men and >55 years for women). Risk factor equivalent: diabetes. If HDL cholesterol is over 60 

mg/dL (1.6 mmol/L), subtract 1 risk factor from the total.

† Therapeutic lifestyle changes refer to reducing saturated fat and cholesterol intake; enhancing the reduction in LDL cholesterol level by the 

use of plant stanols/sterols and increased soluble fiber; weight reduction; and increased 

physical activity.

** CHD, coronary heart disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.

Source: Schambelan M, Benson CA, Carr A, et al. Management of Metabolic Complications Associated with Antiretroviral Therapy for HIV-1 

Infection: Recommendations of an International AIDS Society--USA Panel. J Acquir Immune defic Syndr. 31:262. Nov 1, 2002. Adapted from 

Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and 

Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497.Reprinted with permission of Lippincott 

Williams and Wilkins, http://lww.com. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 43

6

LIPODYSTROPHY

What	is	lipodystrophy?

Although lipodystrophy was first reported in the mid1990’s, investigators have not agreed on a standardized, 

objective definition for this disorder. Most researchers 

and clinicians loosely define lipodystrophy as any 

significant change in body morphology that does not 

result from either weight gain or weight loss. The general 

term lipodystrophy now typically includes 3 subsets of 

morphologic changes: generalized fat accumulation, focal 

fat accumulation, and fat atrophy. Fat accumulation most 

often occurs in the abdominal, breast, or dorsocervical 

region. Fat atrophy most often occurs as buccal fat pad 

atrophy (facial wasting) or subcutaneous fat wasting 

in the buttocks or extremities. Because a standardized 

definition for lipodystrophy is lacking, the incidence 

varies depending on the exact criteria investigators use 

to define lipodystrophy in their specific study. Tests for 

abnormalities in body fat distribution have included 

computed tomography (CT) scanning, magnetic resonance 

imaging (MRI), bioelectrical impedance analysis (BIA), 

DEXA (dual energy x-ray absorptiometry) scans, and 

anthropometric measurements. The CT and MRI tests are 

generally considered the most accurate, but not practical 

for routine screening purposes, primarily because of their 

high cost. Anthropometric measurements can estimate 

visceral adipose tissue and subcutaneous adipose tissue 

and can easily be performed in the clinic without major 

costs. Despite the many options available for measuring 

abnormalities in fat distribution, no technique has shown 

adequate sensitivity and specificity to recommend 

performing routinely. 

What	causes	lipodystrophy	in	HIV-infected	

persons?

Despite intense investigation, the exact pathogenesis of 

lipodystrophy remains unclear. Initial reports linked PI use 

with lipodystrophy, but subsequent reports have identified 

lipodystrophy in patients who had never received a PI. 

Several studies have shown that the most important risk 

factors for development of lipodystrophy are a history of 

severe immune suppression (nadir CD4 count <100 cells/

mm3), older age, prolonged use of antiretroviral drugs, 

and highly active antiretroviral therapy. Investigators 

have found that patients with lipodystrophy often have 

high insulin levels and evidence of insulin resistance, a 

finding that suggests insulin resistance is associated with 

lipodystrophy, but does not prove that insulin resistance 

causes lipodystrophy. Many clinicians have observed that 

fat accumulation is more often associated with PI-based 

therapy, whereas fat wasting has been most closely linked 

to NRTIs, particularly stavudine (d4T). In 96-week data 

from a trial that compared stavudine plus lamivudine 

(3TC) plus efavirenz (EFV) with tenofovir (TDF) plus 

lamivudine plus efavirenz, those patients in the stavudine 

arm had substantially higher rates of lipodystrophy.

Can	fat	redistribution	be	reversed?

First, it is important to evaluate the severity of the 

lipodystrophy, the degree to which the patient is bothered 

by the body changes, and how strongly the patient 

wants to try to reverse the lipodystrophy. Although fat 

redistribution does not appear to directly alter health 

outcome, many patients experience notable unfavorable 

changes in their phyical appearance that may affect 

their quality of life. Morever, these changes in body 

appearance may broadcast their HIV diagnosis. That 

lipodystrophy changes thus may even lead some to 

stop their antiretroviral medications. If lipodystrophy 

develops, there are 3 treatment options: 1) Switch 

therapy, meaning a substitution for the implicated drug. 

This usually involves a substitute for stavudine (d4T) if 

lipoatrophy has developed or a change to a non-PI-based 

regimen if fat accumulation has occurred. Initial results 

with switches showed limited success, and when there 

was a response it took a long time. More promising results 

were seen in a recent study in which replacing stavudine 

(d4T) with abacavir (ABC) or zidovudine (AZT) resulted 

in significant improvement after 48 weeks in patients 

with stavudine-induced lipoatrophy (McComsey, et al, 

2004). 2) Drug therapy is another option. Metformin, 

thiazolidinediones, testosterone, other anabolic steroids, 

and growth hormone have been used with partial success 

with fat accumulation, but all have drawbacks and do not 

address the underlying lipoatrophy. 3) The third option is 

plastic surgery, which may be particularly useful for buccal 

fat atrophy or dorsothoracic fat accumulations; however, 

results have been highly variable, and these procedures 

are usually regarded as cosmetic surgery and not covered 

by insurance companies.

LACTIC ACIDOSIS

What	are	ART-related	hyperlactatemia	and	

lactic	acidosis?

ART-related abnormalities of serum lactate levels 

(hyperlactatemia) range from asymptomatic 

hyperlactatemia to symptomatic hyperlactatemia with 

mild acidosis, to fulminant lactic acidosis, liver failure, 

and death. In addition, some patients develop hepatic 

steatosis. The development of fulminant lactic acidosis, 

although very rare, has clearly emerged as one of the 

most dreaded adverse effects associated with ART.
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

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

6

What	antiretroviral	drugs	cause	

hyperlactatemia?

Hyperlactatemia and lactic acidosis result from 

abnormal mitochondrial toxicity caused by NRTIs 

that inhibit the critical enzyme mitochondrial DNA 

polymerase gamma. There is no evidence that NNRTIs 

or PIs cause mitochondrial toxicity or abnormalities 

in serum lactate levels. In vitro data and retrospective 

clinical data show that stavudine (d4T) and didanosine 

(ddI) are the most likely medications in the NRTI class 

to cause this complication, especially if used together. 

Zidovudine poses some risk but significantly less than 

either stavudine or didanosine. Tenofovir (TDF), abacavir 

(ABC), emtricitabine (FTC), and lamivudine (3TC) 

appear to pose the least risk of causing lactic acidosis. 

Identified risk factors, in addition to the use of NRTIs, 

include pregnancy, female gender, obesity, or concurrent 

treatment with ribavirin, hydroxyurea, or metformin. 

How	do	you	collect	and	interpret	a	serum	

lactate	test?

The normal serum lactate level is <2 mmol/dL. Proper 

blood collection and appropriate transport are essential 

for obtaining an accurate result. The patient should not 

exercise for 24 hours prior to the test and should be 

well hydrated, and should rest for at least 5 minutes 

prior to the blood draw. The blood should be drawn 

without tourniquet and the patient should be instructed 

not to clench his or her fist. The sample should be 

submitted promptly for processing using a pre-chilled 

fluoride-oxalate tube transported on ice. The specimen 

should be processed within 4 hours after being drawn.

For interpretation, levels of 2-5 mmol/dL are often 

associated with no symptoms, levels of 5-10 mmol/dL 

are usually associated with symptoms that require 

discontinuation of NRTIs, and levels of >10 mmol/dL 

are associated with a fatality of >30% and require 

immediate intervention. Abnormal levels should usually 

be confirmed. 

How	do	you	diagnose	lactic	acidosis?

Routine monitoring of serum lactate levels in 

asymptomatic patients is not recommended (see Table 

6-2), but obtaining a serum lactate level is critical if 

hyperlactatemia is suspected (see previous question 

for correct technique). Patients with mild increases in 

serum lactate levels generally do not have significant 

symptoms, and if symptoms are present, they are 

most likely nonspecific. With more severe increases in 

serum lactate levels, patients may have marked fatigue, 

nausea, anorexia, vomiting, abdominal pain, dyspnea, 

and hyperventilation. Although a chemistry panel may 

show a decreased serum bicarbonate level or increased 

anion gap level, some reports have documented 

patients with severe lactic acidosis who do not have 

abnormal serum bicarbonate or increased anion 

gap measurements. CT scan of the liver may show 

enlargement and fatty infiltration. 

How	do	you	manage	severe	hyperlactatemia	or	

lactic	acidosis?

Patients with severe hyperlactatemia or lactic acidosis 

should immediately discontinue ART (see Table 6-

3). Seriously ill patients may require IV bicarbonate, 

mechanical ventilation, or dialysis. Most respond 

to drug withdrawal. Case reports have suggested 

improvement in lactic acidosis with use of compounds 

such as riboflavin, thiamine, L-carnitine, or co-enzyme 

Q, with the benefit hypothetically resulting from 

improvement in mitochondrial function; however, the 

use of these agents to prevent hyperlactatemia and 

lactic acidosis has not been studied. Unfortunately, even 

after discontinuing ART, recovery from lactic acidosis 

typically takes about 8 weeks, since regeneration of 

severely damaged mitochondria is a prolonged process. 

Once	a	lactic	acidosis	episode	is	resolved,	can	a	

patient	resume	ART?

For those patients who recover from an episode of 

lactic acidosis, the optimal management of their 

subsequent ART remains unclear. For those patients 

who clearly need ART, the safest option would be to 

use a regimen that does not contain an NRTI, such as 

lopinavir plus ritonavir plus efavirenz (LPV/r + EFV), 

saquinavir plus ritonavir (SQV + RTV), or indinavir 

plus ritonavir plus efavirenz (IDV + RTV + EFV). 

Available data suggest tenofovir (TDF), lamivudine 

(3TC), emtricitabine (FTC), and abacavir (ABC) are the 

NRTIs least likely to cause severe hyperlactatemia or 

lactic acidosis. In a report of 17 patients who developed 

symptomatic hyperlactatemia while receiving stavudine 

(d4T), the patients were rechallenged with abacavir 

or zidovudine; none of the 17 had a recurrence of 

symptomatic hyperlactatemia. Nevertheless, providers 

should obtain expert consultation and also observe 

the patient closely when restarting a new regimen 

that includes one or more NRTIs in any patient with a 

history of lactic acidosis.
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

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6

OTHER METABOLIC

COMPLICATIONS

Does	ART	cause	hyperglycemia	and	diabetes?

Although several studies have shown that PIs can have a 

direct effect on glucose metabolism, predominantly by 

increasing insulin resistance, it remains unclear whether 

ART significantly increases the risk for developing 

diabetes mellitus. Available data would suggest that ART, 

particularly with PIs, likely causes a slightly increased 

risk of developing overt diabetes mellitus. Routine 

monitoring for hyperglycemia is recommended for any 

patient on a PI-based regimen (see Table 6-3). Studies of 

patients with hyperglycemia and insulin resistance have 

consistently shown that switching from a PI to either 

nevirapine (NVP), efavirenz (EFV), or abacavir (ABC) 

will significantly improve the hyperglycemia and insulin 

resistance. Nevertheless, further study is needed to 

better clarify the risk of a patient’s developing diabetes 

mellitus while taking a PI and the long-term clinical 

benefit of switching from a PI to a regimen that causes 

less insulin resistance. 

Does	ART	cause	abnormalities	in	bone	density?

Several retrospective reports have suggested that ART 

may cause decreases in bone mineral density and, 

rarely, avascular necrosis. Recently, the relationship 

between ART and decreases in bone mineral density 

has become very controversial and prospective 

studies are needed to resolve the issue. From a clinical 

perspective, avascular necrosis should be suspected 

when a patient complains of focal bone pain; either CT 

or MRI can confirm the diagnosis. Avascular necrosis 

most often involves the femoral or humeral head, can 

consist of necrosis at a single or multiple sites, does 

not respond to medical therapy, and typically requires 

surgical intervention (see Table 6-3). There are no data 

regarding modifying an ART regimen either to prevent 

avascular necrosis or to improve the condition once it 

has already developed. 

KEY POINTS

Metabolic complications include the 

long-term consequences of antiretroviral 

agents: lactic acidosis (due to NRTIs 

[nucleosides]), dyslipidemia (usually due 

to PIs), insulin resistance (usually due 

to PIs), fat redistribution (usually due to 

NRTIs and PIs).

All PIs except atazanavir (ATV) are 

associated with variable increases in the 

LDL cholesterol and/or triglycerides.

Cardiovascular risks of dyslipidemia 

associated with PI therapy are assumed 

to be the same as for persons without 

HIV infection; they are usually managed 

with lifestyle changes (smoking cessation, 

diet modifications, and exercise) and, if 

necessary, lipid-lowering drugs; if statins 

are used, pravastatin or atorvastatin are 

preferred to avoid drug interactions with 

the PIs.

Patients receiving PIs should have blood 

lipids and glucose monitored at baseline, 

at 3-6 months and then at least annually, 

and more frequently depending on other 

risks and severity of abnormalities.

ART is associated with fat redistribution, 

both fat accumulation (abdomen, breasts, 

dorsocervical) and fat wasting (buccal 

fat with face thinning, buttocks, and 

extremities). These changes can result 

in major unfavorable changes in physical 

appearance and can have a significant 

impact on quality of life. 

There are no effective treatments 

for reversing fat redistribution. 

Discontinuing or switching therapy has 

moderate effect at best and improvement 

requires a very long time; with face 

thinning the best results are with 

discontinuing stavudine (d4T) early. 

Lactic acidosis is a result of mitochondrial 

toxicity caused by prolonged use 

of NRTIs, primarily stavudine (d4T), 

didanosine (ddI) and to a lesser degree 

zidovudine (AZT).

The usual symptoms of lactic acidosis 

are fatigue, abdominal pain, nausea, and 

weight loss; the usual laboratory finding 

is a serum lactate exceeding 5 mmol/dL. 

The main treatment is to discontinue the 

implicated drugs or switch to NRTIs that 

are less likely to cause this.

Type 2 diabetes is an occasional 

complication of PI therapy due to insulin 

resistance. Monitoring should include 

fasting blood glucose at baseline and at 5-

8 months with subsequent measurements 

depending on risk and prior results.
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

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

6

SUGGESTED RESOURCES

Bozzette SA, Ake CF, Tam HK, Chang 

SW, Louis TA. Cardiovascular and 

cerebrovascular events in patients treated 

for human immunodeficiency virus 

infection. N Engl J Med. 2003;348:702-710.

Carr A, Cooper DA. Adverse effects of 

antiretroviral therapy. Lancet. 2000;356:

1423-1430.

Dube MP. Disorders of glucose metabolism 

in patients infected with human 

immunodeficiency virus. Clin Infect Dis.

2000;31:1467-1475.

Dube MP, Stein JH, Aberg JA, Fichtenbaum 

CJ, et al: Guidelines for the evaluation 

and management of dyslipidemia in 

human immunodeficiency virus-infected 

adults receiving antiretroviral therapy: 

Recommendations of the HIV Medicine 

Association of the Infectious Disease 

Society of America and the Adult AIDS 

Clinical Trials Group. Clin Infect Dis. 

2003;37:613-627.

Moyle G, Carr A. HIV-associated 

lipodystrophy, metabolic complications, 

and antiretroviral toxicities. HIV Clin Trials.

2002;3:89-98. 

Moyle GJ, Datta D, Mandalia S, Morlese J, 

Asboe D, Gazzard BG. Hyperlactataemia 

and lactic acidosis during antiretroviral 

therapy: relevance, reproducibility and 

possible risk factors. AIDS. 2002;16:1341-

1349.

Orenstein R. Presenting syndromes of 

human immunodeficiency virus. Mayo Clin 

Proc. 2002;77:1093-1102.

Smith KY. Selected metabolic and 

morphologic complications associated 

with highly active antiretroviral therapy. 

J Infect Dis. 2002;185 Suppl 2:S123-127.

REFERENCES

Friis-Moller N, Sabin CA, Weber R, et al. 

Combination antiretroviral therapy and the 

risk of myocardial infarction. N Engl J Med.

2003;349:1993-2003.

McComsey GA, Ward DJ, Hessenthaler SM, et 

al. Improvement in lipoatrophy associated 

with highly active antiretroviral therapy in 

human immunodeficiency virus-infected 

patients switched from stavudine to abacavir 

or zidovudine: the results of the TARHEEL 

study. Clin Infect Dis. 2004;38:263-270.

Schambelan M, Benson CA, Andrew Carr A, et 

al. Management of metabolic complications 

associated with antiretroviral therapy for 

HIV-1 infection: Recommendations of an 

International AIDS Society-USA Panel. J Acquir 

Immune Defic Syndr. 2002; 31:257-275. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 6: Metabolic Complications of Antiretroviral Therapy 

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6

CASES

1.	

A 36-year-old HIV-infected man has received stavudine (d4T) plus lamivudine (3TC) plus indinavir (IDV) 

for approximately 4 years. This regimen was his first regimen and before starting therapy his HIV RNA 

was 59,000 copies/mL and his CD4 count was 34 cells/mm3. His antiviral and immunologic response 

has been excellent, with HIV RNA levels persistently less than 50 copies/mL and a CD4 count that 

has increased to 526 cells/mm3. In the past 9 months, however, he has developed hyperlipidemia, 

hyperglycemia, and body fat changes, most notably enlargement of his abdominal region and facial 

thinning. He has been very hesitant to change his regimen but now comes into the clinic to discuss this 

matter again. 

Question:		 If he changes his antiretroviral regimen, will he likely continue to have excellent 

control of HIV?

Answer:	

Since this patient has experienced excellent long-term viral suppression and this was his first regimen, it 

is highly likely that a switch from a PI to a NNRTI (efavirenz [EFV] or nevirapine [NVP]) would maintain 

continued viral suppression. Similarly, a change from one NRTI to another would likely have no adverse 

affect on HIV suppression. In patients who have previously developed resistance and are currently on 

a salvage regimen, changing a medication because of side effects can pose a much greater risk of not 

maintaining excellent virologic control. 

Question:		 What improvements would he likely expect if he makes a change?

Answer:	

Among the problems this patient has developed as a complication of ART, insulin resistance and 

hyperlipidemia are the most likely to improve with a regimen change. In particular, several studies have 

shown switching from a PI to either nevirapine, efavirenz, or abacavir (ABC) typically leads to significant 

improvement in hyperglycemia and insulin resistance. Improvements in lipids are most likely to occur if the 

PI is switched to either nevirapine or abacavir. Switching from one PI to the new PI atazanavir (ATV) may 

provide significant improvement in lipid abnormalities. Unfortunately, changing from a PI to an NNRTI 

has not produced reliable improvements in lipodystrophy. Changing from stavudine to either abacavir or 

tenofovir (TDF) may provide some improvement in lipodystrophy for some patients. Although tenofovir 

causes less lipodystrophy than stavudine, studies that examine the effect of changing stavudine to 

tenofovir have not been performed. 
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2.	

A 33-year-old woman on stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) presents with severe 

fatigue. No obvious cause for the fatigue is discovered and 1 week later she returns with even worse 

fatigue. Serum chemistries now are notable for a bicarbonate of 17 mmol/L. A serum lactate level is 

drawn and a lactate level of 6.3 mmol/L is reported from the laboratory. The patient is not taking any 

other medications and is not taking any herbal preparations. 

Question:	 Is the serum lactate level of 6.3 mmol/L concerning in this patient?

Answer:	

Experts have stratified serum lactate levels based on the risk of developing complications from 

hyperlactatemia. Those with a serum lactate level of 2.1-5.0 mmol/L are considered to have mild 

hyperlactatemia, those with a serum lactate level of at least 5 mmol/L have serious hyperlactatemia, 

and those with a lactate level at least 5 mmol/L plus a bicarbonate level less than 20 mmol/L have lactic 

acidosis. Accordingly, the patient’s serum lactate of 6.3 mmol/L (along with the serum bicarbonate of 17 

mmol/L) is extremely concerning and suggests lactic acidosis, a potentially life-threatening problem. 

Question:	 If lactic acidosis is suspected, how should the patient be managed?

Answer:	

Because hyperlactatemia and lactic acidosis result from NRTI-induced mitochondrial toxicity, the first step 

in managing this problem is to immediately discontinue ART. Although several case reports have suggested 

improvement in lactic acidosis by using compounds such as riboflavin, thiamine, L-carnitine, or co-enzyme 

Q, supportive care remains the mainstay of therapy. After discontinuing ART, regeneration of severely 

damaged mitochondrial typically requires prolonged periods, and recovery from lactic acidosis can take 

several months. Following recovery, the optimal management of subsequent antiretroviral therapy remains 

unclear. Preliminary reports suggest changing the NRTIs (typically replacing stavudine) can safely be 

performed, but should be done with expert consultation. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 7: Adherence to HIV Therapies

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7

OVERVIEW

What	is	meant	by	medication	adherence?

Medication adherence means a patient takes 

the prescribed dose of prescribed medications 

on the prescribed schedule, following prescribed 

dietary instructions. Patient adherence to medical 

appointments and to behaviors that minimize the risk 

of transmission of HIV to others correlates strongly with 

adherence to medications and is an important part of 

primary care of HIV-infected patients but will not be 

addressed in this chapter. 

Why	is	medication	adherence	so	important	in	

HIV	therapy?	

Nonadherence to prescribed therapy is a ubiquitous 

problem in medicine. In chronic diseases, including 

asthma, diabetes, and hypertension, only 50% of 

patients take their medication as prescribed more than 

80% of the time. The same is true of patients with HIV 

infection. However, because of the rapid multiplication 

and mutation rate of HIV and the relatively low potency 

and short half-life of most antiretrovirals, very high 

levels of adherence to antiretroviral schedules are 

necessary to avoid viral resistance. In comparison with 

patients who are adherent to antiretroviral therapy 

(ART), nonadherent patients have: 1) Higher mortality 

(2.5 adjusted relative hazard) (Wood, et al, 2003), 2) 

Lower increase in CD4 cell count (6 cells/mm3 increase 

for nonadherent patients versus 83 cells/mm3 increase 

for adherent patients) (Paterson 2000), and 3) Increased 

hospital days (12.9 days/1000 days of followup for 

nonadherent patients versus 2.5 hospital days/1000 

days for adherent patients) (Paterson, et al, 2000). 

How	adherent	do	patients	need	to	be	to	avoid	

viral	resistance?	

Results of a study of adherence and response to 

therapy among primarily antiretroviral-experienced 

patients taking protease inhibitors (PIs) showed that 

a >95% adherence rate was necessary for 78% of 

patients to achieve an undetectable viral load (Paterson, 

2000); however, some patients with significantly less 

adherence also had success (see Figure 7-1). Exactly 

how adherent individual patients need to be is not 

known and probably depends on several factors, 

including preexisting antiretroviral resistance, viral 

load, viral genetic barriers to the development of 

drug resistance, and drug half-life. Patients should be 

counseled that the risk of viral resistance increases with 

nonadherence and that nearly perfect adherence is the 

goal. Of note, patients with very low levels of adherence 

may be at decreased risk of developing viral resistance 

because there is not enough selective pressure 

(Bangsberg, et al, 2003). 

ASSESSMENT

What	factors	impact	adherence?	

Many factors contribute to a patient’s ability to adhere 

to medication schedules (Table 7-1). Note that race, 

education level, and income are generally not predictive 

of adherence. Providers must remember that factors 

predicting adherence or nonadherence are only 

associations and are not absolutely predictive. For 

example, although patients who use addictive substances 

are more likely to be nonadherent, some patients with 

heavy alcohol or drug use are adherent to ART. 

Chapter	7:	

Adherence	to	HIV	Therapies Laura W. Cheever, MD, ScM

OVERVIEW

ASSESSMENT

INTERVENTIONS

KEY POINTS

SUGGESTED RESOURCES

REFERENCES

CASES
A Guide to Primary Care of People with HIV/AIDS

Chapter 7: Adherence to HIV Therapies

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

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Figure 7-1: Adherence Rates Predict 

Viral Load Response

Viral Load

<400 (% Patients)

Adherence with Protease Inhibitor Therapy

<70 70-79 80-89 90-94

0

20

40

60

80

100

>95

18

29 33

45

78

Source: Adapted from Paterson DL, Swindells S, Mohr J, et al. 

Adherence to protease inhibitor therapy and outcomes in patients 

with HIV infection. Ann Intern Med. 2000;133:21-30. Copyright 

American College of Physicians. modified with permission.

One of the primary predictors of adherence is “selfefficacy” or patient readiness. Patients who have 

confidence in their ability to take their medications as 

instructed (ie, they have good self-efficacy) are much 

more likely to be compliant than patients who lack this 

confidence. Among HIV-infected patients, the common 

comorbidities of substance abuse and untreated 

mental illness contribute significantly to nonadherence. 

Because side effects of the medications also are a 

significant barrier to patient adherence, providers need 

to vigorously address complaints of side effects. 

What	is	the	best	way	to	assess	a	patient’s	

adherence?

There is no gold standard for measuring adherence. 

A provider’s “impression” of a patients’ adherence, 

without specific assessments, is very unreliable. 

Mechanisms to measure adherence include assessment 

of serum drug levels, electronic monitoring of pill 

bottle openings, pill counts made at clinic visits or at 

surprise home visits, pharmacy record reviews, and 

patient responses to questioning. In general these 

different measures have good correlations to adherence 

levels, although asking the patient will be more likely 

to overestimate adherence than objective measures. 

Computer-assisted questioning of patients will improve 

self-reporting reliability. Serum drug level assessment 

provides only information about the most recent dose 

and is quite costly and not practical in clinical practice..

Table 7-1: Factors that Promote Patients’ 

Adherence to Medication Regimens

Patient-related factors

Absence of mental illness/depression

Absence of substance abuse (alcohol and other drugs of 

abuse)

Perceived ability to take medication as instructed (self-efficacy) 

Older age

Higher literacy

Strong social support network

Adherence with medical appointments

Stable housing

Adherence with previous therapies

Positive attitude toward efficacy of medication

Medication-related factors

Fewer medications

Fewer doses

Fewer pills

Fewer side effects

Lack of dietary restrictions

Shorter time on therapy 

Good “fit” of regimen into patient’s daily routine

Health system-related factors

Trusting relationship with health care provider

Patient education: 

• Patients understand their regimen, including food 

restrictions

• Patients understand the association of adherence 

and resistance

Convenient access to medications and refills

How	should	providers	ask	patients	about	

adherence	to	get	the	most	reliable	information?	

With appropriate education at the start of ART, a 

patient should know the importance of adherence. It 

is important to approach the discussion of adherence 

at follow-up visits in a nonjudgmental way and “give 

permission” for missing doses. Also, asking specific 

questions will yield specific information. An example of 

an inquiry might be: “Everyone misses doses of their 

medication some of the time. How many times in the 

last 3 days/week/month have you missed taking doses of 

your medicine?” From there, a discussion of the specific 

events that led to missing doses can lead to problemsolving with the patient to overcome these barriers. 
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The provider should ask patients to recount exactly 

when and how they are taking their medications in 

order to identify any lack of understanding of the 

regimen itself or of special dietary instructions. 

INTERVENTIONS

What	can	be	done	to	improve	adherence?	

The most important intervention is making sure 

patients start medication only when they are “ready.” 

Providers need to discuss with patients the risks 

associated with nonadherence that can result from 

starting medications before they are ready versus 

waiting while they “prepare.” Preparing can mean 

entering into substance abuse treatment, finding stable 

housing, or attending a support group to overcome 

fears of medication side effects and concerns about 

confidentiality. Pregnant women and patients with 

serious complications of HIV infection and very low 

CD4 counts may not have the luxury of postponing 

therapy, but for others, being ready to adhere may be 

critical to the outcome of ART.

Interventions to improve adherence in chronic diseases 

tend to have, at best, modest effects on adherence. 

They are most effective if they are multifaceted, ie, they 

target several aspects of the adherence behavior and 

are repeated over time. Barriers to adherence differ 

among patients. Thus, interventions should be tailored 

to the patient’s specific needs. In addition, barriers to 

adherence vary over time, so interventions need to 

vary as well. Interventions can occur at the level of the 

provider, care team, clinic, and/or pharmacy. Ideally, 

interventions are occurring throughout the patient’s 

medical visit and beyond. 

The most commonly used interventions address 

patient readiness using both one-on-one education and 

support groups. Peer counseling and support are key 

for many patients to work through concerns related 

to medication-taking. Making patients partners in the 

decisionmaking process about when to start and which 

regimen to use is also important. The regimen should 

be as simple as possible and should be the one least 

likely to cause the side effects that the patient fears the 

most. Substance abuse and mental illness should be 

treated before starting medication whenever possible. 

After the patient begins the regimen, close followup 

and monitoring of adherence is critical, often through 

frequent clinic visits during the first weeks of therapy 

even if other medical interventions are not necessary. 

Providers should ask patients about adherence and 

address barriers to adherence at each followup visit. 

Providers should be open to changing the regimen if a 

patient has significant problems with it, whether related 

to side effects or to scheduling. Patients should be 

encouraged to use pill boxes and incorporate reminder 

systems as needed. Various kinds of interventions have 

been used in HIV and other chronic diseases (see 

Table 7-2).

What	is	the	role	of	Directly	Observed	Therapy	

(DOT)	for	medication	adherence?

Directly observed therapy (DOT) refers to medical staff 

supervising patients taking each dose of medication. 

DOT has increased treatment completion and 

decreased the resistance rates of tuberculosis therapy. 

Whether it is feasible in HIV therapy is currently under 

investigation. A majority of ongoing studies are using 

modified DOT, with only 1 daily dose of medication 

observed over the first several months of therapy or 

during the administration of methadone maintenance 

therapy. The results of these studies will provide 

valuable information about the long-term patient 

acceptability, cost, and efficacy of this approach to 

improve adherence over the long term.
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Table 7-2: Interventions That Have Been Used to Support Adherence 

in HIV and Other Chronic Diseases

Intervention Comments

The Patient

Start when patients are ready For patients with complications of HIV infection, low CD4 cell counts, or pregnancy, the cost-benefit analysis of 

treatment is different.

Treat substance abuse and 

depression before initiating 

ART

If there is no antiretroviral emergency, patients with active substance abuse and depression should have these 

comorbidities addressed before starting an antiretroviral regimen. 

Engage patients in medication 

tailoring

Discuss with patients in detail how the medications will fit into their daily routine- ie, when (and if) meals are 

eaten, what patients do on a daily basis that can be linked to dosing times.

Educate (group/individual) 

regarding:

- the regimen

- side effects management

- consequences of 

nonadherence

- Patient education is essential -- both group and one-on-one.

- Involve caretakers and patient support network in educational efforts. 

- Patients need to know exactly how to take their medication. A daily calendar with pills on it will help a patient 

visualize the regimen.

- Prior to initiating therapy, patients should know which side effects to expect, what they can to do to manage 

them, and when to call the provider.

- Patients need to understand the serious consequences of nonadherence and what to do in the event of a late or 

missed dose.

Increase support Patients should enlist the aid of family and friends to promote their adherence. The HIV health care team can 

provide support through office visits, home visits, and telephone calls, especially in the early days and weeks of 

ART.

Use skill building exercises Patients who are concerned about their ability to adhere should use a trial of jellybeans in a pill box to accustom 

themselves to their pill taking schedule prior to initiating therapy. This may not increase adherence, but it may 

give patients insight into their adherence and affect their decision to start medications. 

Address barriers to adherence - Have patients consider when medications are likely to be missed and make plans to decrease these events. 

- Some patients store a few doses in places where they spend a lot of time, such as at the houses of friends and 

relatives.

Use reminders - Alarm clocks, in the form of watch alarms, pagers, or pill boxes can decrease missed doses due to simply 

forgetting. 

- Patients can place medications in locations where they will notice them at dosing times, such on the breakfast 

table. 

The Regimen

Simplify as much as possible - Once or twice-a-day regimens are easiest for patients.

- Use as few pills and medications as possible.

- Try to use regimens than can be followed without regard to food intake.

Tailor the regimen to the 

patient’s lifestyle (and not 

the patient’s lifestyle to the 

regimen)

- Ask patients about their daily routine and comfort in taking medications in front of others and at work. 

- Construct a regimen that works for the patient.

Use pill boxes - Use of pill boxes allows patients a mechanism for carrying their daily medication.

- Pill boxes allow patients to easily recognize when they have missed taking a dose.

Make refills accessible - Develop policies to allow patients ready access to refills.

The Clinician-Patient Relationship

Develop a trusting relationship - Rarely is initiation of antiretroviral regimens required at the first visit. Invest in the doctor-patient relationship 

prior to initiating therapy.

Ask about adherence - Providers cannot predict adherence; they must ask patients.

- Ask in a nonjudgmental way, with a specific time frame, to get good information.

- Give permission for missed doses prior to asking.

- Ask repetitively over time.

Use positive reinforcement Share viral load and CD4 results and reinforce the relationship to adherence.

Listen to the patient -Individualize therapy based on patient preferences regarding fear of specific side effects or specific medication. 

-Negotiate the regimen with patients.

System of Care

Maintain close followup at 

initiation of regimen

Have telephone, office, or home contact with patients within first few days of therapy to assess for side effects and 

accurate understanding of regimen.

Develop patient education 

program

- Consider using nurses, case managers, pharmacists, and peers in patient education.

- Have written materials accessible.

Incorporate the adherence 

message throughout the 

medical practice

- All staff members need to understand and promote the importance of adherence.

- Have pill boxes, alarms, and other adherence aids available to patients.
A Guide to Primary Care of People with HIV/AIDS

Chapter 7: Adherence to HIV Therapies

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7

KEY POINTS

Medication adherence is a significant 

challenge in all chronic diseases, but is 

particularly important in ART because of 

the high levels of adherence that must be 

maintained to prevent viral resistance.

Patients should not start taking 

antiretroviral medications until they 

are ready. Providers should take the 

time to assess their readiness, conduct 

interventions to prepare them to begin 

therapy, and follow them closely once 

they start.

Interventions to support adherence should 

be multifaceted and repeated over time. 

However, interventions have a modest 

effect on adherence.

SUGGESTED RESOURCES

Antinori A, Ammassari A, Wu AW. 

Proceedings of the 1st workshop on 

HAART adherence: state of the art. JAIDS. 

2002;31:S95-169.

Bangsberg DR, Hecht, FM, Charlebois ED, 

et al. Adherence to protease inhibitors, 

HIV-1 viral load, and development of drug 

resistance in an indigent population. AIDS. 

2000 14:357-366. 

Roter DL, Hall JA, Merisca R, Nordstrom 

B, Cretin D, Svarstad B. Effectiveness 

of interventions to improve patient 

compliance: a meta-analysis. Medical Care. 

1998;36:1138-1161.

Sackett DL, Haynes RB, Gibson ES, et al: 

Randomized clinical trial of strategies 

for improving medication compliance in 

primary hypertension. Lancet. 1975;1:

1265-1268.

Stone, VE: Strategies for optimizing 

adherence to highly active antiretroviral 

therapy: lessons from research and clinical 

practice. Clin Infect Dis. 2001; 33:865-872.

REFERENCES

Bangsberg DR, Charlebois ED, Grant RM, 

et al. High levels of adherence do not 

prevent accumulation of HIV drug resistance 

mutations. AIDS. 2003;17:1925-1932.

Paterson DL, Swindells S, Mohr J, et al. 

Adherence to protease inhibitor therapy and 

outcomes in patients with HIV infection. Ann 

Intern Med. 2000;133:21-30.

Shingadia D, Viani Rm, Yogev R, et al: 

Gastrostomy tube insertion for improvement 

of adherence to highly active antiretroviral 

therapy in pediatric patients with human 

immunodeficiency virus. Pediatrics. 2000;

105:E80.

Wood E, Hogg RS, Yip B, et al. Effect of 

medication adherence on survival of HIVinfected adults who start highly active 

antiretroviral therapy when the CD4+ cell 

count is 0.200 to 0.350x109 cells/mL. Ann 

Intern Med. 2003;39:810-816. 
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54 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau

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CASES

1.	

AR is a 37-year-old woman who uses heroin and cocaine daily and has a CD4 count of 300 cells/mm3

and an HIV viral load of 150,000 copies/mL. Since she was diagnosed with HIV infection 10 years ago 

she has primarily sought care when acutely ill. She comes to clinic for the first time in 6 months because 

she has decided to start “the cocktail.” 

Question:	How do you manage this patient?

Answer:	

This patient is not engaged in primary care and is using heroin daily. Although she might be able to 

adhere to therapy, she probably won’t. Beginning ART is reasonable given her CD4 cell count and viral 

load; however nothing makes it critical to start therapy immediately.

The patient did not agree with her physician’s assessment that her substance abuse was a barrier to 

medical care or medication adherence. She agreed to contract with her physician to start ART after she 

made 5 consecutive clinic visits. After several attempts at consecutive visits, the patient enrolled in a 

methadone-based substance abuse treatment program. She began to come regularly to clinic, engaged 

in in-depth medication education, and eventually started ART. She had good adherence, maintaining an 

undetectable viral load for 18 months before a drug abuse relapse. When she began to miss doses, she 

stopped all her medications as instructed and did not develop significant resistance.

2.	

DP is a 4-year-old with perinatally-acquired HIV infection. He is taken care of by his maternal greatgrandmother, who is also caring for 3 other great-grandchildren. He resists taking ART because of the 

taste, so that it takes his great-grandmother 30-60 minutes to administer each dose when she can get him 

to take it. Although she has worked closely with the behavior modification team at the pediatric clinic, the 

situation has not improved. His viral load and CD4 cell count have not changed significantly on therapy. 

Question:	What do you do to treat this patient?

Answer:	

Given the patient’s refusal to take medication, the decision was made to place a g-tube for ease of 

administration. Within 1 month the viral load was undetectable, and the time to administer medications 

had decreased to less than 10 minutes per dose. The great-grandmother reported a significant 

improvement in their relationship and in DP’s behavior in a number of domains. Although this may seem 

extreme, this is an example of individualizing the intervention to the barriers that exist for the patient 

(Shingadia, et al 2000).
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8

WORKUP OF SYMPTOMS

How	should	you	approach	the	workup	of	

symptoms	in	patients	infected	with	HIV?

Symptom evaluation in HIV-infected patients must 

include knowledge of the CD4 count and viral load 

as well as close attention to the medication list. An 

opportunistic disease (OD) is an unlikely cause of 

symptoms in patients with CD4 cell counts >200/mm3. 

Antiretroviral medications are a common cause of HIVrelated symptoms.

MEDICATION-RELATED

ISSUES

What	are	the	most	common	symptoms	related	

to	antiretroviral	medications?

Nausea and diarrhea are the two most common 

symptoms associated with antiretroviral therapy (ART). 

Pruritus and skin rashes are also common, especially 

with nonnucleoside drugs. Lower extremity pain due 

to neuropathy is seen with didanosine (ddI), stavudine 

(d4T), and zalcitabine (ddC).

What	are	the	common	side	effects	of	each	of	

the	antiretroviral	drugs?

The different classes of drugs have many similar as well 

as distinct side effects (see Table 8-1).

What	symptoms	could	be	due	to	lifethreatening	acute	drug	reactions?	

Symptoms of life-threatening acute drug reactions 

are not to be missed. A patient with myalgias, 

nausea, vomiting, diarrhea, abdominal pain, fever, 

rash, malaise, and extreme fatigue who has started 

taking abacavir (ABC) within the previous 6 weeks is 

probably suffering from an abacavir hypersensitivity 

reaction. In this case, abacavir should be permanently 

discontinued. The hypersensitivity reaction occurs in 

up to 5% of patients starting on abacavir and can lead 

to hypotension and death if the patient is rechallenged 

with abacavir. If a patient taking one of the “d-drugs” 

(didanosine [ddI], zalcitabine [ddC], stavudine [d4T], 

dapsone [for Pneumocystis pneumonia prophylaxis]) 

has rapid onset of nausea/vomiting and constant, severe 

abdominal pain in the epigastrium or upper quadrants 

that radiates to the back, drug-induced pancreatitis 

is possible. Patients taking a nucleoside (NRTI) who 

have vague symptoms including nausea, vomiting, 

abdominal pain, weight loss, malaise, fatigue, dyspnea, 

or fever must have lactic acidosis with hepatic steatosis 

ruled out. This occurs 5-13 months after initiating 

therapy and has a 60% fatality rate. Patients taking 

nevirapine (NVP) who have fatigue, malaise, nausea, 

vomiting, jaundice, and right-upper-quadrant abdominal 

pain could have nevirapine-induced hepatitis. Also, 

up to half the patients taking nevirapine may have a 

rash; however, if the rash is moist, involves the mucous 

membranes, or is extensive with an associated fever, 

Stevens-Johnson syndrome, which also occurs in 

patients taking trimethoprim-sulfamethoxazole (TMP/

sulfa), must be considered. Severe cases of StevensJohnson syndrome, including toxic epidermal necrolysis 

(TEN), are medical emergencies and must be managed 

as burn cases. For all drug-induced, life-threatening 

illnesses, immediate discontinuation of the offending 

drug is the crucial first step in care. 

What	are	the	most	important	drug	interactions	

that	occur	with	antiretroviral	medications?

Drug interactions are frequently the cause of symptoms 

and must be closely watched for. Not only do 

antiretroviral drugs react with each other, they react 

with numerous prescribed drugs and recreational drugs 

(see Tables 4-8 in the Pocket Guide).

Chapter	8:	

Symptom	Management Tara Evans Nysoe, MD

Douglas S. Paauw, MD, FACP

WORKUP OF SYMPTOMS 

MEDICATION-RELATED ISSUES

NAUSEA

PULMONARY SYMPTOMS

FATIGUE

NEUROPATHIC PAIN

DERMATOLOGIC SYMPTOMS

MOUTH LESIONS 

WASTING

MYALGIAS

DIARRHEA

HEADACHE

KEY POINTS

SUGGESTED RESOURCES

CASES
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Table 8-1. Side Effects of 

Antiretroviral Drugs

Drug Side effects

Nucleosides (NRTIs)

Class effect Hepatic steatosis/lactic acidosis

abacavir (ABC) Hypersensitivity reaction (nausea, 

anorexia, fever, rash, dyspnea, cough)

didanosine (ddI) Pancreatitis, peripheral neuropathy, 

nausea, diarrhea

lamivudine (3TC) Very few side effects

stavudine (d4T) Peripheral neuropathy, pancreatitis

tenofovir (TDF) (a 

nucleotide)

Nausea, vomiting, diarrhea

zalcitabine (ddC) Peripheral neuropathy, mucosal ulcers, 

pancreatitis

zidovudine (AZT) Anemia, myopathy, headache, nausea

emtricitabine (FTC) Nausea, very few side effects

Nonnucleoside reverse 

transcriptase inhibitors (NNRTIs)

efavirenz (EFV) Confusion, insomnia, rash, disturbing 

dreams

nevirapine (NVP) Rash (15%), hepatitis

Protease inhibitors (PIs)

Class effect Hyperglycemia, hyperlipidemia, 

lipodystrophy, hepatitis

amprenavir (APV) Nausea, diarrhea, rash, paraesthesias

atazanavir (ATV) Elevated bilirubin

fosamprenavir 

(FAPV)

Diarrhea

indinavir (IDV) Nausea, renal sludging, renal stones, 

increased indirect bilirubin

lopinavir+ritonavir 

(LPV/r or Kaletra)

Nausea, vomiting, diarrhea

nelfinavir (NFV) Diarrhea common (can be limiting)

ritonavir (RTV) Nausea, vomiting, circumoral 

paraesthesias, hepatitis, taste 

abnormalities

saquinavir (SQV) Nausea, diarrhea

What	natural	products	are	potentially	useful	in	

treating	the	symptoms	of	patients	with	HIV?

Some commonly used complementary medicine 

treatments are listed in Table 8-2. Ginger for the 

treatment of nausea is probably the most effective of 

the natural products for symptom management.

Table 8-2. Complementary Medicine 

Treatment Options for Various Symptoms

Problem Treatment 

option

Comments

Nausea Ginger Studies have 

shown possible 

benefit

Hepatitis Milk thistle Inconclusive longterm benefit; may 

inhibit the p450 

system

Migraine 

prophylaxis

Riboflavin Randomized 

controlled trial 

showed benefit

Immune system 

dysfunction

Co-enzyme Q Studies have 

shown possible 

benefit in CD4 

cell counts but no 

outcome benefit 

has been shown

NAUSEA

What	are	the	important	causes	of	nausea	in	

patients	with	HIV?

The most common cause of nausea in patients with 

HIV is medication side effects. Many of the antiretroviral 

drugs can result in prominent nausea. Full dose 

ritonavir (RTV) probably causes the most severe and 

frequent symptoms, but nausea can be seen with 

all of the protease inhibitors (PIs). Zidovudine (AZT) 

frequently causes nausea when first taken. Didanosine 

(ddI), stavudine (d4T), and zalcitabine (ddC) can all 

cause nausea, or nausea may be an early sign of the 

pancreatitis these drugs can lead to. All classes of 

antiretroviral drugs can cause hepatitis, which may 

present as intense nausea and fatigue. Nevirapine (NVP) 

and PIs are the most likely to do this, but nucleosides can 

cause life-threatening lactic acidosis in association with 

hepatic steatosis. Nausea can be a component of abacavir 

(ABC) hypersensitivity reaction, usually associated with 

fever, rash, vomiting, and anorexia. The commonly 

used antibiotics trimethoprim-sulfamethoxazole (for 

Pneumocystis pneumonia [PCP] prophylaxis) and 

azithromycin or clarithromycin (for Mycobacterium avium

complex [MAC] prophylaxis) can cause nausea.

Nonmedication causes to consider include viral 

hepatitis (acute hepatitis A, B, or C). Nausea is a 

common feature of cryptococcal meningitis; other 

sources of increased intracranial pressure such as CNS 

lymphoma or toxoplasmosis can also present with 

severe nausea and vomiting.
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What	are	the	best	options	for	managing	

nausea?

If nausea is due to medications, stopping the 

medication or removing an interacting drug is the best 

option. Symptomatic therapy with prochlorperazine or 

metoclopramide may help. A natural product option 

is ginger, at a dose of 2 grams daily (no more than 

4 grams/day). Switching the time of the dose of the 

offending drug to be taken with food may be helpful.

PULMONARY SYMPTOMS

What	are	the	possible	causes	of	cough	in	an	

HIV-infected	patient?

The CD4 cell count is crucial information in determining 

the cause of cough. In patients with CD4 cell counts 

>200/mm3, viral upper respiratory infections, 

bacterial pneumonia (caused by S. pneumoniae or H. 

influenzae most commonly), tuberculosis (TB), and 

sinusitis with post-nasal drip are all important causes 

of cough. Bacterial bronchitis is more common in 

patients with HIV than in non-HIV-infected patients. 

In patients with low CD4 cell counts (<200/mm3) 

Pneumocystis carinii pneumonia must be considered. 

The risk of PCP is markedly diminished if the patient 

is taking trimethoprim-sulfamethoxazole for PCP 

prophylaxis. The cough that occurs with PCP is usually 

dry and persistent and will usually have been present 

for several weeks before a patient seeks evaluation. 

Fungal disease due to cryptococcus, histoplasmosis, or 

coccidioidomycosis is more common with lower CD4 

cell counts.

What	workup	is	appropriate?

In patients with CD4 cell counts >200/mm3 the history 

and physical exam should determine what testing to 

do. If the patient has a cough but no fever or productive 

sputum, no dyspnea, and a normal pulmonary exam, 

then chest x-ray is not necessary. A patient at high 

risk for TB should have an x-ray if there is a prolonged 

cough (>2-3 weeks) regardless of CD4 cell count. In 

a patient with a low CD4 cell count (<200/mm3) the 

possibility of PCP is much more likely and an aggressive 

approach is warranted; a chest x-ray can begin the 

workup. If it is normal, then consider obtaining 

oxygen saturation measurements with ambulation. An 

individual who has oxygen desaturations should have 

further workup. For evaluation of suspected PCP see 

Chapter 9, Management of Opportunistic Diseases.

Are	patients	infected	with	HIV	at	increased	

risk	of	developing	bacterial	pneumonia?

Available data clearly suggest that HIV-infected 

patients have an increased risk of developing bacterial 

pneumonia. In the 1993 CDC classification system, 

recurrent pneumonia (2 or more episodes in 1 year) 

is defined as a category C (AIDS-indicator) condition. 

Pneumococcal pneumonia is the most common 

bacterial pneumonia in persons infected with HIV, 

and it occurs approximately 10 times more frequently 

than in persons not infected with HIV. In addition, 

the development of pneumococcal pneumonia can 

occur early in the course of HIV disease, before other 

manifestations of immune suppression. HIV-infected 

persons with pneumococcal pneumonia have clinical 

signs and symptoms similar to those in HIV-negative 

individuals, but they have an approximately 20-fold 

higher risk of developing pneumococcal bacteremia. 

Treatment of pneumococcal pneumonia is generally the 

same in persons with and without HIV infection. Several 

studies have shown that HIV-infected persons have a 

slightly increased risk of developing pneumonia caused 

by Pseudomonas aeruginosa. 

How	common	is	sinus	disease	in	patients	

with	HIV?

Sinus disease is very common in patients with HIV. The 

lower the CD4 cell count, the more severe and more 

widespread (number of sinuses involved) sinusitis is. In 

patients with lower CD4 cell counts, chronic sinusitis 

and lack of response to therapy are more common. The 

most common organisms involved are Streptococcus 

pneumoniae, Streptococcus viridans, and Pseudomonas 

aeruginosa. Pseudomonal sinus infections are more 

common in patients with CD4 cell counts of <50/mm3. 

Fungal (Aspergillus) and viral (Cytomegalovirus) sinusitis 

can occur in patients with CD4 cell counts <100/mm3. 

Aggressive treatment of sinus disease with saline 

irrigation, antihistamine/decongestant combinations 

and full-dose nasal steroids is appropriate. Antibiotics 

should be given for the normal duration for episodes of 

acute sinusitis (3-6 week course). If antibiotic therapy 

and aggressive irrigation do not resolve the problem, 

referral to an ENT specialist for drainage procedures 

and for consideration of sinus surgery is appropriate.
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FATIGUE

What	are	the	common	causes	of	chronic	fatigue	

in	patients	with	HIV?

Fatigue can have a large impact on the quality of a 

patient’s life. Common descriptors of fatigue include 

tiredness, weakness, lack of energy, sleepiness, and 

exhaustion. Of the many possible causes of chronic 

fatigue in patients with HIV, the most common 

is depression. Other psychosocial causes include 

stress, anxiety, use of recreational substances, sleep 

disturbances, domestic abuse, and lack of exercise. 

ODs must be considered as a possible cause of fatigue 

in patients with low CD4 cell counts. Other disease 

states such as anemia, hypothyroidism, hypogonadism, 

adrenal insufficiency, influenza and other nonopportunistic infections, diabetes, liver disease, and 

malnutrition can also present as fatigue. Fatigue can be 

a side effect of ART and other medications commonly 

taken by patients with HIV. HIV-associated fatigue is a 

diagnosis of exclusion. 

How	do	you	determine	the	cause	of	a	patient’s	

fatigue?

Ask if the patient is having other symptoms of 

depression: change in sleep or appetite patterns, 

depressed mood, anhedonia, agitation or retardation, 

difficulties with concentration, decreased self-esteem, 

and suicidal ideation. Take a thorough social history 

and determine if multiple life stressors are present. 

Inquire as to how many hours of sleep the patient is 

getting per night and the number of middle-of-thenight awakenings; ask if the patient feels rested in 

the morning. Important history questions that help 

differentiate a physical from a psychological etiology 

for fatigue are in Table 8-3. Identify any barriers to 

effective sleep. Ask about the patient’s diet and exercise 

habits, and determine if the patient drinks alcohol or 

uses recreational drugs, including caffeine. Thoroughly 

review the patient’s medication list and identify any 

medications, such as certain antiretroviral drugs, betablockers, antihistamines, etc., that can be associated 

with fatigue. Do a complete review of systems and 

physical exam to elicit other symptoms or signs that 

may suggest an OD or other disease state. Simple 

laboratory tests, such as alanine aminotransferase (ALT), 

blood glucose, thyroid stimulating hormone (TSH), 

and hematocrit, can help to rule out common diseases 

that can cause fatigue. Electrolyte abnormalities can 

suggest adrenal insufficiency. Order other laboratory or 

diagnostic tests as symptoms and signs direct.

Table 8-3. History Questions to 

Differentiate Physical from Psychological 

Causes of Fatigue

Psychological 

cause

Physical 

cause

Onset Often follows 

problem or conflict

Related to onset of 

physical ailments

Duration Chronic Of recent onset

Progression Fluctuates Increases as 

disease advances

Effect of sleep Unaffected by 

sleep

Relieved by sleep

Diurnal Present in 

morning, may 

improve

Increases as the 

day progresses 

NEUROPATHIC PAIN

What	is	the	most	common	cause	of	neuropathic	

pain	and	paresthesias	in	patients	with	HIV?	

Distal symmetrical polyneuropathy (DSP) is most 

commonly caused by antiretroviral drugs. The drugs 

didanosine (ddI), zalcitabine (ddC), stavudine (d4T) 

can all cause DSP at high doses. Studies have shown 

zalcitabine to be the most likely to cause neuropathy 

at standard doses; concurrent alcohol use or vitamin 

B12 deficiency may increase risk. HIV-related DSP is 

less common than drug-induced DSP. The two types of 

neuropathies present similarly, although onset may be 

more acute in drug-induced DSP. HIV-related DSP does 

not appear to respond to viral suppression with ART. 

How	do	you	diagnose	and	treat	DSP?

Diagnose drug-related DSP by linking the onset of the 

symptoms with the initiation of drug therapy. Treat 

by drug removal; symptoms may worsen temporarily 

but should regress within several weeks. Residual 

painful symptoms of DSP may be treated with tricyclic 

antidepressants, narcotic analgesics, or gabapentin. 

The topical medication capsacin may be helpful if the 

neuropathy is limited to a small surface area. 
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DERMATOLOGIC

SYMPTOMS

How	do	you	manage	generalized	pruritus	in	a	

patient	with	no	cutaneous	signs	on	exam?

If a patient with HIV has generalized pruritus with no 

obvious cutaneous diagnosis, acute drug reactions 

such as Stevens-Johnson syndrome, which can be lifethreatening, and coexisting systemic illness such as 

hepatic dysfunction must be ruled out (see Table 8-4 

and earlier section on medication-related issues). Order 

a complete blood count, liver function tests, and blood 

chemistries. Occasionally, scabies can present with 

minimal to no cutaneous signs. Pruritus due solely to 

HIV infection is a diagnosis of exclusion; it can respond 

to ART. (Symptomatic treatments for generalized pruritus 

are listed in Table 8-5.) In general, if a clear cause is not 

identified, xerosis, a common condition in patients with 

HIV disease, will be the most likely diagnosis. In this 

case, decreasing the amount of bathing, avoiding dry 

soaps, using emollient creams, and ceasing scratching 

are the basis of symptomatic treatment. In addition, 

general agents such as H-1 antagonists can be used. The 

best studied of these is hydroxyzine, which offers the 

benefit of sedation for nocturnal itching. 

Table 8-4. Common Causes of Pruritus in 

Patients with HIV

Very common Less common

• Staphylococcal folliculitis

• Xerosis

• Atopic dermatitis

• Scabies

• Psoriasis

• Hypersensitivity to insect 

bites

• Drug reactions

• HIV-associated pruritus

• Eosinophilic folliculitis

• Granuloma annulare

• Lymphoma

• Hepatic failure

• Renal failure

How	does	scabies	manifest	differently	in	HIVinfected	persons?

Among HIV-infected persons with mild-to-moderate 

immune suppression, scabies causes similar clinical 

manifestations as seen in persons without HIV infection, 

namely multiple pruritic papular lesions. Treatment 

consists of applying 30-60 g of 5% permethrin cream 

to the entire body from the neck down, leaving it on for 

8-12 hours, then washing it off, and repeating the entire 

process one week later. In HIV-infected persons with 

severe immune suppression (CD4 count of <100 cells/

mm3), an atypical form of scabies known as crusted 

or “Norwegian” scabies may develop. Crusted scabies 

is characterized by an enormous number of scabies 

mites and manifests as nonpruritic, thick, grayish-white, 

plaque-like lesions. In severe cases, the large lesions 

can develop deep fissures. Treatment of crusted scabies 

consists of ivermectin 200μg/kg orally with a repeat dose 

a week later.

Table 8-5. Therapy Strategies and 

Treatment Options for Generalized Pruritus

Therapy Comment

Prevention of scratching Scratching causes secondary 

irritation

Lubrication with ointments 

and creams with a fatty basis

eg, propylene glycol, wax 

esters

Avoidance of histamine 

induction by heat

eg, bathing in lukewarm or 

cold water

Avoidance of irritating 

substances

eg, alkaline soaps, wool 

clothing

Antihistamines The evidence is sparse; watch 

for side effects

Topical agents

• Coolants

• Anesthetic agents

eg, menthol, phenol

eg, EMLA® Cream 

(lidocaine 2.5% and 

prilocaine 2.5%)

Lindane Empiric treatment for scabies 

if risk factors

UVB therapy Three times a week, up to 

20 treatments for maximal 

benefit

Hypnosis Studies have demonstrated 

benefit

What	are	the	causes	and	treatments	of	blisters	

and	cutaneous	ulcers	in	persons	with	HIV?

Several studies have suggested that HIV-infected 

persons, when compared with age-matched HIV-negative 

persons, have an approximately 10-fold increased risk 

of developing “shingles,” a complication resulting from 

reactivation of varicella-zoster virus. Herpes zoster can 

occur at any CD4 cell count and thus does not require 

advanced HIV-related immune suppression. Indeed, 

the development of herpes zoster may serve as one 

of the first clinical events prompting an HIV-infected 

person to seek medical care. Persons with HIV can have 

more than one episode of herpes zoster. For unknown 

reasons, HIV-infected persons who start aggressive ART 

have an increased risk of developing herpes zoster in the 

6-month period after starting ART; in this scenario, the 

herpes zoster does not reflect worsening immunologic 

function or waning effectiveness of ART. 
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Because immune-suppressed persons who develop 

herpes zoster have an increased risk of disseminated 

herpes zoster, most experts recommend that all HIVinfected persons with zoster receive therapy. As long as 

the patient has no evidence of disseminated disease, 

central nervous system disease, or cranial nerve 

involvement, oral therapy can be used. Therapy for 

localized dermatomal zoster consists of 7-10 days of 

oral therapy with valacyclovir (1000 mg tid), acyclovir 

(800 mg 5x/day), or famciclovir (500 mg tid). In 

addition, acute zoster-associated pain often requires 

therapy. Therapy for zoster in HIV-infected persons 

should not include corticosteroids. No evidence exists 

to suggest HIV-infected persons have a higher risk of 

developing post-herpetic neuralgia as a complication of 

zoster infection. 

Among HIV-infected persons with mild or moderate 

immune suppression (CD4 count >350 cells/mm3), 

herpes simplex virus (HSV) infections cause clinical 

manifestations similar to those in HIV-negative 

persons, namely self-limited oral or genital lesions that 

typically appear with vesicular or ulcerated lesions. 

Recommended therapy for episodic HSV infection 

consists of either acyclovir 400 mg po tid x 5-10 days, 

famciclovir 500 mg po bid x 5-10 days, or valacyclovir 

1000 mg po bid x 5-10 days. In persons with more 

advanced immune suppression, particularly those with 

severe immune suppression (CD4 count <100 cells/

mm3), HSV infection may present as a non-healing, 

large, ulcerated lesion anywhere on the body. Therapy 

for these chronic, ulcerated lesions typically requires 

longer duration. In addition, those HIV-infected persons 

with severe immune suppression who receive chronic 

suppressive therapy for HSV have an increased risk of 

developing acyclovir-resistant HSV infection. 

How	does	molluscum	contagiosum	manifest	in	

severely	immunosuppressed	persons	with	HIV?

Among HIV-infected patients with severe immune 

suppression (CD4 count <100 cells/mm3), molluscum 

contagiosum typically presents as flesh-colored, papular 

lesions, most often on the face, neck, chest, or genitalia. 

In contrast to immune competent patients who typically 

have a self-resolving illness, HIV-infected persons 

with severe immune suppression generally have a 

progressive increase in the number and size of the 

molluscum lesions, often culminating in very large and 

disfiguring lesions referred to as “giant molluscum.” 

These lesions are particularly problematic if located on 

the face. Extremely large lesions may require surgical 

removal, moderate-sized lesions typically respond to 

liquid nitrogen therapy, and multiple small lesions are 

best treated with topical tretinoin 0.025% applied once 

a day. In addition, effective ART with improvement in 

immune function may help in managing molluscum. 

How	do	you	recognize	and	treat	seborrheic	

dermatitis?

Although seborrheic dermatitis is a well-known 

dermatologic disorder in persons who do not have HIV 

infection, this disorder occurs with increased frequency 

and severity among HIV-infected persons. Patients with 

HIV infection and seborrheic dermatitis typically have 

symmetrical erythematous, scaled patches and flaking, 

most often on the scalp, eyebrows, beard, central chest, 

and axillae. Typically, seborrheic dermatitis spares the 

central part of the face. Most patients respond to topical 

antifungal creams, such as 2% ketoconazole cream. In 

some instances, adding 1% hydrocortisone cream may 

be required. 

MOUTH LESIONS

Many	patients	with	HIV	have	mouth	pain:	

what	are	the	most	common	mouth	lesions?

The two most common oral lesions in HIV patients are 

oral candidiasis and oral hairy leukoplakia; they are 

clinical markers of symptomatic HIV infection. Oral 

hairy leukoplakia is a raised, white lesion that is usually 

seen on the lateral surface of the tongue. Hair-like 

projections can occasionally be visualized. It is usually 

asymptomatic, but may cause discomfort and impair 

taste and eating as it grows in size. The lesion appears 

more frequently in patients with lower CD4 counts and 

is thought to be caused by the Epstein-Barr virus. 

Mucosal candida infections are seen as the CD4 

cell count falls below 200-300 cells/mm3. The 

manifestations vary; they can involve the hard and 

soft palates, buccal mucosa, tongue, pharynx, and 

hypopharynx. The most common presentation is 

pseudomembranous candidiasis, or thrush. “Cottage 

cheese” plaques are seen on the soft palate, tonsils, 

and buccal mucosa and can be removed with a 

tongue blade. Atrophic candidiasis is a less seen and 

underdiagnosed form of candidiasis, consisting of 

flat, erythematous plaques in the same distribution as 

pseudomembranous candidiasis but lacking the white 

exudates. Mouth pain and loss of acuity of taste are 

common symptoms with atrophic candidiasis. 
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Diagnosis of a candida infection is commonly based 

on physical exam findings. Examination of a KOH 

preparation of a plaque scraping may also be used; 

culturing is rarely necessary. Response to a trial of 

topical antifungal agents (clotrimazole troches are easier 

than liquid nystatin to use) establishes the diagnosis. If 

the above diagnostics do not suggest Candida, a biopsy 

of the lesion may be performed. Oral hairy leukoplakia 

needs to be treated only if it causes mouth pain. It can 

be treated with high-dose acyclovir, valacyclovir, or 

famciclovir.

What	are	the	causes	of	painful	oral	ulcers	in	

patients	with	HIV?

Oral ulcers are common in patients with HIV. HSV 

causes primary or recurrent small, smooth, painful 

ulcers on the lips, gums, hard palate, or buccal mucosa. 

They can present as solitary lesions or in clusters. 

Lesions often last weeks, and treatment with acyclovir 

can shorten the course. Patients with disseminated 

cytomegalovirus (CMV) infection can occasionally 

have a large, solitary oral lesion. Aphthous stomatitis 

can present as single or multiple painful ulcers on 

the buccal and labial mucosa and the lateral aspect 

of the tongue. Aphthous ulcers are often exudative 

or necrotic in patients with HIV, and the course is 

usually more prolonged than in patients without 

HIV. Drug therapy with zalcitabine (ddC) can also 

cause ulcers. In managing oral ulcers, biopsy and 

viral culture establishes the etiology; some suggest 

treating empirically for HSV. If the lesion is consistent 

with aphthous ulcers, treat either with topical or oral 

steroids or thalidomide. An oral suspension consisting 

of diphenhydramine, viscous lidocaine, tetracycline, and 

dexamethasone may offer some pain relief. Removal 

of the offending drug is the treatment for drug-induced 

ulcers.

How	do	you	recognize	and	treat	gingivitis	and	

periodontal	disease?

These diseases can develop either insidiously or 

abruptly in patients with HIV and may be severe. 

Gingivitis is common and can occur at any CD4 cell 

count. Severe pain, foul breath, bleeding gums, and 

loosening of teeth are common symptoms, and exam 

may show a bright red marginal line on the gingiva, 

gingival erosion, necrosis and ulceration of interdental 

papillae, exfoliation of enamel, and loose teeth. The 

cause is unclear, although aerobic and anaerobic 

gram-negative bacteria, spirochetes, and yeast have 

been implicated. Severe, ulcerating gingivitis can 

be caused by Klebsiella pneumoniae, Enterobacter 

cloacae, and other gram-negative bacilli. Treatment 

includes debridement, irrigation with povidone-iodine/

chlorhexidine oral solutions, and topical antiseptic 

agents or metronidazole.

WASTING

What	are	the	common	causes	of	weight	loss	

and	wasting	in	patients	with	HIV?

There can be many different psychological and physical 

causes of weight loss in HIV disease (see Table 8-6).

Table 8-6. Common Causes of Weight Loss 

in Patients with HIV

Inadequate dietary intake resulting from

Depression

Painful oral lesions

Esophageal lesions causing dysphagia

Reduced taste sensation (thrush/meds)

Medication side effects (eg, nausea)

Chronic diarrhea (malabsorption) resulting from

Cryptosporidia

Giardia

Hypermetabolic states

Infection

Occult malignancy (eg, B-cell lymphoma)

Endocrine problems

Hypogonadism

Adrenal insufficiency

Diabetes (PI-induced)

How	do	you	work	up	a	patient	with	weight	loss	

and	wasting?

The workup is driven by results of the history, physical 

exam, and CD4 cell count; a higher CD4 count is more 

suggestive of causes such as endocrine disorders, 

malignancies, depression, or medication side effects. 

Serum testosterone, glucose, and thyroid tests to assess 

hormone status may be ordered. If malnutrition is 

suspected, it is important to address this promptly, 

since malnutrition decreases the function and number 

of immunity cells and leads to increased morbidity 

and mortality. Evaluation of GI function, calculation 

of caloric intake, estimation of protein and energy 

requirements, measurement of serum prealbumin, 

albumin, folate, and vitamin B12, and determination 

of the extent of lean body mass lost make up a 

comprehensive nutritional assessment. Body cell 
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mass can be measured using mid-arm circumference. 

Specific dietary deficiencies should be addressed, 

vitamin and mineral supplements should be prescribed, 

and high-calorie protein-containing foods should be 

recommended. In the patient with a low CD4 count 

(<100 cells/mm3), OIs such as Mycobacterium avium

complex (MAC), tuberculosis, cytomegalovirus infection, 

cryptosporidiosis, and Pneumocystis carinii pneumonia 

(PCP) should be ruled out, as well as lymphoma. Order 

a complete blood count, chemistries, blood cultures, 

chest x-ray, oximetry, and gastrointestinal biopsies or 

stool cultures as indicated. Referral to a nutritionist or 

registered dietician is often helpful. Also see Health Care 

and HIV: Nutritional Guide for Providers and Clients under 

Suggested Resources for practical assessment tools and 

algorithms for providers as well as patient handouts.

What	are	the	medical	treatment	options	for	

AIDS	wasting?

If an underlying cause of wasting has been identified, 

treatment of that cause is the first step in restoring 

weight. One important factor may be switching to ART 

that does not cause gastrointestinal/anorexia symptoms 

preventing food intake. Any infectious process should 

be identified and treated. For nonspecific AIDS 

wasting, the mainstay of treatment is nutritional 

supplementation along with appetite stimulants and 

antiemetics. Institution of ART and prevention of OIs 

are important in restoring weight. Human growth 

hormone has been shown to rebuild lean body mass, 

although it is expensive and survival advantage is 

controversial; some recommend that it be reserved for 

patients who have intractable, unexplained weight loss 

and require short-term treatment to maintain body 

cell mass during an acute illness (see Table 8-7 for 

treatment options).

MYALGIAS

What	are	some	common	causes	of	myalgias	in	

patients	with	HIV?

HIV can cause an inflammatory myopathy at any stage 

of infection. Symptoms include slowly progressive, 

proximal muscle weakness of the extremities with or 

without myalgias. Myopathy due to zidovudine (AZT) 

toxicity presents similarly to HIV-associated myopathy, 

and it may be difficult to distinguish between these 

two disorders. Zidovudine toxicity occurs usually after 

several months of therapy (most commonly after 6 

or more months of continual therapy). Myopathy or 

rhabdomyolysis due to HMG coenzyme A reductase 

inhibitors (statins) or fibrates are another important 

concern with HIV-infected patients. Many patients are 

on these drugs for treatment of hyperlipidemia caused 

by treatment with PIs. PIs decrease the metabolism 

of statins, which can increase the chance of toxicity. 

Moreover, many patients are on both gemfibrozil and a 

statin, which can interact to increase the risk of muscle 

toxicity. Simple myalgias are more common than 

rhabdomyolysis or myopathy caused by the statins.

Table 8-7. Treatment Options for Specific 

Causes of Weight Loss

Cause of 

weight loss

Treatment 

options

Comments

Anorexia Appetite stimulants

•dronabinol 

2.5-5 mg/d

•megestrol 

acetate 800 

mg/d

Some studies 

show that weight 

gained is from 

body fat and not 

lean body stores. 

Megestrol can raise 

blood sugar levels, 

especially when 

used with protease 

inhibitors. 

Hypogonadism testosterone

• IM 200-300 mg 

every 2-3 weeks

•Transdermally 

- Patch 5 mg/

day

- 1% gel 5-10 

g/day 

oxandrolone 

nandrolone

Liver function tests 

must be monitored 

with use of oral 

anabolic agents.

How	do	you	evaluate	and	manage	a	patient	

with	myalgias	or	myopathy?

The first step is to check creatinine phosphokinase (CPK) 

levels. This should be done for any patient on zidovudine 

(AZT) or a statin who has symptoms of myalgias or 

muscle weakness. Periodic (every 3-6 months) monitoring 

of CPK levels is appropriate for patients who are on a 

statin/PI or statin/gemfibrozil combination. Muscle biopsy 

should be performed if signs and symptoms of myopathy 

do not remit within about a month after drug removal 

or if a patient has muscle enzyme elevations and is not 

on a drug known to cause muscle damage. Organisms 

may be seen on muscle biopsy, indicating an infectious 

myopathy. If no organisms are seen and there are signs 

of inflammation on biopsy, an inflammatory myopathy 

secondary to HIV is likely, and a trial of corticosteroids or 

therapy with intravenous immune globulin (IVIG) should 

be implemented. 
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DIARRHEA

What	are	the	common	causes	of	diarrhea	in	

patients	with	HIV?

The main causes of diarrhea are related to either 

infections or medications. Infectious diarrhea can be 

caused by a number of organisms, dependent on the 

patient’s CD4 cell count (see Table 8-8). Nelfinavir 

(NFV) is the antiretroviral drug most commonly 

associated with diarrhea. All the PIs can cause diarrhea. 

Didanosine (ddI) is the nucleoside most associated with 

diarrhea, but diarrhea is less common when the enteric 

coated (EC) form is used. Metformin, a drug used for 

treatment of lipodystrophy syndrome and diabetes, 

commonly causes diarrhea.

Table 8-8. Infectious Causes of Diarrhea in 

Patients with HIV

Any CD4 cell count (acute diarrhea)

Viruses (especially Norwalk virus)

Clostridium difficile (previous antibiotic exposure)

Salmonella spp

Shigella spp

Campylobacter spp

Any CD4 cell count (chronic diarrhea)

Clostridium difficile

Giardia lamblia

CD4 count <300 cells/mm3 (chronic diarrhea)

Microsporidia

Cryptosporidia

Mycobacterium avium complex (CD4<100)

Isospora belli

Cytomegalovirus (CD4 count <100/mm3)

Idiopathic

What	is	the	best	approach	to	the	evaluation	of	

chronic	diarrhea	in	the	patient	with	HIV?

For patients who are on medication that can cause 

intractable diarrhea, one option is a trial of antidiarrheal 

medications (loperamide or atropine/phenoxylate 

either alone or in combination) and continuation of the 

previous antiretroviral regimen. If this does not work, 

another option is a trial off medication. If a patient is 

on ART, stop all medications for the 1-week evaluation 

period. If there is a response, then a new agent can be 

substituted for the most likely causative drug, usually 

nelfinavir (NFV) or lopinavir plus ritonavir (LPV/r, or 

Kaletra). If there is no response when medications 

are stopped, then stool studies should be done. If the 

patient has a high CD4 cell count (>300/mm3), start 

with C. difficile toxin and Giardia antigen. If the CD4 

cell count is low (<300/mm3), do a full workup with C. 

difficile, Giardia antigen, Microsporidia/Cryptosporidia

assay, and modified AFB stain for cryptosporidia. If 

no organisms are identified, in patients with very low 

CD4 cell counts (<100/mm3) obtain blood cultures 

for Mycobacterium avium, and if these are negative, 

pursue lower endoscopy with particular emphasis on 

detection of cytomegalovirus on biopsy. In patients 

with higher CD4 cell counts, clinical followup and trials 

of antimotility drugs are a reasonable approach before 

pursuing endoscopy.

HEADACHE

What	are	the	important	causes	of	headaches	

in	HIV-infected	patients?

The causes of headache vary according to CD4 cell 

count. Patients with a CD4 count of >300 cells/mm3

usually have headaches with common causes such as 

muscle tension, migraine, or drug side effect. Sinusitis 

is more frequent in patients with than without HIV 

and may cause headaches. In patients with low CD4 

counts (<200 cells/mm3) opportunistic infections (eg, 

Cryptococcal meningitis, toxoplasmic encephalitis) and 

malignancies (eg, CNS lymphoma) are important causes 

to consider.

How	should	you	work	up	patients	with	

headache?

Patients with CD4 counts of <200 cells/mm3 should 

have a contrast head CT scan or MRI, followed by 

lumbar puncture if the scan does not reveal a cause. In 

a study of CT scans for evaluation of headaches in HIVpositive patients all cases with mass lesions or whitematter lesions occurred in patients with CD4 counts 

of <200 cells/mm3. Serologic tests for cryptococcal 

antigen and Toxoplasma titers are helpful in patients 

with CD4 counts of <200 cells/mm3.
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KEY POINTS

Antiretroviral medications are a common 

cause of HIV-related symptoms. Some 

drugs can cause life-threatening reactions 

and conditions, including hypersensitivity 

reaction, pancreatitis, lactic acidosis, and 

Stevens-Johnson syndrome. 

The CD4 cell count and viral load are 

important in symptom evaluation; 

symptoms associated with OIs in 

immunocompromised patients have 

other causes in patients with intact 

immune function.

Nausea and diarrhea, very common side 

effects of PIs, zidovudine, and didanosine, 

can be managed by switching drugs or 

with symptomatic therapy.

Pneumococcal pneumonia, the most 

common bacterial pneumonia in persons 

with HIV, can occur early in the course of 

the disease, before other manifestations 

of immune suppression. Sinus disease is 

also common in persons with HIV. 

Chronic fatigue requires a careful 

assessment to differentiate psychological 

from physical etiologies so that the 

underlying cause can be addressed.

Painful neuropathy, frequently caused by 

antiretroviral medications, can also result 

from HIV disease. Treatment may include 

stopping a drug or treating with tricyclic 

antidepressants, narcotic analgesics, or 

gabapentin. 

Dermatologic problems common in HIV 

disease include pruritus, crusted scabies, 

herpes zoster, molluscum contagiosum, 

and seborrheic dermatitis.

Common oral lesions include oral 

candidiasis, oral hairy leukoplakia, ulcers, 

and gingivitis. Common causes of oral 

ulcers are zalcitabine, HSV, and aphthous 

ulcers.

Wasting may have a treatable cause, but 

even nonspecific AIDS wasting can be 

treated with nutritional supplementation, 

appetite stimulants and antiemetics.

Myalgia, an especially common side 

effect of taking a PI and a statin, may 

require muscle biopsy and treatment with 

either an antibiotic or IVIG or steroids 

if the condition does not improve after 

stopping the implicated medications.

Headaches, common with HIV disease, 

may be due to a CNS infection or 

neoplasm if the CD4 count is less than 

200 cells/mm3.

SUGGESTED RESOURCES

Graham CB, Wippold FJ, Pilgram TK, 

Fisher EJ, Smoker WR. Screening CT of the 

brain determined by CD4 count in HIVpositive patients presenting with headache. 

Am J Neuroradiol. 2000; 21:451-454.

Health Care and HIV: Nutritional Guide 

for Providers and Clients. 2002. Rockville, 

MD: Health Resources and Services 

Administration. Available at http//:

www.aidsetc.org. Accessed 12/03.

Penzak Sr, Chuck SK, Stajich GV. Safety and 

efficacy of HMG-CoA reductase inhibitors 

for treatment of hyperlipidemia in patients 

with HIV infection. Pharmacotherapy. 

2000;209:1066-1071.
A Guide to Primary Care of People with HIV/AIDS

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CASES

1.	

A 45-year-old HIV-positive man, last CD4 count 150 cells/mm3, comes to see you reporting aching in his 

right arm for 3 weeks. It began with only mild tenderness, but in the last week has become more painful 

and seems swollen. He is on ART with zidovudine (AZT), efavirenz (EFV), and nelfinavir (NFV). He is taking 

atorvastatin for hyperlipidemia. On physical exam, he is febrile, and his right arm is edematous and 

radiating heat without erythema. You obtain a CPK level which is normal.

Question:	What is the most likely diagnosis?

Answer:	

This patient has symptoms and signs of infectious myositis or pyomyositis, which usually develops 

insidiously over 2-3 weeks. In the first phase of infection, the involved muscle is tender with mild 

swelling. After 2-3 weeks a second phase manifests, usually with fever and edema, heat, and painful 

induration of the involved muscle. Erythema over the muscle is usually not seen. Laboratory values are 

usually notable for a lower than expected CPK but may include an elevated sedimentation rate and 

leukocytosis. Zidovudine-induced, statin-induced, and HIV-associated myopathy are less likely, as CPK 

would be elevated in these disorders, and the symptoms and signs in this patient are localized to one 

muscle group. Confirm the diagnosis of infectious myopathy with ultrasound or CT or MRI scanning, 

which will show a purulent abscess in the involved muscle. Blood cultures are not useful. If not treated, 

septic shock often ensues.

Question:	What is the most likely cause?

Answer:	

Most cases of infectious myositis are due to infection with Staphylococcal aureus. Other organisms 

reported have included Streptococcus, Toxoplasma gondii, cytomegalovirus, Microsporidia, Cryptococcus 

neoformans, Mycobacterium avium intracellulare, Salmonella, Nocardia, and gram-negative organisms.
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2.	

A 37-year-old man with Category 3 HIV disease (an AIDS indicator condition plus CD4 count nadir 

of <200 cells/mm3), last CD4 count 350 cells/mm3, comes to your office complaining of fatigue, 

nonspecific abdominal pain, nausea, and vomiting for the past 12 days. Review of systems is otherwise 

negative. He takes stavudine (d4T), zidovudine (AZT), and nelfinavir (NFV) as ART and fluoxetine for 

depression. On physical exam, his temperature is 37.9 degrees, respiratory rate is 25, abdomen is 

diffusely mildly tender to palpation, with increased tenderness in the right upper quadrant, no signs of 

jaundice, guaiac is negative. 

Question:	What is the differential diagnosis of causes related to ART?

Answer:	

The differential diagnosis of ART-related etiologies in this case should include pancreatitis, based on 

symptoms of abdominal pain, nausea, and vomiting in a patient taking stavudine, although pancreatitis 

usually presents more acutely with more severe pain. Hepatitis should be considered with these symptoms 

in patients taking PIs. Lactic acidosis should always be suspected in a patient with these symptoms taking 

a nucleoside.

Question:	What initial lab work should be ordered? 

Answer:

 Initial lab work may include CBC, basic metabolic panel, liver panel, amylase, lipase, lactate level, and 

coagulation studies. In the case of this patient, the lactic acid level was elevated. Further support for the 

diagnosis of lactic acidosis would include an increased anion gap, decreased bicarbonate, and elevated 

aminotransferases, lipase, amylase, CPK, and LDH.
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8

WORKUP OF SYMPTOMS

How	should	you	approach	the	workup	of	

symptoms	in	patients	infected	with	HIV?

Symptom evaluation in HIV-infected patients must 

include knowledge of the CD4 count and viral load 

as well as close attention to the medication list. An 

opportunistic disease (OD) is an unlikely cause of 

symptoms in patients with CD4 cell counts >200/mm3. 

Antiretroviral medications are a common cause of HIVrelated symptoms.

MEDICATION-RELATED

ISSUES

What	are	the	most	common	symptoms	related	

to	antiretroviral	medications?

Nausea and diarrhea are the two most common 

symptoms associated with antiretroviral therapy (ART). 

Pruritus and skin rashes are also common, especially 

with nonnucleoside drugs. Lower extremity pain due 

to neuropathy is seen with didanosine (ddI), stavudine 

(d4T), and zalcitabine (ddC).

What	are	the	common	side	effects	of	each	of	

the	antiretroviral	drugs?

The different classes of drugs have many similar as well 

as distinct side effects (see Table 8-1).

What	symptoms	could	be	due	to	lifethreatening	acute	drug	reactions?	

Symptoms of life-threatening acute drug reactions 

are not to be missed. A patient with myalgias, 

nausea, vomiting, diarrhea, abdominal pain, fever, 

rash, malaise, and extreme fatigue who has started 

taking abacavir (ABC) within the previous 6 weeks is 

probably suffering from an abacavir hypersensitivity 

reaction. In this case, abacavir should be permanently 

discontinued. The hypersensitivity reaction occurs in 

up to 5% of patients starting on abacavir and can lead 

to hypotension and death if the patient is rechallenged 

with abacavir. If a patient taking one of the “d-drugs” 

(didanosine [ddI], zalcitabine [ddC], stavudine [d4T], 

dapsone [for Pneumocystis pneumonia prophylaxis]) 

has rapid onset of nausea/vomiting and constant, severe 

abdominal pain in the epigastrium or upper quadrants 

that radiates to the back, drug-induced pancreatitis 

is possible. Patients taking a nucleoside (NRTI) who 

have vague symptoms including nausea, vomiting, 

abdominal pain, weight loss, malaise, fatigue, dyspnea, 

or fever must have lactic acidosis with hepatic steatosis 

ruled out. This occurs 5-13 months after initiating 

therapy and has a 60% fatality rate. Patients taking 

nevirapine (NVP) who have fatigue, malaise, nausea, 

vomiting, jaundice, and right-upper-quadrant abdominal 

pain could have nevirapine-induced hepatitis. Also, 

up to half the patients taking nevirapine may have a 

rash; however, if the rash is moist, involves the mucous 

membranes, or is extensive with an associated fever, 

Stevens-Johnson syndrome, which also occurs in 

patients taking trimethoprim-sulfamethoxazole (TMP/

sulfa), must be considered. Severe cases of StevensJohnson syndrome, including toxic epidermal necrolysis 

(TEN), are medical emergencies and must be managed 

as burn cases. For all drug-induced, life-threatening 

illnesses, immediate discontinuation of the offending 

drug is the crucial first step in care. 

What	are	the	most	important	drug	interactions	

that	occur	with	antiretroviral	medications?

Drug interactions are frequently the cause of symptoms 

and must be closely watched for. Not only do 

antiretroviral drugs react with each other, they react 

with numerous prescribed drugs and recreational drugs 

(see Tables 4-8 in the Pocket Guide).

Chapter	8:	

Symptom	Management Tara Evans Nysoe, MD

Douglas S. Paauw, MD, FACP

WORKUP OF SYMPTOMS 

MEDICATION-RELATED ISSUES

NAUSEA

PULMONARY SYMPTOMS

FATIGUE

NEUROPATHIC PAIN

DERMATOLOGIC SYMPTOMS

MOUTH LESIONS 

WASTING

MYALGIAS

DIARRHEA

HEADACHE

KEY POINTS

SUGGESTED RESOURCES

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

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Table 8-1. Side Effects of 

Antiretroviral Drugs

Drug Side effects

Nucleosides (NRTIs)

Class effect Hepatic steatosis/lactic acidosis

abacavir (ABC) Hypersensitivity reaction (nausea, 

anorexia, fever, rash, dyspnea, cough)

didanosine (ddI) Pancreatitis, peripheral neuropathy, 

nausea, diarrhea

lamivudine (3TC) Very few side effects

stavudine (d4T) Peripheral neuropathy, pancreatitis

tenofovir (TDF) (a 

nucleotide)

Nausea, vomiting, diarrhea

zalcitabine (ddC) Peripheral neuropathy, mucosal ulcers, 

pancreatitis

zidovudine (AZT) Anemia, myopathy, headache, nausea

emtricitabine (FTC) Nausea, very few side effects

Nonnucleoside reverse 

transcriptase inhibitors (NNRTIs)

efavirenz (EFV) Confusion, insomnia, rash, disturbing 

dreams

nevirapine (NVP) Rash (15%), hepatitis

Protease inhibitors (PIs)

Class effect Hyperglycemia, hyperlipidemia, 

lipodystrophy, hepatitis

amprenavir (APV) Nausea, diarrhea, rash, paraesthesias

atazanavir (ATV) Elevated bilirubin

fosamprenavir 

(FAPV)

Diarrhea

indinavir (IDV) Nausea, renal sludging, renal stones, 

increased indirect bilirubin

lopinavir+ritonavir 

(LPV/r or Kaletra)

Nausea, vomiting, diarrhea

nelfinavir (NFV) Diarrhea common (can be limiting)

ritonavir (RTV) Nausea, vomiting, circumoral 

paraesthesias, hepatitis, taste 

abnormalities

saquinavir (SQV) Nausea, diarrhea

What	natural	products	are	potentially	useful	in	

treating	the	symptoms	of	patients	with	HIV?

Some commonly used complementary medicine 

treatments are listed in Table 8-2. Ginger for the 

treatment of nausea is probably the most effective of 

the natural products for symptom management.

Table 8-2. Complementary Medicine 

Treatment Options for Various Symptoms

Problem Treatment 

option

Comments

Nausea Ginger Studies have 

shown possible 

benefit

Hepatitis Milk thistle Inconclusive longterm benefit; may 

inhibit the p450 

system

Migraine 

prophylaxis

Riboflavin Randomized 

controlled trial 

showed benefit

Immune system 

dysfunction

Co-enzyme Q Studies have 

shown possible 

benefit in CD4 

cell counts but no 

outcome benefit 

has been shown

NAUSEA

What	are	the	important	causes	of	nausea	in	

patients	with	HIV?

The most common cause of nausea in patients with 

HIV is medication side effects. Many of the antiretroviral 

drugs can result in prominent nausea. Full dose 

ritonavir (RTV) probably causes the most severe and 

frequent symptoms, but nausea can be seen with 

all of the protease inhibitors (PIs). Zidovudine (AZT) 

frequently causes nausea when first taken. Didanosine 

(ddI), stavudine (d4T), and zalcitabine (ddC) can all 

cause nausea, or nausea may be an early sign of the 

pancreatitis these drugs can lead to. All classes of 

antiretroviral drugs can cause hepatitis, which may 

present as intense nausea and fatigue. Nevirapine (NVP) 

and PIs are the most likely to do this, but nucleosides can 

cause life-threatening lactic acidosis in association with 

hepatic steatosis. Nausea can be a component of abacavir 

(ABC) hypersensitivity reaction, usually associated with 

fever, rash, vomiting, and anorexia. The commonly 

used antibiotics trimethoprim-sulfamethoxazole (for 

Pneumocystis pneumonia [PCP] prophylaxis) and 

azithromycin or clarithromycin (for Mycobacterium avium

complex [MAC] prophylaxis) can cause nausea.

Nonmedication causes to consider include viral 

hepatitis (acute hepatitis A, B, or C). Nausea is a 

common feature of cryptococcal meningitis; other 

sources of increased intracranial pressure such as CNS 

lymphoma or toxoplasmosis can also present with 

severe nausea and vomiting.
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What	are	the	best	options	for	managing	

nausea?

If nausea is due to medications, stopping the 

medication or removing an interacting drug is the best 

option. Symptomatic therapy with prochlorperazine or 

metoclopramide may help. A natural product option 

is ginger, at a dose of 2 grams daily (no more than 

4 grams/day). Switching the time of the dose of the 

offending drug to be taken with food may be helpful.

PULMONARY SYMPTOMS

What	are	the	possible	causes	of	cough	in	an	

HIV-infected	patient?

The CD4 cell count is crucial information in determining 

the cause of cough. In patients with CD4 cell counts 

>200/mm3, viral upper respiratory infections, 

bacterial pneumonia (caused by S. pneumoniae or H. 

influenzae most commonly), tuberculosis (TB), and 

sinusitis with post-nasal drip are all important causes 

of cough. Bacterial bronchitis is more common in 

patients with HIV than in non-HIV-infected patients. 

In patients with low CD4 cell counts (<200/mm3) 

Pneumocystis carinii pneumonia must be considered. 

The risk of PCP is markedly diminished if the patient 

is taking trimethoprim-sulfamethoxazole for PCP 

prophylaxis. The cough that occurs with PCP is usually 

dry and persistent and will usually have been present 

for several weeks before a patient seeks evaluation. 

Fungal disease due to cryptococcus, histoplasmosis, or 

coccidioidomycosis is more common with lower CD4 

cell counts.

What	workup	is	appropriate?

In patients with CD4 cell counts >200/mm3 the history 

and physical exam should determine what testing to 

do. If the patient has a cough but no fever or productive 

sputum, no dyspnea, and a normal pulmonary exam, 

then chest x-ray is not necessary. A patient at high 

risk for TB should have an x-ray if there is a prolonged 

cough (>2-3 weeks) regardless of CD4 cell count. In 

a patient with a low CD4 cell count (<200/mm3) the 

possibility of PCP is much more likely and an aggressive 

approach is warranted; a chest x-ray can begin the 

workup. If it is normal, then consider obtaining 

oxygen saturation measurements with ambulation. An 

individual who has oxygen desaturations should have 

further workup. For evaluation of suspected PCP see 

Chapter 9, Management of Opportunistic Diseases.

Are	patients	infected	with	HIV	at	increased	

risk	of	developing	bacterial	pneumonia?

Available data clearly suggest that HIV-infected 

patients have an increased risk of developing bacterial 

pneumonia. In the 1993 CDC classification system, 

recurrent pneumonia (2 or more episodes in 1 year) 

is defined as a category C (AIDS-indicator) condition. 

Pneumococcal pneumonia is the most common 

bacterial pneumonia in persons infected with HIV, 

and it occurs approximately 10 times more frequently 

than in persons not infected with HIV. In addition, 

the development of pneumococcal pneumonia can 

occur early in the course of HIV disease, before other 

manifestations of immune suppression. HIV-infected 

persons with pneumococcal pneumonia have clinical 

signs and symptoms similar to those in HIV-negative 

individuals, but they have an approximately 20-fold 

higher risk of developing pneumococcal bacteremia. 

Treatment of pneumococcal pneumonia is generally the 

same in persons with and without HIV infection. Several 

studies have shown that HIV-infected persons have a 

slightly increased risk of developing pneumonia caused 

by Pseudomonas aeruginosa. 

How	common	is	sinus	disease	in	patients	

with	HIV?

Sinus disease is very common in patients with HIV. The 

lower the CD4 cell count, the more severe and more 

widespread (number of sinuses involved) sinusitis is. In 

patients with lower CD4 cell counts, chronic sinusitis 

and lack of response to therapy are more common. The 

most common organisms involved are Streptococcus 

pneumoniae, Streptococcus viridans, and Pseudomonas 

aeruginosa. Pseudomonal sinus infections are more 

common in patients with CD4 cell counts of <50/mm3. 

Fungal (Aspergillus) and viral (Cytomegalovirus) sinusitis 

can occur in patients with CD4 cell counts <100/mm3. 

Aggressive treatment of sinus disease with saline 

irrigation, antihistamine/decongestant combinations 

and full-dose nasal steroids is appropriate. Antibiotics 

should be given for the normal duration for episodes of 

acute sinusitis (3-6 week course). If antibiotic therapy 

and aggressive irrigation do not resolve the problem, 

referral to an ENT specialist for drainage procedures 

and for consideration of sinus surgery is appropriate.
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FATIGUE

What	are	the	common	causes	of	chronic	fatigue	

in	patients	with	HIV?

Fatigue can have a large impact on the quality of a 

patient’s life. Common descriptors of fatigue include 

tiredness, weakness, lack of energy, sleepiness, and 

exhaustion. Of the many possible causes of chronic 

fatigue in patients with HIV, the most common 

is depression. Other psychosocial causes include 

stress, anxiety, use of recreational substances, sleep 

disturbances, domestic abuse, and lack of exercise. 

ODs must be considered as a possible cause of fatigue 

in patients with low CD4 cell counts. Other disease 

states such as anemia, hypothyroidism, hypogonadism, 

adrenal insufficiency, influenza and other nonopportunistic infections, diabetes, liver disease, and 

malnutrition can also present as fatigue. Fatigue can be 

a side effect of ART and other medications commonly 

taken by patients with HIV. HIV-associated fatigue is a 

diagnosis of exclusion. 

How	do	you	determine	the	cause	of	a	patient’s	

fatigue?

Ask if the patient is having other symptoms of 

depression: change in sleep or appetite patterns, 

depressed mood, anhedonia, agitation or retardation, 

difficulties with concentration, decreased self-esteem, 

and suicidal ideation. Take a thorough social history 

and determine if multiple life stressors are present. 

Inquire as to how many hours of sleep the patient is 

getting per night and the number of middle-of-thenight awakenings; ask if the patient feels rested in 

the morning. Important history questions that help 

differentiate a physical from a psychological etiology 

for fatigue are in Table 8-3. Identify any barriers to 

effective sleep. Ask about the patient’s diet and exercise 

habits, and determine if the patient drinks alcohol or 

uses recreational drugs, including caffeine. Thoroughly 

review the patient’s medication list and identify any 

medications, such as certain antiretroviral drugs, betablockers, antihistamines, etc., that can be associated 

with fatigue. Do a complete review of systems and 

physical exam to elicit other symptoms or signs that 

may suggest an OD or other disease state. Simple 

laboratory tests, such as alanine aminotransferase (ALT), 

blood glucose, thyroid stimulating hormone (TSH), 

and hematocrit, can help to rule out common diseases 

that can cause fatigue. Electrolyte abnormalities can 

suggest adrenal insufficiency. Order other laboratory or 

diagnostic tests as symptoms and signs direct.

Table 8-3. History Questions to 

Differentiate Physical from Psychological 

Causes of Fatigue

Psychological 

cause

Physical 

cause

Onset Often follows 

problem or conflict

Related to onset of 

physical ailments

Duration Chronic Of recent onset

Progression Fluctuates Increases as 

disease advances

Effect of sleep Unaffected by 

sleep

Relieved by sleep

Diurnal Present in 

morning, may 

improve

Increases as the 

day progresses 

NEUROPATHIC PAIN

What	is	the	most	common	cause	of	neuropathic	

pain	and	paresthesias	in	patients	with	HIV?	

Distal symmetrical polyneuropathy (DSP) is most 

commonly caused by antiretroviral drugs. The drugs 

didanosine (ddI), zalcitabine (ddC), stavudine (d4T) 

can all cause DSP at high doses. Studies have shown 

zalcitabine to be the most likely to cause neuropathy 

at standard doses; concurrent alcohol use or vitamin 

B12 deficiency may increase risk. HIV-related DSP is 

less common than drug-induced DSP. The two types of 

neuropathies present similarly, although onset may be 

more acute in drug-induced DSP. HIV-related DSP does 

not appear to respond to viral suppression with ART. 

How	do	you	diagnose	and	treat	DSP?

Diagnose drug-related DSP by linking the onset of the 

symptoms with the initiation of drug therapy. Treat 

by drug removal; symptoms may worsen temporarily 

but should regress within several weeks. Residual 

painful symptoms of DSP may be treated with tricyclic 

antidepressants, narcotic analgesics, or gabapentin. 

The topical medication capsacin may be helpful if the 

neuropathy is limited to a small surface area. 
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DERMATOLOGIC

SYMPTOMS

How	do	you	manage	generalized	pruritus	in	a	

patient	with	no	cutaneous	signs	on	exam?

If a patient with HIV has generalized pruritus with no 

obvious cutaneous diagnosis, acute drug reactions 

such as Stevens-Johnson syndrome, which can be lifethreatening, and coexisting systemic illness such as 

hepatic dysfunction must be ruled out (see Table 8-4 

and earlier section on medication-related issues). Order 

a complete blood count, liver function tests, and blood 

chemistries. Occasionally, scabies can present with 

minimal to no cutaneous signs. Pruritus due solely to 

HIV infection is a diagnosis of exclusion; it can respond 

to ART. (Symptomatic treatments for generalized pruritus 

are listed in Table 8-5.) In general, if a clear cause is not 

identified, xerosis, a common condition in patients with 

HIV disease, will be the most likely diagnosis. In this 

case, decreasing the amount of bathing, avoiding dry 

soaps, using emollient creams, and ceasing scratching 

are the basis of symptomatic treatment. In addition, 

general agents such as H-1 antagonists can be used. The 

best studied of these is hydroxyzine, which offers the 

benefit of sedation for nocturnal itching. 

Table 8-4. Common Causes of Pruritus in 

Patients with HIV

Very common Less common

• Staphylococcal folliculitis

• Xerosis

• Atopic dermatitis

• Scabies

• Psoriasis

• Hypersensitivity to insect 

bites

• Drug reactions

• HIV-associated pruritus

• Eosinophilic folliculitis

• Granuloma annulare

• Lymphoma

• Hepatic failure

• Renal failure

How	does	scabies	manifest	differently	in	HIVinfected	persons?

Among HIV-infected persons with mild-to-moderate 

immune suppression, scabies causes similar clinical 

manifestations as seen in persons without HIV infection, 

namely multiple pruritic papular lesions. Treatment 

consists of applying 30-60 g of 5% permethrin cream 

to the entire body from the neck down, leaving it on for 

8-12 hours, then washing it off, and repeating the entire 

process one week later. In HIV-infected persons with 

severe immune suppression (CD4 count of <100 cells/

mm3), an atypical form of scabies known as crusted 

or “Norwegian” scabies may develop. Crusted scabies 

is characterized by an enormous number of scabies 

mites and manifests as nonpruritic, thick, grayish-white, 

plaque-like lesions. In severe cases, the large lesions 

can develop deep fissures. Treatment of crusted scabies 

consists of ivermectin 200μg/kg orally with a repeat dose 

a week later.

Table 8-5. Therapy Strategies and 

Treatment Options for Generalized Pruritus

Therapy Comment

Prevention of scratching Scratching causes secondary 

irritation

Lubrication with ointments 

and creams with a fatty basis

eg, propylene glycol, wax 

esters

Avoidance of histamine 

induction by heat

eg, bathing in lukewarm or 

cold water

Avoidance of irritating 

substances

eg, alkaline soaps, wool 

clothing

Antihistamines The evidence is sparse; watch 

for side effects

Topical agents

• Coolants

• Anesthetic agents

eg, menthol, phenol

eg, EMLA® Cream 

(lidocaine 2.5% and 

prilocaine 2.5%)

Lindane Empiric treatment for scabies 

if risk factors

UVB therapy Three times a week, up to 

20 treatments for maximal 

benefit

Hypnosis Studies have demonstrated 

benefit

What	are	the	causes	and	treatments	of	blisters	

and	cutaneous	ulcers	in	persons	with	HIV?

Several studies have suggested that HIV-infected 

persons, when compared with age-matched HIV-negative 

persons, have an approximately 10-fold increased risk 

of developing “shingles,” a complication resulting from 

reactivation of varicella-zoster virus. Herpes zoster can 

occur at any CD4 cell count and thus does not require 

advanced HIV-related immune suppression. Indeed, 

the development of herpes zoster may serve as one 

of the first clinical events prompting an HIV-infected 

person to seek medical care. Persons with HIV can have 

more than one episode of herpes zoster. For unknown 

reasons, HIV-infected persons who start aggressive ART 

have an increased risk of developing herpes zoster in the 

6-month period after starting ART; in this scenario, the 

herpes zoster does not reflect worsening immunologic 

function or waning effectiveness of ART. 
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Because immune-suppressed persons who develop 

herpes zoster have an increased risk of disseminated 

herpes zoster, most experts recommend that all HIVinfected persons with zoster receive therapy. As long as 

the patient has no evidence of disseminated disease, 

central nervous system disease, or cranial nerve 

involvement, oral therapy can be used. Therapy for 

localized dermatomal zoster consists of 7-10 days of 

oral therapy with valacyclovir (1000 mg tid), acyclovir 

(800 mg 5x/day), or famciclovir (500 mg tid). In 

addition, acute zoster-associated pain often requires 

therapy. Therapy for zoster in HIV-infected persons 

should not include corticosteroids. No evidence exists 

to suggest HIV-infected persons have a higher risk of 

developing post-herpetic neuralgia as a complication of 

zoster infection. 

Among HIV-infected persons with mild or moderate 

immune suppression (CD4 count >350 cells/mm3), 

herpes simplex virus (HSV) infections cause clinical 

manifestations similar to those in HIV-negative 

persons, namely self-limited oral or genital lesions that 

typically appear with vesicular or ulcerated lesions. 

Recommended therapy for episodic HSV infection 

consists of either acyclovir 400 mg po tid x 5-10 days, 

famciclovir 500 mg po bid x 5-10 days, or valacyclovir 

1000 mg po bid x 5-10 days. In persons with more 

advanced immune suppression, particularly those with 

severe immune suppression (CD4 count <100 cells/

mm3), HSV infection may present as a non-healing, 

large, ulcerated lesion anywhere on the body. Therapy 

for these chronic, ulcerated lesions typically requires 

longer duration. In addition, those HIV-infected persons 

with severe immune suppression who receive chronic 

suppressive therapy for HSV have an increased risk of 

developing acyclovir-resistant HSV infection. 

How	does	molluscum	contagiosum	manifest	in	

severely	immunosuppressed	persons	with	HIV?

Among HIV-infected patients with severe immune 

suppression (CD4 count <100 cells/mm3), molluscum 

contagiosum typically presents as flesh-colored, papular 

lesions, most often on the face, neck, chest, or genitalia. 

In contrast to immune competent patients who typically 

have a self-resolving illness, HIV-infected persons 

with severe immune suppression generally have a 

progressive increase in the number and size of the 

molluscum lesions, often culminating in very large and 

disfiguring lesions referred to as “giant molluscum.” 

These lesions are particularly problematic if located on 

the face. Extremely large lesions may require surgical 

removal, moderate-sized lesions typically respond to 

liquid nitrogen therapy, and multiple small lesions are 

best treated with topical tretinoin 0.025% applied once 

a day. In addition, effective ART with improvement in 

immune function may help in managing molluscum. 

How	do	you	recognize	and	treat	seborrheic	

dermatitis?

Although seborrheic dermatitis is a well-known 

dermatologic disorder in persons who do not have HIV 

infection, this disorder occurs with increased frequency 

and severity among HIV-infected persons. Patients with 

HIV infection and seborrheic dermatitis typically have 

symmetrical erythematous, scaled patches and flaking, 

most often on the scalp, eyebrows, beard, central chest, 

and axillae. Typically, seborrheic dermatitis spares the 

central part of the face. Most patients respond to topical 

antifungal creams, such as 2% ketoconazole cream. In 

some instances, adding 1% hydrocortisone cream may 

be required. 

MOUTH LESIONS

Many	patients	with	HIV	have	mouth	pain:	

what	are	the	most	common	mouth	lesions?

The two most common oral lesions in HIV patients are 

oral candidiasis and oral hairy leukoplakia; they are 

clinical markers of symptomatic HIV infection. Oral 

hairy leukoplakia is a raised, white lesion that is usually 

seen on the lateral surface of the tongue. Hair-like 

projections can occasionally be visualized. It is usually 

asymptomatic, but may cause discomfort and impair 

taste and eating as it grows in size. The lesion appears 

more frequently in patients with lower CD4 counts and 

is thought to be caused by the Epstein-Barr virus. 

Mucosal candida infections are seen as the CD4 

cell count falls below 200-300 cells/mm3. The 

manifestations vary; they can involve the hard and 

soft palates, buccal mucosa, tongue, pharynx, and 

hypopharynx. The most common presentation is 

pseudomembranous candidiasis, or thrush. “Cottage 

cheese” plaques are seen on the soft palate, tonsils, 

and buccal mucosa and can be removed with a 

tongue blade. Atrophic candidiasis is a less seen and 

underdiagnosed form of candidiasis, consisting of 

flat, erythematous plaques in the same distribution as 

pseudomembranous candidiasis but lacking the white 

exudates. Mouth pain and loss of acuity of taste are 

common symptoms with atrophic candidiasis. 
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Diagnosis of a candida infection is commonly based 

on physical exam findings. Examination of a KOH 

preparation of a plaque scraping may also be used; 

culturing is rarely necessary. Response to a trial of 

topical antifungal agents (clotrimazole troches are easier 

than liquid nystatin to use) establishes the diagnosis. If 

the above diagnostics do not suggest Candida, a biopsy 

of the lesion may be performed. Oral hairy leukoplakia 

needs to be treated only if it causes mouth pain. It can 

be treated with high-dose acyclovir, valacyclovir, or 

famciclovir.

What	are	the	causes	of	painful	oral	ulcers	in	

patients	with	HIV?

Oral ulcers are common in patients with HIV. HSV 

causes primary or recurrent small, smooth, painful 

ulcers on the lips, gums, hard palate, or buccal mucosa. 

They can present as solitary lesions or in clusters. 

Lesions often last weeks, and treatment with acyclovir 

can shorten the course. Patients with disseminated 

cytomegalovirus (CMV) infection can occasionally 

have a large, solitary oral lesion. Aphthous stomatitis 

can present as single or multiple painful ulcers on 

the buccal and labial mucosa and the lateral aspect 

of the tongue. Aphthous ulcers are often exudative 

or necrotic in patients with HIV, and the course is 

usually more prolonged than in patients without 

HIV. Drug therapy with zalcitabine (ddC) can also 

cause ulcers. In managing oral ulcers, biopsy and 

viral culture establishes the etiology; some suggest 

treating empirically for HSV. If the lesion is consistent 

with aphthous ulcers, treat either with topical or oral 

steroids or thalidomide. An oral suspension consisting 

of diphenhydramine, viscous lidocaine, tetracycline, and 

dexamethasone may offer some pain relief. Removal 

of the offending drug is the treatment for drug-induced 

ulcers.

How	do	you	recognize	and	treat	gingivitis	and	

periodontal	disease?

These diseases can develop either insidiously or 

abruptly in patients with HIV and may be severe. 

Gingivitis is common and can occur at any CD4 cell 

count. Severe pain, foul breath, bleeding gums, and 

loosening of teeth are common symptoms, and exam 

may show a bright red marginal line on the gingiva, 

gingival erosion, necrosis and ulceration of interdental 

papillae, exfoliation of enamel, and loose teeth. The 

cause is unclear, although aerobic and anaerobic 

gram-negative bacteria, spirochetes, and yeast have 

been implicated. Severe, ulcerating gingivitis can 

be caused by Klebsiella pneumoniae, Enterobacter 

cloacae, and other gram-negative bacilli. Treatment 

includes debridement, irrigation with povidone-iodine/

chlorhexidine oral solutions, and topical antiseptic 

agents or metronidazole.

WASTING

What	are	the	common	causes	of	weight	loss	

and	wasting	in	patients	with	HIV?

There can be many different psychological and physical 

causes of weight loss in HIV disease (see Table 8-6).

Table 8-6. Common Causes of Weight Loss 

in Patients with HIV

Inadequate dietary intake resulting from

Depression

Painful oral lesions

Esophageal lesions causing dysphagia

Reduced taste sensation (thrush/meds)

Medication side effects (eg, nausea)

Chronic diarrhea (malabsorption) resulting from

Cryptosporidia

Giardia

Hypermetabolic states

Infection

Occult malignancy (eg, B-cell lymphoma)

Endocrine problems

Hypogonadism

Adrenal insufficiency

Diabetes (PI-induced)

How	do	you	work	up	a	patient	with	weight	loss	

and	wasting?

The workup is driven by results of the history, physical 

exam, and CD4 cell count; a higher CD4 count is more 

suggestive of causes such as endocrine disorders, 

malignancies, depression, or medication side effects. 

Serum testosterone, glucose, and thyroid tests to assess 

hormone status may be ordered. If malnutrition is 

suspected, it is important to address this promptly, 

since malnutrition decreases the function and number 

of immunity cells and leads to increased morbidity 

and mortality. Evaluation of GI function, calculation 

of caloric intake, estimation of protein and energy 

requirements, measurement of serum prealbumin, 

albumin, folate, and vitamin B12, and determination 

of the extent of lean body mass lost make up a 

comprehensive nutritional assessment. Body cell 
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mass can be measured using mid-arm circumference. 

Specific dietary deficiencies should be addressed, 

vitamin and mineral supplements should be prescribed, 

and high-calorie protein-containing foods should be 

recommended. In the patient with a low CD4 count 

(<100 cells/mm3), OIs such as Mycobacterium avium

complex (MAC), tuberculosis, cytomegalovirus infection, 

cryptosporidiosis, and Pneumocystis carinii pneumonia 

(PCP) should be ruled out, as well as lymphoma. Order 

a complete blood count, chemistries, blood cultures, 

chest x-ray, oximetry, and gastrointestinal biopsies or 

stool cultures as indicated. Referral to a nutritionist or 

registered dietician is often helpful. Also see Health Care 

and HIV: Nutritional Guide for Providers and Clients under 

Suggested Resources for practical assessment tools and 

algorithms for providers as well as patient handouts.

What	are	the	medical	treatment	options	for	

AIDS	wasting?

If an underlying cause of wasting has been identified, 

treatment of that cause is the first step in restoring 

weight. One important factor may be switching to ART 

that does not cause gastrointestinal/anorexia symptoms 

preventing food intake. Any infectious process should 

be identified and treated. For nonspecific AIDS 

wasting, the mainstay of treatment is nutritional 

supplementation along with appetite stimulants and 

antiemetics. Institution of ART and prevention of OIs 

are important in restoring weight. Human growth 

hormone has been shown to rebuild lean body mass, 

although it is expensive and survival advantage is 

controversial; some recommend that it be reserved for 

patients who have intractable, unexplained weight loss 

and require short-term treatment to maintain body 

cell mass during an acute illness (see Table 8-7 for 

treatment options).

MYALGIAS

What	are	some	common	causes	of	myalgias	in	

patients	with	HIV?

HIV can cause an inflammatory myopathy at any stage 

of infection. Symptoms include slowly progressive, 

proximal muscle weakness of the extremities with or 

without myalgias. Myopathy due to zidovudine (AZT) 

toxicity presents similarly to HIV-associated myopathy, 

and it may be difficult to distinguish between these 

two disorders. Zidovudine toxicity occurs usually after 

several months of therapy (most commonly after 6 

or more months of continual therapy). Myopathy or 

rhabdomyolysis due to HMG coenzyme A reductase 

inhibitors (statins) or fibrates are another important 

concern with HIV-infected patients. Many patients are 

on these drugs for treatment of hyperlipidemia caused 

by treatment with PIs. PIs decrease the metabolism 

of statins, which can increase the chance of toxicity. 

Moreover, many patients are on both gemfibrozil and a 

statin, which can interact to increase the risk of muscle 

toxicity. Simple myalgias are more common than 

rhabdomyolysis or myopathy caused by the statins.

Table 8-7. Treatment Options for Specific 

Causes of Weight Loss

Cause of 

weight loss

Treatment 

options

Comments

Anorexia Appetite stimulants

•dronabinol 

2.5-5 mg/d

•megestrol 

acetate 800 

mg/d

Some studies 

show that weight 

gained is from 

body fat and not 

lean body stores. 

Megestrol can raise 

blood sugar levels, 

especially when 

used with protease 

inhibitors. 

Hypogonadism testosterone

• IM 200-300 mg 

every 2-3 weeks

•Transdermally 

- Patch 5 mg/

day

- 1% gel 5-10 

g/day 

oxandrolone 

nandrolone

Liver function tests 

must be monitored 

with use of oral 

anabolic agents.

How	do	you	evaluate	and	manage	a	patient	

with	myalgias	or	myopathy?

The first step is to check creatinine phosphokinase (CPK) 

levels. This should be done for any patient on zidovudine 

(AZT) or a statin who has symptoms of myalgias or 

muscle weakness. Periodic (every 3-6 months) monitoring 

of CPK levels is appropriate for patients who are on a 

statin/PI or statin/gemfibrozil combination. Muscle biopsy 

should be performed if signs and symptoms of myopathy 

do not remit within about a month after drug removal 

or if a patient has muscle enzyme elevations and is not 

on a drug known to cause muscle damage. Organisms 

may be seen on muscle biopsy, indicating an infectious 

myopathy. If no organisms are seen and there are signs 

of inflammation on biopsy, an inflammatory myopathy 

secondary to HIV is likely, and a trial of corticosteroids or 

therapy with intravenous immune globulin (IVIG) should 

be implemented. 
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DIARRHEA

What	are	the	common	causes	of	diarrhea	in	

patients	with	HIV?

The main causes of diarrhea are related to either 

infections or medications. Infectious diarrhea can be 

caused by a number of organisms, dependent on the 

patient’s CD4 cell count (see Table 8-8). Nelfinavir 

(NFV) is the antiretroviral drug most commonly 

associated with diarrhea. All the PIs can cause diarrhea. 

Didanosine (ddI) is the nucleoside most associated with 

diarrhea, but diarrhea is less common when the enteric 

coated (EC) form is used. Metformin, a drug used for 

treatment of lipodystrophy syndrome and diabetes, 

commonly causes diarrhea.

Table 8-8. Infectious Causes of Diarrhea in 

Patients with HIV

Any CD4 cell count (acute diarrhea)

Viruses (especially Norwalk virus)

Clostridium difficile (previous antibiotic exposure)

Salmonella spp

Shigella spp

Campylobacter spp

Any CD4 cell count (chronic diarrhea)

Clostridium difficile

Giardia lamblia

CD4 count <300 cells/mm3 (chronic diarrhea)

Microsporidia

Cryptosporidia

Mycobacterium avium complex (CD4<100)

Isospora belli

Cytomegalovirus (CD4 count <100/mm3)

Idiopathic

What	is	the	best	approach	to	the	evaluation	of	

chronic	diarrhea	in	the	patient	with	HIV?

For patients who are on medication that can cause 

intractable diarrhea, one option is a trial of antidiarrheal 

medications (loperamide or atropine/phenoxylate 

either alone or in combination) and continuation of the 

previous antiretroviral regimen. If this does not work, 

another option is a trial off medication. If a patient is 

on ART, stop all medications for the 1-week evaluation 

period. If there is a response, then a new agent can be 

substituted for the most likely causative drug, usually 

nelfinavir (NFV) or lopinavir plus ritonavir (LPV/r, or 

Kaletra). If there is no response when medications 

are stopped, then stool studies should be done. If the 

patient has a high CD4 cell count (>300/mm3), start 

with C. difficile toxin and Giardia antigen. If the CD4 

cell count is low (<300/mm3), do a full workup with C. 

difficile, Giardia antigen, Microsporidia/Cryptosporidia

assay, and modified AFB stain for cryptosporidia. If 

no organisms are identified, in patients with very low 

CD4 cell counts (<100/mm3) obtain blood cultures 

for Mycobacterium avium, and if these are negative, 

pursue lower endoscopy with particular emphasis on 

detection of cytomegalovirus on biopsy. In patients 

with higher CD4 cell counts, clinical followup and trials 

of antimotility drugs are a reasonable approach before 

pursuing endoscopy.

HEADACHE

What	are	the	important	causes	of	headaches	

in	HIV-infected	patients?

The causes of headache vary according to CD4 cell 

count. Patients with a CD4 count of >300 cells/mm3

usually have headaches with common causes such as 

muscle tension, migraine, or drug side effect. Sinusitis 

is more frequent in patients with than without HIV 

and may cause headaches. In patients with low CD4 

counts (<200 cells/mm3) opportunistic infections (eg, 

Cryptococcal meningitis, toxoplasmic encephalitis) and 

malignancies (eg, CNS lymphoma) are important causes 

to consider.

How	should	you	work	up	patients	with	

headache?

Patients with CD4 counts of <200 cells/mm3 should 

have a contrast head CT scan or MRI, followed by 

lumbar puncture if the scan does not reveal a cause. In 

a study of CT scans for evaluation of headaches in HIVpositive patients all cases with mass lesions or whitematter lesions occurred in patients with CD4 counts 

of <200 cells/mm3. Serologic tests for cryptococcal 

antigen and Toxoplasma titers are helpful in patients 

with CD4 counts of <200 cells/mm3.
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KEY POINTS

Antiretroviral medications are a common 

cause of HIV-related symptoms. Some 

drugs can cause life-threatening reactions 

and conditions, including hypersensitivity 

reaction, pancreatitis, lactic acidosis, and 

Stevens-Johnson syndrome. 

The CD4 cell count and viral load are 

important in symptom evaluation; 

symptoms associated with OIs in 

immunocompromised patients have 

other causes in patients with intact 

immune function.

Nausea and diarrhea, very common side 

effects of PIs, zidovudine, and didanosine, 

can be managed by switching drugs or 

with symptomatic therapy.

Pneumococcal pneumonia, the most 

common bacterial pneumonia in persons 

with HIV, can occur early in the course of 

the disease, before other manifestations 

of immune suppression. Sinus disease is 

also common in persons with HIV. 

Chronic fatigue requires a careful 

assessment to differentiate psychological 

from physical etiologies so that the 

underlying cause can be addressed.

Painful neuropathy, frequently caused by 

antiretroviral medications, can also result 

from HIV disease. Treatment may include 

stopping a drug or treating with tricyclic 

antidepressants, narcotic analgesics, or 

gabapentin. 

Dermatologic problems common in HIV 

disease include pruritus, crusted scabies, 

herpes zoster, molluscum contagiosum, 

and seborrheic dermatitis.

Common oral lesions include oral 

candidiasis, oral hairy leukoplakia, ulcers, 

and gingivitis. Common causes of oral 

ulcers are zalcitabine, HSV, and aphthous 

ulcers.

Wasting may have a treatable cause, but 

even nonspecific AIDS wasting can be 

treated with nutritional supplementation, 

appetite stimulants and antiemetics.

Myalgia, an especially common side 

effect of taking a PI and a statin, may 

require muscle biopsy and treatment with 

either an antibiotic or IVIG or steroids 

if the condition does not improve after 

stopping the implicated medications.

Headaches, common with HIV disease, 

may be due to a CNS infection or 

neoplasm if the CD4 count is less than 

200 cells/mm3.

SUGGESTED RESOURCES

Graham CB, Wippold FJ, Pilgram TK, 

Fisher EJ, Smoker WR. Screening CT of the 

brain determined by CD4 count in HIVpositive patients presenting with headache. 

Am J Neuroradiol. 2000; 21:451-454.

Health Care and HIV: Nutritional Guide 

for Providers and Clients. 2002. Rockville, 

MD: Health Resources and Services 

Administration. Available at http//:

www.aidsetc.org. Accessed 12/03.

Penzak Sr, Chuck SK, Stajich GV. Safety and 

efficacy of HMG-CoA reductase inhibitors 

for treatment of hyperlipidemia in patients 

with HIV infection. Pharmacotherapy. 

2000;209:1066-1071.
A Guide to Primary Care of People with HIV/AIDS

Chapter 8: Symptom Management 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 65

8

CASES

1.	

A 45-year-old HIV-positive man, last CD4 count 150 cells/mm3, comes to see you reporting aching in his 

right arm for 3 weeks. It began with only mild tenderness, but in the last week has become more painful 

and seems swollen. He is on ART with zidovudine (AZT), efavirenz (EFV), and nelfinavir (NFV). He is taking 

atorvastatin for hyperlipidemia. On physical exam, he is febrile, and his right arm is edematous and 

radiating heat without erythema. You obtain a CPK level which is normal.

Question:	What is the most likely diagnosis?

Answer:	

This patient has symptoms and signs of infectious myositis or pyomyositis, which usually develops 

insidiously over 2-3 weeks. In the first phase of infection, the involved muscle is tender with mild 

swelling. After 2-3 weeks a second phase manifests, usually with fever and edema, heat, and painful 

induration of the involved muscle. Erythema over the muscle is usually not seen. Laboratory values are 

usually notable for a lower than expected CPK but may include an elevated sedimentation rate and 

leukocytosis. Zidovudine-induced, statin-induced, and HIV-associated myopathy are less likely, as CPK 

would be elevated in these disorders, and the symptoms and signs in this patient are localized to one 

muscle group. Confirm the diagnosis of infectious myopathy with ultrasound or CT or MRI scanning, 

which will show a purulent abscess in the involved muscle. Blood cultures are not useful. If not treated, 

septic shock often ensues.

Question:	What is the most likely cause?

Answer:	

Most cases of infectious myositis are due to infection with Staphylococcal aureus. Other organisms 

reported have included Streptococcus, Toxoplasma gondii, cytomegalovirus, Microsporidia, Cryptococcus 

neoformans, Mycobacterium avium intracellulare, Salmonella, Nocardia, and gram-negative organisms.
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Chapter 8: Symptom Management 

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

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2.	

A 37-year-old man with Category 3 HIV disease (an AIDS indicator condition plus CD4 count nadir 

of <200 cells/mm3), last CD4 count 350 cells/mm3, comes to your office complaining of fatigue, 

nonspecific abdominal pain, nausea, and vomiting for the past 12 days. Review of systems is otherwise 

negative. He takes stavudine (d4T), zidovudine (AZT), and nelfinavir (NFV) as ART and fluoxetine for 

depression. On physical exam, his temperature is 37.9 degrees, respiratory rate is 25, abdomen is 

diffusely mildly tender to palpation, with increased tenderness in the right upper quadrant, no signs of 

jaundice, guaiac is negative. 

Question:	What is the differential diagnosis of causes related to ART?

Answer:	

The differential diagnosis of ART-related etiologies in this case should include pancreatitis, based on 

symptoms of abdominal pain, nausea, and vomiting in a patient taking stavudine, although pancreatitis 

usually presents more acutely with more severe pain. Hepatitis should be considered with these symptoms 

in patients taking PIs. Lactic acidosis should always be suspected in a patient with these symptoms taking 

a nucleoside.

Question:	What initial lab work should be ordered? 

Answer:

 Initial lab work may include CBC, basic metabolic panel, liver panel, amylase, lipase, lactate level, and 

coagulation studies. In the case of this patient, the lactic acid level was elevated. Further support for the 

diagnosis of lactic acidosis would include an increased anion gap, decreased bicarbonate, and elevated 

aminotransferases, lipase, amylase, CPK, and LDH.
A Guide to Primary Care of People with HIV/AIDS

Chapter 9: Management of Opportunistic Diseases

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 67

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OVERVIEW

What	are	the	major	opportunistic	diseases	

(ODs)	in	patients	with	HIV/AIDS?		

The diseases that occur as a result of HIV-related 

immunodeficiency include both opportunistic infections 

(OIs) and malignancies. The risk of developing an OI 

has declined dramatically with the widespread use of 

potent combination antiretroviral therapy (ART) (see 

Figure 9-1). The major OIs that occur in patients with 

HIV are Pneumocystis carinii pneumonia (the organism 

that causes human disease in PCP is now classified as

Pneumocystis jiroveci, but PCP remains the conventional 

abbreviation in clinical use), tuberculosis, disseminated 

Mycobacterium avium complex (MAC) disease, 

cytomegalovirus (CMV) disease, Candida esophagitis, 

central nervous system (CNS) infections such as 

cryptococcal meningitis or Toxoplasma encephalitis, 

and cryptosporidiosis. While Mycobacterium tuberculosis 

is an infection that occurs in both immunocompetent 

and immunosuppressed patients, it remains one of the 

most common opportunistic co-infections in persons 

with HIV disease and is responsible for considerable 

morbidity and mortality worldwide. A host of other 

OIs may be seen less commonly or in patients in 

geographic areas where specific infections are endemic, 

eg, histoplasmosis in the central Midwest part of the 

U.S. or isosporiasis in 

South Florida and Puerto 

Rico. 

What	factors	are	

associated	with	higher	

risk	of	developing	an	OI?	

OIs occur primarily in HIV-infected individuals who 

are not receiving either OI prophylaxis or ART (or who 

have not responded to it with an increase in their CD4 

cell counts above the threshold that predicts risk of 

developing an OI). The principal risk of 

Table 9-1. Risk Factors Associated with 

Development of Major Opportunistic 

Infections in HIV-Infected Individuals

Opportunistic 

Infection

CD4 Count 

Risk 

Threshold 

(cells/mm3)

Other Risk Factors

Pneumocystis carinii

pneumonia

≤200 Prior PCP

Percent CD4 cells <14%

Fever of unexplained 

etiology

Presence of oral 

candidiasis

Mycobacterium 

tuberculosis

Any PPD (tuberculin skin test) 

positive

Exposure to an infectious 

contact

Mycobacterium 

avium complex

≤50 Prior respiratory 

or gastrointestinal 

colonization

Prior OD

High viral load (>105

copies/mL)

Cytomegalovirus 

disease

≤50 Seropositive (IgG antibody 

to CMV)

CMV viremia

Prior OD

High viral load 

(>105 copies/mL)

Cryptococcal 

meningitis

≤50-100 Environmental exposure

Toxoplasmosis ≤100-200 Seropositive (IgG antibody 

to T. gondii)

Candida esophagitis ≤100 Prior Candida colonization

High viral load 

(>105 copies/mL)

Cryptosporidiosis ≤100 Environmental exposure 

(contaminated water, soil, 

animal exposure)

Histoplasmosis ≤100 Exposure (endemic areas 

– Midwest, Southeast U.S.)

Coccidioidomycosis ≤100 Exposure (endemic areas 

– Southwest U.S., Mexico)

Chapter	9:	

Management	of	Opportunistic	Diseases

Constance A. Benson, MD

OVERVIEW

PNEUMOCYSTIS JIROVECI (CARINII) PNEUMONIA (PCP) 

MYCOBACTERIUM AVIUM COMPLEX (MAC) 

CYTOMEGALOVIRUS INFECTION (CMV) 

CANDIDA ESOPHAGITIS

CENTRAL NERVOUS SYSTEM DISEASES

MYCOBACTERIUM TUBERCULOSIS

MALIGNANCIES

KEY POINTS

SUGGESTED RESOURCES

See	Pocket	

Guide	Adult	OI	

Tables	1–6
A Guide to Primary Care of People with HIV/AIDS

Chapter 9: Management of Opportunistic Diseases

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

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Figure 9-1 Decline in the Incidence of 

Opportunistic Infections in HIV-1-Infected 

Individuals Receiving Potent Combination 

Antiretroviral Therapy

No. of OIs per 100

person-years

1994 1995 1996 1998

0

5

10

15

20

2000

MAC

Declining U.S. Incidence of OIs

with Potent ARV Therapy

CMV

PCP

2

Source: Adapted from Palella FJ Jr, Delaney KM, Moorman AC, et al. 

Declining morbidity and mortality among patients with advanced 

human immunodeficiency virus infection. HIV Outpatient Study 

Investigators. N Engl J Med. 1998;338:853-860. Copyright 1998 by 

the Massachusetts Medical Society. Modified with permission (data 

extrapolated through 2000).

developing a specific OI is determined by the degree 

of immunosuppression, as measured by the CD4 

cell count. The CD4 threshold of risk differs for each 

specific OI (see Table 9-1). It is uncommon for an OI to 

occur in HIV-infected individuals with CD4 cell counts 

above its threshold. For patients with the same CD4 

cell count, those with high viral loads (plasma HIV 

RNA levels >100,000 copies/mL) have a greater risk 

for developing an OD than those with a low viral load. 

Other factors that contribute to increased risk for ODs 

include previous exposure to or infection with a specific 

pathogen, prior occurrence of an OD, environmental 

exposure in the absence of a host response, and the use 

of ART. 

What	malignancies	are	associated	with	

HIV	infection?		

The most common are Kaposi sarcoma (KS) and 

lymphomas. There is also a modest increase in the 

frequency of cervical cancer. In general, these 3 forms 

of malignancies correlate with immunosuppression, 

meaning the frequency increases with low CD4 cell 

counts, but the association is less strong than it is with 

the traditional AIDS-defining ODs. The rate of KS is 

approximately 20,000-fold higher with HIV infection 

compared with the general population, the frequency 

of non-Hodgkin lymphoma is 200- to 600-fold more 

frequent with HIV infection, and the rate of cervical 

cancer is 5-fold greater. Both lymphomas and KS are 

less frequent in the era of ART. 

PNEUMOCYSTIS JIROVECI

(CARINII) PNEUMONIA (PCP) 

What	are	the	clinical	manifestations	of	PCP	in	

patients	with	HIV	infection?	

PCP usually presents as an acute or subacute respiratory 

illness associated with fever, dyspnea, nonproductive 

cough, and fatigue. Physical findings on examination 

include tachypnea, fever, and inspiratory rales. Rarely, 

disseminated Pneumocystis occurs in HIV-infected 

patients with profound immunosuppression. Laboratory 

abnormalities associated with PCP include leukocytosis, 

hypoxemia, an elevated lactate dehydrogenase (LDH), 

and chest radiographic findings of localized or diffuse 

interstitial infiltrates. Occasionally, nodular or cavitary 

lesions may be observed. Pneumothorax in patients 

with advanced HIV is almost always associated with 

underlying Pneumocystis infection. The degree of 

hypoxemia is a measure of disease severity; severe PCP 

is defined as an arterial blood gas PO2 of <70 mm Hg 

with an arterial-alveolar O2 gradient (AaO2) of >35 mm 

Hg. The diagnosis is confirmed by demonstrating the 

presence of P. jiroveci organisms in sputum or tissue 

samples obtained by sputum induction, bronchoscopy 

with bronchoalveolar lavage, or tissue biopsy. In the 

rare circumstance in which acute PCP presents very 

early with a normal chest radiograph, a gallium scan 

may demonstrate diffuse uptake in the lung compatible 

with an interstitial inflammatory process; however, this 

diagnostic test is nonspecific. 

How	should	you	manage	PCP?	

The preferred initial treatment for PCP in HIV-infected 

individuals is trimethoprim-sulfamethoxazole (TMPSMX). Route of administration (oral or parenteral) is 

generally based on the severity of the disease. For those 

with severe PCP, parenteral therapy with trimethoprim 

15-20 mg/kg and sulfamethoxazole 75-100 mg/kg, in 

6-8 hour divided doses, is recommended. In addition, 

adjunctive treatment with corticosteroids, in a dose 

equivalent to 40 mg twice a day of prednisone for the 

first 5 days, followed by a tapering schedule of 40 mg/

day for days 6-10, and then 20 mg/day to complete 21 

days of therapy, should be initiated as soon as possible 

after starting treatment but preferably within the first 

72 hours. For patients with mild to moderate PCP (PO2

>70 mmHg and AaO2 gradient <35 mmHg), oral 

treatment with 2 double-strength tablets of TMP-SMX 

every 8 hours is recommended. Gradual dose escalation 

may reduce the rate of occurrence of adverse reactions 

to TMP-SMX. For those unable to tolerate TMP-SMX, 

a number of alternative regimens are available for 

treatment (see Table 9-2). 
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Table 9-2. Alternative Regimens for 

the Treatment of Pneumocystis carinii

Pneumonia in Those Unable to Tolerate 

Trimethoprim and Sulfamethoxazole

Disease 

Presentation

Alternative Treatment 

Regimens

Severe 

(PO2 <70 mm Hg; 

A-a O2 gradient >35 

mm Hg)

Pentamidine 3-4 mg/kg/d IV

IV Trimetrexate 45 mg/M2/d IV + 

Leucovorin 0.5 mg/kg IV q6h

Primaquine 15-30 mg/d (base) po + 

Clindamycin 600-900 mg IV q8h

Mild-moderate Trimethoprim 15-20 mg/kg/d po + 

Dapsone 100 mg/d po q8h

Primaquine 15-30 mg/d (base) p.o. 

+ Clindamycin 300-450 mg 

po q6-8 hours

Atovaquone suspension 750 mg 

po bid

What	adverse	reactions	occur	with	treatment	

for	PCP?	

Patients should be carefully monitored for adverse 

reactions to treatment and response to therapy. Many 

patients will demonstrate acute worsening of signs 

and symptoms and have radiographic abnormalities in 

the first 3-5 days of treatment. This is the rationale for 

adjunctive corticosteroids in those with severe PCP. Five 

to 7 days of treatment may be required before a clinical 

response is observed, defined as a reduction in fever, 

and improvement in hypoxemia, respiratory symptoms, 

and radiographic abnormalities. 

Adverse reactions to treatment are common in patients 

with AIDS. Many patients can be treated through 

these with supportive care and adjunctive medications 

to ameliorate symptoms; however, severe adverse 

reactions may require substituting alternative treatment 

regimens. Adverse effects most often associated with 

TMP-SMX include skin rash (rarely, Stevens-Johnson 

syndrome or toxic epidermal necrolysis), fever, 

hepatotoxicity, leukopenia, thrombocytopenia, renal 

dysfunction, and hyperkalemia. Major side effects of 

pentamidine include pancreatitis, renal dysfunction, 

dysglycemia, electrolyte abnormalities, and cardiac 

dysrhythmias. Toxicities commonly observed with 

trimetrexate include bone marrow suppression 

(particularly in those who are not treated with 

leukovorin), fever, rash, and hepatitis. Dapsone may 

cause fever, skin rash, and methemoglobinemia with 

hemolysis (particularly in those with G-6-PD deficiency). 

Primaquine also causes methemoglobinemia and 

anemia, and clindamycin toxicities include nausea, 

rash, hepatitis, Clostridium difficile toxin-associated 

diarrhea, and rarely toxic megacolon. Atovaquone is 

associated with nausea, vomiting, diarrhea, rash, fever, 

and hepatitis. 

Is	secondary	prophylaxis	or	maintenance	

therapy	required	af ter	treatment	of	the	acute	

episode	of	PCP?		

All patients with a CD4 count of <200 cells/mm3

should receive primary prophylaxis to prevent PCP. 

All patients who have experienced an episode of PCP 

should receive secondary prophylaxis to prevent a 

recurrence of PCP. Prophylaxis should be continued 

for life unless immune recovery occurs with ART. 

Prophylaxis for PCP should be discontinued if the CD4 

count increases to levels of >200 cells/mm3 and is 

sustained for at least 3 months. Prophylaxis should 

be restarted if the CD4 count declines to <200 cells/

mm3 or if PCP recurs regardless of CD4 cell count. 

Table 9-3 summarizes recommended and alternative 

regimens for primary and secondary prevention of PCP. 

It should be noted that TMP-SMX and dapsone plus 

pyrimethamine are also adequate for prevention of 

toxoplasmosis in susceptible individuals; dapsone alone, 

atovaquone alone, and aerosolized pentamidine are not.

Table 9-3. Recommended and Alternative 

Regimens for the Prevention of 

Pneumocystis carinii Pneumonia in 

Persons with HIV-1 Infection

Agents Doses

Preferred

TrimethoprimsulfamethoxazoleOne double-strength tablet 

po qd

One single-strength tablet 

po qd

Alternative

Trimethoprimsulfamethoxazole

Dapsone

Atovaquone

Dapsone + pyrimethamine + 

leucovorin

Aerosolized pentamidine 

(Respirgard II)

One double-strength tablet 

po 3x/week

100 mg po qd or 3x/week

1500 mg po qd

200 mg + 75 mg + 25 mg 

po once/week

300 mg once/month
A Guide to Primary Care of People with HIV/AIDS

Chapter 9: Management of Opportunistic Diseases

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MYCOBACTERIUM AVIUM

COMPLEX (MAC) 

What	are	the	symptoms	of	MAC?	

Disseminated M. avium complex disease is a 

multiorgan infection, usually occurring in patients 

with AIDS who have CD4 counts of <50 cells/mm3

and principally affecting blood and lymphoreticular 

organs (lymph nodes, spleen, liver, bone marrow). 

Symptoms are nonspecific, usually consisting of high 

fevers, night sweats, weight loss, anorexia, and fatigue. 

Hepatosplenomegaly and less commonly central or 

peripheral lymphadenopathy are seen. Respiratory tract 

disease with interstitial or occasionally lobar or cavitary 

pulmonary infiltrates is a less common manifestation 

but may be seen in the context of multiorgan infection. 

Although there are no specific laboratory abnormalities 

associated with disseminated MAC, isolated elevation of 

alkaline phosphatase, marked anemia, and leukopenia 

or thrombocytopenia secondary to bone marrow 

infiltration may occur. The diagnosis is confirmed by 

the isolation of the organism from a biopsy or a sample 

obtained for culture from blood or involved tissue; 80%-

85% of those with disseminated multiorgan disease 

have a positive mycobacterial blood culture. Blood 

cultures may require 7-10 days of incubation before 

growth of M. avium is detectable. 

What	is	the	recommended	approach	to	

treatment	for	disseminated	MAC?	

Disseminated MAC should be treated with a 

combination of clarithromycin 500 mg twice a day 

or azithromycin 500-600 mg/day plus ethambutol 15 

mg/kg/day. The addition of rifabutin, 300-450 mg/day, 

as a third drug decreases the occurrence of relapse due 

to drug-resistant mycobacteria and is associated with 

improved survival in profoundly immunosuppressed 

individuals. This approach should be considered for 

those with very low CD4 cell counts who are not 

receiving or responding to ART. Treatment should be 

continued for life unless immune recovery occurs 

following ART that results in an increase in CD4 cells 

to levels >100/mm3 sustained for at least 6 months. 

In this setting, antimycobacterial therapy for those 

who have completed at least 12 months of effective 

treatment and have no signs or symptoms of disease 

may be discontinued. Therapy should be re-started if 

the CD4 cell count again declines to <100/mm3. 

Primary prophylaxis to prevent disseminated M. avium

complex disease is recommended for all HIV-infected 

adults and adolescents who have a CD4 count of <50 

cells/mm3. The preferred regimens are azithromycin 

1200 mg once a week or clarithromycin 500 mg twice 

a day. Azithromycin is preferred when patients are 

receiving other drugs metabolized by the cytochrome 

P450 3A4 isoenzyme system, to avoid drug-drug 

interactions with clarithromycin. Rifabutin 300 mg/day 

is a second line alternative for prophylaxis, but is less 

effective than azithromycin or clarithromycin, and 

also must be monitored and dose-adjusted when used 

with other drugs metabolized by the cytochrome 3A4 

isoenzyme. 

CYTOMEGALOVIRUS (CMV) 

INFECTION 

What	are	the	major	clinical	syndromes	

associated	with	CMV	infection	in	patients	

with	HIV	infection	and	how	are	they	

diagnosed?	

Cytomegalovirus retinitis is the most common CMVassociated clinical syndrome observed in patients with 

AIDS. Patients with CMV retinitis involving peripheral 

portions of the retina may have no symptoms, or only 

minor visual complaints such as floaters or peripheral 

visual field defects. Central lesions may result in central 

scotomata and loss of central vision. The diagnosis is 

based on ophthalmologic examination demonstrating 

creamy white retinal exudates with hemorrhage; lesions 

obscure visualization of underlying vessels and other 

retinal structures. Retinitis is bilateral in up to 20% of 

patients. Disease progresses rapidly to blindness unless 

treated. 

The second-most common clinical syndrome associated 

with CMV disease is gastrointestinal disease, either 

CMV colitis or CMV esophagitis. CMV colitis presents 

with fever, diarrhea, weight loss, and colon ulceration 

often with bleeding. Appropriate diagnosis usually 

requires colonoscopy and biopsy of ulcerations; tissue 

histopathology confirms the presence of characteristic 

intranuclear inclusions in mucosal cells or CMV antigens 

on immunohistochemical staining. CMV esophagitis 

presents with fever, odynophagia, and retrosternal 

pain. Exudative ulcers are demonstrated by esophageal 

endoscopic exam. Biopsy and histopathologic 

examination are necessary to confirm the diagnosis. 

Other less common CMV clinical syndromes in patients 

with AIDS are CMV encephalitis/encephalopathy, 

interstitial pneumonitis, hepatitis, and pancreatitis. 
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Chapter 9: Management of Opportunistic Diseases

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What	is	the	recommended	treatment	for	

CMV	retinitis?		

CMV retinitis should be managed in cooperation with 

an experienced ophthalmologist. For patients with CMV 

retinitis that is immediately sight-threatening (central 

lesions approaching or involving the optic nerve or the 

fovea) systemic therapy with either IV ganciclovir or oral 

valganciclovir is the preferred initial treatment; many 

experts would also recommend surgical treatment 

with a ganciclovir intraocular implant (see Table 9-4). 

IV ganciclovir or oral valganciclovir is administered in 

an acute “induction” dose for 14-21 days, followed by 

a once-a-day chronic maintenance therapy dose. This 

approach is superior to other alternatives for preventing 

or delaying disease progression and provides systemic 

treatment to prevent other organ system involvement. 

If effective ART is not administered or patients remain 

immunosuppressed, the ocular implant should be 

replaced every 7-8 months. For patients with peripheral 

CMV retinitis that is not immediately sight-threatening, 

oral valganciclovir is the preferred treatment because 

of its ease of administration compared with other 

parenteral alternatives. 

Table 9-4. Treatment Options for 

Cytomegalovirus Disease

Drug Induction 

dose

Maintenance 

therapy dose

Ganciclovir 

implant

N/A Replace every 7-8 

months

Oral valganciclovir 900 mg bid x 14-

21d

900 mg/d

IV ganciclovir 5 mg/kg bid x 

14-21d

5 mg/kg/d

Foscarnet 90 mg/kg bid x 

14-21d

90 mg/kg/d

IV cidofovir 

(+ probenecid)

5 mg/kg once/w x 

2 wks

5 mg/kg every 2 

weeks

Chronic maintenance treatment for CMV retinitis should 

be continued for life unless ART results in a sustained 

increase in CD4 counts to levels of >100 cells/mm3 

for at least 6 months. If the CD4 count again declines 

to <100 cells/mm3, maintenance therapy should be 

reinitiated. Immune recovery vitritis is a recognized 

complication of acute rises in CD4 cell counts and 

decreases in plasma HIV RNA levels following initiation 

of ART. It may be associated with an acute decrease in 

visual acuity due to the inflammatory cells clouding the 

vitreous fluid. Treatment with local corticosteroids while 

continuing anti-CMV therapy is associated with rapid 

improvement in most patients. 

What	is	the	recommended	treatment	for	

CMV	gastrointestinal	disease?	

Treatment with either oral valganciclovir or IV 

ganciclovir or IV foscarnet is the recommended 

approach to treatment of CMV esophagitis or CMV 

colitis. In general, clinical symptoms and signs resolve 

within 2-3 weeks, and the suggested duration of 

treatment is 21-28 days, depending on the severity 

of the clinical presentation. Chronic maintenance 

treatment is not recommended unless recurrent 

episodes occur. 

Strategies for treatment in those with relapse or 

progressive disease include either re-induction followed 

by maintenance therapy with the same agent, or 

switching to an alternative agent, a combination of 

2 agents, or specifically for those with CMV retinitis, 

systemic therapy coupled with intravitreal injection. 

Recurrent or progressive disease should be managed by 

an expert. 

CANDIDA ESOPHAGITIS

What	are	the	presenting	signs	and	symptoms	

of	Candida	esophagitis	and	how	is	it	diagnosed?	

The most common manifestations of Candida 

esophagitis are fever, anorexia, odynophagia, and 

retrosternal pain. Occasionally, nausea and rarely UGI 

bleeding from ulceration may occur. Esophagoscopy 

reveals adherent whitish plaques with shallow ulcers 

surrounded by erythematous borders. Invasive 

esophageal candidiasis can occur in the absence of oral 

candidiasis and must be distinguished from esophagitis 

due to CMV, herpes simplex virus, and aphthous 

esophagitis, all of which may be seen in patients with 

HIV infection. Isolation of Candida species in culture 

from a specimen obtained from the mucosal surface or 

the base of an ulcer provides supportive information but 

is not diagnostic, as colonization of mucosal surfaces 

with Candida is common in immunosuppressed 

individuals, particularly those who are receiving 

antibacterial therapies such as TMP-SMX for prophylaxis 

of PCP. The diagnosis can be confirmed by a biopsy 

of the ulcer and demonstration of yeast forms in 

tissue. The finding of oral candidiasis associated with 

esophageal symptoms has a positive predictive value 

of close to 100% for Candida esophagitis. In patients 

with oral candidiasis and esophageal symptoms empiric 

therapy for Candida esophagitis should be given. If there 

is no clinical response after 5-7 days, upper endoscopy 

should be performed. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 9: Management of Opportunistic Diseases

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

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How	do	you	treat	Candida	esophagitis?	

Candida esophagitis requires systemic therapy. A 

number of options are available; however, the preferred 

treatment is fluconazole 100 mg/d for 14 days. 

Ketoconazole and itraconazole are effective alternatives, 

but drug-drug interactions with other anti-HIV therapies 

are common, and absorption is diminished in those 

with primary or drug-induced hypo- or achlorhydria. 

For patients unable to tolerate oral therapy, parenteral 

amphotericin B is effective. Chronic maintenance 

therapy or secondary prophylaxis is not recommended, 

but may be considered for patients who have frequent 

recurrent episodes. Chronic suppressive therapy with 

fluconazole has been associated with an increased risk 

of fluconazole (and other azole) resistant disease. 

CENTRAL NERVOUS

SYSTEM DISEASES

How	do	you	distinguish	cryptococcal	

meningitis	from	toxoplasmic	encephalitis	and	

CNS	lymphoma	in	HIV-infected	patients?	

Patients with AIDS and a CD4 count of <200 cells/

mm3 may be at risk for developing CNS OIs such as 

cryptococcal meningitis or toxoplasmosis, as well 

as CNS lymphoma; most infections occur in those 

with CD4 counts of <100 cells/mm3. Toxoplasmic 

encephalitis is rare in patients who are seronegative 

for Toxoplasma gondii (negative IgG antibody). CNS 

infection due to T. gondii and Cryptococcus spp. as well 

as CNS lymphoma may be relatively insidious in onset 

and associated with symptoms of fever, headache, 

and mental status changes. Focal neurological deficits 

and seizures are more likely to occur with toxoplasmic 

encephalitis and CNS lymphoma, although they 

sometimes occur in those with cryptococcal meningitis 

as well. The best diagnostic tests for a differential 

diagnosis of CNS disease are radiographic imaging of 

the CNS (with either a contrast-enhanced computerized 

tomographic [CT] scan or magnetic resonance imaging 

[MRI] scan) and lumbar puncture with cerebrospinal 

fluid (CSF) examination. Multiple localized enhancing 

lesions are common with toxoplasmic encephalitis; MRI 

is more sensitive than a CT scan for detecting these. 

CNS lymphoma is more likely to be associated with 

single and less commonly multiple space-occupying 

lesions, while cryptococcal meningitis is only rarely 

associated with space-occupying lesions. The CSF 

may demonstrate a normal to mild lymphocytic 

pleocytosis, normal to slightly elevated protein, and 

normal to mildly decreased glucose for each, but a CSF 

cryptococcal antigen will be positive in 99%-100% of 

individuals with cryptococcal meningitis. Confirmation 

of the diagnosis of toxoplasmic encephalitis generally 

requires either demonstration of the organism in 

CSF by polymerase chain reaction (PCR) or culture 

(may not be routinely available) or a brain biopsy and 

demonstration of the organism in tissue. In practice, 

a trial of therapy is usually the first diagnostic tool 

for patients who have suggestive neuroimaging and 

positive Toxoplasma serology. Brain biopsy is reserved 

for patients who do not respond to empiric therapy. A 

brain biopsy is necessary to confirm the diagnosis of 

CNS lymphoma. 

How	do	you	treat	cryptococcal	meningitis?	

Amphotericin B (0.7 mg/kg/d or the dose equivalent of 

liposomal or lipid complex amphotericin B), combined 

with flucytosine 100 mg/kg/day in divided doses, for 

the first 2 weeks, is the recommended initial treatment 

for cryptococcal meningitis. If a treatment response 

is evident this regimen is followed by fluconazole 400 

mg/day for an additional 8 weeks or until CSF cultures 

are negative. The CSF opening pressure should always 

be measured when a lumbar puncture is performed, 

and if elevated above 200 mg H2O, measures to 

reduce the pressure should be implemented. These 

may include serial lumbar puncture with CSF drainage 

sufficient to reduce the pressure by 50%, or in the case 

of severe increased intracranial pressure, the use of a 

lumbar drain or ventriculoperitoneal shunt. Secondary 

prophylaxis or chronic maintenance therapy with 

fluconazole, 200 mg/day, should be continued for life 

unless ART results in immune recovery. In this instance, 

maintenance therapy may be discontinued for those 

who have successfully completed a course of therapy 

for cryptococcal meningitis, have no residual signs or 

symptoms, and have a sustained increase in CD4 count 

to levels of >100-200 cells/mm3 for at least 6 months. 

Maintenance therapy should be re-initiated if the CD4 

count again decreases to <100-200 cells/mm3. 

MYCOBACTERIUM

TUBERCULOSIS

Does	the	presentation	of	tuberculosis	differ	in	

HIV-infected	and	non-HIV-infected	individuals?	

Patients with HIV infection have an increased risk of 

infection with Mycobacterium tuberculosis following 

exposure to a person with active disease, and an 
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9

increased risk of developing active disease following an 

exposure. The risk of developing active disease is 30%-

40% in the first year following a new exposure, and 

for HIV-infected patients with a positive tuberculin skin 

test related to prior TB exposure, the risk of developing 

active disease may be as high as 7%-8% per year. 

For patients with a CD4 count of >250 cells/mm3, 

the clinical signs and symptoms of tuberculosis are 

generally the same as for HIV-noninfected persons. 

Pulmonary tuberculosis accompanied by fever, cough, 

sputum production, chest pain, night sweats, weight 

loss, and anorexia is the principal manifestation. As 

immunosuppression progresses, the likelihood of 

extrapulmonary or disseminated (miliary) disease 

increases, although in most instances, pulmonary 

involvement is also present. Chest radiograph 

demonstrates lobar consolidation with cavitation, 

usually involving upper lobes, when reactivation 

tuberculosis is present. In those with primary 

tuberculous pneumonia, lower lobe infiltrates are more 

common. Hilar or mediastinal lymphadenopathy, 

pleural effusion, and interstitial infiltrates may be more 

common in patients with lower CD4 cell counts. 

How	do	you	diagnose	TB	in	persons	with	HIV?	

The diagnosis is the same as for non-HIV-infected 

persons, relying on a combination of compatible 

clinical signs and symptoms, radiographic findings, 

a positive tuberculin skin test, and a sputum sample 

demonstrating acid-fast bacilli (AFB). The diagnosis 

is confirmed by culture of the organism from 

sputum, blood, or other tissue. However, patients 

with advanced immunosuppression may have less 

extensive consolidation or lung cavitation, and sputum 

AFB smears may be positive in a lower proportion, 

because of the lower mycobacterial burden in the lung. 

Also, tuberculin skin tests are less likely to be positive 

because of impaired cell-mediated immune function. 

In immunocompromised patients, more aggressive 

means for making a diagnosis may be necessary, 

such as bronchoscopy with bronchoalveolar lavage or 

transbronchial biopsy to obtain samples for AFB smear 

and culture. Biopsy or culture of specimens obtained 

from extrapulmonary sites such as bone marrow 

and lymph nodes may be useful. All initial isolates 

of M. tuberculosis should be tested for susceptibility 

to antimycobacterial drugs, and susceptibility testing 

should guide the choice of initial treatment. 

How	do	you	treat	tuberculosis	in	patients	with	

HIV	infection?	

The recommendations for treatment of tuberculosis in 

patients with HIV infection depend in part on whether 

or not patients are on ART, and if they are, the specific 

antiretroviral regimens employed. All patients should 

receive directly observed therapy. See Adult OI Tables 

2 - 7 for the recommendations for treatment of latent 

tuberculosis and drug-susceptible tuberculosis disease. 

Treatment with 4 drugs (isoniazid, rifampin or rifabutin, 

ethambutol, and pyrazinamide) is recommended 

either for the first 2 months of therapy or until results 

of susceptibility testing are available. If patients have 

drug-susceptible disease, 2 drugs, isoniazid and 

rifampin or rifabutin, should then be continued for 

at least 18 additional weeks. The continuation phase 

of therapy should be extended to 28 weeks (total 

duration of 9 months) for HIV-infected patients with 

advanced immunosuppression (CD4 count of <100 

cells/mm3) or who have an inadequate initial response 

or cavitary disease. Rifabutin should replace rifampin 

and doses should be appropriately adjusted for those 

who are receiving ART with agents likely to interact 

with rifamycins. The timing of initiation of ART and the 

most appropriate ART regimen for use in conjunction 

with antimycobacterial therapy remain controversial. 

Concurrent ART and tuberculosis treatment should be 

managed by an expert. 

MALIGNANCIES

How	does	Kaposi	sarcoma	(KS)	present?		

KS is a poorly understood multicentric tumor of 

endothelial cells. The cause is human herpesvirus 8 

(HHV-8), an infection that is more frequent in men who 

have sex with men. The mechanism of transmission 

is unclear, but the best evidence suggests transmission 

via saliva and semen. Many carry the virus with no 

consequences; it causes disease primarily in the 

presence of immunosuppression. The presentation 

is highly characteristic, with multiple purple to 

brown-black macules, or nodules that are usually 

asymptomatic and occur most frequently on the legs, 

face, oral cavity, or genitalia. The major complications 

include lymphedema (especially of the legs, face, 

and genitalia) and visceral involvement. Visceral 

involvement is common in the lung and GI tract, but is 

usually asymptomatic. 
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How	do	you	diagnose	KS?		

The skin lesions are usually sufficiently characteristic 

to make this diagnosis clinically based on appearance, 

but a biopsy should be done when there is a need 

for confirmation. The differential diagnosis includes 

bacillary angiomatosis (which can be proven by biopsy 

with silver stain), hematoma, nevus, hemangioma, 

B-cell lymphoma, and pyogenic granuloma. When 

there is visceral involvement, the usual method used 

to establish the diagnosis is endoscopic examination 

to show typical mucosal surface lesions. With lung 

involvement, the x-ray is variable and may show 

nodules, infiltrates, effusions, and/or mediastinal/

hilar nodes. Lung biopsy is often negative, but the 

bronchoscopic exam often shows a characteristic 

cherry-red bronchial nodule. With GI tract involvement, 

the usual screening test is stool for occult blood, and 

endoscopy is the usual method to make the diagnosis 

by showing a hemorrhagic nodule; the biopsy is often 

negative because of the submucosal location of the 

tumor. 

How	do	you	treat	KS?		

Many patients require no therapy except possibly 

makeup to cover the characteristic lesions. Topical 

treatment for skin involvement includes vinblastine, 

Panretin gel, liquid nitrogen, radiation, cryosurgery, or 

laser. Systemic chemotherapy is preferred when there 

is an extensive burden, defined as >25 skin lesions, 

symptomatic visceral involvement, extensive edema, 

systemic (B) symptoms, or failure to respond to local 

treatment. The favored forms of chemotherapy are 

liposomal anthracyclines (Doxil or DaunoXome) or, less 

frequently, paclitaxel (Taxol). Immune reconstitution 

with ART is associated with a substantial reduction in 

the frequency of KS and a therapeutic improvement 

in those who already have these lesions. It should be 

noted that there is no cure for KS, and the goal of local 

therapy or systemic chemotherapy is to reduce tumor 

burden and relieve symptoms. 

What	lymphomas	are	associated	with	HIV	

infection?		

The subtypes of lymphomas associated with HIV 

infection include B-cell large cell lymphoma, primary 

body effusion lymphomas, B-cell CNS lymphoma, 

Burkitt lymphoma, plasmablastic lymphoma, and 

Hodgkin disease. The most common is non-Hodgkin 

lymphoma. 

What	are	the	symptoms	of	non-Hodgkin	

lymphoma	(NHL)?		

Compared with the general population, patients 

with this complication have high rates of stage IV 

disease with systemic (B) symptoms and sparse 

node involvement. Common symptoms are fever of 

unknown origin, liver dysfunction, marrow suppression, 

lung disease (effusions, multinodular infiltrates, mass 

lesions, diffuse infiltrates, and/or hilar adenopathy), GI 

involvement (any level with pain and weight loss), and 

CNS with mass lesions. 

How	do	you	diagnose	lymphomas?		

Fine needle aspirates of enlarged nodes are helpful if 

positive, but false negatives are common. Biopsy is 

usually necessary. 

How	are	lymphomas	treated	and	what	should	

be	expected?		

The usual treatment is chemotherapy with 

cyclophosphamide, doxorubicin, adriamycin, 

vincristine, and prednisone (CHOP); methotrexate, 

bleomycin, doxorubicin, cyclophosphamide, vincristine, 

and dexamethasone + G-CSF (M-BACOD); or etoposide, 

prednisone, vincristine, cyclophosphamide, and 

doxorubicin (EPOCH). Response rates are 50%-60%, 

but the long-term prognosis is poor unless there is 

immune reconstitution with ART. 

How	do	you	diagnose	and	treat	primary	CNS	

lymphomas?		

The typical presentation is confusion, headache, 

memory loss, focal neurologic changes, usually without 

fever and usually with a CD4 cell count of <50/mm3. 

The MRI shows single or multiple lesions that are 

isodense or hypodense. The differential diagnosis 

is primarily toxoplasmosis. Factors suggesting CNS 

lymphoma are the characteristic MRI findings, negative 

T. gondii serology, failure to respond to empiric 

treatment of toxoplasmosis within 1-2 weeks, thallium 

single-photon emission computed tomography (thallium 

SPECT) scan results, and CSF positive by polymerase 

chain reaction (PCR) for Epstein Barr virus (EBV) DNA. 

The definitive diagnosis can be made by stereotactic 

brain biopsy. Treatment is radiation and corticosteroids, 

often combined with chemotherapy. The prognosis is 

poor without immune reconstitution. 
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KEY POINTS

The risk of persons with HIV developing 

specific ODs is related to the degree of 

their immunosuppression, as measured 

by the CD4 cell count. 

All patients with a CD4 count of <200 

cells/mm3 should receive primary 

prophylaxis to prevent PCP. PCP usually 

presents as an acute or subacute 

respiratory illness associated with fever, 

dyspnea, nonproductive cough, and 

fatigue. 

All patients with a CD4 cell count of 

<50/mm3 should receive primary 

prophylaxis to prevent disseminated 

MAC. Disseminated MAC is a multiorgan 

infection that usually occurs at CD4 cell 

counts of <50/mm3. Symptoms are 

nonspecific, usually consisting of high 

fever, night sweats, weight loss, anorexia, 

and fatigue. 

CMV retinitis, the most common CMVassociated clinical syndrome, progresses 

rapidly to blindness unless treated. CMV 

gastrointestinal disease, either colitis or 

esophagitis, presents with fever, diarrhea, 

weight loss, and colon ulceration often 

with bleeding. 

The most common manifestations of 

Candida esophagitis are fever, anorexia, 

odynophagia, and retrosternal pain. 

Treatment requires systemic therapy. 

Patients with a CD4 count of <200 

cells/mm3 are at risk for developing CNS 

ODs such as cryptococcal meningitis 

or toxoplasmosis, as well as CNS 

lymphoma. After initial treatment, 

chronic maintenance therapy should 

be continued for life unless immune 

recovery occurs as a result of ART. 

Patients with HIV are at increased 

risk of infection with Mycobacterium 

tuberculosis and of developing active 

tuberculosis. Immunosuppression 

increases the likelihood of 

extrapulmonary or disseminated 

(miliary) disease. Because tuberculin 

skin tests are less likely to be positive in 

immunocompromised patients, more 

aggressive means for making a diagnosis 

may be necessary. 

All HIV-infected patients with active 

tuberculosis should receive directly 

observed therapy. Treatment of 

tuberculosis in persons with HIV 

co-infection should be managed by 

an expert because treatment is 

complex and the infection is potentially 

life-threatening. 

The major complications of KS, a 

multicentric tumor of endothelial cells, 

include lymphedema (especially of the 

legs, face, and genitalia) and visceral 

involvement. Extent of involvement 

determines whether treatment is required 

and whether it is topical or systemic. 

The most common lymphoma associated 

with HIV is non-Hodgkin lymphoma. 

Common symptoms are fever of 

unknown origin, liver dysfunction, 

marrow suppression, lung disease, GI 

involvement (any level with pain and 

weight loss), and CNS mass lesions. 

SUGGESTED RESOURCES

Leav BA, Mackay M, Ward HD. 

Cryptosporidium species: New insights 

and old challenges. Clin Infect Dis. 2003;36:

903-908. 

Official statement of ATS, CDC and IDSA: 

Treatment of tuberculosis. Am J Crit Care 

Med. 2003;167:603-662. Available at http:

//www.aidsinfo.nih.gov. Accessed 1/04. 

USPHS/IDSA Guidelines for the Prevention 

of Opportunistic Infections in Persons 

Infected with HIV. Washington DC: U.S. 

Department of Health and Human 

Services. Nov 28, 2001. Available at http:

//www.aidsinfo.nih.gov. Accessed 1/04.
A Guide to Primary Care of People with HIV/AIDS

Chapter 10: Abnormal Laboratory Values in HIV Disease

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10

COMMON ABNORMALITIES

What	are	some	common	abnormalities	found	

when	screening	asymptomatic	patients?	

Some disease processes associated with HIV can be 

first identified in laboratory screening tests while 

patients are still asymptomatic. The primary care 

provider plays an essential role in monitoring for 

laboratory abnormalities, whether these abnormalities 

result from diseases or from antiretroviral therapy 

(ART). Table 10-1 lists screening tests that assist in 

promptly identifying and managing medical problems 

in asymptomatic patients. Abnormal laboratory tests 

occur more frequently in HIV-infected persons because 

1) HIV is a multi-system disease, 2) HIV causes immune 

suppression that may result in opportunistic infections 

and tumors that involve multiple systems, 3) the drugs 

used routinely in management can cause adverse 

reactions that affect multiple systems, and 4) patients 

at high risk for HIV are often at high risk for other 

medical conditions.

What	constitutes	a	positive	PPD	

in	HIV	disease?

Induration of 5mm or more at 48-72 hours constitutes 

a positive PPD test for tuberculosis in a person with 

HIV. A PPD should be done at baseline and repeated 

annually if the initial test was negative and the patient 

is in a high-risk category for tuberculosis. The test has 

a relatively high rate of false-negative results in patients 

with a CD4 cell count of <200/mm3. Therefore, if the 

initial test was done when the CD4 cell count was low, 

it should be repeated when the CD4 cell count increases 

to >200/mm3 following ART. Patients with a positive 

PPD test need a chest x-ray and evaluation for active 

disease before isoniazid (INH) prophylaxis is initiated.

What	is	the	role	of	a	baseline	chest	x-ray?

A chest x-ray is recommended for detection of latent 

or active tuberculosis and other lung diseases and as a 

baseline for patients who are at high risk for pulmonary 

disease, especially bacterial pneumonia, Pneumocystis 

pneumonia, and tuberculosis. The x-ray is particularly 

important for any patients with a positive PPD skin test.

What	do	you	do	when	a	patient	has	a	positive	

VDRL	or	RPR?

The standard screening tests for syphilis in sexually 

active patients are the nontreponemal tests, the 

VDRL or RPR. Any positive screening test should be 

confirmed with a fluorescent treponemal antibody 

absorbed test (FTA-ABS). Confirmation is particularly 

important because for biologic false-positive tests are 

more common with injection drug use, pregnancy and 

HIV infection. With a positive test, primary, secondary, 

and early latent syphilis (less than 1 year) should be 

treated with a single injection of benzathine penicillin 

(2.4 million units IM) once, late latent syphilis (more 

than 1 year or of unknown duration) should be treated 

with 3 doses at 1-week intervals of benzathine penicillin 

(2.4 million units IM with each dose), and neurosyphilis 

should be treated with aqueous penicillin G, 18-24 

million units/day IV for 10-14 days. Patients who are not 

pregnant and do not have neurosyphilis who cannot 

receive penicillin may be treated with doxycycline (100 

mg po bid) given for 14 days for primary, secondary, 

and early latent syphilis and for 28 days for late latent 

syphilis. Because the efficacy of doxycycline is not well 

established, patients who received doxycycline need 

extra followup. With penicillin allergy and neurosyphilis 

or pregnancy, there should be penicillin skin testing; 

if negative, penicillin is given, and if positive the 

patient should undergo penicillin desensitization 

followed by penicillin treatment. A lumbar puncture is 

recommended for any patient with neurologic signs or 

Chapter	10:	

Abnormal	Laboratory	Values	in	HIV	Disease

David H. Spach, MD 

John G. Bartlett, MD COMMON ABNORMALITIES

HEMATOLOGIC COMPLICATIONS

LIVER DISEASE

RENAL DISEASE

KEY POINTS

SUGGESTED RESOURCES

REFERENCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 10: Abnormal Laboratory Values in HIV Disease

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

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Table 10-1. Abnormalities Identified in 

Screening Tests

Test Implications of abnormal 

findings

CBC Anemia – usually due to HIV or 

zidovudine

Neutropenia – usually due to HIV 

or drugs, especially ganciclovir and 

zidovudine

Thrombocytopenia – usually due to 

HIV

Alanine 

aminotransferase 

(ALT)

Usual causes of elevated levels 

are chronic hepatitis (HBV, HCV), 

alcoholic liver disease, or adverse 

drug reactions.

Creatinine Usual causes of renal failure are 

common medical conditions in this 

population (hypertension, heroin 

use, diabetes, IgA nepropathy, etc), 

adverse reactions to drugs (including 

indinavir), or HIV nephropathy

Toxoplasma titer Positive results in 10% of adults in 

US, higher in other countries. This 

indicates latent disease with possible 

activation if CD4 count <100/mm3

VDRL or RPR If positive, need confirmatory 

FTA-ABS

Screen for N. 

gonorrhoeae and C. 

trachomatis

Positive results indicate high-risk 

behavior and need for treatment

PPD Induration ≥5mm indicates need 

for evaluation for active TB and, if 

negative, INH treatment

Chest x-ray Ghon complex, adenopathy, or 

evidence of chronic lung disease

CD4 count Barometer of immune function

Viral load Indicates rate of progression of 

untreated HIV and response to 

HAART

Hepatitis panel

Anti-HCV Positive results ± confirmatory HCV 

RNA usually indicates chronic HCV 

infection

Anti-HBc or 

Anti-HBs 

serology

Positive results indicate prior 

antigenic experience with HBV

HBsAg Indicates HBV; if positive >6 months 

indicates chronic HBV

Anti-HAV Positive test indicates prior antigenic 

experience due to HAV infection or 

vaccination

symptoms, patients with therapeutic failure (persistent 

clinical evidence of syphilis or a sustained 4-fold 

increase in titer), and all patients with latent syphilis, 

which includes latent syphilis of unknown duration. 

Some experts have recommended performing lumbar 

puncture for all HIV-infected persons with syphilis, 

regardless of the stage of syphilis. With respect to 

followup, the nontreponemal test should be done at 3, 

6, 9, 12, and 24 months. 

HEMATOLOGIC

COMPLICATIONS

What	are	the	common	causes	of	anemia?	

Anemia, which is common in HIV disease, is usually 

caused by 1) late-stage HIV, presumably due to viral 

infection of progenitor cells, 2) associated complications 

that infiltrate the marrow, 3) nutritional deficiency, 

4) adverse drug reactions, or 5) iron deficiency. The 

findings and management are summarized in 

Table 10-2.

What	causes	thrombocytopenia?	

Most cases are attributed to HIV infection of the multilineage hematopoietic progenitor cells in the marrow. 

This HIV-associated thrombyocytopenia can occur in 

relatively early HIV, but is more common with latestage disease. Although zidovudine (AZT) may cause 

anemia or neutropenia, early studies showed that it 

reverses thrombocytopenia. For patients not receiving 

ART, the preferred treatment for HIV-associated 

thrombocytopenia is to promptly initiate ART. The 

decision to intervene with intravenous immune globulin 

(IVIG) or corticosteroids is driven by signs or symptoms 

of active bleeding, the need to do an invasive 

procedure, or a lack of response to ART. 

What	causes	neutropenia?	

Neutropenia is most commonly related to drug 

therapy, especially with zidovudine (AZT), ganciclovir, 

or valganciclovir, but it can also be caused by latestage HIV or marrow-infiltrate disease. With absolute 

neutrophil counts of <500/mm3 it is important to 

monitor for infection and intervene with empiric 

antibiotics rapidly when appropriate. Address 

neutropenia by discontinuing the implicated agent or by 

providing cytokine therapy using G-CSF or GM-CSF.
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LIVER DISEASE

What	are	the	common	causes	of	abnormal	liver	

function	tests?	

Abnormal screening liver function tests reflect 

associated conditions (hepatitis B or C viral infection 

as discussed below), adverse drug reactions, alcoholic 

hepatitis, and HIV-related complications, including 

Kaposi sarcoma, lymphoma, Mycobacterium avium 

complex (MAC), tuberculosis, cytomegalovirus (CMV), 

or histoplasmosis. Start by defining the process as 

cholangiopathic or hepatocellular based on results of 

liver function tests (LFTs).

• AIDS cholangiopathy typically presents with right 

upper quadrant pain, high alkaline phosphatase, 

characteristic duct dilatation on ultrasound, and 

a CD4 cell count of <100/mm3. The usual causes 

are infection (microsporidia, cytomegalovirus, or 

cryptosporidia) or idiopathic. Most cases respond 

temporarily to endoscopic biliary sphincterotomy. 

• Hepatocellular injury is much more common and is 

caused by diverse conditions, including 1) hepatitis 

viruses, 2) alcoholic hepatitis, 3) cirrhosis, and 

4) adverse drug reactions. All antiretroviral drugs 

are potentially hepatotoxic, but the indications for 

intervention vary depending on the mechanism and 

severity (see Table 10-3).

When	should	you	stop	antiretroviral	drugs	

because	of	hepatotoxicity?	

There are 3 situations in which antiretroviral drugs 

should be stopped because of hepatotoxicity (see 

Table 10-3):

- Hypersensitivity syndrome (drug rash with 

eosinophilia and systemic symptoms [DRESS])

The hypersensitivity reaction seen with abacavir 

(ABC) and nevirapine (NVP) is characterized by fever, 

eosinophilia, rash, and GI complaints, and usually 

occurs during the first 6 weeks of therapy. This 

situation should be urgently managed, and deaths 

have been reported. 

- Symptomatic lactic acidosis This is ascribed to drugs 

in the NRTI class, which should be stopped.

- Increased transaminase levels This is ascribed to 

the PIs and the NNRTIs nevirapine (NVP) and 

efavirenz (EFV). The most serious reactions have 

occurred with nevirapine-associated hepatoxicity. 

The mechanism is unclear, and treatment interruption 

is often considered necessary only when clinical 

hepatitis occurs.

Do	patients	infected	with	HIV	have	increased	

rates	of	hepatitis	B	virus	(HBV)	and	hepatitis	

C	virus	(HCV)	infection,	and	does	coinfection	

affect	the	natural	progression	of	HIV?

HIV-infected patients have higher rates of chronic 

HBV infection after exposure to HBV. With HBV 

coinfection, there is a higher frequency of evidence 

for HBV replication (higher frequency of HBeAg and 

higher levels of HBV DNA) and higher rates of HBVassociated liver disease. It is not known if HBV alters 

the natural history of HIV, but coinfection is associated 

with increased frequency of hepatotoxicity with ART. 

The relationship with HCV is similar. HIV coinfection 

is relatively common, a frequency of about 30% in all 

HIV-infected patients and as many as 85% in those 

with injection drug use as the risk factor. HIV has an 

Table 10-2. Causes of Anemia in HIV

Cause Cells Reticulocyte count Other tests Treatment

HIV disease Normal Low Low erythropoietin level ART

Recombinant human 

erythropoietin (rHU EPO)

Tumors and 

infectious 

diseases

Normal Low Positive identification of underlying 

disease (eg, lymphoma, KS, MAC, TB, 

CMV, histoplasmosis)

Treatment of underlying 

disease 

Parvovirus Normal 0 Positive serology & PCR for parvovirus IVIG

Nutritional 

deficiency

MCV > 100 

(but not with 

AZT or d4T)

Low Low B12/folate level Folic acid or cobalamin

Iron deficiency MCV low Low Blood loss, low Fe, transferrin Treatment of cause 

Iron therapy

Drug (toxicity) Normal Normal Identify offending drug (zidovudine, 

ganciclovir, TMP-SMX, etc.)

Stop implicated agent

Drug (hemolysis) Normal Increased Identify offending drug (dapsone, 

ribavirin); increased LDH, indirect 

bilirubin/low haptoglobin

RBC therapy 

Stop drug
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important effect on promoting more rapid progression 

of HCV, but it is not clear whether HCV adversely 

affects the rate of HIV progression. Many studies have 

shown that HCV coinfection is a poor prognostic factor 

in the ART era, but this may well reflect the influence 

of injection drug use rather than HCV-associated liver 

disease. 

Who	should	you	test	for	HBV	and	HCV,	and	what	

tests	should	you	perform?

At entry into health care, all patients with HIV should 

be screened for antibodies to HBV and HCV, as well as 

HBV antigen (see Table 3-1 in Chapter 3). Knowledge 

of the HBV and HCV status can provide valuable 

information for those persons with abnormal LFTs. 

In addition, testing can identify patients who are 

seronegative for HBV who can receive HBV vaccination. 

Some patients with HIV have negative HBV surface 

antibody titers, negative HBV antigen, but positive core 

HBV antibody. If they have not recently acquired HBV, 

this serologic pattern suggests a low-level persistent 

immune response to HBV; these individuals probably 

have adequate protection to prevent reinfection, but 

no studies have been done to accurately evaluate their 

risk. Moreover, no formal recommendation exists to 

provide a booster HBV vaccine to those persons with 

negative HBV surface antibody titers but positive HBV 

core antibody. Serologic testing using an enzyme 

immunoassay for HCV is the preferred screening test 

for HCV, and those with positive tests should have a 

confirmatory test with either the RIBA assay or a test 

that detects HCV RNA. Several studies have shown 

that some persons coinfected with HIV and HCV, 

particularly those with severe advanced HIV disease, 

can have a negative HCV antibody test on the enzyme 

immunoassay, but a repeatable positive HCV RNA test. 

Thus, some experts would recommend doing an HCV 

RNA assay on a person with a negative HCV enzyme 

immunoassay if HCV infection is suspected (usually 

because of abnormal LFTs). 

How	should	you	treat	HBV	in	persons	coinfected	

with	HIV?

All coinfected patients should be considered for HBV 

therapy. Recommendations are somewhat arbitrary, 

but most recommend therapy with an alanine 

aminotransferase (ALT) at least 2 times the upper limit 

of normal (ULN), evidence of active HBV replication (e 

antigen or HBV DNA level of >105c/mL), and preferably 

with histologic evidence of moderate disease activity 

or fibrosis. There are 2 major forms of treatment and 

neither is “preferred.” One form is interferon-alfa-2a 

or alfa-2b given subcutaneously 3 times a week or 

once a day for 24-48 weeks. Many authorities now 

Table 10-3. Antiretroviral Drugs That Cause Abnormal Liver Function 

Drugs Frequency of abnormal 

liver function

Comment

NRTIs

 stavudine (d4T)

 didanosine (ddI)

 zidovudine (AZT)

8%-16% Mitochondrial toxicity; risk highest with stavudine and 

didanosine together; risk with zidovudine lower than stavudine

 lamivudine (3TC)

 emtricitabine (FTC)

 abacavir (ABC)

 tenofovir (TDF)

Rare cause of mitochondrial toxicity

 abacavir (ABC) 4%-6% Hypersensitivity-DRESS syndrome

 lamivudine (3TC)

 emtricitabine (FTC)

 tenofovir (TDF)

Withdrawal of these drugs may cause HBV exacerbation

NNRTIs

 nevirapine (NVP)

 efavirenz (EFV)

8%-16% Mechanism not known

 nevirapine (NVP) Rare Hypersensitivity – DRESS syndrome

PIs

 All PIs 4%-6% Mechanism unknown

 indinavir (IDV)

 atazanavir (ATV) 

10%-20%

30%-50%

Elevated indirect bilirubin; usually asyptomatic
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Chapter 10: Abnormal Laboratory Values in HIV Disease

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10

recommend pegylated interferon with subcutaneous 

injections once a week, although there are few published 

studies with this formulation for treatment of HBV. The 

second form of therapy is nucleosides and nucleotides 

with activity against HBV. This gets tricky because many 

of these agents are active against HIV as well, and 

there are variable rates of HBV resistance. Lamivudine 

(3TC) is highly active against HBV but is associated with 

high rates of HBV resistance, up to 90% at 4 years. 

The same applies to emtricitabine (FTC). Alternatives 

are adefovir dipivoxil (trade name Hepsera), which 

is used in a dose that is probably not active against 

HIV but is highly active against HBV, has good activity 

against lamivudine-resistant strains, and has low rates 

of resistance by HBV during treatment. Tenofovir (TDF) 

has the same attributes as adefovir but is also highly 

active against HIV. It should be emphasized that the 

rationale for treating HBV is to reduce viral replication 

and hepatic disease progression but that cure is rarely 

achieved. Other standard components of therapy in 

patients coinfected with HBV are 1) advising them to 

avoid or limit alcohol consumption, 2) teaching them 

appropriate precautions to prevent transmission of both 

viruses, and 3) administering hepatitis A vaccine if they 

are susceptible.

Who	should	receive	HBV	vaccine?

All HIV-infected persons with no evidence of HBV 

infection should receive this vaccine, although the 

response rates are related to age (decreased with 

increasing age) and with CD4 cell counts (responses 

decrease with lower counts). The standard is 3 doses 

followed by a measurement of HBs antibody levels 

about 1 month after the third dose. If the level is <10 

IU/mL the 3-dose series should be repeated. If the 

patient does not respond to the second series, no further 

vaccinations are currently recommended and the patient 

is considered a “non-responder.”

How	do	you	treat	patients	with	HCV	

coinfection?	

Patients coinfected with HIV and HCV should be 

1) advised to avoid or limit alcohol consumption, 

2) counseled to use appropriate precautions to 

prevent transmission of both viruses, and 3) given 

hepatitis A and B vaccine if they are susceptible. The 

prevention message should emphasize that the major 

route of transmission is by shared needles; the risk of 

transmission of HCV perinatally or with sexual contact is 

substantially less than that for HIV or HBV. 

With regard to treatment of HCV, the goal is for cure, 

something that cannot be achieved with HIV or, to a 

large extent, with HBV. All patients with HCV should be 

evaluated for HCV therapy. Standard indications in the 

absence of HIV infection are chronic HCV, detectable 

HCV-RNA, and a liver biopsy showing bridging or portal 

fibrosis. The ALT levels may be elevated, but this finding 

is variable and does not indicate the severity of HCVassociated liver disease and is considered nonspecific. 

The liver biopsy is important for HCV therapeutic 

decisionmaking, but it is indicated only if the patient is 

considered a candidate for treatment based on multiple 

variables including the severity and stability of HIV, 

other comorbidities, probability of adherence, and 

contraindications for interferon. The standard treatment 

is pegylated interferon plus ribavirin for 48 weeks, 

regardless of the genotype. There is limited long-term 

experience with this treatment in patients with HIV 

coinfection, but it appears that the rate of a sustained 

virologic response as indicated by negative HCV DNA 

levels at 6 months post-therapy are significantly lower 

compared to those who are seronegative for HIV. This 

particularly applies to genotype 1, which accounts for 

the majority of cases. It also appears that the optimal 

response occurs when patients have relatively high CD4 

cell counts, so this treatment is often preferred for those 

in early stage disease and for those who have responded 

to ART.

What	HCV	therapy	should	you	use	for	persons	

coinfected	with	HIV	and	HCV?

Currently, there are limited published data regarding 

various HCV treatment regimens for persons coinfected 

with HIV. Trials have generally shown relatively poor 

responses to interferon monotherapy. Based on rapidly 

accumulating data from trials that have not included 

HIV-infected persons, pegylated interferon (pegylated 

interferon-alpha-2a or pegylated interferon-alpha-2b) 

plus ribavirin is now the standard of care. (For treatment 

guidelines, refer to Suggested Resources.) In addition, 

several series involving persons coinfected with HIV 

and HCV have suggested better sustained viral response 

rates with pegylated interferon plus ribavirin than with 

older regimens. For persons not infected with HIV, 

recent guidelines have recommended that those with 

genotypes 2 or 3 receive 24 weeks of therapy and those 

with genotypes 1 and 4 receive 48 weeks of therapy. The 

optimal duration of therapy for persons coinfected with 

HIV and HCV remains unknown, but most trials have 

used 48 weeks, regardless of genotype. 
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Are	there	special	considerations	regarding	

adverse	effects	of	HCV	therapy	in	persons	

coinfected	with	HIV?

Treatment with interferon (or pegylated interferon) 

and ribavirin has significant possible adverse effects, 

including reactions at injection sites, bone marrow 

suppression, thyroid dysfunction, neuropsychiatric 

symptoms, and birth defects. Because interferon may 

cause significant leukopenia, CD4 cell counts should 

be monitored, and patients should be warned that 

CD4 counts might transiently decline while they are 

receiving interferon. Persons coinfected with HCV 

and HIV may suffer drug interactions and toxicities. 

Ribavirin causes anemia; because this complication 

occurs more frequently when ribavirin is combined 

with AZT, either this combination should be avoided 

or more frequent use of erythtopoetin should be 

anticipated. Ribavirin may enhance intracellular 

didanosine (ddI) levels and augment toxicity of the drug 

resulting with higher rates of pancreatitis and lactic 

acidosis; didanosine should not be given with ribavirin. 

Is	liver	transplantation	an	option	for	HIVinfected	persons?

Liver transplantation is an option in some transplant 

centers that combine expertise in HIV management 

with the transplant service. In a study at 5 institutions 

of 24 HIV-infected patients survival rates were similar 

to rates in patients without HIV infection (Ragni et al, 

2003). Nevertheless, management is complicated by 

problems of drug interactions between ART and the 

standard immunosuppressive agents, poor tolerance 

of ART after liver transplantation, and relatively high 

frequency of acute graft rejection. As in patients 

without HIV infection, the prognosis with liver 

transplantion is poorer when liver disease is caused 

by HCV. The recommendation at present is to give 

the highest priority in patients with HIV infection to 

those without HCV and to those receiving and tolerating 

ART who have achieved HIV virologic control and 

immune reconstitution.

RENAL DISEASE

What	are	the	possible	causes	of	abnormal	renal	

function	tests?

Renal function is important to monitor because 

abnormal renal function may require altering drug 

dosage regimens, and it is important to know the cause 

of the abnormality. In general, renal dysfunction in 

patients with HIV infection can be caused by adverse 

drug reactions, HIV-associated nephropathy, and nonHIV-related conditions. The multitude of conditions that 

are not necessarily complications of HIV infection or 

its treatment include hypertension, glomerulonephritis, 

and heroin use. 

For	the	patient	on	ART,	what	drugs	are	most	

likely	to	cause	renal	disease?

Adverse drug reactions that cause renal disease are 

most commonly associated with aminoglycosides, 

amphotericin, foscarnet, and cidofovir. The 

antiretroviral agent that is most frequently implicated 

is indinavir (IDV), which may cause indinavir crystals 

in the collection system, resulting in nephrolithiasis. 

The presentation may be renal colic, or it may be 

asymptomatic with evidence of crystals on urinalysis. 

In addition, indinavir can cause a crystal-induced 

nephropathy. On rare occasions, tenofovir (TDF) may 

cause renal insufficiency.

What	are	the	cause	and	implications	of	HIVassociated	nephropathy?

 HIV-associated nephropathy, which is apparently the 

result of HIV infection of the kidney, presents as large, 

echogenic kidneys on ultrasound, nephrotic-range 

proteinuria, and rapidly progressing renal failure. This 

may occur at any stage of HIV but is most common 

as a late complication. Pre-ART studies show benefit 

from treatment with ACE inhibitors and possibly with 

corticosteroids; more recent studies show anecdotal 

evidence of a sometimes dramatic response to ART, 

but data from controlled trials are not available. Renal 

biopsy is necessary to establish the diagnosis. For 

patients with end-stage renal disease, there is increasing 

interest in and experience with renal transplantation. 

The usual criteria are irreversible renal failure combined 

with HIV response to ART resulting in virologic control 

and a CD4 cell count of >200mm3. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 10: Abnormal Laboratory Values in HIV Disease

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KEY POINTS

Laboratory tests are frequently abnormal 

in HIV disease because 1) HIV is a 

multi-system disease, 2) HIV causes 

immune suppression that may result in 

opportunistic infections and tumors, 3) 

treatment has many potential adverse 

reactions affecting multiple systems, and 

4) patients with HIV are often at high risk 

for other medical conditions.

Hematologic complications 

include anemia, neutropenia, and 

thrombocytopenia. The most common 

causes of anemia and neutropenia are 

either drug toxicity or the direct effect 

of HIV on progenitor cells; the cause of 

thrombocytopenia is most commonly a 

direct effect of HIV.

Liver disease is common because of 

high rates of concurrent viral hepatitis, 

especially HCV, and because all 

antiretrovirals are potentially hepatotoxic.

Abnormal renal function is usually 

a direct effect of HIV infection of the 

kidneys resulting in a rapid progression 

with nephrosis and end-stage renal 

disease; abnormal renal function from 

any cause is important to know about 

because it requires altering dose regimens 

for nucleosides.

SUGGESTED RESOURCES

Kimmel PL, Barisoni L, Kopp JB. 

Pathogenesis and treatment of HIVassociated renal diseases. Ann Intern Med.

2003;139:214-226.

Lok ASF, McMahon BJ. AASLD Practice 

Guidelines Hepatology 2001;34:1225-

1241. Available at http://www.cdc.gov/

ncidod/diseases/hepatitis/b/hepatitis_b_

guidelines.pdf Accessed 1/04.

SUGGESTED RESOURCES

(CONTINUED)

Management of Hepatitis C: 2002. NIH 

Consensus and State-of-the-Science 

Statements. 2002 Jun 10-12;19:1-46. 

Available at: http://www.consensus.nih.gov. 

Accessed 12/03.

Ogedegbe AO, Sulkowski MS. 

Antiretroviral-associated liver injury. Clin 

Liver Dis. 2003;7:475-499.

Orenstein R. Presenting syndromes of 

human immunodeficiency virus. Mayo Clin 

Proc. 2002; 77:1093-1102.

Rockstroh JK. Management of hepatitis B 

and C in HIV co-infected patients. J Acquir 

Immune Defic Syndr. 2003;34 Suppl 1:S59-65. 

Sulkowski MS, Thomas DL. Hepatitis C in 

the HIV-infected person. Ann Intern Med

2003;138:197-207.

Volberding P. Consensus statement: 

anemia in HIV infection--current trends, 

treatment options, and practice strategies. 

Anemia in HIV Working Group. Clin Ther. 

2000;22:1004-1020.

WEBSITES

CDC National Center for Infectious 

Diseases: http://www.cdc.gov/ncidod/

diseases/hepatitis/ Accessed 2/04.

Hepatitis B Foundation: http://

www.hepb.org Accessed 2/04.

HIV and Hepatitis: http://

www.hivandhepatitis.com Accessed 2/04.
A Guide to Primary Care of People with HIV/AIDS

Chapter 10: Abnormal Laboratory Values in HIV Disease

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

10

REFERENCES

Ragni MV, Belle SH, Im K, et al. Survival of 

human immunodeficiency virus-infected 

liver transplant recipients. J Infect Dis. 

2003;188:1412-20.
A Guide to Primary Care of People with HIV/AIDS

Chapter 11: Postexposure Prophylaxis 

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11

OVERVIEW

What	is	postexposure	prophylaxis	(PEP)?

Postexposure prophylaxis (PEP) prevents or aborts 

transmission of HIV with rapid initiation of short-term 

antiretroviral therapy (ART) following occupational or 

nonoccupational exposure. PEP should be considered 

in all health care personnel (HCP) and non-HCP 

exposed to blood or potentially infectious body fluids 

via percutaneous, mucous membrane, and nonintact 

skin exposures, injection drug use, intentional or 

unintentional sexual exposures, and human bites. 

Hepatitis B infection may be prevented following 

administration of immune globulin and vaccination 

when indicated.

PEP policies should be instituted in all health care 

settings. The essential elements include: 

• Written protocols for documenting and managing 

exposures 

• Assessment, counseling, and intervention 

immediately after any exposure 

• Rapid access to medications and/or immunization, 

if indicated

What	do	we	know	about	the	effectiveness	

of	PEP	for	HIV?

Retrospective case-control studies support the efficacy of 

PEP for occupational exposure to HIV, and 4 factors are 

associated with increased transmission rates: 1) deep 

injury, 2) visible blood on device, 3) needle placement 

in artery or vein, and 4) late stage HIV disease in source 

(this risk factor was identified prior to viral load testing, 

thus high viral load is likely an independent risk factor). 

Evidence of the effectiveness of nonoccupational PEP 

comes from small observational human studies, 

extrapolation of data showing the interruption of 

maternal-infant transmission, and animal studies 

showing some degree of protection from genitally 

and intravenously acquired HIV. Even with optimal 

implementation, the degree of protection afforded by 

PEP is incomplete. Studies of PEP have demonstrated 

the greatest reduction in HIV transmission when 

antiretroviral medications are administered immediately 

after exposure to HIV-infected blood and body fluids. 

The efficacy of PEP is diminished after 36 hours and is 

minimal after 72 hours. 

What	do	we	know	about	the	effectiveness	

of	PEP	for	hepatitis	B	and	C?

Hepatitis B transmission can be prevented through 

administration of immune globulin and hepatitis B 

vaccine. PEP for hepatitis C virus (HCV) has thus far 

proven to be ineffective. 

What	body	fluids	are	infectious	for	HIV,	

HBV,	HCV?

Blood is the most infectious body fluid. In the health 

care setting, cerebrospinal, synovial, pleural, peritoneal, 

pericardial, and amniotic fluids are all considered 

potentially infectious, although the only documented 

cases of occupational HIV infection have been with 

blood, body fluids with visible blood, or HIV viral 

cultures. Unless there is visible blood with the exposure, 

saliva, nasal discharge, tears, sweat, vomit, urine, and 

feces are not infectious. Semen and vaginal secretions 

are infectious for HIV, HBV, and HCV in the setting of 

nonoccupational exposure.

Chapter	11:	

Postexposure	Prophylaxis Renslow Sherer, MD

Bruce D. Agins, MD, MPH

Caroline J. Teter, PA-C, MPH

OVERVIEW 

INTERVENTIONS FOR PEP IN HEALTH CARE SETTINGS

INTERVENTIONS FOR NONOCCUPATIONAL PEP (NPEP) 

HIV PEP TREATMENT RECOMMENDATIONS

HEPATITIS PEP TREATMENT RECOMMENDATIONS

KEY POINTS

SUGGESTED RESOURCES

REFERENCES

CASES
A Guide to Primary Care of People with HIV/AIDS

Chapter 11: Postexposure Prophylaxis 

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

11

INTERVENTIONS FOR PEP 

IN HEALTH CARE SETTINGS

What	types	of	exposures	merit	consideration	

of	PEP	in	health	care	personnel	(HCP)?

HCP are at increased risk from percutaneous, mucous 

membrane, and nonintact skin exposures to bloodborne 

pathogens, including hepatitis B, hepatitis C, and HIV. 

The risk of transmission is dependent on many factors, 

including the type, amount, route, and severity of 

exposure, the infection status of the source, and the HBV, 

HCV, and HIV immunity of the exposed worker (see 

Tables 11-1 and 11-2).

Table 11-1. High-risk 

Occupational Exposures

Exposures with higher risk of 

transmission of bloodborne pathogens

Deep percutaneous injury

Injury with a hollow-bore blood-filled needle

Exposure to blood of a patient in an advanced disease stage 

(high viral load)

Exposure to a large quantity of blood or body fluids

Table 11-2. Exposures with Low Risk of 

Transmission of Bloodborne Pathogens

Exposures with low risk of 

transmission (PEP not recommended)

Blood or fluid splashes on intact skin

Minor scratches or abrasions without evidence of percutaneous 

penetration

Penetration by small-bore needles without visible blood

An accurate history of the exposure is essential in 

determining the real risk of transmission. In studies, 

transmission of HIV by occupational exposure has an 

estimated 0.3% risk with percutaneous exposure and 

0.09% with mucous membrane splash (Bell, 1997). 

The risk of infection for HBV (in individuals who have 

not been vaccinated to hepatitis B, or who were vaccine 

unresponsive) after percutaneous exposure is 37%-62% 

when the source is hepatitis B surface antigen (HbsAg) 

positive and hepatitis B e antigen (HBeAg) positive, and 

the risk of developing clinical hepatitis is 22%-31%. 

When the source is HbsAg positive and hepatitis B e 

antigen negative, the risk of HBV seroconversion is 

1%-6%, and the risk of developing clinical hepatitis is 

23%-37%. The risk of transmission is higher, ie 22%-

31%, when the source has clinically evident hepatitis 

B hepatitis (Werner and Grady, 1982; CDC, 2001). 

Transmission of HCV through occupational exposure 

carries an average risk of 1.8%. 

What	are	immediate	actions	and	initial	

considerations	in	PEP	following	a	possible	

occupational	exposure?

First aid for the HCP is the first immediate action, 

followed by collection of information in order to assess 

the situation and make rapid decisions regarding 

appropriate treatment (see Tables 11-3, 11-4, and 11-5). 

Quick, expert action by the care provider is essential 

because the effectiveness of PEP is variable and 

depends on the inoculum, type of injury, potency of 

the PEP regimen, and speed with which treatment is 

started. The decision to prescribe medications, as well 

as medication administration, should be made within 

4 hours of the exposure, and must be made within 

72 hours, and preferably sooner because of studies 

suggesting that the efficacy of PEP is diminished after 

36 hours. Even with optimal implementation, ie within 

the first 4 hours, the protection afforded by PEP is not 

100%.

What	counseling	and	education	should	you	

give	the	HCP?

The exposed HCP needs immediate counseling to 

assist in coping with the emotional stress of the 

exposure, and may require follow up care by a mental 

health professional. Psychological services should be 

available 24 hours a day, 7 days a week. A local crisis 

management team or an employee assistance program 

(EAP) may be effective ways to address this need. 

The HCP should be told the relative risk of infection 

with HIV, HBV, and HCV following exposure, the 

effectiveness of PEP, and the risks and benefits of 

PEP. Exposed persons should be advised to return 

immediately if symptoms of acute HIV seroconversion 

occur, including fever, malaise, rash, swollen lymph 

nodes, fatigue or myalgias (most likely to occur 2-6 

weeks after exposure). 

Providers should advise exposed HCPs to prevent 

transmitting HIV to others, by means of the following 

measures, until the HCP has a negative HIV test 6 

months after exposure:

• Refrain from donating blood, plasma, organs, tissue, 

or semen.

• Use barrier protection during sexual activity. 

• If HCP is female, avoid pregnancy.

• If breast feeding, consider discontinuing, to avoid the 

risk of HIV transmission through breast milk. 

If exposed to HBV, the HCP should follow infection 

control procedures that are in place at the institution. 
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11

Table 11-3: Algorithm for Actions after Occupational Exposure to Blood or other Body 

Fluids Potentially Contaminated with Bloodborne Pathogens

1. Treat exposure site • Wash the exposure site immediately (not using soap). 

• Flush mucous membranes with water.

• Flush eyes with water or saline solution. 

• Do NOT apply caustic agents or antiseptics or inject disinfectants into the wound, because they may 

injure viable tissue and facilitate transmission. 

2. Gather information 

about the exposure

• Date and time of exposure

• Details of incident

• Where and how exposure occurred

• If related to a sharp device, type and brand

• Details of exposure

• Type and amount of fluid or material

3. Obtain information 

about the exposure 

source

• Determine if possible whether source materials contained HIV, HBV, or HCV (see Table 11-4).

• If the source patient is HIV-positive, obtain a history of the stage of disease, viral load, history of ART, 

and information on ART resistance.

4. Obtain information 

about the health care 

provider 

• Determine HIV status (rapid test, if possible) and, HBV vaccination and vaccine-response status (see 

Table 11-5).

• Obtain medical history, including pregnancy and breastfeeding.

5. Assess the indication 

for PEP 

• Using this information, assess the risk of exposure to HIV and decide whether PEP is warranted in this 

situation. 

• Assess the risk of exposure to HBV. 

6. Manage the exposure • Ensure appropriate and immediate access to informed counseling for all exposed HCPs, even when 

PEP is not recommended. 

• If treatment for exposure to HIV is indicated, initiate medication regimen as soon as possible, and 

definitely within 36 hours. Do not initiate treatment after 72 hours. 

• If treatment for exposure to hepatitis B is indicated, initiate treatment as soon as possible within 24 

hours of exposure; the efficacy of HVIG after 7 days is unknown. 

• Document counseling, postexposure management, and followup.

Table 11-4. Evaluation of Occupational Exposure Sources

Known sources

Test known sources for HbsAg, anti-HCV, and HIV antibody a, b:

• Direct virus assays for routine screening of source patients are not recommended.

• Use a rapid HIV-antibody test if available.

• If the source person is not infected with a bloodborne pathogen, baseline testing or further followup of the exposed person is not 

necessary.

For sources whose infection status remains unknown (eg, the source person refuses testing), consider medical diagnoses, clinical 

symptoms, and history of risk behaviors.

Do not test discarded needles for bloodborne pathogens.

Unknown sources

For unknown sources, evaluate the likelihood of exposure to a source at high risk for infection.

Consider likelihood of bloodborne pathogen infection among patients in the exposure setting.

a With attention to State regulations regarding confidentiality and informed consent. 

b If positive, confirmatory tests should be performed as appropriate including HBeAg, HIV Western blot, and HCV RNA.

Source: Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures 

to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR. 2001;50(RR11):20. 
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Table 11-5. Laboratory Evaluation and 

Followup of Exposed Health Care Personnel

Lab tests Comment Frequency

HIV antibody test Test HCP if source 

patient is HIV 

positive regardless 

of whether PEP is 

given

Baseline, 6 weeks, 

12 weeks, 6 

months (rapid 

test at baseline, if 

possible)

HBV Test if source 

patient is HBsAg or 

HBeAg positive

Baseline and 4-6 

months ( or 1-2 

months after last 

HBV vaccine)

Anti HCV Test if source 

patient is HCV 

positive

Baseline and 4-6 

months; HCV RNA 

at 4-6 weeks is 

optional

Liver enzymes Test if source 

patient is HCV 

positive

Baseline and 4-6 

months

CBC, renal 

function, and 

hepatic function

If PEP is warranted Prior to initiating 

PEP and repeated 

in 2 weeks

Are	there	special	considerations	for	PEP	in	

dental	set tings?

Although the number of exposures is relatively high 

in dental settings, the risk of transmission is low and 

no different from other HCP settings. Factors that are 

associated with increased risk of transmission are 

failure to follow PEP protocols, failure to use punctureproof containers, treating >20 patients per day, failure 

to use eye protection or masks, and male gender. For 

more information, see Suggested Resources.

INTERVENTIONS FOR

NONOCCUPATIONAL PEP 

(NPEP)

What	is	the	role	of	nPEP	for	nonoccupational	

exposure?

PEP for nonoccupational exposure to HIV (nPEP) is 

routinely being administered in cases of sexual assault 

in hospital emergency departments and is increasingly 

being made available during other cases of sexual 

exposure or injection drug use exposure and in nonhospital settings. This issue is particularly relevant in 

the care of HIV discordant couples. Research on risk 

of HIV transmission from a single nonoccupational 

exposure is relatively lacking compared with 

occupational exposures (see Table 11-6). A national 

registry has been developed to gather the data with 

which to develop a CDC recommendation for HIV PEP 

in the nonoccupational setting. Information about this 

registry can be found at http://www.hivpepregistry.org. 

In general, PEP for non-HCP is modeled after PEP 

interventions and procedures for HCP. 

Table 11-6. Estimated Risk of HIV Transmission 

Following Different Types of Exposures 

Type of exposure Estimated risk

Needle-sharing exposure with 

an infected source

0.67%

Receptive anal intercourse with 

an infected source

0.5%-3.0%

Receptive vaginal intercourse 

with an infected source

0.1%

Insertive anal intercourse with 

an infected source

0.065%

Insertive vaginal intercourse 

with an infected source

0.05%

Oral sex with ejaculation with 

an infected source

Conflicting data; however, 

risk is considered to be 

extremely low 

(<0.05%)

Source: Mayer KH, Anderson DJ. Heterosexual HIV transmission. 

Infect Agents Dis. 1995;4:273-284. 

What	needs	to	be	evaluated	for	the	possible	

administration	of	PEP	in	the	nonoccupational	

set ting?

Factors to be considered when considering PEP for 

nonoccupational exposure are similar to those for 

occupational exposure, including 1) HIV status of 

potentially exposed person (a rapid test can be done 

in 20 minutes), 2) timing (within 72 hours, with rare 

exception) and frequency of exposure (recurrent 

exposure would require ongoing PEP and suggests 

need for prevention counseling as the primary 

intervention), 3) HIV status of source (if unknown, 

PEP can be initiated while this is being assessed and 

discontinued if HIV infection of the source cannot 

be confirmed), 4) transmission risk of behavior (see 

Table 11-6), 5) presence of other sexually transmitted 

diseases, particularly genital ulcer disease (which can 

facilitate HIV transmission). Exposures to persons who 

have recently seroconverted may carry a higher risk of 

tranmission because of high HIV viremia. 
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Chapter 11: Postexposure Prophylaxis 

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11

What	is	the	role	of	PEP	for	discordant	couples?

Discordant couples (couples in which one person 

is infected and the other is not) should be routinely 

educated about how to protect the noninfected 

person. Both partners should be made aware of the 

possible effectiveness of PEP in cases of intended or 

unintended exposures and the importance of early 

initiation of PEP if it is to be used. Repeated, frequent 

exposures should signal providers to exercise caution 

about administration of PEP, since PEP should not be 

a substitute for avoidance of high-risk behavior. Any 

request for PEP should prompt additional counseling 

and psychosocial support to enhance behaviors to 

prevent HIV infection.

What	is	the	role	of	PEP	following	sexual	

assault?	

Persons who have been sexually assaulted should 

be considered at risk for HIV and HBV, as well as 

other STDs. The decision to begin PEP should not be 

based on the perpetrator’s likelihood of infectivity or 

delayed pending the test results of the source (unless 

immediately available). Pregnancy is an important 

consideration when considering PEP, and emergency 

contraception should be considered for women who 

have been sexually assaulted. 

A survivor of sexual assault may have had multiple 

exposures. When considering PEP, the most recent 

exposure should be considered, and PEP should be 

initiated if the exposure took place within 72 hours 

before the patient arrived at the health care facility. As 

with any consideration for PEP, weighing the benefits 

of PEP versus the possibility of medication side effects, 

the importance of completing the 28-day regimen and 

adherence issues should all be considered. 

The provider should be sensitive to the psychosocial 

needs of the person who was sexually assaulted; the 

patient may not be physically or emotionally able 

to weigh the pros and cons about beginning PEP. 

Therefore, it is important to follow up within 24 hours 

to either emphasize the importance of adherence or 

to continue the discussion about initiating PEP if is to 

occur within the 72-hour window.

See Suggested Resources for more information and 

resources in addressing issues of sexual assault.

What	if	the	person	who	is	exposed	is	a	minor?

In cases involving minors, parental or guardian 

participation is extremely important, but parental 

or guardian consent for PEP may not be required. 

Nonetheless, in all cases, parental or guardian 

participation should continue to be sought in the 

emergency situation and during followup. State laws 

and hospital policy must be considered.

HIV PEP TREATMENT

RECOMMENDATIONS

If	PEP	is	found	to	be	appropriate,	what	

information	does	the	exposed	person	need	

regarding	treatment?

The exposed person must understand the risks and 

benefits of HIV PEP, potential medication toxicities and 

side effects, instructions on how and when to take the 

medication, and the importance of adherence to the 

regimen, including completing the course of 28 days. 

Women should understand pregnancy-associated risks, 

including perinatal transmission and teratogenicity. 

Breast-feeding should be discontinued until the woman 

receives an HIV-negative result 6 months after exposure. 

What	are	HIV	treatment	recommendations	and	

options	for	PEP?

Currently recommended regimens are shown in Tables 

11-7, 11-8, and 11-9; however, these recommendations 

may be altered if the source patient has a history of 

ART or known viral resistance, is pregnant, breastfeeding, has hepatic or renal disease, or is taking certain 

medications. If viral resistance in the source patient is 

known or suspected, an HIV expert should be consulted 

prior to initiating HIV PEP medications. 

Basic HIV PEP regimens include 2 NRTIs. These 

regimens are relatively simple, ie 1 or 2 pills twice a 

day, well tolerated, and of sufficient potency to meet 

the needs of PEP. However, they are substantially less 

potent than 3-drug regimens. As noted below, some 

experts, including the authors, believe that only 3-drug 

regimens should be used for PEP, particularly in the 

current era of greatly simplified and somewhat better 

tolerated 3-drug regimens.

Three-drug regimens, comparable to highly active 

antiretroviral therapy (HAART) regimens used to 

treat HIV infection, are recommended for more 

severe exposures, which carry a higher risk of 

HIV transmission, or with exposures to sources 

with known HIV resistance mutations. The 3-drug 

regimens increase the risk of medication toxicity 

and may worsen adherence, all of which should be 

weighed when choosing an HIV PEP regimen. The 

majority of exposures in the past have resulted in the 

administration of 2 medications; 3-drug regimens 
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Table 11-7. Recommended HIV Postexposure Prophylaxis for 

Mucous Membrane Exposures and Nonintact Skin∞ Exposures

Infection Status of Sources

Exposure Type HIV-Positive Class 

1*

HIV-Positive Class 

2*

Source of unknown 

HIV status+ Unknown sourceØ HIV-Negative

Small Volume¶ Consider basic 2-

drug PEP

Recommend basic 

2-drug PEP

Generally, no PEP 

warranted; however, 

consider basic 2-drug 

PEP** for source with 

HIV risk factors§

Generally, no PEP 

warranted; however, 

consider basic 2-

drug PEP** in settings 

where exposure to 

HIV-infected persons 

is likely

No PEP warranted

Large Volume† Recommend basic 

2-drug PEP

Recommend 

expanded 3-drug PEP

Generally, no PEP 

warranted; however, 

consider basic 2-drug 

PEP** for source with 

HIV risk factors§

Generally, no PEP 

warranted; however, 

consider basic 2-

drug PEP** in settings 

where exposure to 

HIV-infected persons 

is likely

No PEP warranted

∞ For skin exposures, follow-up is indicated only if there is evidence of compromised skin integrity (e.g., dermatitis, abrasion, or open wound).

* HIV-Positive, Class 1 asymptomatic HIV infection or known low viral load (e.g., <1,500 RNA copies/mL). HIV-Positive, Class 2 – symptomatic HIV infection, AIDS, 

acute seroconversion, or known high viral load. If drug resistance is a concern, obtain expert consultation. Initiation of postexposure prophylaxis (PEP) should not be 

delayed pending expert consultation, and, because expert consultation alone cannot substitute for face-to-face counseling, resources should be available to provide 

immediate evaluation and follow-up care for all exposures.

+ Source of unknown HIV status (e.g., deceased source person with no samples available for HIV testing).

Ø Unknown source (e.g. splash from inappropriately disposed blood).

¶ Small volume (i.e., a few drops).

** The designation , “consider PEP,” indicates that PEP is optional and should be based on an individualized decision between the exposed person and the treating 

clinician.

§ If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued.

† Large volume (i.e., major blood splash).

Source: Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV 

and Recommendations for Postexposure Prophylaxis. MMWR 2001;50(RR11):25. 

Table 11-8: Recommended HIV Postexposure Prophylaxis for Percutaneous Injuries

Infection Status of Sources

Exposure Type HIV-Positive Class 

1*

HIV-Positive Class 

2*

Source of unknown 

HIV status+ Unknown sourceØ HIV-Negative

Less Severe¶ Recommend basic 

2-drug PEP

Recommend 

expanded 3-drug PEP

Generally, no PEP 

warranted; however, 

consider basic 2-drug 

PEP** for source with 

HIV risk factors§

Generally, no PEP 

warranted; however, 

consider basic 2-

drug PEP** in settings 

where exposure to 

HIV-infected persons 

is likely

No PEP warranted

More Severe† Recommend 

expanded 3-drug PEP

Recommend 

expanded 3-drug PEP

Generally, no PEP 

warranted; however, 

consider basic 2-drug 

PEP** for source with 

HIV risk factors§

Generally, no PEP 

warranted; however, 

consider basic 2-

drug PEP** in settings 

where exposure to 

HIV-infected persons 

is likely

No PEP warranted

* HIV-Positive, Class 1 asymptomatic HIV infection or known low viral load (e.g., <1,500 RNA copies/mL). HIV-Positive, Class 2 – symptomatic HIV infection, AIDS, 

acute seroconversion, or known high viral load. If drug resistance is a concern, obtain expert consultation. Initiation of postexposure prophylaxis (PEP) should not be 

delayed pending expert consultation, and, because expert consultation alone cannot substitute for face-to-face counseling, resources should be available to provide 

immediate evaluation and follow-up care for all exposures.

+ Source of unknown HIV status (e.g., deceased source person with no samples available for HIV testing).

Ø Unknown source (e.g. a needle from a sharps disposal container).

¶ Less severe (e.g., solid needle and superficial injury).

** The designation , “consider PEP,” indicates that PEP is optional and should be based on an individualized decision between the exposed person and the treating 

clinician.

§ If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued.

† More severe (e.g, large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or vein.

Source: Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV 

and Recommendations for Postexposure Prophylaxis. MMWR 2001;50(RR11):24. 
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Table 11-9. Treatment Options 

for 2- and 3-drug PEP

Treatment Options

Basic 

2-drug PEP

zidovudine (AZT) 300 mg bid + lamivudine 

(3TC) 150 mg bid (may be taken as Combivir 

bid)

stavudine (d4T) 40 mg bid + 3TC 150 mg bid

stavudine (D4T) 40 mg bid + didanosine (ddI) 

400 mg qd on an empty stomach (No longer 

recommended because of increased toxicity 

unless a suitable alternative is not available.)

3-drug PEP One of the above NRTI* combinations plus 

a third drug, usually a PI**, an NTRTI#,or an 

NNRTI,*** to be determined in consultation 

with an HIV expert.

nevirapine (NVP) (No longer recommended 

for PEP due to the potential for severe liver 

toxicity.) 

* NRTI: nucleoside or nucleoside reverse transcriptase inhibitor

** PI: protease inhibitor 

# NTRTI: nucleotide reverse transcriptase inhibitor, i.e., tenofovir (TDF)

*** NNRTI: non-nucleoside reverse transcriptase inhibitors, i.e., efavirenz (EFV) 

should be chosen with the advice of an HIV expert. 

In accordance with the same principles that are used 

in treating HIV-positive persons; some experts believe 

that 3-drug PEP regimens should be the mainstay of 

PEP and that 2-drug regimens should be used only 

during extenuating circumstances such as an inability to 

tolerate a protease inhibitor (PI). For example, the New 

York State PEP Guidelines now recommend zidovudine 

and lamivudine (Combivir) plus tenofovir (two pills in 

the morning and one pill in the evening) as the standard 

PEP intervention. (http:\\www.hivguidelines.org)

Although the current data on PEP for nonoccupational 

HIV exposures are scant, treatment recommendations 

for occupational PEP can be generalized to 

nonoccupationally exposed persons. As in the case of 

PEP in HCP, nonjudgmental counseling directed towards 

the reduction of future exposures is an important part 

of PEP in nonHCP.

What	are	the	side	effects	of	HIV	PEP?	

 Side effects of HIV PEP regimens are common and 

occur in 30%-50% of patients. Severe side effects 

occur in 5%-30% of patients and often require 

discontinuation. Common side effects include 

gastrointestinal symptoms such as nausea, vomiting, 

diarrhea, and abdominal pain; rash; fatigue; headache 

and dizziness; cytopenia; neuropathy; hepatitis; and 

many others. In reported series to date, over half of 

HCP in PEP programs fail to complete their 28-day 

regimens because of side effects. Regularly scheduled 

followup either in person or by phone has been 

shown to greatly improve adherence. Refer to other 

chapters for more detail on symptom management and 

metabolic complications with ART.

What	medication	toxicities	should	be	

monitored?	

Regular laboratory evaluation for medication toxicity 

and seroconversion should be performed (see Table 

11-5). A complete blood count and renal and hepatic 

function tests should be done before initiating PEP 

and repeated in 2 weeks. Continued monitoring 

is recommended for abnormal lab test results, 

and medication changes should be considered 

if abnormalities are severe. Specific monitoring 

parameters vary with the regimen; for example, glucose 

levels should be monitored if a PI is used. If the PI is 

indinavir (IDV) a urinalysis should also be checked to 

monitor for crystalluria and hematuria. Tenofovir (TDF) 

is well tolerated, but should be used with caution and 

careful monitoring in patients with compromised renal 

function (Refer to Drug Information Tables in the Pocket 

Guide for medication side effects.) 

Two regimens deserve special consideration. 

Hepatotoxicity, Stevens-Johnson syndrome, and fatal 

hepatic necrosis have occurred in HCP treated with 

nevirapine (NVP) as part of their PEP regimen, and 

therefore its use is not recommended, given the 

variety of other options. Pregnant women treated with 

stavudine (d4T) and didanosine (ddI) were found to be 

at increased risk for fatal and non-fatal lactic acidosis, 

and therefore this combination is not recommended 

in the treatment of pregnant women. In addition, 

recent clinical trial data showed a higher rate of 

adverse effects with the combination of stavudine and 

didanosine in adults, and their use in combination is 

not recommended unless other alternatives are not 

available.

What	are	the	treatment	recommendations	

when	the	source	patient	is	known	to	have	

specific	HIV	resistance	mutations?

Resistance to HIV medications is an important 

consideration in the treatment of HIV-positive persons, 

and known resistance in the source patient should be a 

consideration when choosing an appropriate HIV PEP 

regimen. In addition, because of reported increases in 

resistance mutations in recently acquired HIV infection 

in several cities in the United States, resistance is 

increasingly a concern in untreated patients, and thus 

for PEP in exposures to unknown sources. HIV PEP 

failures attributed to exposure to resistant virus have 

been reported in the literature. 
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Unfortunately, resistance test results are often 

unavailable at the time of the consideration of PEP, 

and PEP should not be unduly delayed while this 

information is sought. A thorough drug, adherence, and 

HIV history from the source patient and consultation 

with an HIV expert is needed to make the optimal 

treatment recommendation. 

When	should	expert	consultation	be	sought?

Expert consultation is potentially valuable in many 

circumstances with PEP. As above, expert consultation 

is indicated in the setting of known or suspected drug 

resistance in the source in order to select drugs to 

which the patient’s virus is likely to be susceptible. 

Other situations include:

• Delayed report of exposure, since the interval after 

which there is no benefit from PEP is undefined, in 

order to determine if PEP is still indicated

• Unknown status of the source, since the decision 

regarding the use of PEP should be individualized, 

based on the estimated likelihood of risk to the HCP, 

considering the severity of the exposure and the 

epidemiologic likelihood of HIV exposure

• Known or suspected pregnancy in the exposed 

person, in which case specific treatment 

recommendations may require modification 

• Possible toxicity of the initial PEP regimen, in which 

case modification of the regimen and/or treatment of 

the adverse side effect may be considered

HEPATITIS PEP 

TREATMENT

RECOMMENDATIONS

What	are	the	treatment	recommendations	and	

options	for	possible	hepatitis	B	exposure?	

HBIG and immunization against HBV following 

exposure are the most effective methods to prevent 

HBV transmission (see Table 11-10). PEP for HBV with 

multiple doses of HBIG has been shown to be 75%-

95% effective. Pregnant women can safely receive both 

the HBV vaccination and HBIG. When considering PEP 

for HBV exposures, both the source patient’s HbsAg 

status and the exposed person’s vaccination status and 

antibody response should be considered. Both HBIG 

and the hepatitis B vaccine should be administered 

within 24 hours of exposure. Anti-HBs should be drawn 

1-2 months after completion of the third vaccine, but it 

is unreliable if the exposed person has received HBIG 

within the past 3-4 months. 

Table 11-10. Recommended Postexposure 

Prophylaxis for Exposure to Hepatitis B Virus

Vaccination 

and antibody 

response 

status of 

exposed 

workers*

Treatment

Source 

HBsAg positive+

Source 

HBsAg+

negative

Source of 

unknown or 

not available 

for testing

Unvaccinated HBIG§ x 1 and 

initiate HR vaccine 

series¶

Previously vaccinated

Known 

responder**

No treatment No 

treatment

No Treatment

Known 

nonresponderØ

HBIG x 1 

and initiate 

revaccination or 

HVIG x 2†

No 

treatment

If know high risk 

source, treat as 

if sources were 

HBsAg positive

Antibody response 

unknown

Test exposed 

person for antiHBs¶¶

1. If adequate,** 

no treatment is 

necessary

2. If inadequateØ, 

administer HBIG x 1 

and vaccine booster

No 

treatment

Test exposed 

person for antiHBs

1. If adequate¶, 

no treatment is 

necessary

2. If inadequate¶, 

administer 

vaccine booster 

and recheck titer 

in 1-2 months

* Persons who have previously been infected with HBV are immune to 

reinfection and do not require postexposure prophylaxis.

+ Hepatitis B surface antigen.

§ Hepatitis B immune globulin; dose is 0.06 mL/kg intramuscularly.

¶ Hepatitis B vaccine.

** A responder is a person with adequate levels of serum antibody to HBsAg 

(ie, anti-HBs ≥ 10mlU/mL).

Ø A nonresponder is a person with inadequate response to vaccination (ie, 

serum anti-HBs < 10mlU/mL).

† The option of giving one dose of HBIG and reinitiating the vaccine series 

is preferred for nonresponders who have not completed a second 3-dose 

vaccine series. For persons who have previously completed a second vaccine 

series but failed to respond, two doses of HBIG are preferred.

¶¶ Antibody to HBsAg.

Source: Centers for Disease Control and Prevention. Updated U.S. Public Health 

Service Guidelines for the Management of Occupational Exposures to HBV, 

HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR 

2001;50(RR11):22. 

What	are	the	treatment	recommendations	and	

options	for	possible	hepatitis	C	exposure?

There are no recommended prophylactic treatments 

after exposure to HCV blood or body fluids. Current 

data do not support treatment during acute HCV 

infection at this time; referral of an individual with 

recently acquired HCV to a specialist in HCV care is 

appropriate.

Following exposure, testing should be performed 

on the source for anti-HCV. If positive, the exposed 

person should be tested for anti-HCV and alanine 
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aminotransferase (ALT) initially and in 4-6 months. 

HCV-RNA and ALT at 4-6 weeks are optional. All antiHCV results should be confirmed by recombinant 

immunoblot assay; if positive an HCV RNA should be 

drawn. Drawing an HCV RNA at 4-6 weeks may be 

done for earlier diagnosis, but the person should be 

counseled that false-positives do occur. Current research 

supports early diagnosis of HCV as basis for the most 

effective management after exposure are known. 

Exposed persons should be counseled to refrain from 

donating blood, plasma, organs, tissue, or semen. 

Although the transmission risk by sexual activity is 

low, it is reasonable to recommend a barrier method 

until the results of testing 6 months after exposure 

are known. There are currently no recommendations 

to make any changes in breast-feeding, pregnancy, or 

professional activities. Mental health counseling should 

be offered as needed.

KEY POINTS

The goals of PEP are to prevent or abort 

the transmission of HIV and hepatitis B 

virus (HBV) and to enable early diagnosis 

of hepatitis C virus (HCV). 

All exposed persons need followup within 

24-48 hours depending on the pathogen. 

HIV PEP, if determined to be appropriate, 

should be provided preferably 

immediately, and definitely within 

36 hours of exposure. PEP is NOT 

recommended for minor exposures. If the 

provider is inexperienced in using HIV 

medications or managing PEP patients, 

an HIV specialist should be consulted 

before initiating treatment.

The risk of transmission of HBV is far 

greater than of HIV or HCV. All HCPs 

should be vaccinated against HBV. 

HBIG is highly effective in preventing 

transmission of HBV.

There is currently no recommended 

PEP medication for HCV. If possible, the 

source should be tested for antiHCV, and 

if positive, the exposed person should be 

monitored.

PEP should be available in all health 

care settings. PEP protocols should 

be developed, regularly updated, and 

included in regular employee training 

programs. 

PEP for nonoccupational exposure (nPEP) 

is modeled after PEP for occupational 

exposures. nPEP is routinely administered 

in cases of sexual assault in emergency 

departments, and is increasingly being 

made available for other cases of sexual 

exposure or injection drug use exposure 

in non-hospital settings. 
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SUGGESTED RESOURCES

Guidelines for the Management of Occupational 

Exposures to HBV, HCV, and HIV and 

Recommendations for Postexposure Prophylaxis.

Available at http://aidsinfo.nih.gov/guidelines/.

PEP Steps–a pocket summary of the 2001 PEP 

Guidelines. Mountain Plains AIDS Education and 

Training Center. Available at http://www.uchsc.edu/

mpaetc/hivresources.htm or by telephone at 303-

315-2516. 

Practice recommendations for health-care facilities 

implementing the U.S. Public Health Service 

guidelines for management of occupational 

exposures to bloodborne pathogens. MMWR 

2001;50(RR-11):43-44. Available at http:

//www.cdc.gov/mmwr/preview/mmwrhtml/

rr5011a2.htm.

Recommendations for the Use of Antiretroviral 

Drugs in Pregnant HIV-1 Infected Women for 

Maternal Health and Interventions to Reduce 

Perinatal HIV-1 Transmission in the United States. 

Available at http://www.hivatis.org. 

WEBSITES

Food and Drug Administration: http://www.fda.gov. 

Accessed 1/04.

Hepatitis information: http://www.cdc.gov/hepatitis. 

Accessed 1/04.

HIV PEP registry, for nonoccupational exposures: 

http://www.hivpepregistry.org. Accessed 1/04.

National Rape, Abuse, & Incest National Network: 

http://www.rainn.org/. Accessed 1/04.

Needlestick website, a web-based expert system 

to help providers manage and document 

occupational exposures to blood and bodily fluids: 

http://www.needlestick.mednet.ucla.edu. 

Accessed 1/04.

New York State Department of Health 

AIDS Institute, PEP guidelines: http://

www.hivguidelines.org. Accessed 1/04.

STD/HIV Prevention Training Centers (PTCs): http:

//depts.washington.edu/nnptc Accessed 10/03.

Contact State and local health departments for 

additional information.

TELEPHONE

National Rape Crisis Hotline: 1-800-658-HOPE. 

National Clinicians’ Post-Exposure Prophylaxis 

Hotline (PEPline), expert consultation for providers 

on occupational exposures to bloodborne 

pathogens: 1-888-HIV-4911 (1-888-448-4911 

or http://www.ucsf.edu/hivcntr/resources/pep. 

Accessed 1/04.

Warmline: National HIV telephone consultation 

service: 1-800-933-3413

REFERENCES

Bell DM. Occupational risk of human 

immunodeficiency virus infection in 

healthcare workers: an overview. Am J Med.

1997;102(suppl 5B):9-15. 

Cardo DM, Culver DH, Ciesielski CA, et al. 

A case-control study of HIV seroconversion 

in health care workers after percutaneous 

exposure. N Engl J Med. 1997;337:1485-1490. 

Centers for Disease Control and Prevention. 

Updated guidelines for the management of 

occupational exposures to HBV, HCV, and 

HIV and recommendations for postexposure 

prophylaxis. Public Health Service. MMWR. 

2001:50(RR11):1-42.

Centers for Disease Control and Prevention. 

Management of possible sexual, injectingdrug-use, or other nonoccupational 

exposure to HIV, including considerations 

related to antiretroviral therapy. Public 

Health Service Statement. MMWR. 1998; 

47(RR-17):1-14.

Centers for Disease Control and Prevention. 

Recommendations for the prevention and 

control of hepatitis C virus (HCV) infection 

and HCV-related chronic disease. MMWR. 

1998; 47(RR-19):1-39.

Gerberding JL. Occupational exposure to 

HIV in health care settings. N Engl J Med.

2003;348:826-833.

New York State Department of Health AIDS 

Institute. HIV PEP Guidelines. Available at 

http://www.hivguidelines.org Accessed 1/04.

Mayer KH, Anderson DJ. Heterosexual HIV 

transmission. Infect Agents Dis. 1995;4:273-284.

Stephenson J. PEP talk: treating 

nonoccupational HIV exposure. JAMA. 

2003;289:287-288.

Werner BG, Grady GF. Accidental hepatitis-Bsurface-antigen-positive inoculations: use of 

e antigen to estimate infectivity. Ann Intern 

Med. 1982;97:367-369. 
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CASES

1.	

An employee states that she has just punctured herself with a needle after drawing a patient’s blood. The 

patient has already left the clinic and no one knows anything about his medical history. The employee 

completed the HBV vaccination series and is hepatitis B surface antibody (HBsAb) positive. During the 

investigation the HIV prevalence in this setting was found to be low. 

Question:	What is the risk of HIV transmission?

Answer:	

The risk of HIV transmission after a puncture wound with a hollow-bore needle is 0.3%. It is important to 

remember that the risk of infection is higher when there is a large-volume exposure, a deep percutaneous 

injury, or an injury with a hollow-bore, blood-filled needle, or if the source has advanced HIV disease 

or has a high level of HIV viremia. The current CDC recommendations advise against HIV PEP when the 

source is unknown and in settings where the HIV prevalence is low.

Question:	What counseling and followup should be recommended?

Answer:	

Because of the low prevalence of HIV in this setting, the employee should be advised against taking HIV 

medications. Also, because she is HBsAb positive she is not a candidate for HBV PEP. The HCP should be 

advised to refrain from donating blood, plasma, organs, or tissue, to use barrier methods during sexual 

activities, and to refrain from sharing any injection or other drug use equipment. She should also be 

counseled about universal precautions and administration should take steps to reduce the risk of future 

accidental needle sticks. She should be educated about the symptoms of acute HIV and advised to return 

immediately if those symptoms occur. Mental health counseling should also be offered.

A baseline HIV antibody and anti-HCV should be drawn. HIV anibody should be repeated at 6 weeks, 3 

months and 6 months after exposure. A 12-month followup is recommended if the source is found to be 

coinfected with HIV and HCV, or if the exposed becomes infected with HCV following exposure. Anti-HCV 

and ALT should be repeated within 4-6 months and if positive should be confirmed with supplemental tests. 
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2.

A patient known to be HIV negative 6 months ago comes to the clinic stating that last night he was the 

receptive partner of unprotected sexual intercourse with his HIV-positive partner when the condom broke. 

His partner has been HIV-positive for 5 years, currently has an undetectable viral load, and is taking 

Combivir (zidovudine + lamivudine) and efavirenz (EFV). He has never had a resistance test. 

Question:	Should the patient take HIV PEP medications?

Answer:	

Although the current recommendations for nonoccupational exposures were released in 1998 and at that 

time found that PEP for nonoccupational HIV exposure was still unproven, current data support treating. 

Receptive anal intercourse with an HIV-positive partner carries with it a risk of transmission of 0.5%-3.0%. 

Your patient’s risk is likely lower because of his partner’s low level of viremia. PEP in nonoccupational 

settings is modeled after PEP for HCPs. In this case, the patient had a large exposure from a known HIVpositive source with an undetectable viral load. 

Following the model for PEP for HCPs, the patient should be treated ASAP, ie within 4 to 72 hours but not 

more than 72 hours after exposure and receive 2 medications, although some experts would recommend 

using 3 medications. It would be reasonable to place the patient on the same combination as his partner 

because his partner has exhibited good adherence and good virologic control. Treatment should continue 

for 28 days. 

The patient should be counseled about medication side effects and the importance of adherence and 

followup. Common side effects should be anticipated and pre-empted with counseling and, in some cases, 

treatment. Changing medications and/or modifying the dosage regimen may increase the likelihood of 

completion of the HIV PEP regimen. And finally, the patient should be educated about the symptoms of 

acute HIV infection and advised to return immediately if those symptoms occur.

Question:	What lab specimens should be drawn?

Answer:

A baseline HIV Ab should be drawn and repeated at 6 weeks, 3 months, 6 months and 12 months after 

exposure, as well as an HBsAg, HBsAb, and HCV Ab. If he were unvaccinated against HAV or HBV then 

vaccination should be initiated immediately. Laboratory monitoring for drug toxicity should be performed 

at baseline and then 2 weeks after initiating therapy. The medical record of the patient’s partner should 

immediately be reviewed, and treatment for HBV, HCV, or other sexually transmitted diseases should occur, 

if any of these are found. Expert consultation should be sought if needed.
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CARE OF HIV-POSITIVE

WOMEN OF CHILDBEARING

AGE

When	should	you	provide	pregnancy	counseling	

to	women	living	with	HIV	who	are	of	

childbearing	age?

More than half the pregnancies in the United States are 

unplanned. For women living with HIV, education and 

counseling about pregnancy and HIV should be done 

early in the course of HIV care, not delayed until the 

woman is pregnant, so that she can make informed 

decisions about contraception and pregnancy. Many 

women with HIV mistakenly assume they cannot get 

pregnant and need to be educated before it is too late. 

What	counseling	interventions	should	be	

included	in	primary	care?

All women of childbearing age should receive the 

benefit of preconceptional counseling as part of routine 

primary medical care (ACOG, 1995). Women who have 

HIV should also be counseled about:

• The impact of HIV on the course and outcome of 

pregnancy 

• The impact of pregnancy on HIV progression

• Appropriate contraception to prevent unintended 

pregnancies

• Perinatal transmission risks, including strategies to 

reduce the risk of perinatal transmission

• Permanency planning (guardian issues for children)

What	primary	care	interventions	are	

appropriate	for	women	with	HIV	who	want	to	

become	pregnant?

Certain measures can help facilitate a successful 

pregnancy if a woman with HIV wants to become 

pregnant:

• Institute routine preconceptional care such as genetic 

screening, screening for STDs, PAP smear, and 

initiation of folic acid supplementation.

• For women already on antiretroviral therapy (ART) 

or who have indications for therapy, ensure that 

medications are not contraindicated in pregnancy 

(efavirenz [EFV] is contraindicated) and optimize 

therapy to reduce viral load and reduce side effects.

• Vaccinate as indicated.

• Optimize maternal nutritional status.

• Screen for psychological and substance abuse 

disorders and treat.

• Refer for perinatal consultation as needed.

Are	there	options	for	HIV-positive	individuals	

who	are	considering	reproduction?	

There are centers in the United States and in Europe 

that provide “sperm washing” to decrease the 

possibility of HIV transmission to the woman during 

planned conception. However, this method has not 

been well studied and, as a practical matter, is not 

available to most HIV discordant couples (Kim et al, 

1999). Discordant couples who choose to become 

pregnant need to be educated about the risk of HIV 

transmission. To reduce the risk if the man is HIVpositive, his viral load should be as low as possible, 

Chapter	12:	

Family	Planning	and	Pregnancy	

María del Carmen Ríos, MD, MPH

José Rafael Morales, MD, FACOG

CARE OF HIV-POSITIVE WOMEN OF CHILDBEARING AGE

PREVENTING MOTHER-TO-CHILD TRANSMISSION (MTCT) 

PERINATAL CARE FOR PREGNANT WOMEN WITH HIV

KEY POINTS

SUGGESTED RESOURCES

REFERENCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 12: Family Planning and Pregnancy

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

12

intercurrent STDs should be treated, and attempts to 

conceive should be well timed around ovulation to avoid 

unnecessary exposures during periods of decreased 

fertility. The American College of Obstetricians and 

Gynecologists has recently endorsed the use of 

reproductive technology in HIV-infected patients (ACOG, 

2004). Which patients should be offered assisted 

reproduction and what the optimal methods are of 

decreasing heterosexual and perinatal HIV transmission 

must be determined. 

When	should	pregnancy	testing	be	done?	

Since most pregnancies are unplanned, the diagnosis of 

pregnancy frequently occurs late in the first trimester, 

when organogenesis is nearly complete. In order to 

make the diagnosis earlier, pregnancy tests should be 

done when sexually active women have: 

• Late or missed menses (unless she is using Norplant 

or Depo-Provera)

• Irregular bleeding (unless she is using Norplant or 

Depo-Provera)

• New onset of irregular bleeding after prolonged 

amenorrhea with Norplant/Depo-Provera

• New onset of pelvic pain

• Enlarged uterus or adnexal mass on exam

In addition, women with the potential of becoming 

pregnant should be tested before starting potentially 

teratogenic therapies such as efavirenz (EFV), which 

is the only antiretroviral drug that is contraindicated 

in pregnancy. Patients should be alerted to potential 

teratogenic effects on the fetus, and suitable 

contraception should be prescribed. 

What	contraceptive	methods	are	recommended	

for	women	with	HIV	who	do	not	want	to	

become	pregnant?

Condoms are the most common contraceptive method 

used by women living with HIV. Condoms, consistently 

used, have the added advantage of providing protection 

against STDs, including potential reinfection with HIV. 

This benefit should be emphasized when contraceptive 

advice is given to an HIV-positive or at-risk woman even 

if she is not seeking or does not need contraception but 

is sexually active.

Hormonal methods of contraception are also frequently 

used (delivered orally, by injection, or by skin patch). 

However, there are many important drug interactions 

between hormonal contraceptives and drugs used to 

treat HIV infection and HIV-related complications (see 

next question). 

What	are	the	most	common	drug	interactions	

between	oral	contraceptives	and	drugs	used	in	

HIV	disease?	

Oral contraceptives significantly interact with 

amprenavir/fosamprenavir (APV/FAPV), efavirenz (EFV), 

lopinavir (LPV), nelfinavir (NFV), nevirapine (NVP), and 

ritonavir (RTV); an additional method of contraception, 

such as condoms, is recommended. Similarly, other 

drugs commonly used by HIV-infected patients, 

including tetracycline, rifampin, oral anticoagulants, 

beta-blockers, and antidepressants interact with 

oral contraceptives, and an additional means of 

contraception is advisable. Indinavir and atazanavir do 

not appear to have an interaction. 

What	contraceptive	methods	are	not	highly	

recommended	for	women	with	HIV	who	do	not	

want	to	become	pregnant?

Spermicides: Generally, a spermicide should be 

used along with a barrier method to increase its 

effectiveness. However, in some studies nonoxynol-9 

(the active ingredient in spermicidal contraceptives) 

has been found to cause vaginal irritation and epithelial 

inflammation when used as the sole contraceptive 

method and on a regular and frequent basis. This may 

increase the risk of HIV transmission. 

Intrauterine Device: The intrauterine device (IUD) is 

not recommended for HIV-infected women. The IUD is 

associated with pelvic inflammatory disease and is also 

associated with increased menstrual flow. Some studies 

even suggest that this device is linked to increased 

susceptibility to HIV transmission.

PREVENTING MOTHER- TO-CHILD TRANSMISSION

(MTCT)

Which	are	the	current	recommendations	for	

HIV	testing	of	pregnant	women?	

Since prevention of vertical transmission (from mother 

to child) of HIV is so effective, identification of HIV 

infection in all women who are pregnant is imperative. 

Therefore:

• HIV testing should be a routine part of prenatal care 

for all women. The “opt out” method, in which HIV 

testing is included in the routine bloodwork and 

pregnant women have to refuse the test, results in 

higher test rates and should be used. 
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Chapter 12: Family Planning and Pregnancy 

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12

• Testing should be performed as early as possible 

in pregnancy to allow for timely interventions and 

decisions.

• HIV-negative women who are at high risk of acquiring 

HIV should be retested in the third trimester of 

pregnancy (ideally before 36 weeks). Women are at 

high risk if they have a history of STDs, exchange sex 

for money or drugs, have multiple sex partners during 

pregnancy, use illicit drugs, have HIV-positive or highrisk sex partners, and/or show signs and symptoms of 

seroconversion.

• Women whose HIV status is unknown and/or who 

present late in pregnancy or already in labor should 

be assessed promptly for HIV infection, using rapid 

HIV testing, to allow for timely prophylactic treatment. 

Standard confirmatory tests should be done after 

delivery for women with positive rapid test results.

• CDC recommends timely, routine screening of an 

infant if the mother has not been tested during 

pregnancy or delivery (CDC, 2003). 

How	should	HIV	testing	be	done?

HIV testing should be voluntary, and providers should 

carefully document informed consent. Providers 

should offer pre- and post-test counseling that includes 

information on modes of transmission of the virus, risk 

factors that might be present even if a woman has only 

one sex partner, and effective interventions to reduce 

the risk of perinatal transmission of HIV. There should 

be a discussion of services available for the provision 

of medical care, and the woman should be reassured 

that care for her and her infant will not be denied if she 

declines the test. Laws and regulations on HIV screening 

of pregnant women and their infants vary by State. 

Therefore, providers should be familiar with the State 

regulations and policies that apply to them (CDC, 2001). 

When	does	transmission	from	mother	to	

infant	occur	and	what	are	risk	factors	for	

transmission?

Vertical transmission can occur during the perinatal 

period and infancy, that is, before or close to the time 

of birth or during breastfeeding. Risk factors associated 

with vertical transmission include (CDC, 2001):

• Advanced disease in the mother

• High plasma viral load

• Maternal injection drug use during pregnancy 

• Preterm delivery

• HCV coinfection

• Failure to follow the recommended regimen of 

zidovudine prophylaxis

• Breast-feeding 

• Delivery more than 4 hours after rupture of 

membranes 

• Concurrent STDs 

• Chorioamnionitis 

• Certain obstetrical procedures 

How	common	is	vertical	transmission	of	HIV	

with	and	without	ART?	

In the absence of antiretrovirals, the perinatal 

transmission rate of HIV infection is approximately 

25%. There is a direct correlation between maternal 

viral load as measured by plasma HIV-1 RNA and 

probability of perinatal transmission. A large study 

showed that the rate of perinatal transmission among 

women with viral load >100,000 c/mL was 40.6%, 

with 50,001 to 100,000 c/mL it was 30.9%, with 10,001 

to 50,000 c/mL it was 21.3%, with 1,000 to 10,000 

c/mL it was 16.6%; and with <1,000 c/mL it was 0% 

(Garcia et al, 1999).

 Treatment with zidovudine (AZT) alone can reduce 

transmission to close to 8%. Multi-agent antiretroviral 

therapy can reduce the transmission rate even further 

(see Table 12-1). 

Table 12-1. Antiretroviral Treatment and 

Perinatal Transmission

Treatment 

category

Number 

treated

HIV 

transmission rate

(95% confidence interval)

Untreated 396 20.0% (16.1, 23.9)

AZT monotherapy 710 10.4% (8.2, 12.6)

Dual therapy, nonHAART186 3.8 % (1.1, 6.5)

HAART 250 1.2% (0, 2.5)

Source: Cooper ER, Charurat M, Mofenson L, et al. Combination 

antiretroviral strategies for the treatment of pregnant HIV-1-infected 

women and prevention of perinatal HIV-1 transmission. J Acquir 

Immune Defic Syndr. 2002;29:484-494.

Do	pregnant	women	with	very	low	or	

undetectable	viral	loads	need	ART?

Yes. All pregnant women should receive ART. Analysis 

of the first study of the effectiveness of ART in reducing 

perinatal transmission (ACTG 076 study) showed 

that zidovudine (AZT) significantly reduced perinatal 

transmission even when the baseline viral load was 

<1,000 c/mL (Ioannidis et al, 2001). This study 

provides the rationale for zidovudine monotherapy in 

untreated pregnant women with a baseline viral load of 

<1,000 c/mL. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 12: Family Planning and Pregnancy

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

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What	pharmacologic	interventions	are	

recommended	to	reduce	the	risk	of	MTCT?

ART should be offered to all HIV-infected pregnant 

women, and zidovudine chemoprophylaxis should be 

incorporated into the antiretroviral regimen to prevent 

perinatal transmission because safety and efficacy data 

are greatest for zidovudine (PHS, 2002) (see Pocket 

Guide Pregnancy Table 1). Zidovudine prophylaxis 

is associated with significant reduction in perinatal 

transmission that is independent of viral load (Sperling, 

1996; Shapiro et al, 1999) and of zidovudine resistance 

(Eastman et al, 1998). 

Are	there	additional	interventions	to	reduce	

the	risk	of	MTCT	and	improve	maternal/fetal	

health?

When the woman is HIV positive there are interventions 

that can reduce the risk of MTCT. 

• Pregnant women with HIV should be counseled to 

refrain from cigarette smoking, injection and illicit 

drug use, and unprotected sexual intercourse with 

multiple sex partners. 

• STDs in pregnancy should be treated since they are 

associated with a higher risk of vertical transmission. 

Can	cesarean	section	reduce	the	risk	of	MTCT?	

Elective cesarean section reduces the risk of perinatal 

transmission and should be offered at 38 weeks to 

pregnant women when the viral load is likely to be 

>1,000 c/mL at delivery (Dominguez, 2003). ACOG 

in a joint statement with the American Academy of 

Pediatrics (AAP) recommended offering HIV-positive 

pregnant women scheduled cesarean section at 38 

weeks gestation (AAP, ACOG, 1999; CDC, 2001), rather 

than waiting until 39 weeks. There is no evidence of 

benefit of C-section after onset of labor, after rupture of 

membranes, or in women with viral loads of <1000 c/mL. 

What	interventions	should	occur	during	a	

scheduled	cesarean	section?

When a scheduled cesarean section is planned, 

intravenous zidovudine should start 3 hours before 

surgery according to standard dosing (see Pocket 

Guide Pregnancy Table 5). Since infectious morbidity is 

potentially increased, the obstetrician should consider 

antibiotic prophylaxis. Other antiretrovirals should not 

be interrupted at the time of delivery regardless of route 

of delivery. 

What	should	you	advise	mothers	about	

breastfeeding?	

The risk of HIV transmission with breastfeeding is 

approximately 16%. Avoidance of breastfeeding 

is recommended in the United States and other 

industrialized countries since replacement feeding is 

safe and accessible. In resource-poor countries where 

risks of replacement feeding include malnutrition 

and infections other than HIV, the World Health 

Organization recommends exclusive breastfeeding 

during the first 3 months of life since exclusive 

breastfeeding carries a lower risk of HIV transmission 

than mixed feeding. To minimize the risk of HIV 

transmission in these settings, breastfeeding by HIVpositive women should be discontinued as soon as 

feasible, taking into consideration local circumstances 

and the risks of replacement feeding (WHO, 2001).

What	testing	should	neonates	of	HIV-positive	

mothers	receive?

When neonates are born to HIV-positive mothers, serial 

testing for HIV should be done within the first few days 

of life, at age 1 month, and again at 4-6 months or 

later (AAP, ACOG, 2002). Early identification of HIV in 

neonates is crucial for adequate management. Since 

maternal antibody may be present, HIV antibody 

testing is not useful until the baby is 18 months old. 

Using either HIV-DNA PCR or HIV culture, however, 

pediatricians can usually determine the HIV status of 

infants by the age of 4 months.

PERINATAL CARE FOR

PREGNANT WOMEN

WITH HIV

What	medical	and	counseling	interventions	are	

appropriate	for	pregnant	women	with	HIV?

Initial evaluation of an HIV-positive pregnant woman 

should include an assessment of her HIV disease status. 

Besides the standard components of prenatal care 

indicated for all pregnant women, the provider should 

obtain CD4 cell counts and viral loads, and resistance 

tests should be performed. Viral loads and CD4 counts 

should be repeated every 3 months. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 12: Family Planning and Pregnancy 

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12

The goals of ART during pregnancy are to: 

• optimize the health of the woman

• protect the fetus from HIV

• provide regimens that are neither toxic for the woman 

nor teratogenic for the fetus. 

Clinicians should discuss short- and long-term 

benefits and risks for both the woman and the fetus 

before initiating or modifying ART. Options should be 

presented in a non-coercive way, and the final decision 

always lies with the patient. A long-term plan should 

be developed, and the importance of adherence to ART 

should be stressed.

What	antiretroviral	regimens	are	

recommended	for	pregnant	women	with	HIV?

The use of the 3-part zidovudine (AZT) 

chemoprophylaxis regimen, alone or in combination 

with other antiretroviral agents, should always be 

offered and discussed with all infected pregnant 

women to reduce the risk of perinatal HIV transmission 

(see Pocket Guide Pregnancy Table 3). Any pregnant 

woman with HIV should be offered a treatment 

regimen that adheres to the currently recommended 

treatment for HIV-infected adults, which generally 

consists of 2 reverse transcriptase inhibitors into which 

zidovudine is incorporated, plus a protease inhibitor 

(see Pocket Guide Pregnancy Table 4). Efavirenz (EFV) 

is contraindicated in the first trimester because it has 

been associated with birth defects in a monkey model. 

Referral to providers who are experienced in the care of 

pregnant HIV-infected women is recommended.

Are	there	special	considerations	when	a	woman	

already	on	ART	becomes	pregnant?

When an HIV-infected women receiving ART is found 

to be pregnant after the first trimester she should be 

counseled to continue therapy. Zidovudine should be 

a component of the antenatal ART regimen after the 

first trimester whenever possible, although this may 

not always be feasible. A woman receiving ART whose 

pregnancy is recognized during the first trimester 

should be counseled regarding the benefits and 

potential risks of continuing ART during this period 

of organogenesis. As discussed above, efavirenz (EFV) 

is contraindicated in the first trimester. Also, dapsone, 

a folic acid antagonist, has been reported to 

increase the risk for neural tube defects. Maternal 

absorption and metabolism of protease inhibitors 

(PIs) change during pregnancy, and there are specific 

recommendations for dose adjustments of nelfinavir 

(NFV) (http://www.aidsinfo.nih.gov). 

What	are	some	of	the	problems	that	may	occur	

when	antiretroviral	agents	are	prescribed	

during	pregnancy?

Hyperglycemia and diabetic ketoacidosis have been 

reported with PI use during pregnancy. Therefore, 

pregnant women using PIs should be carefully 

instructed to watch for symptoms of hyperglycemia, 

and blood glucose levels should be closely monitored.

Lactic acidosis is more common in the last trimester 

of pregnancy, and hepatic enzymes and serum 

electrolytes should be monitored frequently during the 

last trimester in pregnant women receiving nucleoside 

analogues. The combination of stavudine (d4T) and 

didanosine (ddI) in HIV-positive pregnant women is not 

recommended as it has been associated with maternal 

mortality from severe lactic acidosis.

Hyperemesis gravidarum is a common complication 

of pregnancy. If a women needs to discontinue ART 

because of pregnancy-related hyperemesis, she should 

not restart medications until sufficient time has elapsed 

to ensure that the drugs will be tolerated; all drugs should 

be stopped at once and reintroduced simultaneously to 

reduce the potential for emergence of resistance.

What	medical	and	counseling	interventions	are	

appropriate	for	postpartum	followup	of	women	

with	HIV?

Comprehensive care and support services, including 

primary, obstetric, pediatric, and HIV specialty care, 

family planning services, mental health and substance 

abuse treatment, and coordination of care through case 

management for the woman, her children, and other 

family members are important for women with HIV 

and their families. Maternal medical services during the 

postpartum period must be coordinated between the 

obstetric care provider and the HIV specialist. When 

treatment is required for the woman’s HIV infection, 

continuity of ART must be assured.

What	followup	should	be	done	for	the	infants	

of	mothers	with	HIV?

Infants of HIV-positive women on ART should be 

followed for potential side effects of antiretroviral 

medications even if the infants are HIV-negative; 

followup should continue into adulthood because of the 

theoretical concerns regarding potential carcinogenicity 

of the nucleoside analogue antiretroviral drugs. Infected 

children should be followed to determine their need 

for prophylactic treatment or ART, as well as to assess 

possible delays in growth and development.
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Chapter 12: Family Planning and Pregnancy

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

12

Where	should	prenatal	exposure	cases	be	

reported?

Cases of prenatal exposure should be reported to the 

Antiretroviral Pregnancy Registry. This registry collects 

anonymous observational data. The Registry can be 

contacted at: 

Antiretroviral Pregnancy Registry

115 N. Third St., Suite 28401

Wilmington, NC 28401

Tel: 800-258-4263

FAX: 800-800-1052

KEY POINTS

All HIV-positive women of childbearing 

age should receive information about the 

impact of HIV on the course and outcome of 

pregnancy, the impact of pregnancy on HIV 

progression, and appropriate contraception 

to prevent unintended pregnancy.

To assure early identification of pregnancy 

in women with HIV who are sexually active, 

pregnancy tests should be done whenever 

they have late or missed menses or other 

signs of possible pregnancy. Women 

with the potential of becoming pregnant 

should be tested before starting potentially 

teratogenic therapies such as efavirenz 

(EFV). Patients should be alerted on potential 

teratogenic effects on the fetus, and suitable 

contraception should be prescribed.

Contraceptive methods recommended for 

women with HIV include condoms, which 

also protect against STDs and prevent 

HIV transmission to their partners, and 

hormonal methods. The drug interactions 

between oral contraceptives and many 

drugs used in HIV disease make an 

additional means of contraception advisable 

in many cases. Spermicides and intrauterine 

devices are not recommended for use by 

HIV-infected women.

HIV testing should be a routine part of 

prenatal care for all women. HIV testing 

should be voluntary using the “opt out” 

method (the HIV test is part of routine 

bloodwork and the woman may opt to 

refuse the test). Pre- and post-test HIV 

counseling should be provided.

All pregnant women infected with HIV 

should receive antiretroviral therapy. 

Zidovudine monotherapy can be provided to 

untreated pregnant women with a baseline 

viral load of <1,000 c/mL, but a 3-part 

ART regimen including zidovudine should 

always be offered and discussed. Pregnant 

women should be offered the currently 

recommended treatment regimens for HIVinfected adults, except that efavirenz (EFV) is 

contraindicated in the first trimester.

Medical problems associated with ART 

during pregnancy include hyperglycemia 

and diabetic ketoacidosis, lactic acidosis, and 

hyperemesis gravidarum.
A Guide to Primary Care of People with HIV/AIDS

Chapter 12: Family Planning and Pregnancy 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 103

12

SUGGESTED RESOURCES

Al-Kahn A, Colon J, Palta V, Bardeguez 

A. Assisted reproductive technology for 

men and women infected with human 

immunodeficiency virus type1. Clin Infect 

Dis. 2003;36:195-200.

Anderson J. HIV and reproduction. In 

Anderson J, ed. A Guide to the Clinical 

Care of Women with HIV. Rockville 

MD: Health Resources and Services 

Administration, 2001:212-221. Available 

at http://www.hab.hrsa.gov. 

Bartlett J. Recommendations for 

antiretroviral therapy in pregnancy. 2003 

Medical Management of HIV Infection. 

Baltimore MD: Johns Hopkins University 

School of Medicine. 2003:96-105. Available 

at http://www.hopkins-aids.edu/. 

Pham P, Barditch-Crovo P. Pharmacologic 

Considerations in HIV-Infected Pregnant 

Patients. In Anderson J, ed. A Guide to the 

Clinical Care of Women with HIV. Available 

at http://www.hab.hrsa.gov.

Public Health Service Task Force. Guidelines 

for the Use of Antiretroviral Agents in HIVInfected Adults and Adolescents. Available 

at http://www.aidsinfo.nih.gov.

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-1 Transmission 

in the United States. Available at http://

www.aidsinfo.nih.gov. 

Wang C, Celum C. Prevention of HIV. In 

Anderson J, ed. A Guide to the Clinical 

Care of Women with HIV. Available at http:

//www.hab.hrsa.gov.

World Health Organization. (2001) Global 

Strategy for Infant and Young Child Feeding. 

Document A54/7. 

REFERENCES

American Academy of Pediatrics, 

American College of Obstetricians and 

Gynecologists. Guidelines for Perinatal Care.

5th Ed. Elkgrove, IL: American Academy of 

Pediatrics; 2002.

American College of Obstetricians and 

Gynecologists. Ethics in Obstetrics and 

Gynecology, 2nd Ed. Washington, DC: 

American College of Obstetricians 

and Gynecologists; 2004. Available at 

http://www.acog.org/from%5Fhome/

publications/ethics Accessed 2/04.

American College of Obstetricians and 

Gynecologists. Human immunodeficiency 

virus screening. Joint statement of the 

American Academy of Pediatrics and the 

American College of Obstetricians and 

Gynecologists. Pediatrics. 1999;104:128.

American College of Obstetricians and 

Gynecologists. Technical Bulletin Number 

205: Preconceptional Care. Washington, 

DC: American College of Obstetricians and 

Gynecologists; 1995.

Centers for Disease Control and Prevention. 

Advancing HIV Prevention: New Strategies 

for a Changing Epidemic – United States, 

2003. MMWR. 2003;52:329-332.

Centers for Disease Control and Prevention. 

Revised Recommendations for HIV 

Screening of Pregnant Women. MMWR. 

2001;50(RR19):59-86. Available at http:

//www.cdc.gov/mmwr/PDF/rr/rr5019.pdf. 

Accessed 1/04.

Centers for Disease Control and Prevention. 

Recommendations of the U.S. Public Health 

Service Task Force on the Use of Zidovudine 

to Reduce Perinatal Transmission of 

Human Immunodeficiency Virus. MMWR. 

1995;43(RR11):1-20.

Cooper ER, Charurat M, Mofenson L, et al. 

Combination antiretroviral strategies for 

the treatment of pregnant HIV-1-infected 

women and prevention of perinatal HIV-1 

transmission. J Acquir Immune Defic Syndr.

2002;29:484-494.
A Guide to Primary Care of People with HIV/AIDS

Chapter 12: Family Planning and Pregnancy

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

12

Dominguez KL, Lindergren ML, D’Almada PJ, 

et al. Increasing trend of cesarean deliveries in 

HIV-infected women in the United States from 

1994 to 2000. J Acquir Immune Defic Syndr.

2003;33:232-238.

Eastman PS, Shapiro DE, Coombs RW, et al. 

Maternal viral genotypic zidovudine resistance 

and infrequent failure of zidovudine therapy 

to prevent perinatal transmission of human 

immunodeficiency virus type 1 in pediatric 

AIDS Clinical Trials Group Protocol 076. J Infect 

Dis. 1998;177:557-564.

Garcia PM, Kalish LA, Pitt J, et al. Maternal 

levels of plasma human immunodeficiency 

virus type 1 RNA and the risk of perinatal 

transmission. N Engl J Med. 1999;341:394-402.

Ioannidis JP, Abrams EJ, Ammann A, 

et al. Perinatal transmission of human 

immunodeficiency virus type 1 by pregnant 

women with RNA virus loads <1000 copies/

ml. J Infect Dis. 2001;183:539-545.

Kim LU, Johnson MR, Barton S, et al. 

Evaluation of sperm washing as a potential 

method of reducing HIV transmission in HIVdiscordant couples wishing to have children. 

AIDS. 1999;13:645-651.

Public Health Service Task Force (2002). 

Recommendations for Use of Antiretroviral 

Drugs in Pregnant HIV-1 Infected women for 

Maternal Health and Interventions to Reduce 

Perinatal HIV-1 Transmission in the United States. 

Available at http://www.aidsinfo.nih.gov.org.

Shapiro DE, Sperling RS, Coombs RW. 

Effect of zidovudine on perinatal HIV1 transmission and maternal viral load. 

Lancet.1999;354:156-158. 

Sperling RS, Shapiro DE, Coombs RW, et al. 

Maternal viral load, zidovudine treatment, 

and the risk of transmission of human 

immunodeficiency virus type 1 from mother 

to infant. Pediatric AIDS Clinical Trials Group 

Protocol 076 Study Group. N Engl J Med.

1996;335:1621-1629. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 13: Management of Substance Abuse 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 105

13

ASSESSMENT OF

SUBSTANCE ABUSE

PROBLEMS

What	is	the	definition	of	a	substance	abuser?	

A substance abuser is an individual who repeatedly 

uses an addictive substance or performs a certain 

behavior even with the knowledge of its negative health 

consequences. A person is drug dependent or addicted 

if he or she uses drugs repeatedly despite the social, 

interpersonal, or other problems associated with their 

use and has a physical or psychological tolerance to the 

drug and experiences withdrawal symptoms after the 

effects of the drug wear off. Long-term drug abuse can 

interfere with normal brain activity and metabolism and 

can become a chronic, relapsing condition characterized 

by compulsive drug craving and drug seeking. There are 

other kinds of addiction that may not involve the use of 

substances, such as gambling, sex, and eating-related 

disorders, all of which involve a range of dysfunctional 

behaviors with undesirable social, medical, and 

economic consequences (see Table 13-1).

Table 13-1: Range of Substances and 

Behaviors That Can Be Abused 

Addictive substances Behaviors

• Marijuana

• Cocaine

• Heroin

• Amphetamines, other 

stimulants

• Tranquilizers

• Hallucinogens

• Steroids and 

recreational drugs

• Eating disorders: 

anorexia, bulimia, 

binging

• Sex disorders: 

compulsive sexual 

activity

• Gambling

• Internet addictions: 

compulsive use of the 

internet

How	should	primary	care	providers	address	

substance	use	problems	in	their	patients?	

The first task is to consciously look for behavioral and 

physical signs of maladaptive drug use and to use a 

simple screening tool such as the CAGE examination 

(described below) to detect it. Common indicators of 

drug abuse are frequent absence from work or school, 

recurrent injuries, motor vehicle accidents, depression, 

anxiety, labile hypertension, sleep problems, sexual 

dysfunction, or abdominal symptoms. Physical signs of 

drug abuse such as tremor, liver disorders, and physical 

changes such as nasal irritation caused by cocaine are 

well known to health care providers.

The second task is to tell the patient his or her diagnosis 

of drug abuse or dependence. Providers are often 

concerned about upsetting a patient with a stigmatizing 

diagnosis. Giving a concise, objective description 

of clinical findings without making judgments is 

important. Common pitfalls for providers to avoid 

during this discussion are listed as the DEATH Glossary 

(Table 13-2). 

The third task before sending a patient to treatment 

is to try a brief intervention in the office. It has 

clearly been shown that brief interventions given in 

community centers, hospitals, and ambulatory clinics 

decrease the morbidity and mortality associated with 

drug abuse (see Suggested Resources). For physicians 

who have received training on buprenorphine treatment 

for opiate addicts, there is the added opportunity to 

treat opiate drug users in the private practice setting 

without referring the individuals to drug use centers 

(see section on Treatment of Substance Abuse below). 

Chapter	13:	

Management	of	Substance	Abuse

Henry Francis, MD

ASSESSMENT OF SUBSTANCE ABUSE PROBLEMS

TREATMENT OF SUBSTANCE ABUSE PROBLEMS

MEDICAL AND PAIN MANAGEMENT ISSUES

HIV/AIDS ISSUES

KEY POINTS

SUGGESTED RESOURCES

REFERENCES
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Table 13-2: The DEATH Glossary

Common Pitfalls for Providers to Avoid when 

Diagnosing Drug Abuse Problems

D

Drinking or 

Drug-use

Details are not relevant; talking with a person 

on drugs is not useful. The simple issue here is 

talking to the patient when he or she is sober, 

ie, has not taken a drug before the visit.

E

Etiology

Do not spend much time on how drug use 

started but focus on getting the person to 

treatment.

A

Argument

Avoid arguing at all costs. No meaningful 

conversation will occur in an argument.

T

Threats

Guilt and shame do not promote recovery from 

chemical dependency. Threats or evoking guilt 

will not promote successful therapy.

H

Hedging

Hedging hurts your credibility. Being ambivalent 

about giving the diagnosis will not help the 

patient. If the patient disagrees with you, 

unequivocally agreeing to disagree is a valid 

starting point for getting to successful recovery.

Why	is	substance	abuse	such	a	big	issue	in	

HIV	care?

Injection drug use is estimated to be responsible for 

25% of HIV transmission in the United States and 

is directly or indirectly responsible for 57% of HIV 

transmission to women. Less well appreciated is the 

fact that drug-using behaviors may be a significant 

HIV transmission risk factor for many men who do 

not inject drugs. In a recent study of men who have 

sex with men (MSM), up to 16% may have drug use 

as a risk factor for acquiring HIV (Chesney, 2003). 

The high degree of association between injection and 

noninjection drug use underscores the importance of 

primary care providers’ being able to diagnose drug 

using behaviors.

Diagnosing drug or alcohol dependence or addiction 

is not an easy task. Many people who are addicted 

to alcohol or drugs attempt to conceal or deny that 

they have an addiction. In addition, diagnostic tests 

for drug dependence and addiction lack specificity 

and sensitivity. Although blood and urine tests are 

usually quite reliable at detecting recent drug use, 

individuals can be adept at avoiding being tested or 

at manipulating test results. See Table 13-3 for the 

duration of time substances are detectible in urine.

Table 13-3: Duration of Time Drugs Are 

Detectable in Urine

Substance Duration

Alcohol 48 hours

Amphetamines 12 hours

Barbiturates 10-30 days

Valium 4-5 days

Cocaine 24-72 hours

Heroin 24 hours

Marijuana 3-30 days (in heavy users)

Methaqualone 4-24 days

Phencyclidine (PCP) 3-10 days

Methadone 3 days

Sex, food, gambling Not applicable

Are	there	tools	to	help	providers	assess	

patients	for	drug	and	alcohol	use?	

Experts in addiction medicine use a combination of 

behavioral and clinical testing to diagnose drug abuse. 

There are 9 commonly used drug-use screening tests: 

Addiction Severity Index (ASI), Alcohol Dependence 

Scale, Alcohol Use Disorders Identification Test (AUDIT), 

CAGE (see below), Clinical Institute Withdrawal 

Assessment for Alcohol, Revised (CIWA-Ar), Drinker 

Inventory of Consequences (DrInC), Michigan Alcohol 

Screening Test (MAST and SMAST), Problem Oriented 

Screening Instrument for Teenagers (POSIT), and 

Self-Administered Alcoholism Screening Test (SAAST) 

(American Society of Addiction Medicine, 1998). Six of 

them are specifically designed to detect alcohol use. 
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Which	screening	tests	are	most	useful	in	

primary	care	practice?	

The CAGE test is a non-threatening quick screening 

test for detecting drug use in adults (see Table 13-4) 

and the POSIT test useful for screening adolescents 

aged 12-19. The questions below are designed to 

assess key substance-using behaviors. The letters in 

CAGE correspond to important emotions or behaviors 

indicative of drug use. 

Table 13-4: The CAGE Screening Test

C 1. Have you felt that you ought to Cut down 

on your drinking or drug use?

A 2. Have people Annoyed you by criticizing 

your drinking or drug use?

G 3. Have you ever felt bad or Guilty about your 

drinking or drug use?

E

4. Have you ever had a drink or used drugs 

first thing in the morning (Eye opener) to 

steady your nerves, to get rid of a hangover, 

or to get the day started?

The Problem Oriented Screening Instrument for 

Teenagers (POSIT) examination is a 139 item yes/no 

questionnaire for assessing adolescent risk factors in 

substance abuse, physical health, mental health, family 

and peer relationships, educational and vocational 

status, social skills, leisure and recreation, aggressive 

behavior, and delinquency. A nonexperienced 

provider can conduct the test in 20 to 25 minutes. The 

questionnaire is available free in English and Spanish 

from the National Clearinghouse for Alcohol and Drug 

Information by mail at P.O. Box 2345, Rockville, MD 

20847-2345 or by telephone at 1-800-729-6686.

What	would	provide	a	more	in-depth	

assessment	of	drug	and	alcohol	use?

Two detailed evaluations of drug and alcohol use are the 

Diagnostic and Statistical Manual of Mental Disorders, 

fourth edition (DSM-IV) and Addiction Severity Index 

(ASI) for alcohol or drug use. The DSM-IV defines 

the diagnostic criteria for substance dependence 

as a maladaptive pattern of substance use, leading 

to clinically significant impairment or distress, as 

manifested by 3 or more of the following, occurring at 

any time in the same 12-month period:

1. Presence of drug withdrawal symptoms

2. Escalation of drug doses

3. Persistent inability to reduce or control drug use

4. Increased time spent obtaining drugs

5. Personal and business activities reduced by drug use

6. Development of drug tolerance

7. Knowing drug use’s negative health and personal 

effects, yet continuing to use drugs

TREATMENT OF SUBSTANCE

ABUSE PROBLEMS

What	should	you	do	before	referring	a	person	

for	treatment?

The decision to refer a person for drug abuse treatment 

should come after the provider has detected a 

substance use problem, conducted initial evaluations 

to determine the degree of drug use and physical harm 

done by the drug use, and provided brief interventions 

to stop drug abuse. After the diagnosis and brief 

interventions (if appropriate), the provider should refer 

the patient to a drug treatment system or an addiction 

physician.

What	role	does	the	primary	care	provider’s	

at titude	play	in	successful	drug	abuse	

treatment?

Drug abuse treatment is successful if the provider 

addresses his or her own biases about addiction, 

understands the factors contributing to addiction, 

provides appropriate pharmacologic and behavioral 

care, and recognizes that drug addiction is a chronic 

disease problem. Many drug abuse treatment failures 

are associated with hostile or unsupportive providers 

whose behaviors are based on the assumption that drug 

use is voluntary. Since successful drug abuse therapy 

depends on adherence to treatment regimens, any 

factors that facilitate adherence will foster successful 

treatment outcomes. The patient’s perception that the 

primary care provider is nonjudgmental and supportive 

is an essential factor in successful therapy. 

How	can	the	primary	care	provider	enhance	

the	success	of	drug	abuse	treatment?

The primary care provider must prevent or treat 

exogenous factors that negatively affect successful 

drug abuse therapy. We now recognize significant 

environmental (social), genetic, biologic, and behavioral 

factors that facilitate drug addiction: 
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Environmental factors Common factors are family 

or sibling drug use, poverty, poor education, and 

homelessness. Patient referral to social services and 

family referral into drug treatment will facilitate the 

patient’s therapy.

Genetic factors Ten percent of drug users have 

multifactorial genetic predispositions to drug use. Many 

patients have significant severe drug use problems 

requiring care from addiction specialists as soon as 

possible.

Biologic factors Many patients have preexisting mental 

health problems such as depression and attention deficit 

and hyperactivity disorder (ADHD) which, if recognized 

and treated, may prevent or modulate drug use.

Behavioral risk factors For adolescents, peer pressure 

is a common cause of drug use. Early education by 

parents and the primary care physician about drug 

use are very important for preventing drug use by 

adolescents.

What	is	the	role	of	drug	detoxification	in	drug	

abuse	treatment?

Drug detoxification is the transitional therapy 

between identifying drug abuse and beginning a 

comprehensive program to treat it. The objective of 

drug detoxification is to facilitate a safe drug withdrawal 

process in supportive surroundings. Detoxification 

is not a treatment or cure for drug addiction; it 

is an intervention to get a person to the stage of 

comprehensive drug abuse therapy. Two common 

medical interventions to modulate symptoms are 

benzodiazepines in alcohol withdrawal and clonidine in 

opiate withdrawal. 

What	are	the	components	of	a	comprehensive	

drug	abuse	treatment	plan?

Effective drug abuse treatment encompasses a 

combination of behavioral and pharmacologic therapies 

to treat the individual’s particular substance abuse 

problems and needs. Drug use medication is only one 

element of successful, comprehensive drug treatment, 

which includes addressing the individual’s medical, 

psychological, social, vocational, and legal problems 

(see Table 13-5). Behavioral drug abuse prevention 

and treatment programs are provided in residential 

settings and in prisons. These programs may provide 

medications to treat drug abuse, medical treatment for 

coexisting illnesses, and /or behavioral interventions 

using a number of personal, family, and community 

interventions. The most important community 

interventions are the 12-step or self help programs such 

as Narcotics Anonymous, Cocaine Anonymous, and 

Alcoholics Anonymous.

What	should	you	do	af ter	the	patient	has	

completed	a	drug	treatment	program?

The primary care provider’s task in assuring successful 

drug addiction treatment is to treat drug abuse as a 

chronic disease. Drug abuse treatment is effective if 

provided correctly and consistently. Approximately 

50% of alcoholics, 60% of opiate addicts, 55% of 

cocaine addicts, and 30% of nicotine (cigarette) 

addicts are successfully treated. Note the success rate 

is generally lower for the legal addictive drugs, which 

may be because of ready access to those substances. 

For the illicit drug addictions, success occurs only if 

the drug abuse therapy is given on a continual basis 

for the lifetime of the patient. Drug use studies have 

clearly shown that drug abusers will relapse as any 

patient would who has a chronic disease. In direct 

comparisons, drug-addicted patients are actually less 

likely to relapse into addiction and are more adherent to 

their medication than persons with diabetes mellitus or 

hypertension.

Table 13-5: Components of Drug 

Abuse Treatment

Personal needs Treatment needs

• Family services

• Housing and transport

• Financial services

• Legal services

• AIDS/HIV services

• Educational service

• Medical service

• Vocational service

• Child care service

• Behavioral therapy

• Clinical and case 

management

• Intake and processing

• Treatment plans

• Pharmacotherapy

• Continuing care

• Substance use monitoring

• Self help/peer support 

groups
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How	do	you	use	maintenance	medications	in	

treating	drug	abuse?

 Maintenance treatment medications, important adjuncts 

to comprehensive drug abuse and dependence treatment, 

are used in the same way the nicotine patch is used for 

cigarette smokers. The medications help stabilize the 

drug user by reducing drug craving and thereby reducing 

high-risk behaviors associated with acquiring illicit drugs 

to attain the drug-induced high. Medication is used most 

effectively by patients who have good social support and 

higher education levels and are highly motivated to get off 

illicit drugs. 

What	are	the	common	medications	used	in	drug	

abuse	treatment?

Use of medications to treat illicit drug use is limited 

because most of the approved medications are for opiate 

addiction and alcohol abuse. Effective opiate addiction 

medications are divided into 2 classes: opiate agonists 

and opiate antagonists. Opiate agonists are used to 

substitute for the opiate without causing the euphoria 

associated with drug abuse. The opiate agonists include 

methadone, L-alpha-acetyl-methadol (LAAM), and 

buprenorphine, which has recently been approved for 

medical use in the United States (Johnson, 2000). The 

other class is the opiate antagonists, the most important 

of which is naltrexone. Buprenorphine, actually a partial 

agonist-antagonist, may be used by physicians who 

undergo an 8-hour training course on how to use the 

medication. This medication has the highest potential for 

providing care in the private practice setting. Details for 

obtaining buprenorphine training and certification are 

available at the Office of Substance Abuse and Mental 

Health Administrations website, www.samhsa.gov, in the 

addiction treatment section under office-based therapies. 

How	do	you	detect,	manage,	and	prevent	relapse?

After the patient has been treated and is off drugs, the 

responsibility of the primary care physician does not 

end. The most common complication after patients have 

stopped using drugs is relapse. Four points to remember: 

1) relapse should be expected to occur in most users; 

2) on average 3-4 episodes may occur before complete 

abstinence; 3) relapse is not a treatment failure; it is 

a time to intensify treatment; and 4) the primary care 

provider is critical in preventing episodes of relapse. The 

most critical issues for the primary care provider to keep 

track of in the detection and prevention of relapses are to: 

• Provide close followup. 

• Do not make medical care dependent on drug 

abstinence.

• Recognize missed appointments as a sign of relapse and 

need for followup.

• Encourage and monitor the drug treatment/sobriety 

program of the patient.

• Treat comorbid psychiatric conditions aggressively.

• Identify drug use trigger points with the patient and 

discuss how to avoid them.

• Develop a plan to identify and manage relapse early.

• Make every effort to keep communication open and 

nonjudgmental.

MEDICAL AND PAIN

MANAGEMENT ISSUES

What	exactly	do	drugs	do	to	the	brain?

Researchers continue to explore the variety of functional 

and structural changes that occur in the brain during drug 

use. Drug dependencies have been linked to disturbances 

in the dopaminergic pathways of the mesolimbic reward 

system, which lies deep in the brain. This system 

interconnects the ventral tegumentum to the nucleus 

accumbens with other connections to the limbic system 

and orbitofrontal cortex (Leshner, 1997). Disturbances in 

these areas are responsible for the behavioral changes and 

drug craving that characterize the drug-addicted person. 

Brain imaging studies have suggested that the changes 

in the brain are chronic, even after the person stops 

consuming drugs and may cause the relapses of most 

drug users. 

What	are	the	common	medical	problems	of	

patients	who	inject	drugs?

Patients who inject drugs often have comorbid clinical 

conditions, which are listed below with specific 

recommendations. 

Mental health problems Treat early. Depression is the 

most common problem. 

Hepatitis C Screen all drug users for hepatitis C and B 

and treat when indicated. Consult a specialist in HIV/

AIDS and hepatitis C for coinfected patients. Screen 

for depression before initiating therapy for hepatitis 

C. Treating hepatitis is important for preventing 

hepatotoxicity associated with ART.

Sexually transmitted diseases Screen regularly and 

provide safe sex education. Like other people, drug users 

often do not stop having sex even if they are infected with 

multiple diseases. 
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Tuberculosis Past tuberculosis exposure is common in 

injection drug users (as many as 30% are PPD positive); 

they should be screened for TB. 

Skin and soft tissue infections Cellulitis and skin 

abscesses are very common in injection drug users. The 

practice of “skin popping” markedly increases the risk 

of abscess formation.

Noninfectious health problems Treat accordingly. Drug 

users and alcoholics have multiple health problems 

that should be treated aggressively. The fewer medical 

problems patients have, the more likely they are to 

adhere to the treatment plan. Common problems to be 

aware of: 

• Drug interactions (between medications and between 

medications and illicit drugs)

• Diabetes mellitus and hypertension

• Social environment (housing, child care)

• Pain management

How	do	you	manage	pain	in	opiate-addicted	

patients?

It is incorrect to assume that individuals addicted to 

opiates or any other kind of drug should receive less 

pain medication because they are addicted. They 

should receive pain therapy based on the diagnosed 

cause of the pain just like nonaddicted patients. The 

therapeutic approach differs according to whether the 

pain is acute or chronic.

How	should	you	treat	acute	pain	in	a	person	

diagnosed	as	a	drug	abuser?

Appropriate actions to take for drug-abusing patients in 

acute pain related to a recent diagnosable injury involve 

managing the pain:

1. Determine the source of the pain.

2. Provide pain medication that relieves the symptoms. 

Opiates may be used if they are what will stop the 

pain.

3. Give the medication in regularly scheduled doses. This 

prevents undesirable drug-seeking behaviors resulting 

from treatment on an as-needed (PRN) basis.

4. If pain is persistent or the cause is unclear, check for 

underlying psychiatric problems or an undetected 

source of pain.

5. If opiates are used, taper the doses slowly to avoid 

drug withdrawal.

How	should	you	treat	chronic	pain	in	a	person	

diagnosed	as	a	drug	abuser?

If the pain is chronic, the treatment strategies shift to 

not only finding the source of the pain, but also to using 

the entire spectrum of pain-relieving strategies with or 

without nonopiate pain medication (see Table 13-6). 

One exception is a patient with cancer-associated pain, 

for whom any effective medication (potentially addictive 

or not) is appropriate. 

Table 13-6: Treatments for Chronic Pain 

in Known Drug Abusers

Medications used for pain control

Nonsteroidal anti-inflammatory drugs (eg, 30 mg 

ketorolactromethamine, which is equivalent to 6-10 mg 

morphine)

Tricyclics

Anticonvulsants

Muscle relaxants

Topical agents

Opiates

Physical interventions for pain control

Thermal: heat and cold are both effective and underutilized

Peripheral counterstimulation: transcutaneous electrical nerve 

stimulation (TENS) and vibration

Manual therapies: massage and chiropractic and osteopathic 

manipulation

Active movement: stretching and active exercise

Orthotics: splints and other supportive devices
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HIV/AIDS ISSUES

Can	HIV	transmission	be	prevented	in	active	

substance	abusers?

A comprehensive HIV prevention strategy in a primary 

care practice includes interventions to provide drug 

treatment, to take care of mental health problems, and 

to prevent HIV transmission during drug use and sexual 

activity. The primary care provider should routinely 

screen for drug abuse and treat or refer for treatment 

as quickly as possible. This is particularly important for 

adolescents who are at high risk for HIV, hepatitis B and 

C, and other infections. One study has shown that once 

adolescents start injecting drugs, over 90% will become 

infected with hepatitis C within 18 months. The 

provider should also counsel patients who are actively 

using drugs not to share needles with others and to take 

advantage of programs that distribute clean needles. 

Programs use the needle distribution strategy as a first 

step to engage individuals who can then be encouraged 

to accept medical and drug abuse treatment services. 

When	is	an	active	substance	abuser	ready	for	

HIV	treatment?	

The most important clinical decision for successful 

treatment of drug-abusing patients with HIV is deciding 

when they are ready -- both substance abuse treatment 

and antiretroviral therapy (ART). Patients fall into 3 

categories: those who do not want treatment, those 

who are ambivalent, and those who want treatment. 

For patients who do not want treatment, the provider 

should continue to be available with information on 

HIV and drug abuse treatment until they are ready 

to consider treatment. For those who are ambivalent 

about treatment, time is well spent during several 

clinical visits discussing the health issues of AIDS and 

drug abuse until they are ready for treatment. For 

patients who are ready for treatment the next step is 

to assess what factors will affect their adherence (see 

Chapter 7: Adherence to HIV Therapies). History of 

injection drug use, race, gender, age, socioeconomic 

status, level of education, and occupation are poor 

predictors of medication adherence. Accurate predictors 

of adherence are:

• The patient’s health beliefs

• Ease of access to health care providers

• Familiarity with the treatment setting

• Existence of a social support system 

• Perceived support from clinical staff members

• Simplicity of medication regimens

Interaction with providers and ambiance of the 

treatment setting account for almost half of the support 

factors needed to encourage drug users to adhere to 

treatment regimens. This pattern is true for active drug 

users, with the possible exception of persons addicted 

to crack cocaine.

Difficult economic and social situations, including 

unemployment and unstable housing, may make 

adherence to clinical treatment plans for both drug 

addiction and HIV even more difficult to follow. For 

these reasons some drug abuse treatment centers 

provide residential treatment to minimize outside 

influences on drug use. Also, methadone clinics provide 

an ideal opportunity for rehabilitated substance users 

to receive adherence support for ART through directly 

observed therapy (DOT) at the clinic. 

What	immunizations	should	drug	abusers	with	

HIV	receive?

Because of the higher risk of tetanus in injection 

drug users, tetanus boosters should be given when 

due. Pneumococcocal and influenza vaccines are 

recommended for all patients with HIV. Drug abusers 

with no antibodies to hepatitis A and hepatitis B should 

be immunized. Hepatitis A can be fatal in individuals 

with hepatitis C.

Are	there	important	drug	interactions	

between	antiretrovirals	and	medications	for	

drug	treatment?

 A common problem in treating patients with HIV 

who are drug users is the drug interactions between 

medications. Studies have shown that interactions of 

methadone and antiretroviral medications are linked 

to CYP450 3A4 sites in the liver. The most significant 

interactions are between methadone and nevirapine 

(NVP) or efavirenz (EFV), which precipitate rapid drug 

withdrawal symptoms (see Table 13-7). Methadone 

programs should be alerted when methadone 

patients are started on efavirenz or nevirapine, as 

dose escalation of methadone will probably be 

required. When methadone and didanosine (ddI) 

are coadministered the uptake of didanosine may be 

lowered requiring a higher dose of didanosine (See 

Drug Tables 7 and 8 in the Pocket Guide). Other 

interactions caused by drugs such as abacavir 
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(ABC) and all the PIs except indinavir (IDV), though 

pharmacologically measurable, are not clinically 

apparent and standard doses are appropriate. Potential 

interactions between illicit drugs and HIV medications 

are less well understood. Methamphetamine products 

have been associated with sudden death in individuals 

on protease inhibitors. Anecdotal reports describe 

how selective serotonin reuptake inhibitor (SSRI) 

antidepressant medications may produce side effects 

that mimic drug withdrawal and may decrease AIDS 

medication adherence. 

Table 13-7: Antiretroviral Drugs that 

Affect Methadone Levels

NRTI NNRTI PI

zidovudine (ZDV)↔ nevirapine (NVP) ↓ indinavir (IDV) ↔

didanosine (ddI) ↔ delavirdine (DLV) ↑ ritonavir (RTV) ↓

zalcitabine (ddC)↔ efavirenz (EFV) ↓ nelfinavir (NFV) ↓

stavudine (d4T) ↔ saquinavir (SQV) ?

abacavir (ABC) ↓ amprenavir (APV) ↓

lopinavir (LPV) ↓

atazanavir (ATV) ↓

↓ = decreases methadone blood levels 

↔ = indeterminate effect

↑ = increases methadone blood levels

Source: Adapted from Gourevitch MN, Friedland GH. Interactions 

between methadone and medications used to treat HIV infection: a 

review. Mt Sinai J Med 2000 67:429-436.

Why	are	HIV	and	drug	abuse	both	such	

noticeable	issues	now?

HIV and substance abuse are both significant public 

health problems that merit the attention of public 

health officials and policymakers. Today, an estimated 

40 million people worldwide are living with HIV. Of 

these, 2 to 3 million people are injection drug users. 

In the United States, approximately a third of HIV/

AIDS cases are related to injection drug use. Research 

shows that use of drugs, injected or not, can affect 

decisionmaking – particularly about engaging in unsafe 

sex – that can endanger the health of the drug user 

and of others. Substance abuse is a double-edged 

sword because it increases an individual’s risks for 

continuing drug use while also increasing the likelihood 

of exposure to HIV and other bloodborne infections. 

Infectious diseases that are more prevalent among 

injection drug users than in the general population 

are HIV, other STDs, including hepatitis B and C, and 

tuberculosis. Prevention and early treatment of drug 

abuse and drug-related diseases are critical public 

health measures to reduce the spread of new infections.
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KEY POINTS

Substance abuse and addiction involve 

compulsive drug-seeking behavior that 

interferes with an individual’s ability to 

function normally in many aspects of 

daily life. Substance abuse and mental 

health problems often occur together 

and, unless treated, can lead to chronic 

social and medical consequences.

Accurate and reliable diagnosis of 

substance abuse or dependence is not a 

perfect science. Screening techniques, in 

concert with a thorough medical history 

and evaluation, are important in detecting 

and correctly diagnosing a substance 

abuse-related disorder. 

HIV transmission is preventable in people 

who use drugs. For drug users and the 

community at large, drug addiction 

treatment is disease prevention. 

Hepatitis C is extremely common in 

patients with a past or current history 

of injection drug use. All patients with 

hepatitis C should be vaccinated against 

hepatitis A and B if serologic studies show 

no prior exposure.

The clinical issues to be addressed are 

to treat comorbid conditions as soon 

as possible, treat drug use and HIV 

aggressively, and be aware of common 

drug interactions seen in patients treated 

for drug use and HIV simultaneously.

SUGGESTED RESOURCES

Brief Interventions and Brief Therapies for 

Substance Abuse. Treatment Improvement 

Protocol (TIP) Series 34. Rockville, MD: 

Substance Abuse and Mental Health 

Services Administration Center for 

Substance Abuse Treatment; 1999. DHHS 

Publication No. (SMA) 99-3353. Available 

at http://www.health.org/govpubs/BKD341/

Accessed 1/04.

Klein MB, Lalonde RG, Suissa S. The 

impact of hepatitis C virus coinfection on 

HIV progression before and after highly 

active antiretroviral therapy. J Acquir 

Immune Defic Syndr. 2003;33:365-372.

WEBSITES

American Society of Addiction Medicine: 

http://www.asam.org/ Accessed 11/03.

National Institute on Drug Abuse: 

http://www.nida.nih.gov

Accessed 11/03.

Erowid (detailed biochemical and other 

information on drugs): 

http://www.erowid.org

Accessed 11/03.

Office on National Drug Control Policy: 

http://www.whitehousedrugpolicy.gov/

Accessed 11/03.

Substance Abuse and Mental Health 

Services Administration (drug abuse 

statistics, clinical treatment information): 

http://www.samhsa.gov

Accessed 11/03.
A Guide to Primary Care of People with HIV/AIDS

Chapter 13: Management of Substance Abuse 

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

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REFERENCES

American Psychiatric Association. Diagnostic 

and Statistical Manual of Mental Disorders.

4th ed. Washington, DC: American 

Psychiatric Association Press; 1994.

American Society of Addiction Medicine. 

Screening Instruments. In: Graham AW, 

Schultz TK, Mayo-Smith MF, Ries RK, Wilford 

BB, eds. Principles of Addiction Medicine. 

Chevy Chase MD: American Society of 

Addiction Medicine; 1998:1283-1286. 

Chesney MA, Koblin BA, Barresi PJ, et al. An 

individually tailored intervention for HIV 

prevention: baseline data from the EXPLORE 

Study. Am J Public Health. 2003;93:933-938.

Gourevitch MN, Friedland GH. Interactions 

between methadone and medications used 

to treat HIV infection: a review. Mt. Sinai J 

Med. 2000;67:429-436.

Hyman SE, Malenka RC. Addiction and the 

brain: the neurobiology of compulsion and 

its persistence [Review]. Nat Rev Neurosci. 

2001;2:695-703. 

Johnson RE, Chutuape MA, Strain EC, Walsh 

SL, Stitzer ML, Bigelow GE. A comparison of 

levomethadyl acetate, buprenorphine, and 

methadone for opioid dependence. New Engl 

J Med. 2000;343:1290-1697. 

Leshner, AL. Addiction is a brain disease, and 

it matters. Science. 1997;278:45-47.

McLellan AT. Have we evaluated addiction 

treatment correctly? Implications from a 

chronic care perspective. Addiction. 2002;97:

249-252.

O’Brien CP. A range of research-based 

pharmacotherapies for addiction. Science. 

1997;278:66-70.

Principles of Drug Addiction Treatment: 

A Research-Based Guide. Bethesda, MD: 

National Institute on Drug Abuse; 1999. NIH 

Publication 99-4180. Available at http://

www.drugabuse.gov/PubCat/PubsIndex.html

Accessed 1/04.

Principles of HIV Prevention in Drug-Using 

Populations: A Research-Based Guide. 

Bethesda, MD: National Institute on Drug 

Abuse; 2002. NIH publication 02-4733. 

Available at http://www.drugabuse.gov/

PubCat/PubsIndex.html Accessed 1/04.

Samet JH, Rollnick S, Barnes H. Beyond 

CAGE. A brief clinical approach after 

detection of substance abuse. Arch Intern 

Med. 1996;156:2287-93.
A Guide to Primary Care of People with HIV/AIDS

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14

OVERVIEW

Why	is	it	important	to	address	mental	health	

disorders	in	persons	living	with	HIV?

HIV infection increases the risk of developing 

psychiatric disorders, including depression, mania, 

psychosis, and substance abuse (Treisman, 1999). For 

patients with preexisting mental illness, a diagnosis 

of HIV can significantly impact their ability to cope 

with HIV disease, adhere to treatment regimens, and 

take advantage of support networks and care systems, 

and can result in deterioration in their quality of life. 

Individuals with previous histories of mood, cognitive, 

or anxiety disorders may exhibit a reemergence or 

exacerbation of symptoms. As persons with HIV/AIDS 

live longer and the focus of care shifts from acute to 

chronic, the long-term psychological impact of HIV 

disease becomes more apparent. 

What	common	HIV-related	medical	conditions	

have	psychiatric	symptoms?

It is essential for primary care providers to be aware 

of the need for a comprehensive evaluation of 

psychiatric symptoms in persons with HIV disease. 

Many psychiatric symptoms can indicate an underlying 

opportunistic disease or other condition (see Table 14-1). 

What	are	the	most	common	mistakes	made	in	

mental	health	management	of	HIV-infected	

patients?

Primary care providers commonly 1) under-diagnose 

depression, 2) under-dose antidepressant medications, 

3) neglect substance use management and treatment, 

4) stigmatize patients with psychiatric disorders, and 

5) assume that psychotherapy implies a lengthy and 

detailed conversation.

Table 14-1. HIV-Related Conditions That 

Can Present With Psychiatric Symptoms

Type of problem Condition

Opportunistic brain 

infections

Toxoplasmosis, cryptococcal 

meningitis, cytomegalovirus infection, 

tuberculosis, progressive multifocal 

leukoencephalopathy, neurosyphilis

Opportunistic 

malignancies

Lymphoma, Kaposi sarcoma

Metabolic 

complications

Fever, anemia, blood infections, 

hypoxia, hypotestosteronism

Drug toxicity Corticosteroids, alpha-interferon, 

efavirenz (EFV)

Substance abuse 

complications

Recreational drugs (cocaine, alcohol, 

methamphetamine, hallucinogens, 

nitrate inhalant, opiates)

Prescribed drugs (benzodiazepines, 

opiates, psychostimulants)

What	conditions	warrant	psychiatric	

consultation?

Providers should obtain psychiatric consultation in 

1) major depression refractory to medication trials, 

2) bipolar disorder, 3) schizophrenia, and 4) suicidal 

or homicidal thoughts.

DISORDERS OF ATTENTION

OR COGNITION

What	are	the	characteristics	of	delirium	in	

patients	with	HIV	infection?

Delirium, which is a state of global derangement of 

cerebral function, occurs more frequently in medically 

Chapter	14:	

Mental	Health	Disorders Linda Frank, PhD, MSN, ACRN

Glenn J. Treisman, MD, PhD

Niccolo D. Della Penna, MD

OVERVIEW

DISORDERS OF ATTENTION OR COGNITION

PERSONALITY DISORDERS

MOOD DISORDERS

ANXIETY DISORDERS

SUGGESTED RESOURCES

REFERENCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 14: Mental Health Disorders 

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

14

ill, brain injured, or metabolically unstable patients. 

The clinical presentation and the differential diagnosis 

in HIV patients are the same as in HIV noninfected 

individuals, with the additional possibility that delirium 

is HIV-related. Presentation may vary in the presence 

of psychomotor agitation or retardation. Emotional 

changes are common and often unpredictable, and 

hallucinations and delusions are frequently seen. 

Electroencephalography may show diffuse slowing 

of the background alpha rhythm, which resolves 

as confusion clears. The syndrome has an acute or 

sub-acute onset and remits fairly rapidly once the 

underlying cause is treated.

How	do	you	manage	delirium	in	patients	with	

HIV	infection?

Non-pharmacologic treatments include identification 

and removal of the underlying cause, reorientation 

of the patient (calendars, clocks, view of outside 

world, and active engagement with staff members), 

and pharmacologic management of behavior or 

psychosis. Low doses of high-potency antipsychotic 

agents such as haloperidol are often useful. Newer, 

atypical antipsychotics are currently being used with 

some success, but those with more anticholinergic 

activity may worsen the condition. Benzodiazepines 

should be used cautiously, as they may contribute to 

delirium in some patients, except in cases of alcohol or 

benzodiazepine withdrawal deliria. Physical restraint 

should be used as little as possible as it often worsens 

delirium. 

How	do	you	diagnose	and	treat	

minor	cognitive-motor	disorder	(MCMD)?

MCMD is a less severe neurocognitive disorder of earlier 

HIV infection, and the symptoms are often overlooked 

because they may be very subtle. Cognitive and motor 

slowing are most prominent and are often discovered as 

a result of a minor complaint, such as taking longer to 

read a novel, dysfunction when performing fine motor 

tasks, or an increased tendency to stumble. Diagnosis 

is made by the finding of 2 or more of the following 

symptoms for more than a month: impaired attention 

and concentration, mental slowing, impaired memory, 

slowed movements, lack of coordination, and changes 

in personality (irritability or emotional lability). Some 

patients continue to have minor problems, while others 

progress to frank dementia. Antiretroviral therapy (ART) 

may be of some benefit in slowing progression, but this 

conclusion is confounded by a lack of understanding of 

factors that lead some patients to progress while others 

remain static. 

How	do	you	diagnose	and	treat	HIV-associated	

dementia?

HIV-associated dementia presents with the typical triad 

of symptoms seen in other subcortical dementias—

memory and psychomotor speed impairments, 

depressive symptoms, and movement disorders. 

Initially, patients may notice slight problems with 

reading, comprehension, memory, and mathematical 

skills. Patients later develop global dementia, with 

marked impairments in naming, language, and praxis. 

Clouding of consciousness is absent, and there is no 

evidence of another cause. Motor symptoms are often 

subtle in early stages, including occasional stumbling 

while walking or running, slowing of fine repetitive 

movements, and slight tremor. There may be impaired 

saccadic eye movements, dysdiadochokinesia, and 

hyperreflexia. Apathy is also a common early symptom, 

often causing noticeable withdrawal from social activity. 

A frank depressive syndrome also commonly develops, 

typically with irritable mood and anhedonia instead of 

sadness and crying spells. Sleep disturbances are quite 

common, as is weight loss. Psychosis may develop in a 

significant number of patients and generally presents 

with paranoid beliefs, although hallucinations may 

exist. In 5%-8% of patients, a syndrome known as 

AIDS mania develops in addition to the HIV-associated 

dementia. In later stages, there may be frontal release 

signs and rather severe motor symptoms, including 

marked difficulty in smooth limb movements, especially 

in the lower extremities.

HIV dementia is typically seen in late stages of illness, 

usually in patients who have had a CD4 count nadir 

of <200 cells/mm3. Certain risk factors have been 

associated with eventual development of HIV dementia, 

namely, higher HIV RNA viral load, lower education 

level, older age, anemia, illicit drug use, and female 

sex. Prognosis is rather poor, with a rapidly progressive 

nature, usually ending in death within 2 years.

Standard of care is to ensure an optimal ART regimen 

and treat associated symptoms aggressively. Depression 

can be treated with standard antidepressants, and 

in some cases methylphenidate or other stimulants 

may be useful in the treatment of apathy. Safety 

assessments should be performed as with any other 

case of dementing illness. 

What	is	the	relationship	between	psychosis	

and	HIV?

Psychosis, including schizophrenia, contributes to 

behaviors that may lead to HIV infection, including 

higher rates of injection drug use, unprotected sex, 
A Guide to Primary Care of People with HIV/AIDS

Chapter 14: Mental Health Disorders 

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14

multiple sex partners, trading sex for money or other 

goods, and sex while intoxicated (Cournos et al, 1994). 

Providers who see patients with psychosis should be 

sensitive to the risk of acquiring HIV and should screen 

patients carefully for risk behaviors.

Accumulating evidence suggests that HIV infection may 

be directly linked to the onset of psychosis. Psychosis 

can be a manifestation of delirium, affective disorders, 

or schizophrenia, but can it occur in the absence of 

these conditions. Estimates of the prevalence of newonset psychosis in patients with HIV range from 0.5%-

15%, which is higher than in the general population 

(Kendler et al, 1996; Sewell et al, 1994). New-onset 

psychosis may also be a manifestation of HIVassociated encephalopathy. History of substance abuse 

also is more common among patients with psychosis. 

How	do	you	treat	HIV-infected	patients	with	

schizophrenia?

The principles of treatment for HIV-infected patients 

with schizophrenia follow the same basic principles 

as for any other patient with schizophrenia, namely, 

control of symptoms with medications and psychosocial 

support and rehabilitation. Quite often, patients require 

long-term treatment and require various antipsychotic 

medications to control the delusions, hallucinations, 

and overall level of disorganization. 

PERSONALITY DISORDERS

What	is	the	relationship	between	personality	

disorders	and	HIV	infection?

Personality disorders represent extremes of normal 

personality characteristics and are disabling conditions. 

Clinical observation suggests that patients with 

personality disorders who are highly extroverted 

and highly neurotic are most prone to engage in HIV 

risk behavior. These individuals are preoccupied by 

and act upon their feelings, and their actions tend to 

be unpredictable and inconsistent. Past experience 

and future consequences have little salience in 

decisionmaking for individuals who are ruled by feeling; 

the present is paramount. Their overarching goal is 

to achieve immediate pleasure or removal of pain, 

regardless of circumstances. Patients are more fixed 

upon the reward of sex and remarkably inattentive 

to the STDs they may acquire. In addition, substance 

abuse is more likely a comorbidity with these patients. 

Injection drug use is markedly more common because 

the experience is much more intense and pleasurable. 

Thus, patients with personality disorders are at risk for 

HIV infection, and if they are already HIV-positive they 

are at risk for transmitting HIV to others. Management 

of patients with personality disorders includes 

encouraging a focus on thoughts rather than feelings, 

use of a behavioral contract, emphasis on constructive 

rewards, use of relapse prevention strategies, and 

coordination with additional health and psychosocial 

care providers. 

MOOD DISORDERS

What	are	characteristics	of	adjustment	

disorders	in	patients	with	HIV?

Adjustment disorders are common emotional responses 

to HIV and often account for the “hopeful highs” and 

“helpless lows” experienced by some patients. These 

reactions are typically situational and transient, but 

reflect significant distress in the patient. Adjustment 

issues vary according to a variety of factors in addition 

to stage of illness, risk factors, socieoeconomic status, 

level of education, characteristics of support networks, 

and comorbid psychiatric disorders. Adjustment 

reactions are most likely to occur at the time of 

significant medical events, especially during transition 

points in the illness. These conditions typically are 

accompanied by less severe depression and/or anxiety 

than are classic mood disorders. Treatment is usually 

non-pharmacologic and includes promotion of a 

structured environment, reassurance, engagement of 

the patient in the treatment process, close monitoring 

for progression of symptoms, and supportive counseling 

and psychotherapy.

How	do	you	diagnose	bipolar	disorder	in	

patients	with	HIV?

Bipolar disorder, also known as manic-depressive 

illness, is a condition in which patients classically 

alternate between extended episodes of depression and 

briefer periods of hypomania or mania with increased 

mood, increased energy, increased confidence, and 

grandiose ideas. Manic episodes are associated with 

increased rates of substance abuse and impulsive 

behavior, and there has been speculation that bipolar 

disorder may be a risk factor for HIV infection. AIDSrelated mania appears to be specifically associated with 

late-stage HIV infection and is associated with cognitive 

impairment and a lack of previous episodes or family 
A Guide to Primary Care of People with HIV/AIDS

Chapter 14: Mental Health Disorders 

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

14

history. The history will usually reveal progressive 

cognitive decline prior to the onset of mania. Irritable 

mood is more typical than euphoria, and prominent 

psychomotor slowing may replace the expected 

hyperactivity of mania, complicating the diagnosis. The 

presentation is usually quite severe in its course. AIDS 

mania appears to be more characteristically chronic, 

has few spontaneous remissions, and readily relapses 

with cessation of treatment (Lyketsos et al, 1997). 

How	do	you	treat	bipolar	disorder	in	patients	

with	HIV?

The treatment of mania in early-stage HIV infection 

is responsive to mood stabilizing medications, 

particularly lithium, valproic acid, and carbamazepine. 

Antipsychotic agents, particularly atypical agents, 

are often utilized in the acute phase as well. These 

medications decrease manic symptoms and may 

prevent recurrence. Treatment strategies may be 

somewhat different in advanced HIV disease. AIDS 

mania may respond to treatment with antipsychotics 

alone. In general, patients are often exquisitely sensitive 

to dosage changes that might otherwise seem trivial. 

Few data exist for the newer anticonvulsants such as 

gabapentin and lamotrigine, and these medications 

should be used sparingly. The major problem with 

lithium in AIDS patients has been rapid fluctuations 

in blood level, even when on previously stable doses. 

Lithium intoxication is not uncommon in this setting. 

Valproic acid has been successfully used when titrating 

to usual therapeutic serum levels of 50-100 ng/dL. 

Hepatotoxicity may significantly limit treatment, 

particularly in the setting of chronic viral hepatitis 

or severe hepatic Mycobacterium avium complex 

infiltration. Hematopoietic abnormalities may also 

occur, requiring close monitoring of white blood cell 

and platelet levels. Carbamazepine may be effective but 

is poorly tolerated because of sedation and potential for 

bone marrow suppression in combination with antiviral 

medications and viral burden. Patients with late-stage 

HIV are also significantly affected by toxic side effects 

of antipsychotic medications, and a much lower dosage 

may be required than in other settings. 

How	do	you	diagnose	major	depressive	disorder	

in	patients	with	HIV?	

Several lines of evidence suggest that HIV is a causal 

factor in depression, and that depression is a causal 

factor in HIV-related morbidity (Ciesla and Roberts, 

2001). Differentiating appropriate sadness from 

pathologic depression may be difficult in the person 

infected with HIV. Psychomotor retardation and apathy 

of AIDS dementia complex may be confused with 

depression, but will often improve in patients who 

are on combination antiretroviral treatment. Organic 

mood disorders may also have symptoms similar to 

major depression and are responsive to antidepressant 

medication. 

Depression is underrecognized, underdiagnosed, 

and undertreated (see Table 14-2). At the same time, 

it is important for providers to consider alternative 

diagnostic possibilities for depressive symptomatology 

(see Table 14-3). 

 Table 14-2. Risk Factors for Depression

History of prior mood disorder

History of substance abuse or active substance use

Prior suicide attempt

History of anxiety disorder

Family history of depression or suicide

Inadequate social support

Nondisclosure of HIV status

Multiple losses

Advancing illness

Treatment failure

Table 14-3. Differential Diagnosis of 

Major Depression

Nonpathologic states of grief and mourning

Dysthymia

Delirium

Dementia

Demoralization

Substance intoxication

Substance withdrawal

CNS injury or infection

Acute medical illness

What	are	the	pharmacologic	treatment	

options	for	major	depression?

Pharmacotherapy is the mainstay of treatment for major 

depression (see Table 14-4). No single antidepressant 

has been found to be superior in treating HIV-infected 

patients as a group. Patient adherence to regimens 

is critical, and those who take adequate doses of 

antidepressants have the best chance of improving. A 

general rule is to start with low doses of any medication, 

titrating up to a full dose slowly, in order to minimize 

early side effects that may act as obstacles to adherence. 
A Guide to Primary Care of People with HIV/AIDS

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14

Table 14-4. Medications to Treat Depression in HIV Disease

Medication Starting 

dose

Usual 

therapeutic 

dose

Serum 

level Advantages Interactions with HIV medications

nortriptyline

(Pamelor)

10-25 mg 

qhs

50-150 mg qhs 70-125 

ng/dL

Promotes sleep, 

weight gain, decreases 

diarrhea

Fluconazole, lopinavir/ritonavir, and

ritonavir increase nortriptyline levels.

desipramine

(Norpramin)

10-25 mg 

qhs

50-200 mg qhs >125 

ng/dL

Promotes sleep, 

weight gain, decreases 

diarrhea

Lopinavir/ritonavir and ritonavir increase 

desipramine levels.

imipramine

(Tofranil)

10-25 mg 

qhs

100-300 mg qhs >225 

ng/dL

Promotes sleep, 

weight gain, decreases 

diarrhea

Lopinavir/ritonavir and ritonavir increase 

imipramine levels.

amitriptyline

(Elavil)

10-25 mg 

qhs

100-300 mg qhs 200-250 

ng/dL

Promotes sleep, 

weight gain, decreases 

diarrhea

Lopinavir/ritonavir and ritonavir increase 

amitriptyline levels.

clomipramine

(Anafranil)

25 mg 

qhs

100-200 mg qhs 150-400 

ng/dL

Promotes sleep, 

weight gain, decreases 

diarrhea

Lopinavir/ritonavir and ritonavir increase 

clomipramine levels.

doxepin

(Sinequan)

10-25 mg 

qhs

150-250 mg qhs 100-250 

ng/dL

Promotes sleep, 

weight gain, decreases 

diarrhea

lopinavir/ritonavir and ritonavir increase 

doxepin levels.

fluoxetine

(Prozac)

10 mg 

qam

20 mg qam unclear Activating, energizing Amprenavir, delavirdine, efavirenz, indinivir, 

lopinavir/ritonavir, nelfinavir, ritonavir, and 

saquinavir increase HIV medication levels.

Nevirapine decreases fluoxetine levels.

sertraline

(Zoloft)

25-50 mg 

qam

50-150 mg qam unclear Lopinavir/ritonavir and ritonavir increase 

sertraline levels.

citalopram

(Celexa)

20 mg 

qam

20-60 mg qam unclear Lopinavir/ritonavir and ritonavir increase 

citalopram levels.

paroxetine

(Paxil)

10 mg 

qhs

20-40 mg qhs unclear Mildly sedating Lopinavir/ritonavir and ritonavir increase 

paroxetine levels.

fluvoxamine

(Luvox)

50 mg 

qhs

150-250 mg qhs unclear Mildly sedating Amprenavir, delavirdine, efavirenz, 

indinavir, lopinavir/ritonavir, nelfinavir, 

ritonavir and saquinivir increase HIV 

medication levels.

Nevirapine decreases fluvoxamine levels.

venlafaxine

(Effexor)

37.5 mg 

qam

75-300 mg qam unclear Lopinavir/ritonavir and ritonavir increase 

venlafaxine levels.

mirtazepine

(Remeron)

7.5-15 

mg qhs

15-45 mg qhs unclear Promotes sleep, weight 

gain

nefazodone

(Serzone)

50 mg bid 300-400 mg/d

 in divided doses

unclear Mildly sedating Efavirenz and indinavir increase HIV 

medication levels.

trazodone

(Desyrel)

50-100 

mg qhs

50-150 mg qhs 

for sleep

200-600 mg qhs 

for depression

unclear Promotes sleep Lopinavir/ritonavir and ritonavir increase 

trazodone levels.

bupropion

(Wellbutrin)

100 mg 

qam

150-400 mg/d

 in divided doses

unclear Activating, no sexual 

side effects
A Guide to Primary Care of People with HIV/AIDS

Chapter 14: Mental Health Disorders 

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

14

The first week of treatment usually determines whether 

a patient will be able to tolerate the medication at all. 

Following this period, the dosage should be increased 

slowly to either a typical therapeutic dose or serum 

level, when appropriate. Patients should be encouraged 

to wait as long as possible for the therapeutic effect, 

which may take at least 6 weeks to achieve. Close 

monitoring for side effects should be done at every 

visit, and the side effects treated whenever possible. 

For example, insomnia because of selective serotonin 

reuptake inhibitor (SSRI) use may respond well to 

low doses of trazodone. Constipation from tricyclic 

antidepressants is often relieved by increasing water 

and fiber intake. Sexual side effects from SSRIs are 

common and may be treated with sildenafil in some, or 

by drug holidays, switching to bupropion, and addition 

of buspirone, cyproheptadine, or ginkgo biloba. 

For patients showing only partial response to 

antidepressant medications after an adequate trial 

period, several other agents are often useful for 

augmentation strategies. The best studied is lithium, 

yet its side-effect profile often prevents use in the 

HIV setting. Olanzapine, risperidone, and pindolol 

have also been reported to be effective augmenting 

agents, as well as addition of a second antidepressant, 

other mood stabilizers, trazodone, methylphenidate, 

benzodiazepines, sleep deprivation, and phototherapy. 

If no benefit is gained from the primary antidepressant, 

even after augmentation, a new primary agent should 

be chosen and similarly titrated slowly, and augmented 

if necessary. There is evidence to suggest that a 

response may be seen from 1 drug where none was 

seen from another in the same class. 

What	are	the	nonpharmacologic	treatments	

for	major	depression?

Psychotherapy is an integral part of the treatment of 

major depression. Treatment with medication plus 

psychotherapy has been shown to be more effective 

for patients than either modality alone. Patients often 

require education about the disease nature of their 

depression, encouragement, and therapeutic optimism 

that the treatments will work. Medical providers 

who keep the concept of psychotherapy in mind will 

structure their interactions with patients to slowly 

empower and enable the patients to take control of 

their lives, thus relying on their providers less and less. 

ANXIETY DISORDERS

How	do	you	diagnose	anxiety	disorder	in	

patients	with	HIV	infection?

Anxiety disorder, which can include generalized anxiety 

disorder, panic disorder, obsessive-compulsive disorder, 

and post-traumatic stress disorder, is a common 

response to the stressors of HIV infection at any stage. 

True anxiety disorders tend to be less prevalent than 

depressive disorders, particularly at later stages of 

HIV infection. Anxiety is often a component of major 

depression, and further history should be ascertained 

for patients presenting with symptoms of panic or 

anxiety. Anxiety may also be due to substance use, and 

neurologic and physical impairment.

What	are	pharmacologic	treatments	for	HIVinfected	patients	with	anxiety?

Physicians must aggressively screen for major 

depression in patients presenting with anxiety 

symptoms, because both conditions often coexist. In 

particular, anxiety is a frequent symptom of major 

depression. Antidepressant medications are very 

effective in most cases.

In particularly debilitating cases, however, anxiolytic 

medications can be used for time-limited intervention 

and in low doses. Exclusion of patients with comorbid 

substance abuse is essential prior to initiation of 

anxiolytic medication, because of the abuse liability. 

Medications with a short half-life should be very 

cautiously used, as dependence may easily develop 

over a short period of usage. Particular attention should 

be given to the issues of hepatic function and choice 

of anxiolytic. Lorazepam, oxazepam, and temazepam 

avoid hepatic glucuronide conjugation by means of an 

alternate metabolic pathway and should be chosen as 

first-line medications for patients with HIV-associated 

liver dysfunction, as in patients with viral hepatitis. 

What	are	nonpharmacologic	treatments	for	

HIV-infected	patients	with	anxiety?

Specific advantages to utilizing nonpharmacologic 

intervention for anxiety include a decrease in pill 

burden, decrease in CNS sedation and cognitive 

impairment, lack of drug-drug interaction, and avoiding 

polypharmacy. Some interventions are 1) muscle 

relaxation, 2) meditation techniques, 3) psychotherapy, 

4) exercise, 5) biofeedback, 6) behavioral techniques, 

7) guided imagery, and 8) cognitive therapy.
A Guide to Primary Care of People with HIV/AIDS

Chapter 14: Mental Health Disorders 

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14

SUGGESTED RESOURCES

Lyketsos CG, Hanson A, Fishman M, 

McHugh PR, Treisman GJ. Screening 

for psychiatric morbidity in a medical 

outpatient clinic for HIV infection: the 

need for a psychiatric presence. Int J 

Psychiatr Med. 1994;24:103-113.

Angelino AF, Treisman GJ. Management of 

psychiatric disorders in patients infected 

with human immunodeficiency virus. Clin 

Infect Dis. 2001;33:847-856.

Treisman G, Fishman M, Schwartz J, 

Hutton H, Lyketsos C. Mood disorders in 

HIV infection. Depress Anxiety. 1998;7:178-

187.

Ickovics JR, Hamburger ME, Vlahov D, 

et al. Mortality, CD4 cell count decline, 

and depressive symptoms among HIVseropositive women: Longitudinal analysis 

from the HIV Epidemiology Research 

Study. JAMA. 2001;285:1466-1474.

Lyketsos CG, Hoover DR, Guccione M, et al. 

Changes in depressive symptoms as AIDS 

develops. Am J Psychiatry. 1996;153:1430-

1437.

Sher KJ, Trull TJ. Substance use disorder 

and personality disorder. Current 

Psychiatry Reports. 2002;4:25-29.

REFERENCES

Ciesla JA, Roberts JE. Meta-analysis of the 

relationship between HIV infection and risk 

for depressive disorders. Am J Psychiatry.

2001;158:725-730.

Cournos F, Guido JR, Coomaraswamy S, 

Meyer-Bahlburg H, Sugden R, Horwath E. 

Sexual activity and risk of HIV infection 

among patients with schizophrenia. Am J 

Psychiatry. 1994;151:228-232.

Kendler KS, Gallagher TJ, Abelson 

JM, Kessler RC. Lifetime prevalence, 

demographic risk factors, and diagnostic 

vulnerability of nonaffective psychosis as 

assessed in a US community sample. The 

National Comorbidity Survey. Arch Gen 

Psychiatry. 1996; 53:1022-1031.

Lyketsos CG, Schwartz J, Fishman M, 

Treisman G. AIDS mania. J Neuropsychiatry 

Clin Neurosci. 1997;9:277-279. 

Sewell DD, Jeste DV, Atkinson JH, et al. HIVassociated psychosis: a study of 20 cases. 

San Diego HIV Neurobehavioral Research 

Center Group. Am J Psychiatry. 1994;151:

237-242.

Treisman GJ. AIDS education for psychiatrists. 

Primary Psychiatry. 1999;6:71-73. 
A Guide to Primary Care of People with HIV/AIDS

Chapter 15: Palliative and End-of-Life Care 

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 123

15

INCORPORATING PALLIATIVE

CARE INTO HIV CARE

What	is	palliative	care?	

Palliative medicine is the discipline devoted to the 

relief of suffering and the promotion of quality of 

life. Palliative, meaning non curative, has often been 

misunderstood to be limited to end-of-life or hospice 

care; it is rather a more general term for the type of 

supportive care needed throughout the trajectory of any 

chronic illness or major injury. 

In traditional medical care, efforts are primarily curative 

or restorative until a poorly defined point when provider 

and patient acknowledge disease progression and 

decide to shift toward less aggressive management (See 

Figure 15-1a). In chronic progressive illnesses supportive 

care might be provided simultaneously assuring 

maximum quality of life throughout the course of illness 

for patients, family and caregivers (Figure 15-1b). 

Why	is	palliative	care	still	needed	for	people	

with	HIV/AIDS,	now	that	antiretroviral	

therapy	(ART)	is	so	successful?	

AIDS, originally considered a terminal illness, has 

transitioned to a chronic disease for those who are able 

to use ART. However, there is still a steady death rate in 

the United States of 15,000 to 16,000 per year. While 

the numbers are low compared with the epidemic in 

the early years, persons living with HIV disease continue 

to experience pain, body habitus changes, and other 

physical and emotional symptoms that negatively impact 

their daily quality of life. Preventing and controlling these 

problems are as relevant as reducing viral load. Setting 

realistic goals and improving self-esteem allow the person 

with HIV disease to remain in control of his/her life and 

to be a productive member of society. 

Chapter	15:	

Palliative	and	End-of-Life	Care

Carla S. Alexander, MD

Kennita R. Carter, MD

INCORPORATING PALLIATIVE CARE INTO HIV CARE

CARE AT THE END OF LIFE

KEY POINTS

SUGGESTED RESOURCES

REFERENCES

Figure 15-1a: Traditional Model of Care (first curative, then palliative) 

Person with Illness

Curative Care

(= disease-specific, restorative)

Diagnosis

Palliative Care

(= supportive,

symptom-oriented)

Dying Death

Disease Progression

Source: World Health Organization. Cancer Pain Relief and Palliative Care, Report of a WHO Expert Committee.

Publication #1100804. Geneva: World Health Organization, 1990.
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What	does	palliative	care	focus	on?	

The following are essential elements of palliative care:

• Goals of care are patient- and family-driven and 

frequently revised.

• Relationships with an interdisciplinary team provide 

the mechanism for care.

• Truth-telling and support for realistic decisionmaking 

are the norm. 

• Aggressive prevention and control of bothersome 

symptoms are paramount.

• It is understood that psychosocial, emotional, and 

spiritual needs significantly impact symptoms.

• Integration of a palliative care approach throughout 

the disease trajectory improves quality of life.

• Early identification of and communication with a 

proxy decisionmaker is a priority.

• Evaluation and treatment decisions are modified 

based upon prognosis.

• Near the end of life, unnecessary drugs are eliminated 

and comfort measures provided.

• Assisting the dying person to achieve psychosocial 

and spiritual closure is a goal of care.

• Family and friends are provided with care techniques 

and communication skills. 

• Care of the caregiver and of the provider are essential 

aspects of providing supportive care. 

• Legal, ethical, and cultural aspects are acknowledged 

and respected. 

• It is recognized that dying is an inevitable part of life, 

not an enemy to be denied.

• Anticipatory grieving and bereavement support for the 

family are included in care.

How	can	palliative	care	be	incorporated	into	

primary	HIV	care?

A palliative approach to HIV disease management 

begins by obtaining an accurate assessment of the 

patient’s support system, life goals, and preferences 

early in the disease process. Then the following 

activities are incorporated into the care plan:

• Open appraisal of stage of disease with appropriate 

goal setting

• Yearly review of goals (more frequently if 

symptomatic)

• Anticipation of and prophylaxis for side effects of ART

• Education regarding advance care planning well 

before patient is symptomatic

• Use of standardized questionnaires to assess presence 

of symptoms and their impact on quality of life

• Provision of separate medical appointments to 

manage symptoms such as pain or weight loss

Figure 15-1b: Integrated Model of Care (curative and palliative together)

Person with Illness

Curative Care

(= disease-specific, restorative)

Diagnosis

Palliative Care

(= supportive, symptom-oriented)

Bereavement

Dying Death

Family

Caregivers

Disease Progression

Support services for

families and caregivers

Source: World Health Organization. Cancer Pain Relief and Palliative Care, Report of a WHO Expert Committee. Publication 

#1100804. Geneva: World Health Organization, 1990.
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• Reduction of diagnostic studies and number of 

medications as prognosis shortens 

• Regular review of health power of attorney and 

support of patient wishes 

• Discussions of prognosis with patient and family soon 

enough to allow closure near the end of life

• Referral to hospice/palliative home care when office 

visits become burdensome for patient

• Maintenance of contact with family during 

bereavement period

• Acknowledgement of staff members’ feelings of loss 

when patients die 

What	are	some	common	symptoms	experienced	

by	persons	with	advanced	HIV	disease?

In surveys, patients receiving ART report experiencing 

the same symptoms as patients reported in the earlier 

years of the epidemic, but the frequencies of symptoms 

have changed (Mathews et al, 2000; Vogl et al, 1998). 

Fatigue, sadness, diarrhea, and fever continue to plague 

patients even when disease is controlled by ART. Pain 

is still experienced by up to 75% of patients and may 

be present in multiple areas at once, including the 

extremities and oral, esophageal, abdominal, or rectal 

sites. Adequate treatment for one type of pain may 

only expose another. This often raises the specter of 

“drug-seeking behavior” when in fact the patient is 

simply able to be aware of the secondary pain after the 

greater pain is relieved (see Chapter 13, Management of 

Substance Abuse). Peripheral neuropathy can be caused 

by ART, HIV disease itself, or unrelated disease such as 

diabetes. This pain does not seem to be related to the 

degree of control of viral burden, and cause must be 

sought through historytaking as many patients seem 

to overlook early manifestations such as numbness. 

Refer to Chapter 8, Symptom Management, as well as 

resources under Suggested Resources for management 

of pain and symptoms.

How	important	is	pain	control	in	advanced	

HIV	disease?

Pain, as with any symptom, should be described, 

quantitated, treated, and promptly reevaluated with 

appropriate dose modification of therapy (see Table 15-1). 

In the Guidelines for Management of Cancer Pain, pain 

experienced by those with HIV disease is compared 

with the chronic pain experienced by persons with 

cancer, which often requires management with opioids 

(AHCPR, 1994). Unlike blood pressure, which might be 

regulated over weeks, pain should be controlled within 

the shortest time possible to prevent the development 

of long-term symptoms such as depression and 

anhedonia. 

Table 15-1. Mnemonic for 

Assessment of Pain

A Ask about pain regularly; Assess systematically

B Believe the patient and family

C Choose treatment options appropriate to patient 

and setting

D Deliver medications on an “around-the-clock” 

basis with adequate “breakthrough” doses

E Evaluate results frequently; Empower patients 

and families to control pain

The following guidelines are helpful in prescribing pain 

medication (American Pain Society, 1999): 

1. Use a grading system (such as the scale of 0–10) to 

document pain severity and compare the number 

obtained to a second number following treatment to 

evaluate response. 

2. Start with a dose that will acutely relieve the pain. 

This may be given intravenously or subcutaneously 

to achieve a rapid response. Care should be taken 

to observe for any signs of respiratory depression in 

opiate-naive patients who receive parenteral opioids.

3. Next, begin a low dose every 3–4 hours (based on the 

half-life of the drug) “around-the-clock,” not on an 

as-needed, basis. The initial dose should be chosen 

based on the age, size, and renal/hepatic function of 

the patient. (See Suggested Resources for additional 

guidance on pain management.) 

4. A “ breakthrough dose” should also be prescribed 

every 1-2 hours prn equal to a sixth of the total daily 

opioid dose. This allows for development of a steady 

state drug level and avoids alternation of great pain 

intensity with somnolence. This is the same approach 

used to control hyperglycemia with a sliding scale of 

regular insulin based on glucometer readings; doses 

are based on pain scores.

5. When pain is fairly well controlled, it is appropriate to 

change the patient to a long-acting pain medication 

for ease of administration. The dose is calculated 

by adding together the total dose taken in 24 hours 

and dividing by the half-life of the new preparation. 

For example, for a medication meant to be given 

every 12 hours: divide the total dose by 2, and this 

number will be the dose every 12 hours. Don’t forget 

the breakthrough dose. This is a short-acting opioid, 

preferably of the same type as the long-acting one 

for use at times when the pain is not adequately 

controlled. 

6. Other forms of administration include liquid 

formulations for persons with difficulty swallowing, 

rectal suppositories, “sprinkles” that can be mixed 

with soft food, and patches that allow absorption of 

the medication through the skin.
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What	is	advance	care	planning?

Advance care planning is an attempt to clarify patient 

wishes near the end of life. Identification of a “health 

care proxy,” a person who makes decisions if the 

patient becomes unable to communicate his or her 

own wishes, should be encouraged and documented 

in the medical record with contact information. Even 

when formal directives have not been written the 

patient should discuss his or her thoughts and concerns 

about the end of life with that person. Hosting a family 

meeting to discuss the issues might also be useful. A 

“living will” may be difficult to write because it is not 

possible to anticipate every event that might occur 

when one is critically ill. It may be better for the person 

to clarify general thoughts about the use of ventilators 

or other intensive support mechanisms for sustaining 

life. Permanency planning should be included in this 

discussion whenever children are involved. 

Family members feel inadequate when confronted 

with end-of-life decisionmaking. Realistic guidance 

provided to the health care proxy can minimize that 

emotional burden (see Table 15-2). The provider 

should discuss in detail what a resuscitation effort 

means and give a specific description of what might 

happen during the use of “life supports” (eg, one 

cannot talk and may not be able to communicate when 

on a respirator; the combination of early dementia 

and an episode of hypoxia might result in significant 

diminution of mental capacities).

What	is	hospice	care?

Hospice can be a philosophy, a place, a type of 

home care, or a reimbursement mechanism (EPEC 

Curriculum, 2003). The goal of hospice care is to reduce 

suffering by controlling symptoms, consolidating 

medications, and supporting the patient and family in 

living fully until death. However, in the United States 

obtaining hospice care for any individual often depends 

on insurance coverage. For a person on Medicare a 

referral to hospice care requires that the patient have 

a life expectancy of less than 6 months if the disease 

runs its normal course. This is a complex determination 

in any chronic illness. Patients who have decided to 

forego restorative therapy or who no longer want to be 

admitted to a hospital are not the norm in HIV disease, 

but working with a local hospice program may make 

this transition less burdensome. For financial reasons 

the patient may be offered “palliative” rather than 

“hospice” care. 

Table 15-2. Useful Questions for Exploring 

Patient and/or Family Concerns

Domain Question

Physical comfort

Tell me about your pain. Can you rate it 

on a 10-point scale?

How much do you suffer from physical 

symptoms like shortness of breath, 

fatigue, or bowel problems?

Continuity with 

one’s self

What makes life most worth living for 

you at this time?

If you were to die sooner rather than 

later, what would be left undone?

Maintaining 

and enhancing 

relationships

How are your family (or loved ones) 

handling your illness?

Have you had a chance to tell your 

family (or loved ones) how they are 

important to you?

Making meaning

of life and death

What kind of legacy do you want to 

leave behind?

What would allow you to feel that going 

through this illness has a purpose?

Do you have spiritual beliefs that are 

important in how you deal with this 

illness?

Achieving a sense 

of control

How would you like your death to go?

Confronting and 

preparing for 

death

How much are you thinking about dying 

now? What are you thinking about it?

Source: Alexander C, Back A, Perrone M. Medical Care at the End 

of Life. In O’Neill JF, Selwyn PA, Schietinger H, eds. A Clinical Guide 

to Supportive and Palliative Care for HIV/AIDS. Rockville MD: Health 

Resources and Services Administration. 2003.

CARE AT THE END OF LIFE

What	are	the	challenges	of	end-of-life	care	for	

the	provider?

Deciding when to make the transition from curative/

restorative mode to one of comfort measures only and 

having the skills to communicate this to the patient are 

probably the greatest challenges facing the provider 

(see Table 15-3). While guidelines exist for having 

difficult conversations effectively, avoiding conveying 
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a message of abandonment is the real difficulty. 

Being adept at managing symptoms such as pain 

can give the provider confidence when initiating this 

conversation. Reassuring the patient and family that 

comfort measures are always possible and isolating one 

problem at a time may minimize their sense of being 

overwhelmed. Simply asking the patient what goals are 

important helps refocus on concrete issues that can be 

successfully mastered. 

Another significant challenge for the provider may be 

foregoing invasive diagnostic studies when the patient 

is moving closer to death. The astute practitioner 

needs to rely on physical assessment and knowledge of 

probabilities to surmise the cause of a symptom. Using 

one medication for multiple outcomes minimizes pill 

burden. For example, steroids may be employed for 

relief from dyspnea; this same drug might also improve 

appetite and sense of well-being, suppress fever, and 

relieve achiness related to prolonged bedrest.

Table 15-3. Mnemonic for 

Breaking Bad News

S Setting and listening Skills

P Patient and family Perception of condition

I Invitation to patient to determine how much Information 

he/she wants to know

K Knowledge; reviewing the facts

E Explore Emotions and Empathize

S Summary & Strategy

Source: Adapted from Baile W, Buckman R. Practical Guide to 

Communication Skills in Clinical Practice. Niagara Falls, NY: Medical 

Audio Visual Communications, Inc, 1998.

What	roles	do	culture	and	spirituality	play	in	

end-of-life	care?	

Culture and spirituality are significant factors affecting 

how end-of-life care should be delivered to each 

individual patient and family. Lack of clarification of 

cross-cultural differences can be a barrier to patients’ 

receiving appropriate end-of-life care. Spirituality, 

connection with a higher power, or a sense of meaning 

can provide tremendous comfort and support. Not 

recognizing these issues or the impact of AIDS-related 

stigma might even add to suffering. It is useful to ask 

the patient if he/she has a faith and how important it 

is to him/her. If the provider does not feel comfortable 

addressing these issues, every attempt should be made 

to have someone on staff or for easy referral to address 

this need. It has been clearly documented in medical 

literature that spiritual concerns might be involved in 

exacerbation of all types of illness.

How	do	you	provide	reality-based	hope	for	the	

person	with	advanced	AIDS?

Hope is an intrinsic value that allows the human 

spirit to persevere even against great difficulty. When 

a person is nearing the end of life, it may not be 

reasonable to want to live until a certain birthday that 

will not occur for several months. In this case, the 

health care staff needs to help with a redefinition of 

hope that is more achievable. Some families in hospice 

programs have celebrated religious holidays a month 

ahead of time, held ceremonies before they were 

originally scheduled, and made videotapes of the dying 

person to be played during an up-coming event. 

How	do	you	conduct	a	family	meeting?

Prior to a family meeting, the provider must prepare a 

mental agenda to identify internal and external barriers 

to achieving a clear and therapeutic picture of the goals 

important to all involved (see Table 15-4).

What	does	the	patient	need	to	accomplish	

before	death?

There are multiple physical, psychosocial, and spiritual 

issues that deserve attention in order for the patient to 

die peacefully and to leave satisfactory memories for 

family and friends. The patient and family need to:

• Appoint a health power of attorney and talk with that 

person about support preferences

• Make a will to avoid conflict following death, including 

guardianship issues

• Attempt to resolve previous misunderstandings or 

estrangements

• Encourage family and friends to openly discuss the 

patient’s deterioration to avoid a “conspiracy of silence”

• Express love and appreciation to family, friends, and staff

• Engage family, friends, and staff in a life review (eg, 

telling stories about accomplishments, regrets, funny 

things that have happened along the way)

• Create a memory book or video tape, or write letters 

for children left behind

• Discuss plans or preferences regarding funeral or 

memorial service

• Say goodbye to family, friends, and caregivers (the 

patient needs reassurance that those left behind will 

be cared for and that he or she will be remembered)
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Table 15-4. Components of a Discussion 

about End-of-life Care

I. Making preparations prior to a discussion about 

end-of-life care:

• Review previous knowledge of the patient and/or their 

significant others

• Review previous knowledge of the patient’s attitudes and reactions

• Review your knowledge of the disease prognosis, treatment options

• Examine your own personal feelings, attitudes, biases, and grieving

• Plan the specifics of location and setting: a quiet, private place

• Have advance discussion with the patient or family about who 

will be present 

II. Holding a discussion about end-of-life care: 

• Introduce everyone present

• If appropriate, set the tone in a non-threatening way: “This is a 

conversation I have with all my patients...”

• Find out what the patient or significant other understands 

• Find out how much the patient or significant other wants to know

• Be aware that some patients do not want to discuss end-of-life care

• Discuss prognosis frankly in a way that is meaningful to the patient

• Do not discourage all hope

• Avoid temptation to give too much medical detail

• Make it clear that withholding life-sustaining treatment is NOT 

withholding caring

• Use repetition to show that you understand what the patient or the 

significant other is saying

• Acknowledge strong emotions and use reflection to encourage 

patients or their significant others to talk about these emotions

• Tolerate silence

III. Finishing a discussion of end-of-life care:

• Achieve common understanding of the disease and treatment issues

• Make a recommendation about treatment

• Ask if there are any questions

• Ensure basic followup plan and make sure the patient and/or 

significant others know how to reach you for questions

Source: Curtis JR. Patient-Clinician Communication. In O’Neill JF, 

Selwyn PS, and Schietinger H, Eds. A Clinical Guide to Supportive and 

Palliative Care for HIV/AIDS. Rockville, MD: Health Resources and 

Services Administration, 2003.

What	steps	should	you	take	af ter	writing	a	Do	

Not	Resuscitate	(DNR)	order?

After writing an order for “No CPR” the provider 

should reverse these letters to offer family and friends 

“RPC” - Reassurance, Presence, and Caring. Facilitate 

conversations that acknowledge the role of family 

and friends in care. Be present for family even if only 

briefly. For hospitalized patients, write orders to 

intervene that assure comfort measures will be 

provided even when antibiotics or pressors might 

be discontinued (see Table 15-5).

Table 15-5: Life’s End

The following mnemonic may be helpful when writing DNR 

orders: LIFE’S END. This stands for

L Keep the Lips and mouth moistened with ice 

chips

I Expect urinary and fecal Incontinence when 

patient is too weak to get out of bed; insert a 

catheter/use bed pad

F Expect Fevers and use around-the-clock 

antipyretics possibly by the rectal route

E Eliminate all but Essential medications

‘S Be aggressive about Symptom management

E Eating decreases; substitute other supportive 

activity for family members who want to 

continue feeding

N Nursing call orders should be revised

D Decubitus ulcer prevention requires turning 

every 2 hours

Source: Copyright Palliative Care Program, University of Maryland, 

Baltimore, MD; 1999. Reprinted with permission.

What	can	the	family	expect	as	their	loved	one	

is	dying?

Many people have little experience with the actual 

process of dying. At a time when family members feel 

grief and a loss of control, it is comforting to have a 

simple description of what to expect as they sit at the 

bedside. The provider needs to offer this information 

(see Table 15-6) as well as to suggest activities the 

family can do to offer comfort and to alleviate their 

feeling of helplessness. 

What	must	the	provider	do	after	the	patient	dies?	

At the time of death, those present need verification 

that in fact their loved one has died. It is useful to 

review what has happened and to offer supportive 

comments to those present as they adjust to this new 

information. It is comforting for them to remain with 

the deceased and say their goodbyes. Cultural beliefs 

will dictate behavior, and it is helpful to have discussed 

these practices ahead of time. Providers can:

• Reassure the family that they provided good and 

loving care

• Allow family members to remain at the bedside as 

long as necessary to bring closure
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• In the hospital, place something on the bed to honor 

the space recently vacated

• Tell family when to expect autopsy findings if autopsy 

is requested

• If an autopsy is performed, schedule time to discuss 

this with the family

• Notify other staff members who may have cared for 

this patient

• Send a condolence card

• Call family 1-2 weeks after the death to listen

Table 15-6: What the Family Should 

Expect of the Patient Prior to Death

1–2 weeks 

prior to death

• Withdrawal from people

• Decreased food and liquid intake

• Talking with those who are already dead

• Sleeping longer periods

• Picking at clothing

• Feeling very fatigued

Days to hours 

prior to death

• Surge of energy; seems like “himself” 

Cheyne-Stokes respirations

• Decreased urine output

• Acral and large joint cyanosis

• “Death rattle”

• Weak pulse and decreased blood 

pressure

Source: Adapted from Kearnes, Gone from My Sight. Depoe Bay OR: 

BK Books; 1995.

How	can	a	primary	care	practice	or	clinic	avoid	

staff	burnout	when	several	of	the	patients	

have	died?	

Providers who suffer from the death of more than 

one patient over a short time period may experience 

symptoms of multiple loss syndrome which, if 

unattended, can lead to symptoms found in posttraumatic stress disorder. They need to take the time 

to effectively grieve. How this is accomplished is a 

personal matter for each individual, but the clinic or 

health care facility must recognize the importance of 

allowing each person to come to a sense of closure 

after a patient’s death. For some, attending the wake 

or funeral may be helpful. For others, a clinic-based 

time for remembering the individual(s) can provide a 

structured outlet for feelings of grief. 

The focus of providers tends to be on caring for others. 

Primary care providers often have not received formal 

training in preventing and identifying burnout. With 

an ever increasing work load and shrinking time for 

office visits and administrative responsibilities it is easy 

to miss signs of stress (see Table 15-7). O’Neill and 

McKinney describe a 2-pronged approach to preventing 

and managing burnout. This involves developing more 

effective individual coping skills as well as creating a 

less stressful work environment (O’Neill and McKinney, 

2003). Examples of personal coping strategies include: 

1) being mindful of eating, exercise, and sleep patterns, 

2) keeping a daily journal to record the events that 

cause stress, and 3) discussing personal experiences 

with someone else. A less stressful work environment 

includes a choice of mechanisms for ‘taking a break’ 

from the steady emotional drain of patient care.

Table 15-7: Common Signs of 

Stress for Caregivers 

Physical Psychological Behavioral

Backaches Anger and 

frustration

Emotional 

outbursts

Change in eating 

patterns

Loss of selfconfidence and 

self-esteem

Withdrawal from 

friends and family

Diarrhea

Loss of interest in 

and commitment 

to work

Loss of punctuality 

and neglect of 

duty

Elevated blood 

pressure

Feelings of 

inadequacy, 

helplessness, and 

guilt

Decrease in 

judgmental ability

Fatigue Feelings of 

restlessness

Inability to focus 

on tasks

Gastrointestinal 

problems Depression Tearfulness

Headaches

Sense of being 

overwhelmed or 

overloaded

Increased use of 

alcohol or other 

drugs

Insomnia Mood swings Difficulty getting 

along with people

Muscle tension Sense of failure Impaired work 

performance

Weight loss Anxiety about the 

future

Resistance to 

change

Source: O’Neill JF, McKinney M. Caring for the caregiver. O’Neill JF, 

Selwyn PA, and Schietinger H, Eds. The Clinical Guide to Supportive 

and Palliative Care for HIV/AIDS. Rockville, MD: Health Resources and 

Services Administration, 2003.
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Chapter 15: Palliative and End-of-Life Care 

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

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KEY POINTS

Palliative medicine is the discipline 

devoted to the relief of suffering and the 

promotion of quality of life. Palliative 

care has often been thought to be limited 

to end-of-life or hospice care; it is rather 

a more general term for the type of 

supportive care needed throughout the 

trajectory of HIV disease.

Advance care planning is an attempt 

to identify a decisionmaker should the 

patient become unable to communicate 

his or her own wishes. 

Deciding when to make the transition 

from curative/restorative mode to one of 

comfort measures only and having the 

skills to communicate this to the patient 

are probably the greatest challenges 

facing the provider.

There are multiple physical, psychosocial, 

and spiritual issues that need resolution 

in order for the patient to die peacefully 

and to leave satisfactory memories for 

family and friends.

The focus of providers tends to be on 

caring for others. Providers who suffer 

from the death of more than one patient 

over a short time period can experience 

symptoms of post-traumatic stress 

disorder. They need to take the time to 

effectively grieve.

SUGGESTED RESOURCES

Alexander C. Palliative and end-of-life 

care. In Anderson J, ed. A Guide to the 

Clinical Care of Women with HIV. Rockville, 

MD: Health Resources and Services 

Administration; 2001. Available at 

http://www.hab.hrsa.gov. 

Doyle D, Hanks GWC, Cherny N, and 

Calman K, eds. The Oxford Textbook of 

Palliative Medicine, 3rd ed. New York: 

Oxford University Press; 2003. 

O’Neill, JF, Selwyn, PA, and Schietinger, H, 

eds. The Clinical Guide to Supportive and 

Palliative Care for HIV/AIDS. Rockville, 

MD: Health Resources and Services 

Administration; 2002. Available at 

http://www.hab.hrsa.gov.

Selwyn PA, Rivard M. Palliative care for 

AIDS: Challenges and opportunities in the 

era of highly active antiretroviral therapy.

J Palliat Med. 2003;6:475-487.
A Guide to Primary Care of People with HIV/AIDS

Chapter 15: Palliative and End-of-Life Care 

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REFERENCES

Agency for Health Care Policy and 

Research. Clinical Practice Guideline Number 

9: Management of Cancer Pain. AHCPR 

Publication #94-0592. Rockville, MD: Agency 

for Health Care Policy and Research; 1994.

American Pain Society. Principles of 

Analgesic Use in the Treatment of Acute 

Pain and Cancer Pain, 5th ed. Glenville IL: 

American Pain Society; 2003. 

Baile W, Buckman R. Practical Guide to 

Communication Skills in Clinical Practice. 

Niagara Falls, NY: Medical Audio Visual 

Communications, Inc; 1998.

Curtis JR. Patient-Clinician Communication. 

In O’Neill JF, Selwyn PS, and Schietinger 

H, eds. A Clinical Guide to Supportive and 

Palliative Care for HIV/AIDS. Rockville, 

MD: Health Resources and Services 

Administration; 2003.

Education for Physicians on End-of-Life Care 

(EPEC) Curriculum. Chicago, IL: American 

Medical Association; 2003. Available at 

http://www.ama-assn.org/ama/pub/category/

2910.html

Kearnes B. Gone from My Sight. Depoe Bay, 

OR: BK Books; 1995. Available at 

http://www.bkbooks.com.

Mathews W, McCutcheon JA, Asch S, et al. 

National estimates of HIV-related symptom 

prevalence from the HIV Cost and Services 

Utilization Study. Med Care. 2000;38;750-762.

O’Neill JF, McKinney M. Caring for the 

caregiver. O’Neill JF, Selwyn PA, and 

Schietinger H, Eds. The Clinical Guide 

to Supportive and Palliative Care for 

HIV/AIDS. Rockville, MD: Health Resources 

and Services Administration; 2003.

Vogl D, Rosenfeld B, Breitbart W, et al. 

Symptom prevalence, characteristics, and 

distress in AIDS outpatients. J Pain Symptom 

Manage. 1999;18:253-262.

World Health Organization. Cancer Pain 

Relief and Palliative Care, Report of a WHO 

Expert Committee. Publication #1100804. 

Geneva: World Health Organization; 1990.
A Guide to Primary Care of People with HIV/AIDS

Chapter 16: Clinic Management

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PATIENT RECRUITMENT

AND RETENTION

How	can	primary	care	clinics	recruit	patients	

with	HIV	into	care?

The persons who were easy to recruit and retain in care 

are already enrolled; the more challenging patients 

await recruitment. Every clinic should 1) be linked to 

agencies providing HIV testing and services for persons 

with HIV and 2) make clinic access easy for the clients 

of those outside services.

Many clinics establish referral linkages with community 

services that provide HIV counseling and testing 

services (CTS), AIDS service organizations (ASOs), STD 

treatment facilities, family planning agencies, drug 

treatment facilities, local health departments, regional 

HIV/AIDS hotlines, and local hospitals and emergency 

rooms. Many clinics also offer free confidential or 

anonymous CTS using State or Federal funding. 

Clinic personnel should build personal relationships 

with agencies that may provide referrals, invite staff of 

community agencies to visit the clinic, or hold an open 

house. Providers from ASOs, such as case managers, 

can be invited to accompany patients on clinic visits. 

Referring agencies must know what services the clinic 

provides and which patients it serves, as well as those it 

cannot serve. Clinics with Ryan White Care Act (RWCA) 

funding should be able to accept patients regardless of 

health insurance or ability to pay. Primary care clinics can 

benefit from having a brochure describing their programs 

and array of services, along with information about 

making appointments, hours of service, and so forth. 

Clinics differ based on the characteristics of the people 

living in their catchment area and the expertise of 

clinic staff. Some successful clinics target a narrow 

but underserved population and concentrate on 

meeting the needs of that population. A youth-friendly 

environment may differ from one targeting the 

working poor.

How	do	clinics	retain	patients	in	care?

Respect, cultural competence: Respecting patients 

and providing them with effective care builds trust 

and keeps them coming back. New clinic attendees 

may have strong feelings related to HIV infection 

(fear of death) or how they acquired it (issues of 

shame or of secrecy). They may lack trust in medical 

care (prior personal experiences or the legacy of the 

Tuskegee syphilis experiments) or in current treatments 

(“Everyone I knew who took AZT died...”). Patients 

encounter barriers where there are cultural differences 

or language barriers between themselves and the 

staff. Staff members should be trained to anticipate, 

recognize, and work with these issues.

Welcoming staff attitude: Patients should always be 

made to feel that they came to the right place (even 

when it is not true, and they must be referred on). 

Patients should receive understanding and support, 

even when they arrive in clinic without obtaining the 

required managed care referral form (at least the first 

few visits). Providers must know the target population 

and build a system that will make patients feel 

welcome. Many RWCA-funded clinics employ patient 

advocates, persons from the target community who 

may or may not themselves be HIV-infected. Advocates 

directly assist patients in negotiating the clinical care 

system and help patients ask questions or make their 

needs known to clinical staff. Advocates or peer support 

persons can be instrumental in helping patients build 

self-esteem and acquire new habits that will enable 

them to use health care services in a proactive manner. 

It is very helpful for patients to be able to forge a 

personal connection with at least one staff member. 

Chapter	16:	

Clinic	Management Jonathan Allen Cohn, MD, MS, FACP

PATIENT RECRUITMENT AND RETENTION

CLINICAL SERVICES NEEDED FOR HIV CARE

SUPPORT SERVICES AND LINKAGES NEEDED FOR HIV CARE

KEY POINTS

SUGGESTED RESOURCES
A Guide to Primary Care of People with HIV/AIDS

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

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Welcoming environment: Physically comfortable 

waiting and examination areas, with linguistically and 

culturally appropriate decoration and reading material, 

are important for patient retention. A clinic that serves 

parents or children should make available toys or 

children’s books. 

Orientation to clinic systems and rules: New patients 

need a brief description of clinic staff and services, 

routine and emergency procedures, prescription refill 

procedures, and after-hours followup. They must 

understand about requirements for referrals from 

managed care providers, and new patients may need 

help with such requirements. Patients must also be 

oriented to what is expected of them (eg, coming on 

time, calling to cancel or reschedule appointments) and 

the consequences of not fulfilling their responsibilities 

(eg, clinic rules regarding late arrivals). A handout or 

pamphlet with staff names, clinic hours and phone 

numbers, and emergency procedures can be very helpful. 

Systems to support attendance: Patients should 

receive reminders (by phone or mail) about 48 hours 

before each appointment. It is also useful to have 

a staff member contact patients who have missed 

appointments to find out what prevented them from 

attending and offer to reschedule. ASOs may have 

funding for transportation (eg, door-to-door taxi service 

for selected patients, van service, vouchers for use on 

public transportation). Other barriers may require a 

coordinated effort by the clinic staff, case manager, and 

others. Clinic sessions should be scheduled at times 

convenient for the patients; mid-to-late afternoon is 

best for school-age children, occasional evenings or 

weekends are good for working people. 

CLINICAL SERVICES

NEEDED FOR HIV CARE

What	is	the	optimum	array	of	services	that	an	

HIV	clinic	should	provide?

All patients with HIV need a similar array of services 

that must be provided either directly or through referral. 

Patients need providers knowledgeable in the diagnosis 

and treatment of HIV infection and its complications, 

including state-of-the-art use of antiretroviral therapy 

(ART). Services must address the clinical conditions 

associated with patients’ current or prior risk behaviors. 

Given improved life expectancy, patients need ageappropriate general preventive and screening services. 

The high rates of premorbid mental health problems in 

persons with HIV and mental health problems related 

to HIV disease make mental health services a key 

component of HIV care. Substance abuse treatment 

is crucial. Confronting the epidemic by including HIV 

prevention activities in clinical care sites is a new 

activity, challenging and critically important (see 

Chapter 4). 

The HIV/AIDS Bureau of the Health Services and 

Resources Administration (HRSA) lists basic services 

required for agencies to receive funding through 

the RWCA Title III (Early Intervention/Primary Care) 

Program (Table 16-1). Some States have produced more 

detailed lists for agencies wishing to receive special 

State-level funding for HIV care; see the New York State 

list for comparison (Table 16-2). Funded programs 

generally must demonstrate continuity in primary 

care, 24-hour access to emergency care, ongoing 

staff training, an administrative apparatus adequate 

to manage the program and its funding, a reporting 

system to meet the grantors’ requirements, and quality 

management. Programs that do not receive explicit 

funding for clinical care and/or support services need to 

rely more on referral networks. 

Table 16-1: HIV/AIDS Bureau 

Requirements for Title III-funded Early 

Intervention/Primary Care Programs

• HIV counseling, testing, and referral

• Counseling and education on living with HIV disease, 

including availability and use of treatment therapies

• Appropriate medical care and monitoring, including CD4 

cell monitoring, viral load testing, antiretroviral therapy, 

and prophylaxis and treatment of opportunistic infections, 

malignancies, and other related conditions

• Oral health care, outpatient mental health care, substance 

abuse treatment, nutritional services, and specialty care 

either directly or through a formal referral mechanism

• Appropriate referrals for other health services

• Perinatal care including therapy to reduce mother to child 

transmission (MTCT)

• Screening/treatment of TB

Source: Adapted from Ryan White C.A.R.E. Act Title III Manual. 

Rockville, MD: HIV/AIDS Bureau, Health Resources and 

Services Administration. 1999(Section II):5. Available at http:

//www.hab.hrsa.gov/CATIE/ Accessed 2/04.Table 16-2. Comprehensive 

Ambulatory HIV Programs from the New York State AIDS Institute 

Monitoring and treating the long-term complications 

of ART, such as insulin resistance, lipodystrophy 

syndromes, dyslipidemia, and osteopenia, are of 

increasing importance. Instituting formal activities 

to assist patients in behavior change is increasingly 

recognized as an essential component of HIV care. 

Hepatitis C diagnosis and management are of particular 

importance for patients who have had blood product 
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16

exposures or who were drug injectors. Screening 

for premalignant human papillomavirus (HPV) 

disease in men using anal Pap smears is potentially 

valuable, although it has not become a universal 

standard of practice. 

Clinics should also have a system in place to protect 

the safety of their employees in regard to occupational 

HIV exposure (See Chapter 10 as well as Suggested 

Resources below). 

Table 16-2. Comprehensive 

Ambulatory HIV Program Standards 

of the New York State AIDS Institute

Clinical services that must be provided by 

ambulatory HIV programs

On site

• Age appropriate, confidential HIV counseling and testing

• Initial and annual comprehensive medical evaluations, 

including substance abuse and mental health assessments

• Cognitive function testing

• Ongoing clinical HIV disease monitoring

• HIV-specific therapies and prophylactic treatments, including 

treatment education and adherence monitoring

• Routine gynecologic care and followup (including reproductive 

counseling, pelvic examinations, and Pap smears)

• Routine family planning services

• Case management

• Patient health education, including risk reduction and nutrition 

counseling

On site or via linkage

• Access to consultations by specialists in infectious diseases

• Core diagnostic and therapeutic services

- laboratory, including early diagnostic methods to establish 

the infection status of children

- radiology, including MRI

- pharmacy

- dental services

- mental health services, including clinical social work, clinical 

psychology, and psychiatry as clinically appropriate

• Other primary care, specialty, and subspecialty services

- obstetrics

- pediatrics, adolescent medicine, and pediatric subspecialties

- ophthalmology

- dermatology

- outpatient surgery

- clinical pharmacy

- subspecialties of internal medicine, including 

gastroenterology, hematology, pulmonology, and oncology

Source: New York State AIDS Institute. Comprehensive 

Ambulatory HIV Program Standards. Part 490 of Title 10 

NYCRR. November 1994.

What	is	different	about	providing	HIV	care	

compared	with	other	types	of	medical	care?

HIV care is new; the epidemic was recognized in 

1981, and potent therapy became available in 1996. 

Therapeutic options are much improved, but there is 

little room for error. Drug resistance may occur rapidly 

and is irreversible. The ongoing development of new 

therapeutic agents is impressive, yet is not rapid enough 

to ensure future therapies to persons who received 

inappropriate prescriptions, or who did not receive the 

requisite education, support, and counseling to succeed 

with their therapy. With therapies that have been in 

use for less than 10 years, much is still unknown about 

long-term outcomes.

Juxtaposed against the need for expertise in HIV care 

is the need to expand access. The only prerequisite 

to developing expertise in HIV care is commitment. 

A wide range of providers may be the HIV experts 

for their communities: midlevel practitioners and 

physicians, generalists and subspecialists. Providing 

infected persons with the tools to succeed in their 

treatment and to avoid future HIV transmission may 

require stepwise behavior change. A persistent and 

nonjudgmental approach is most likely to be effective 

(for more on adherence see Chapter 7). Providers may 

have to change their own behaviors so they can be 

more effective in patient care. 

Most persons receiving HIV care reduce their 

transmission behaviors, lowering the risk of HIV 

infection for others. Others do not change their 

behaviors, or do so only partially, or relapse. Providing 

prevention interventions in a clinic protects the public 

health. Clinic staff may know sex and drug using 

partners of patients, and find themselves with a duty to 

warn those who may be unknowingly exposed. These 

issues will be familiar to those in tuberculosis and STD 

treatment settings; but for many these challenges are 

new (see Chapter 4 on HIV prevention and Chapter 13 

on substance abuse). 

HIV/AIDS is associated with discrimination and stigma 

because of its association with sexual behavior and 

with drug injection, and because HIV is incurable and 

may still be eventually fatal. Historically, there has been 

discrimination because of fear of contagion based on 

misconceptions regarding transmission. Discrimination 

may still be encountered in families and communities 

experiencing HIV for the first time. 
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What	can	clinics	do	to	ensure	that	patients	

receive	the	necessary	array	of	services?

Clinic forms can be designed to remind providers of 

care standards, simplify data collection, and serve other 

purposes as well. Sample forms for initial and followup 

visits are posted on the HRSA HIV/AIDS Bureau (HAB) 

website (http://www.hab.hrsa.gov). They include 

reminders regarding clinical standards, reminders 

of services required for billing levels, checklists built 

around definitions used by RWCA grantees for reporting 

to HRSA, and other data for quality management. Staff 

members may rebel when confronted with new forms; 

however, using checklists often saves time by listing 

required elements of the visit and by reducing the 

amount of writing. Including clinical, data, and quality 

management staff in the process of designing forms 

eases the transition. 

Information systems can produce reports useful 

to providers, for example listing a patient’s prior 

diagnoses, medications, and sequential plasma HIV 

RNA levels and CD4 cell counts (see again the HAB 

website for examples). Similar flow sheets can be 

generated from electronic medical record systems; 

some commercial services also provide such services, 

but confidentiality must be assured. Periodic reports 

of achievement of clinical standards (viral load targets, 

opportunistic infection prophylaxis, vaccination, cancer 

screening, and other health maintenance activities) 

can easily be provided to individual providers, and to 

the clinic medical director, linking implementation of 

the chronic care model (see Chapter 1) and quality 

management (see Chapter 17).

What	enhancements	can	make	an	HIV	clinic	

more	effective?

Clinics can enable patients to better care for themselves 

by providing them with information about HIV and 

by building a community among them. Patients 

should be given education materials; a separate 

area with HIV-related materials may help maintain 

confidentiality. Some clinics display male and female 

condoms with instructions about their use and have 

available other information on safer sex and birth 

control. Much information is available for patients, 

including publications on medications, side effects, and 

adherence. Free materials are available from Federal 

and State web sites, and the pharmaceutical industry 

also produces some excellent materials. 

Many ASOs and clinics host support groups for 

interested patients. Participation must be voluntary, and 

only patients comfortable with revealing their status 

to other patients will be willing to participate. Some 

groups target specific populations. Groups may be more 

successful if an experienced counselor or mental health 

provider leads them. 

Some clinics hold classes on HIV and adherence. Clinics 

serving pregnant women and parents may include 

classes on birth preparation and parenting. Other 

clinics provide periodic symposia to keep patients upto-date on treatment advances. For clinics that have 

a community advisory board, the board can be the 

organizing force for these community updates. Both 

public grants and the pharmaceutical industry support 

these events.

Some youth-oriented clinics arrange social events 

and outings for their patients. Some programs for 

children or mothers provide support services for both 

infected and affected children, ranging from formal 

psychological care to supportive recreational activities 

after school or during school breaks. 

How	can	clinics	implement	interdisciplinary	

care?

It is not enough to have staff from many disciplines 

on the payroll; rather, systems have to be created that 

allow staff to function as a team. Training with followup 

by supervisors is essential. Specific tasks of each staff 

member need to be assigned (Table 16-3). Ideally, 

the staff can meet for a few minutes prior to each 

clinic session to anticipate special needs and allocate 

personnel resources. Some clinics place a checklist 

on each chart at each visit, to indicate which team 

members a patient is meant to see that day and to 

confirm that all intended interactions have occurred. 

The team’s potential can best be utilized if there is 

a regular opportunity to meet and discuss patients 

outside of clinic sessions, often called multidisciplinary 

team meetings. When all members participate, the 

discussions can range from selecting antiretroviral 

regimens based on genotype or phenotype results 

for one patient to addressing chronic mental illness 

for another. Services for infected and affected family 

members can be coordinated at these sessions. 

Should	clinics	have	a	stated	policy	regarding	

controlled	drugs?

Controlled drugs are needed as part of comprehensive 

care of HIV-infected patients, for treatment of 

psychiatric conditions and pain. At the same time, 

many patients with HIV have had prior or have current 

issues with substance abuse. The clinic should have 

policies in place regarding prescription of controlled 
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16

medications: how many prescription refills are provided 

at a time, how new refills are provided, access to 

controlled drug prescriptions or refills outside of 

normal clinic hours, and refills of lost medication or lost 

prescriptions. To avoid confusion or disagreement some 

clinics have patients sign copies of the clinic policy 

regarding use of controlled medications before they 

are given prescriptions. It may be necessary to provide 

formal notification to a substance abuse program or 

parole officer that the clinic is prescribing a controlled 

medication, specifying the drug, dose, and duration of 

treatment. 

Table 16-3. Clinic Staff Responsibilities

Tasks prior to a clinic visit

• Remind every patient of appointments via phone call or 

postcard

• Review charts to list items to address during the visit

Tasks during a clinic visit

• Verify patient’s current contact information and current 

insurance status

• Orient new patients 

• Assist with insurance gaps (teaching about need for 

referrals, help with insurance application or ADAP, etc)

• Assess other barriers to care and psychosocial needs

• Assess medication adherence

• Teach and provide behavior change counseling about 

medications and self-care

• Assess ongoing transmission behaviors

• Teach and provide behavior change counseling about 

transmission behaviors

• Educate about clinical trial opportunities (if applicable)

• Make referrals for psychosocial services

• Make referrals/appointments for medical, dental, mental 

health care

Tasks following clinic sessions

• Make followup calls regarding new medication regimens or 

referrals

• Call or mail postcards to patients who miss their visits

• Help patients overcome barriers to clinic attendance

• Extract data and enter it into the information system (not 

necessary with electronic medical records)

SUPPORT SERVICES AND

LINKAGES NEEDED FOR

HIV CARE

How	do	support	services	enhance	the	clinical	

care	of	persons	with	HIV?

It is a rare clinic that has the funding, personnel, and 

expertise to address all of its patients’ psychosocial 

issues. Most patients need services from an array of 

agencies. Case managers assist patients in accessing 

the range of services and entitlements that can help 

them succeed in treatment. This includes assistance 

in applying for insurance; accessing support groups; 

accessing supplemental food, housing, homemaker 

and other concrete services; accessing mental health 

and substance abuse services. Case managers should 

perform periodic assessments of clients’ needs and 

update comprehensive care plans every 6 months. Home 

visits can be very useful as part of the assessment. Some 

case managers or their agencies will provide selected 

direct services themselves; these may include short-term 

counseling, transportation for clinic visits, accompanying 

patients to clinic visits, and providing financial assistance 

for specific emergencies. Excellent case managers help 

motivate patients. 

Close coordination between clinic staff and case 

management is important to avoid duplication of 

effort and services. Periodic case conferences between 

clinic staff and case managers are ideal. Written 

communication, for example sharing case management 

care plans, can be useful. Case management agencies and 

clinical sites need to obtain written consent from patients 

to share the information that allows coordination.

How	do	clinics	create	useful	linkages	with	

community-based	services?

Clinics can develop relationships with community-based 

case managers or directly with providers of specific 

services, such as metal health, substance abuse, or 

housing. Personal contact between clinic and agency 

is important to establish the relationship, and ongoing 

contacts are necessary for coordination. Community 

organizations are often pleased to give in-service 

education to clinic staff in order to streamline the 

referral process. Clinics should make their expectations 

clear to community-based agencies. Clinics can function 

as advocates to ensure that their patients receive the 

attention and services for which they were referred. 

Periodic interdisciplinary meetings of clinic staff with 

representatives of community-based agencies, including 

case managers, are very useful. 
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How	should	consumers	be	involved	in	the	

provision	of	HIV	clinical	care?

Many clinics have created consumer advisory boards 

to participate in planning and quality management. 

Experiences have varied greatly, with some advisory 

board members educating themselves about the issues 

and providing expert input to these processes. Other 

boards act more as social event or support groups. 

Clinics are likely to have to train board members in 

technical background regarding HIV and care provision, 

and in the role of advisors. Board members must agree 

to confidentiality policies, even though information 

about individual patients or staff members should 

not be discussed. Clinics have to create meaningful 

opportunities for advisory board members to provide 

input: this may involve discussion of workplans in 

writing grant applications, planning outreach activities, 

modifying clinics to enhance recruitment and retention 

of patients, and participating in quality management 

teams. When consumers are living in poverty or 

otherwise difficult conditions, obtaining ongoing 

participation of volunteers may require providing 

transportation to meetings, meals at meetings, and 

reimbursement for childcare or similar expenses. 

Some clinics find it useful to pay officers of their 

advisory boards in order to enable the officers to devote 

adequate amounts of time to the project. If this seems 

contradictory to the spirit of volunteerism, we should 

remember how much continuing education of medical 

and nursing professionals relies on enhancements to 

recruit participation. Creating effective advisory boards 

takes time, but can be a valuable investment. Advisory 

board members, while providing an outside view of the 

clinic to the clinic management, often provide useful 

community outreach and improve public relations. 

Less intensive consumer input involves the use of 

periodic satisfaction surveys or questionnaires of clinic 

patients, confidential or anonymous mechanisms for 

eliciting suggestions, and a publicly accessible grievance 

procedure. Clinics with advisory boards use these 

mechanisms as well.

What	resources	are	required	to	provide	

comprehensive	HIV/AIDS	care?

Financial: Patient access is maximized in clinics that 

can accept Medicare, Medicaid (including Medicaid 

managed care), and county insurance programs. 

Clinics should have a sliding fee scale. Clinics should 

assist appropriate patients to enroll in the AIDS 

Drug Assistance Program (ADAP), to access the drug 

coverage or other clinical services that vary by State. 

Within designated metropolitan areas, RWCA Title I 

funding may be available. Clinics planning to serve a 

moderate-to-high volume of HIV patients can apply for 

a RWCA Title III planning grant. Clinics serving women, 

pregnant women, youth, and families are eligible to 

apply for Title IV funding. Clinics may collaborate with 

other agencies in seeking RWCA funding. 

Personnel: A lone provider whose patients are selfsufficient or can access community-based services 

can “provide” comprehensive HIV/AIDS care. For 

most patients, care is more effective if multiple team 

members are available at the clinical site.

Facilities: In addition to the usual office layout, other 

facilities are useful. An examination room suitable 

for gynecologic exams is important. An apparatus for 

pulse oximetry is very useful in assessing patients 

with respiratory symptoms. Easy access to facilities for 

collecting venous blood, urine, and stool specimens 

should be available. On-site access to rapid tests that 

do not require CLIA certification may be useful, such 

as urine pregnancy tests, capillary blood glucose, and 

perhaps the newly licensed rapid whole blood HIV 

antibody screening test. Laboratory certification to 

perform urine analysis and microscopic examination 

of vaginal fluid specimens is very useful. Refrigeration 

to maintain vaccines and material for tuberculin skin 

testing is necessary. Refrigeration also enables the clinic 

to provide patients with on-site injection of medications 

required once a week or less frequently and to instruct 

patients in the use of more frequent injections. 

Training and technical assistance: Patients look to 

nontechnical staff to corroborate information given by 

physicians and midlevel providers. Further, patients 

expect the same accepting attitude from all staff 

members. Thus, all staff need training in both technical 

and cultural matters. One important resource is the 

local performance site of the AIDS Education and 

Training Center (AETC) funded by HRSA to provide 

training and technical assistance to clinics. The 

local AETC and the National Clinicians’ Consultation 

Warmline provide detailed and patient-specific 

education to assist clinicians in making treatment 

decisions. Written educational materials for staff, such 

as national and regional treatment guidelines, are 

available free on the web and are frequently updated. 

Many regional and national meetings provide training 

in both clinical care and prevention. Assistance with 

enhancing and implementing systems of care, including 

instituting a quality management program, is also 

available from the AETCs. Chapter 18 provides other 

resources for training and information.
A Guide to Primary Care of People with HIV/AIDS

Chapter 16: Clinic Management

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KEY POINTS

In order to recruit persons with HIV who 

are not in care, clinics need to establish 

referral linkages with community 

agencies such as HIV testing services, 

AIDS service organizations that provide 

case management, STD and drug abuse 

treatment facilities, family planning 

agencies, local health departments, 

regional HIV/AIDS hotlines, and local 

hospitals and emergency rooms. 

Clinics can retain patients in care by 

respecting patients, providing them with 

effective care, and addressing cultural and 

language differences between patients 

and staff. Providing a welcoming staff 

attitude and physical environment are 

also important.

Orienting patients to the clinic systems 

and rules and telling them what 

is expected of them can improve 

attendance and adherence to care.

Primary care clinics must be able to 

provide, either directly or through 

referral, an array of clinical and 

psychosocial services that includes 

mental health and substance abuse 

services, support for HIV prevention and 

adherence to care, and close medical 

monitoring. Some issues that differ in HIV 

disease from other medical conditions 

include that there is little room for error 

in providing treatment, that providers 

may need to change their own behaviors 

and attitudes to provide effective care, 

that preventing HIV transmission is 

a critical component of patient care, 

and that patients continue to suffer 

discrimination and stigma. 

Patient services can be enhanced 

in primary care clinics through the 

introduction of mechanisms for 

reminding staff of clinical standards, 

simplifying data collection, and 

monitoring quality improvement. These 

can include forms, checklists, and 

flowsheets, on paper or in electronic 

databases, and can result in feedback 

such as reports to individual providers. 

In addition, educational materials 

and support activities for patients can 

enhance their care.

An interdisciplinary care team, which is 

an important component of HIV primary 

care services, can be developed by 

creating systems for staff collaboration 

and communication, such as training, 

assignment of tasks with checklists on 

patient charts designating responsible 

team members, and multidisciplinary 

team meetings at which the issues of 

individual patients are discussed.

Resources needed to provide 

comprehensive HIV care include the 

capacity to accept Medicare, Medicaid, 

and county insurance programs and 

access to the AIDS Drug Assistance 

Program for coverage of antiretroviral 

drugs. In addition, the Ryan White Care 

Act makes a variety of funding programs 

available for direct funding to clinics 

for care. Ongoing training and technical 

assistance are critical to keep the 

expertise of staff up to date.

SUGGESTED RESOURCES

National HIV/AIDS Clinicians’ Consultation 

Center (Free and confidential advice from 

a multidisciplinary team)

Warmline: 1-800-933-3413

Monday-Friday, 9 am to 8 pm EST

PEP Hotline: 1-800-448-4911

24 hours a day/7 days a week

Website: http://www.ucsf.edu/hivcntr 

Accessed 2/04.

HIV/AIDS Bureau: http://www.hab.hrsa.gov

Accessed 4/04 (An array of technical 

assistance tools for clinic management are 

available at this HRSA website)
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 141

17

OVERVIEW

Quality	Improvement:	Why	Bother?	

An open letter to clinic directors:

You may have dismissed quality improvement from your agenda for many reasons. You may think it is 

someone else’s job, or it’s a lot of extra work with no benefit, or think that you’ve already got a quality 

program in place. You may think that your current system of monitoring the charts in your clinic and giving 

feedback to the providers who aren’t doing the right thing is a quality improvement (QI) program. You may 

also think that your clinic is doing a fantastic job and that you don’t need to monitor its quality. Here’s why 

it’s worth investing the time and effort:

• Data generated from your QI program showing improvements over time demonstrate that the program 

is worth its funding

• QI provides an opportunity to solve problems that are part of the system and not dependent on one individual

• Focus on performance measurement and improvement usually stimulates employees to maximize 

their performance

• Clinicians have the opportunity to provide leadership through championing best outcomes for patient care 

• Innovative problem-solving techniques lead to better care and promote a positive working environment

• QI projects demonstrate compliance with accreditation authorities and grant sponsors

• Quality improvement activities that lead to better outcomes provide a competitive edge when competing 

for alliances with purchasers

• Monitoring systems that are dependent on single individuals will not last when these key players leave the clinic or 

are absent for long periods, whereas a fully functioning quality improvement program that involves staff working 

in teams with a clearly defined infrastructure will keep going when even the most dynamic individuals depart.

This chapter describes how your clinic can develop, implement, and maintain a QI Program and what your 

role in it might be, whether part of a QI Project Team, the Quality Committee, or simply a customer of the 

performance measurement and quality improvement processes.

• • • • • 

Chapter	17:	

Quality	Improvement Bruce D. Agins, MD, MPH

OVERVIEW

DATA COLLECTION

KEY POINTS

“ Quality of care is the degree to which health services for individuals 

and populations increase the likelihood of desired health outcomes and 

are consistent with current professional knowledge.” (Institute of Medicine, 1990)

“ All health care organizations, professional groups, and private and public 

purchasers should pursue six major aims; specifically, health care should be 

safe, effective, patient-centered, timely, efficient, and equitable.” (Institute of Medicine, 2001)

SUGGESTED RESOURCES

REFERENCES
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement 

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

17

What	is	Quality	Improvement	(QI)?	

Quality improvement (QI) includes regular 

measurement of care processes and outcomes to 

analyze processes and systems of care. It involves 

implementation of solutions to improve care and 

monitor their effectiveness with the goal of achieving 

optimal health outcomes for patients. Ongoing cycles 

of change and remeasurement are implemented to test 

and try different ideas to determine which result in 

improved care. QI activities in clinics can range from a 

single team focusing on improving one aspect of care to 

a comprehensive QI program with many teams working 

on a wide variety of improvement projects, with a wellestablished plan and an oversight committee.

The methods of QI are based on core principles that 

are readily translated into a practical approach and 

integrated into the clinical care delivery system (see 

Table 17-1). Successful implementation of QI involves 

actions at 2 different levels: the QI activities and the 

HIV program processes that provide the structural 

backbone for them. This section will articulate the 

core principles and describe activities that can be 

easily adapted into the HIV ambulatory care setting to 

implement a sustainable QI program. 

Table 17-1: Core Principles of 

Quality Improvement

• Focus on the customer: improvement activities result in 

improved patient health

• Measurement: collect and use data to improve care

• Emphasis on systems of care: improve processes that link to 

desired outcomes 

• Involvement of participants: encourage direct participation 

in teams by those individuals who implement the processes 

being evaluated

Descriptions of the chronic care model that serves as 

an important application of QI principles to HIV care 

can be found in Chapter 1, Figure 1-1, and Chapter 

18, the section on Integrating HIV Specialty into 

Practice. A training manual developed from an HIV/

AIDS collaborative is available from the Institute for 

Healthcare Improvement (see Suggested Resources).

Why	aren’t	chart	audits	sufficient	for	QI	

–	Why	can’t	management	just	conduct	QI?

Measurement alone is not sufficient to improve quality. 

A common pitfall in implementing QI programs is to rely 

solely upon performance data, the medical or program 

director’s interpretation of it, and one person’s decisions 

about how to make changes. Successful improvements 

most often result when staff members from the systems 

being assessed work together in teams. When they are 

engaged in the process, they are more likely to generate 

ideas to try and to accept changes.

Which	personnel	should	be	involved	in	QI?

The size of the clinic will determine who participates 

in quality-of-care activities. In small HIV clinics with 

a primary care provider, case manager, nurse, and 

support staff, most of the staff are involved in all 

aspects of QI work. Larger institutions usually establish 

an HIV Quality Committee that includes senior 

management staff of the HIV clinic, designated QI 

staff if there are any, and other key players who work 

in the clinic. A member of this committee represents 

the group in the agency-wide quality committee. 

The Quality Committee identifies the priorities for 

improvement or agrees to use priorities identified by 

staff or patients in the clinic. The Quality Committee 

also charters improvement teams, identifying potential 

members who are key stakeholders in the process 

under investigation or their representatives.

Who	should	be	on	the	teams?

Teams are formed to address the specific care processes 

or systems undergoing improvement. Team members 

should be selected to represent the different functions 

involved in these processes or to represent the 

components of the system under focus. The size of a 

team varies according to the size of the clinic and the 

process under study. In small clinics, the few dedicated 

HIV program staff may constitute the project teams, 

with added representation from different departments 

as needed, such as from the lab, or from other medical 

disciplines. In larger clinics, teams often include 6-10 

members. Membership should include representatives 

from the different groups in the clinic who are 

involved in the care process. In addition to the clinical 

and case management representatives, scheduling 

clerks and medical records staff are often important 

representatives, especially when followup appointments 

and documentation are important components of the 

care process or have been identified as areas that need 

to be improved.

What	are	the	responsibilities	of	the	team?	

Teams are expected to identify areas of change, 

implement pilots to test the change, review 

data assessing the change, and ultimately make 

recommendations about improvements. Team meetings 

should be kept flexible and adapt to the working 

environment of the clinic as much as possible, although 

a few specific guidelines will help keep things running 
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 143

17

smoothly. These include designating a leader for the 

team, developing clear and specific aims and goals, and 

ensuring that a clear line of accountability is defined 

pointing back up to the Quality Committee. Sometimes, 

short impromptu meetings keep the momentum of the 

project going and enable rapid decisionmaking based 

on results as soon as they become available. 

As the Project Team conducts its work and gains 

experience, it will become more independent and 

assume more responsibility for ongoing measurement, 

data collection, and implementation of steps toward 

improvement.

DATA COLLECTION

How	do	you	select	which	components	of	care	

should	be	measured?

Indicators are measurable aspects of care that evaluate 

the extent to which a facility provides a certain element 

of care. Indicators should be based on standards or 

guidelines, meet the primary goals of QI, and reflect 

priorities specific to the community and the clinic. For 

example, in HIV clinics where the population includes 

a large number of women, indicators may include 

rates of routine Pap smears, rates of preconception 

counseling, or other aspects of care specific to women. 

In clinics that care for a high volume of patients with 

severe immunosuppression and advanced HIV disease, 

indicators may include rates of prophylaxis for specific 

opportunistic infections, such as PCP and MAC. Some 

indicators should be selected by soliciting input from 

patients who attend the clinic (see Table 17-2). Staff 

members also often know what aspects of care would 

benefit from being measured and improved and should 

be consulted to determine priorities. If routine data 

collection systems already exist in the clinic, data 

should be reviewed to determine which components of 

care would be prime candidates for improvement (see 

Table 17-3 for sample indicators).

Table 17-2: Methods for Obtaining 

Input from Patients

• Suggestion box

• Surveys

• Focus groups

• Consumer advisory board

Table 17-3: Sample HIV Quality Indicators

Element Of Care Quality Of Care Indicator

HIV staging

CD4 cell count test performed 

every 4 months

Viral load measurement test 

performed every 4 months

Antiretroviral therapy ART drug usage for stable and 

unstable patients

Tuberculosis screening Annual PPD testing

OI prophylaxis

PCP prophylaxis (CD4 count <200 

cells/mm3)

MAC prophylaxis (CD4 count 

<50cells/mm3)

Pneumococcal vaccination

Gynecological care Annual pelvic exam with Pap smear

Syphilis screening Annual syphilis serology 

Substance abuse 

education

Annual discussion of substance use

Annual discussion of tobacco use

Coordination of care Annual dental exam

Once	the	aspect	of	care	has	been	selected,	how	

do	you	develop	and	measure	the	indicators?

Three major activities constitute the process of indicator 

development:

1) Define the measurement population: location, gender, 

age, clinical condition, visits.

2) Define the measures.

3) Develop the data collection plan.

The measurement population is defined by determining 

the location of care being studied, whether both men 

and women are eligible, the applicability of the indicator 

to different age groups, whether any clinical conditions 

are necessary to determine whether the indicator is 

applicable, and whether the patient must have been in 

treatment or visited the clinic more than once. 

After defining the population, the measure needs to 

be defined. For each measure, specific criteria must 

be developed to define the “yes” response and the 

“no” response (see Table 17-4). Often this involves 

deciding during which time period an activity has been 

performed. For example, an indicator measuring viral 

load monitoring must include the frequency with which 

that test should be performed. One simple way to 

construct this measure would be to ask “Was viral load 

measured within the last 4 months?” 
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement 

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

17

Table 17-4. Examples of Specific Measures 

with Definitions of Responses 

Measure Definition of 

measure

Yes/No 

response

TB screening 

(Eligibility: HIVinfected patients 

without a history 

of previous TB 

treatment or 

a history of a 

positive PPD)

Was PPD testing 

performed (placed 

and read within 

72 hours) in the 

past 12 months?

Yes: PPD screening 

was performed 

(placed and read)

No: PPD 

screening was not 

performed (or it 

was placed but 

results were not 

documented)

PCP prophylaxis Did the patient 

with <200 CD4 

cells/mm3 and no 

sustained CD4 cell 

increase to >200/

mm3 during the 

last 6 months of 

the review period 

receive PCP 

prophylaxis?

Yes: The patient 

received PCP 

prophylaxis

No: The patient 

did not receive 

PCP prophylaxis

The data collection plan includes determining the 

source of information, such as whether medical records 

or an electronic database will be used, how the data 

will be recorded, who will record the data, and how a 

sample will be selected. A representative sample will 

allow inferences to be made about the clinic population 

based on observations of the smaller sample. Some 

form of random sampling should be used, either from 

a random numbers table, or a selection of every nth 

record from the list of eligible patients. 

A common pitfall at this point is to think of the 

measurement sample as a research project. For the 

purposes of QI, a sample just needs to be current, 

representative, and readily obtained (ie, sample size 

calculations and the achievement of statistically 

significant results are not necessary). 

Should	you	measure	only	one	indicator	at	a	time?

Definitely not. Several indicators should be measured 

simultaneously, whether abstracted from medical 

records or analyzed through administrative databases. 

Indicators reflecting different aspects of patient 

management should be selected, as well as those 

involving different populations. Indicators should also 

be selected to evaluate different components of the 

health care system, such as the different components of 

the chronic disease model.

How	should	you	analyze	and	display	data?

Data should be reviewed and distributed to all members 

of the team and others involved in the care process 

under evaluation. Whenever possible, data should be 

displayed in graphic format. Once data from several 

time periods have been collected (eg, rates of patients 

with viral load performed every 4 months collected 

in 2 different time periods), a simple line graph (run 

chart) can be constructed with each point representing 

a performance rate (percentage) for a given period of 

time. This is usually the simplest and most effective 

way to show performance data (see Figure 17-1). 

Figure 17-1: Sample Run Chart: Percentage 

of Patients PPD Tested, by Month

0%

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Run Chart: Annual PPD Rate

Source: Measuring Clinical Performace: A Guide for HIV Health Care 

Providers. New York, NY: New York State Department of Health AIDS 

Institute. April, 2002.

How	does	improvement	occur?

Once the data have been reviewed by the team and the 

process for improvement identified, the next step is to 

decide where opportunities for improvement exist. This 

process is described as the PDSA (Plan-Do-Study-Act) or 

PDCA (Plan-Do-Check-Act) cycle (see Figure 17-2). 

The first step is to investigate this care process in 

greater detail. Several techniques are often used to 

accomplish this goal. The simplest is brainstorming, 

in which individuals offer their suggestions for which 

processes are the best candidates for change. Another 

easy method is flowcharting, in which the group breaks 

down the process into its components to identify how 

it is coordinated and how its parts fit together. Then, 

the areas that would be most likely to benefit from 

improvement are selected for change (see Figure 17-3).
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 145

17

Figure 17-2. Plan-Do-Study-Act Cycle

P Plan: Plan the change and collect baseline data

D Do: Test the change and collect data

S Study: Analyze the data

A Act: If the change did not improve the process, 

try another idea. If the change resulted in 

improvement, adopt the change, monitor the 

process periodically and spread the change 

throughout the clinic

Act Plan

Study Do

Source: Institute for Healthcare Improvement. HIV/AIDS Bureau 

Collaborations: Improving Care for People Living with HIV/AIDS 

Disease. Boston: Institute for Healthcare Improvement; 2002. 

Available at http://www.ihi.org/collaboratives/breakthroughseries/

HIV/ChronicCare.pdf.

Once a change in a particular step of the process has 

been selected, a pilot test of the change can be quickly 

implemented and evaluated. A limited implementation 

of the proposed change can be tested – perhaps with 

just the next few patients, or those attending on the 

next day, or those seen by a particular clinician. If the 

pilot does not work, another change can be selected 

and quickly implemented. If the change is feasible and 

improvement is noted, then the change can be adopted 

more widely, before formal remeasurement occurs, 

and a regular period of remeasurement adopted. If the 

change was not successful, then another one can be 

chosen and tested.

What	systems	need	to	be	established	to	

support	QI?

The key to sustaining QI in the clinic is development 

of an infrastructure that supports ongoing QI activities. 

The central components of this infrastructure include: 

• A QI Plan with goals and a process to prioritize 

these goals

• An organizational framework that displays clear 

lines of accountability for QI in the organization

Figure 17-3. Sample Flow Chart 

Flowchart Symbols

Oval shape shows

beginning or ending

step in a process.

Rectangle depicts particular step or task.

Arrows show direction

of process flow.

Diamond indicates

a decision point.

Yes

No

Etc.

Patient in system?

Patient arrives at

front desk.

Nurse asks for

patient’s name and

searches the database

for his/her file.

Ask patient to be seated

in the waiting room.

Nurse asks patient to

complete paperwork for

new clients and return it

to the front desk.

Medical nurse takes patient

into the exam room.

 Source: New York State Department of Health AIDS Institute. 

HIVQUAL Group Learning Guide: Interactive Quality Improvement Exercises 

for HIV Health Care Providers. Available at http://www.hivguidelines.org. 

• Commitment of senior management staff to support 

the program, allocate resources, and celebrate its 

successes

• Creation of a culture that supports quality in the 

program and that values the activities of QI as part 

of the regular work of the clinic (see Table 17-5)

• Establishment of a formal QI Committee to oversee 

quality activities, monitor the Quality Plan, and 

evaluate its effectiveness 

Table 17-5. Tips for Promoting a Culture 

of Quality Improvement: Integration of 

Quality into the Regular Work of the Clinic

• Educate staff about QI and provide them with the skills to 

participate in QI activities

• Communicate results from improvement projects throughout 

the clinic

• Display data and storyboards 

• Celebrate successes 

• Articulate the values of QI in meetings

• Provide opportunities for all staff to participate in QI teams

• Reward staff members through performance evaluation for 

their contributions to the QI Program
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement 

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

17

The regular, ongoing work of the QI Committee, 

supported by the clinic’s leadership, constitutes the 

backbone of the infrastructure that supports ongoing 

QI activities. The committee oversees the dynamic 

process of planning, implementation, and evaluation 

that involves: 

• Analysis of data from the QI projects

• Solicitation of feedback from participating staff

• Decision-making based on the information from its 

analysis

These activities contribute to sustaining the QI Program 

and its activities in the clinic.

Will	improvements	last?

Sustainability is probably the biggest challenge 

that clinics face in the field of QI. All too often, 

improvements do not last once initial projects are 

completed, because the structure and culture to support 

QI is not present or is not supported. The challenge 

of sustainability is therefore two-fold – not only to 

maintain the successes of QI work and its clinical 

outcomes, but also to maintain the systems of QI and 

to keep the QI program vital. By asking questions 

about how care systems can be improved and how QI 

activities are progressing, clinicians play an important 

role in both catalyzing and supporting QI activities.

What	are	the	key	components	of	a	

quality	plan?	

The key elements of a quality plan include a quality 

statement that describes the purpose and goals of the 

QI program, priorities of the program, a description of 

the organizational systems needed to implement the 

program, including committee structure and functions, 

definitions of accountability, roles and responsibilities, 

the process for obtaining consumer input, core 

measures, data collection processes, and a description 

of how the plan will be evaluated. 

KEY POINTS

Providers play an active role in the 

activities of QI and can lead these 

efforts by asking questions to determine 

how improvements can be made. 

Although the QI program may require 

extra work from busy providers, the 

opportunities to systematically measure 

clinical performance will provide useful 

information that leads to better care for the 

patients they serve. 

QI includes regular measurement of 

care processes, analysis of processes and 

systems of care, and implementation of 

solutions to improve care and monitor their 

effectiveness. The goal of QI is to achieve 

optimal health outcomes for patients. 

QI teams identify areas of change, 

implement pilots to test the change, 

review data assessing the change, and 

ultimately make recommendations about 

improvements. When staff members from 

the systems being assessed work together 

in teams and are engaged in the QI process, 

they are more likely to generate ideas and 

to accept changes.

Indicators, measurable aspects of care 

that evaluate the extent to which a facility 

provides a certain element of care, should 

be based on standards or guidelines, 

meet the primary goals of QI, and reflect 

priorities specific to the community and 

the clinic. 

Once data have been reviewed by the 

team and the process for improvement 

identified, the next step is to decide where 

opportunities for improvement exist. This 

process is described as the PDSA (PlanDo-Study-Act) process. The first step is 

to investigate this care process in greater 

detail. Once a change in a particular step of 

the process has been selected, a pilot test 

of the change can be quickly implemented 

and evaluated. If the pilot is successful, the 

change can be adopted widely. If the pilot 

is not successful, another change can be 

selected and tested.

Sustainability is probably the biggest 

challenge that clinics face in the field of 

QI. The key to sustaining QI in the clinic 

is development of an infrastructure that 

supports ongoing QI activities.
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 147

17

SUGGESTED RESOURCES

AETC National Resource Center and New York 

State Department of Health AIDS Institute.

Measuring Clinical Performance: A Guide for 

HIV Healthcare Providers. Available at http:

//www.hivguidelines.org/public_html/center/

quality-of-care/perform_guide/perform-guideintro.htm Accessed 1/04.

Berwick D, Godfrey AB, Roessner J. Curing 

Health Care. San Francisco: Jossey-Bass; 1990.

HIV/AIDS Bureau. Quality Management 

Technical Assistance Manual. Rockville, MD: 

Health Resources and Services Administration; 

2003. Available at http://hab.hrsa.gov.

Institute for Healthcare Improvement. HIV/

AIDS Bureau Collaborations: Improving Care for 

People Living with HIV/AIDS Disease. Boston: 

Institute for Healthcare Improvement; 2002. 

Available at http://www.ihi.org/collaboratives/

breakthroughseries/HIV/ChronicCare.pdf.

Institute of Medicine Committee on Quality of 

Health Care in America. Crossing the Quality 

Chasm: A New Health System for the 21st 

Century. Washington DC: National Academy 

Press: 2001.

Langley GJ, Nolan KM, Norman CL, Provost 

LP, Nolan TW. The Improvement Guide: A 

Practical Approach to Enhancing Organizational 

Performance. San Francisco: Jossey-Bass; 1996.

McGlynn EA, Asch SM. Developing a Clinical 

Performance Measure. Am J Prev Med.

1998;14(3 Suppl):14-21.

New York State Department of Health 

AIDS Institute. HIVQUAL Group Learning 

Guide: Interactive Quality Improvement 

Exercises for HIV Healthcare Providers. http:

//www.hivguidelines.org/public_html/center/

quality-of-care/performance_measurement_

materials/glg/group_learning_guide. 

Scholtes PR, Joiner BL, Streibel BJ. The Team 

Handbook (3rd Ed). Madison: Oriel, 

Inc; 2003.

WEBSITES* 

HIV-Specific Examples

http://hab.hrsa.gov/special/qualitycare.htm

http://hab.hrsa.gov/tools/QM

http://www.hivguidelines.org

Quality of Care Section.

http://www.qualityhealthcare.org/QHC/

Topics/HIVAIDS

http://www.ihi.org/collaboratives/

breakthroughseries/hiv

http://www.qaproject.org

General QI Websites

http://www.qualityhealthcare.org/qhc

http://www.ihi.org

(Institute for Healthcare Improvement)

http://www.isqua.org.au (International 

Society for Quality in Health Care)

http://www.asq.org

(American Society for Quality)

http://www.mytapestry.com

(contains many links to other websites)

http://www.ahrq.gov (Agency for Healthcare 

Research and Quality)

http://www.jcaho.org (Joint Commission on 

Accreditation of Healthcare Organizations)

http://www.nahq.org

(National Association of Healthcare Quality)

http://www.musc.edu/fm_ruralclerkship/

(Family Medicine/Rural Clerkship CQI)

* Websites accessed 1/04.
A Guide to Primary Care of People with HIV/AIDS

Chapter 17: Quality Improvement 

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

17

REFERENCES

Institute for Healthcare Improvement. 

HIV/AIDS Bureau Collaborations: Improving 

Care for People Living with HIV/AIDS 

Disease. Boston: Institute for Healthcare 

Improvement; 2002.

Institute of Medicine. Medicare: A Strategy 

for Quality Assurance. Vol.1. Washington: 

National Academy Press; 1990.

Institute of Medicine. Crossing the Quality 

Chasm. Washington: National Academy 

Press; 2001.

Institute of Medicine. Measuring What Matters: 

Allocation, Planning, and Quality Assessment 

for the Ryan White CARE Act. Washington, DC:

The National Academies Press; 2004.

New York State Department of Health AIDS 

Institute. HIVQUAL Group Learning Guide: 

Interactive Quality Improvement Exercises for 

HIV Health Care Providers. New York, 

NY: New York State Department of Health 

AIDS Institute.

New York State Department of Health AIDS 

Institute. Measuring Clinical Performance: 

A Guide for HIV Health Care Providers. New 

York, NY: New York State Department of 

Health AIDS Institute; April 2002. 
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 159

index

A

addiction. see substance abuse

adherence

assessment, 49–51

case studies, 54

interventions, 51–52

overview, 49

PEP, 89

to quality improvement, 145

substance abuse treatment, 107, 108

adjustment disorders, 117

advance care planning, 126

adverse reactions, 69

advocates, 133

AIDS education and training centers, 149, 

150

AIDS mania, 116, 117–118

alanine aminotransferase (ALT) test, 78

alternative medicine, 16, 56

anemia, 78, 79

anorexia, 62

antiretroviral therapy, 

see Index of Drugs. 165

anxiety disorders, 120

aphthous stomatitis, 61

aphthous ulcers, 61

avascular necrosis, 45

B

bad news, breaking, 127

bartonellosis, 16

behavior modification, 10–11

behavioral modification, 21–22

bipolar disorder, 117

blisters, 59–60

body fluids, 85

breastfeeding, 100

burnout, 129

C

CAGE test, 105, 107

Candida esophagitis, 67, 71–72

Candida infections, 60–61

cardiovascular disease, 40–41

caregiver stress, 129

CBC test, 78

CD4 count

ART indication, 29–30

interpretation, 78

patient education, 15

certification requirements, 155–156

cervical cancer, 68

cesarean section, 100

chest x-ray, 77, 78

chronic care model, 2

clinic visits, 136, 137

clinical failure, 31–32

clinics

effectiveness, 136

resources required, 138

services provided, 134–136

support services, 137–138

coccidioidomycosis, 67

colitis, 70, 71

community-based services, 24, 137

complementary medicine, 16, 56

complications

of ART, 39–45

intitial assessment, 13

metabolic, case studies, 47

conferences, 150, 151

confidentiality, 7

consultation, 92, 151

coordination of care, 5–6

cough, 57

Index	of	Topics See	page	165	for	

Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

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

index

counseling

about adherence, 50–51

interventions, 21–22

patient review, 10–11

PEP, 86

pregnancy, 97

for risk reduction, 15–16, 24, 25

creatinine test, 78

cryptococcal meningitis, 67, 72

cryptosporidium infection, 16, 67

cultural competence, 133

culture, 7, 127

cytomegalovirus (CMV) infection, 67, 

70–71

D

data collection, 143–144

death, preparation for, 128–129

DEATH glossary, 105, 106

delirium, 115–116

dementia, 116

dental care, 88

depression, 58, 118–120

dermatologic symptoms, 59–60

diabetes mellitus, 41, 45

diabetic ketoacidosis, 101

diarrhea, 63

directly observed therapy (DOT), 51

disclosure, 7

discordant couples, 89, 97–98

discrimination, 6–7, 135

distal symmetrical polyneuropathy (DSP), 

58

do not resuscitate (DNR) orders, 128

DOT. see directly observed therapy (DOT)

drug abuse. see substance abuse

DSP. see distal symmetrical 

polyneuropathy (DSP)

E

emotions, 6

encephalitis, 72

end-of-life care, 126–128

esophagitis, 70, 71

F

family meetings, 127

fat redistribution

and ART, 39

case study, 47

monitoring, 40

overview, 43

treatment recommendations, 41

fatigue, 58

financial resources, 138

flow charts, 145

frequently asked questions, 16

G

genotypic resistance

described, 32

regimen choices, 37

testing criteria, 38

gingivitis, 61

guidelines, for HIV treatment, 152

H

hairy leukoplakia, 60

headache, 63

health care model, 2

health care proxy, 126

hepatic steatosis, 55

hepatitis

drug cause, 55

HIV coinfection, 79–80

initial screening, 17

testing, 78

hepatitis B, 80–81, 92–93

hepatitis C

management, 81–82

PEP, 92

and substance abuse, 109

hepatotoxicity, 79

herpes simplex virus (HSV), 60

herpes zoster, 59–60

histoplasmosis, 67

See	page	165	for	

Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 161

index

history

fatigue questions, 58

intitial contact, 14–15

risk assessment, 23

HIV

patient education, 15

postexposure prophylaxis, 89–92

risk factors, 99

and substance use, 106

transmission case studies, 95–96

transmission potential, 22

vertical transmission prevention, 98–

100

HIV care characteristics, 135

hope, 127

hospice care, 126

HSV. see herpes simplex virus (HSV)

hyperemesis gravidarum, 101

hyperglycemia, 45, 101

hyperlactatemia, 44

hypogonadism, 62

hypoxemia, 68

I

immunization, 33

immunologic failure, 31–32

infants, 16, 101

infections, 16

insulin resistance

and ART, 39

monitoring, 40

protease inhibitors, 45

treatment recommendations, 41

intensification, 32

interdisciplinary approach

care model, 134–136

patient benefits, 18

practice integration, 155

intermittent therapy, 34

internet, 151–154

intrauterine devices, 98

intregrated model of care, 123–124

J

journals, 151–152

K

Kaposi sarcoma (KS), 68, 73–74

L

laboratory tests

abnormal values, 77–82

HCV exposure, 92–93

initial contact, 16–17

pregnant women, 100

for STDs, 23–24

for substance abuse, 106

lactic acidosis

and ART, 39

case studies, 48, 65

drug cause, 55

monitoring, 40

overview, 43–44

during pregnancy, 101

lipid abnormalities, 39–42

lipodystrophy. see fat redistribution

liver function tests, 79

lymphoma, 72, 74

M

maintenance medications, 109

malignancies

and HIV infection, 68, 73–74

psychiatric symptoms, 115

malnutrition, 61–62

manic depressive illness, 117

MCMD. see minor cognitive-motor 

disorder (MCMD)

meningitis, 72

mental health, 109, 115

minor cognitive-motor disorder (MCMD), 

116

minorities, 5

mitochondria, 44

molluscum contagiosum, 60

mood disorders, 117
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

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

index

mother-to-child-transmission (MTCT), 

98–100

mouth lesions, 60–61

MTCT. see mother-to-child-transmission 

(MTCT)

myalgia, 62

Mycobacterium avium complex 

(MAC), 67, 70

mycobacterium tuberculosis, 67, 72–73

myopathy, 62

myositis, 65

N

nausea, 56–57

nephropathy, 82

neuropathic pain, 58

neutropenia, 78

New York State AIDS Institute, 135

NNRTIs (non-nucleoside reverse 

transcriptase inhibitors). 

see Index of Drugs

NRTIs (nucleoside reverse transcriptase 

inhibitors). see Index of Drugs

nucleosides. see Index of Drugs

non-Hodgkin lymphoma, 68, 74

nonoccupational exposure PEP, 88–89

notification

of at-risk partners, 16

elements of, 24

treatment considerations, 7–8

O

occupational exposure PEP, 86–88

opportunistic disease, 67–68, 115

opportunistic infection, 67–68

oral candidiasis, 60–61

osteoporosis

ART, 45

monitoring, 40

treatment recommendations, 41

P

pain management, 110, 125

palliative care, 123–126

pancreatitis, 55

patient care challenges, 5

patient education

clinical setting, 136

gaps in, 21

resources, 8–9

patient evaluation, 13–18

patient readiness, 51

patient recruitment, 133

PDAs. see personal digital assistants

PEP. see postexposure prophylaxis

perinatal care, 100–102

periodontal disease, 61

persistence, 33

personal digital assistants (PDAs), 154

personality disorders, 117

pets, 16

phenotypic resistance, 32

physical exam, 55

PIs (protease inhibitors). see Index of 

Drugs

Plan-Do-Study-Act cycle, 144–145

Pneumocystis jiroveci (carinii) pneumonia 

(PCP)

management, 57, 68–69

risk factors, 67

pneumonia, 57

pneumothorax, 68

POSIT. see Problem Oriented Screening 

Instrument for Teenagers

postexposure prophylaxis (PEP)

case studies, 95–96

hepatitis B, 92–93

HIV, 89–92

nonoccupational, 22, 88–89

occupational, 86–88

overview, 85

See	page	165	for	

Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 163

index

PPD test, 77, 78

pregnancy

HBV PEP, 92

HIV PEP, 89

MTCT prevention, 98–100

perinatal care, 100–101

planning for, 97

prevention of HIV

in clinical practice, 26

interventions, 23–26

patient education, 15–16

rationale, 21–22

Problem Oriented Screening Instrument 

for Teenagers (POSIT), 107

pruritus, 59

psychosis, 116–117

psychotherapy, 120

public health, 7–8

pulmonary symptoms, 57

pulse therapy, 34

Q

quality improvement

data collection, 143

integrated practice, 155

overview, 141–143

R

relapses, 108, 109

renal disease, 82

resistance mutation, 91

resistance testing, 32–33

resources

direct contact, 149–151

electronic, 152–154

written materials, 151–152

respect, 133

retinitis, 70, 71

risk assessment

gaps in, 21

patient education, 15

patient review, 10–11

question samples, 23

RPR test, 78

rural practice, 151

Ryan White Care Act (RWCA), 133, 134

S

scabies, 59

schizohrenia, 117

seborrheic dermatitis, 60

self image, 6

serum lactate, 44

sexual assault, 89

sexual orientation, 6–7, 10

sexually transmitted diseases (STDs)

and HIV PEP, 88

initial screening, 15, 17

laboratory tests, 23–24

and substance abuse, 109

shingles, 59–60

side effects, 31–32

sinus disease, 57

spermicides, 98

SPIKES mnemonic, 127

spirituality, 127

staff attitude, 133

staff training, 138

statin drugs, 41–42

STD. see sexually transmitted diseases

Stevens-Johnson syndrome, 55

STI. see structured treatment interruption

stigma, 5, 6–7

stress, 129

structured treatment interruption (STI), 33
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

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

index

substance abuse

adherence, 54

assessment, 105–107

brain changes, 109

DSM-IV definition, 107

HIV transmission, 22

medication policy, 136

pain management, 110

psychiatric symptoms, 115

treatment, 107–109

support groups, 7

support services, 137

syphilis, 77

T

therapeutic drug monitoring (TDM), 33

therapeutic failure, 31–32

thrombocytopenia, 78

thrush, 60

Title III requirements, 134

toxic epidermal necrolysis, 55

toxoplasma titer test, 78

toxoplasmic encephalitis, 72

toxoplasmosis, 16, 67

transplantation, 82

travel, 16

treatment failure, 33

triglycerides, 41–42

tuberculosis

management, 72–73

and substance abuse, 110

testing, 77

U

ulcers (cutaneous), 59–60

ulcers (oral), 61

V

VDRL test, 78

vertical transmission, 98–100

viral load, 15, 30, 78

viral resistance, 49

virologic failure

cause, 31

dealing with, 32

regimen choice, 38

vitritis, 71

W

warmline, 151

wasting, 61–62

websites, 152–154
A Guide to Primary Care of People with HIV/AIDS

Index of Drugs

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 165

index

A

abacavir (ABC)

hypersensitivity reaction, 55

liver function, 80

side effects, 56

adefovir dipivoxil, 81

amitriptyline, 119

amprenavir (APV), 56, 98

antibiotics, 56

antidepressants, 118-119

antipsychotics, 118

antiretroviral therapy

adherence benefit, 49

antidepressant interactions, 119

case studies, 36-38

contraceptive interactions, 98

goals, 29

hepatotoxicity, 79

HIV prevention, 22

initial regimens, 30-31

metabolic complications, 39-45

OI incidence, 68

patient education, 8

PEP, 85-92

post-lactic acidosis, 44

during pregnancy, 101

prenatal exposure, 101

psychiatric symptoms, 115

regimen change, 31-32

starting criteria, 29-30

and substance abuse treatment, 111-112

symptoms management, 55

and vertical transmission, 99

anxiolytics, 120

APV. see amprenavir (APV)

ART. see antiretroviral therapy

atazanavir (ATV)

lipid levels, 42

liver function, 80

side effects, 56

atovaquone, 69

AZT. see zidovudine (AZT)

B

buprenorphine, 109

bupropion, 119

C

citalopram, 119

clindamycin, 69

clomipramine, 119

D

dapsone, 69, 101

ddC. see zalcitabine

ddI. see didanosine

desipramine, 119

didanosine (ddI)

hyperlactatemia, 44

liver function, 80

in PEP, 91

side effects, 56

doxepin, 119

d4T. see stavudine

See	page	159	for	

Index	of	Topics Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Drugs

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

index

E

efavirenz (EFV)

and contraceptive interactions, 98

liver function, 80

during pregnancy, 98, 101

side effects, 56

emtricitabine (FTC)

HBV treatment, 81

liver function, 80

side effects, 56

enfuvirtide (ENF, T-20), 30

F

FAPV. see fosamprenavir

fibric acid derivatives, 42

fluoxetine, 119

fluvoxamine, 119

fosamprenavir (FAPV), 56, 98

FTC. see emtricitabine

fusion inhibitors, 30

I

impramine, 119

indinavir (IDV)

liver function, 80

renal insufficiency, 82

side effects, 56

interferon, 82

L

lamivudine (3TC)

HBV treatment, 81

liver function, 80

side effects, 56

lopinavir (LPV), 56, 98

M

methadone, 111-112

methamphetamines, 112

mirtazepine, 119

N

nefazodone, 119

nelfinavir (NFV)

and contraceptive interactions, 98

diarrhea, 63

side effects, 56

nevirapine (NVP)

and contraceptive interactions, 98

lipid levels, 42

liver function, 80

in PEP, 91

side effects, 56

NFV. see nelfinavir (NFV)

NNRTIs (non-nucleoside reverse 

transcriptase inhibitors). see also

specific drugs

initial regimens, 30-31

liver function, 80

metabolic complications, 39

nortriptyline, 119

NRTIs (nucleoside reverse transcriptase 

inhibitors). see also specific drugs

hyperlactatemia, 44

liver function, 80

metabolic complications, 39

side effects, 56

nucleosides, 30

NVP. see nevirapine

See	page	159	for	

Index	of	Topics
A Guide to Primary Care of People with HIV/AIDS

Index of Drugs

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 167

index

P

paroxetine, 119

pentamidine, 69

PIs (protease inhibitors)

diarrhea, 63

glucose metabolism, 45

initial regimens, 30

lipid abnormalities, 40

liver function, 80

metabolic complications, 39

methamphetamine interaction, 112

nausea, 56

during pregnancy, 101

primaquine, 69

R

ribavirin, 82

ritonavir (RTV)

contraceptive interactions, 98

lipid abnormalities, 40

side effects, 56

S

selective serotonin reuptake inhibitors 

(SSRI), 112

sertraline, 119

stavudine (d4T)

hyperlactatemia, 44

lipid levels, 42

lipodystrophy, 43

liver function, 80

in PEP, 91

side effects, 56

T

3TC. see lamivudine

tenofovir (TDF)

lipid levels, 42

liver function, 80

side effects, 56

TMP-SMX, 69

trazodone, 119

trimetrexate, 69

V

venlafaxine, 119

Z

zalcitabine (ddC)

oral ulcers, 61

polyneuropathy, 58

side effects, 56

zidovudine (AZT, ZDV)

liver function, 80

myopathy, 62

during pregnancy, 99-100
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 159

index

A

addiction. see substance abuse

adherence

assessment, 49–51

case studies, 54

interventions, 51–52

overview, 49

PEP, 89

to quality improvement, 145

substance abuse treatment, 107, 108

adjustment disorders, 117

advance care planning, 126

adverse reactions, 69

advocates, 133

AIDS education and training centers, 149, 

150

AIDS mania, 116, 117–118

alanine aminotransferase (ALT) test, 78

alternative medicine, 16, 56

anemia, 78, 79

anorexia, 62

antiretroviral therapy, 

see Index of Drugs. 165

anxiety disorders, 120

aphthous stomatitis, 61

aphthous ulcers, 61

avascular necrosis, 45

B

bad news, breaking, 127

bartonellosis, 16

behavior modification, 10–11

behavioral modification, 21–22

bipolar disorder, 117

blisters, 59–60

body fluids, 85

breastfeeding, 100

burnout, 129

C

CAGE test, 105, 107

Candida esophagitis, 67, 71–72

Candida infections, 60–61

cardiovascular disease, 40–41

caregiver stress, 129

CBC test, 78

CD4 count

ART indication, 29–30

interpretation, 78

patient education, 15

certification requirements, 155–156

cervical cancer, 68

cesarean section, 100

chest x-ray, 77, 78

chronic care model, 2

clinic visits, 136, 137

clinical failure, 31–32

clinics

effectiveness, 136

resources required, 138

services provided, 134–136

support services, 137–138

coccidioidomycosis, 67

colitis, 70, 71

community-based services, 24, 137

complementary medicine, 16, 56

complications

of ART, 39–45

intitial assessment, 13

metabolic, case studies, 47

conferences, 150, 151

confidentiality, 7

consultation, 92, 151

coordination of care, 5–6

cough, 57

Index	of	Topics See	page	165	for	

Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

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

index

counseling

about adherence, 50–51

interventions, 21–22

patient review, 10–11

PEP, 86

pregnancy, 97

for risk reduction, 15–16, 24, 25

creatinine test, 78

cryptococcal meningitis, 67, 72

cryptosporidium infection, 16, 67

cultural competence, 133

culture, 7, 127

cytomegalovirus (CMV) infection, 67, 

70–71

D

data collection, 143–144

death, preparation for, 128–129

DEATH glossary, 105, 106

delirium, 115–116

dementia, 116

dental care, 88

depression, 58, 118–120

dermatologic symptoms, 59–60

diabetes mellitus, 41, 45

diabetic ketoacidosis, 101

diarrhea, 63

directly observed therapy (DOT), 51

disclosure, 7

discordant couples, 89, 97–98

discrimination, 6–7, 135

distal symmetrical polyneuropathy (DSP), 

58

do not resuscitate (DNR) orders, 128

DOT. see directly observed therapy (DOT)

drug abuse. see substance abuse

DSP. see distal symmetrical 

polyneuropathy (DSP)

E

emotions, 6

encephalitis, 72

end-of-life care, 126–128

esophagitis, 70, 71

F

family meetings, 127

fat redistribution

and ART, 39

case study, 47

monitoring, 40

overview, 43

treatment recommendations, 41

fatigue, 58

financial resources, 138

flow charts, 145

frequently asked questions, 16

G

genotypic resistance

described, 32

regimen choices, 37

testing criteria, 38

gingivitis, 61

guidelines, for HIV treatment, 152

H

hairy leukoplakia, 60

headache, 63

health care model, 2

health care proxy, 126

hepatic steatosis, 55

hepatitis

drug cause, 55

HIV coinfection, 79–80

initial screening, 17

testing, 78

hepatitis B, 80–81, 92–93

hepatitis C

management, 81–82

PEP, 92

and substance abuse, 109

hepatotoxicity, 79

herpes simplex virus (HSV), 60

herpes zoster, 59–60

histoplasmosis, 67

See	page	165	for	

Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 161

index

history

fatigue questions, 58

intitial contact, 14–15

risk assessment, 23

HIV

patient education, 15

postexposure prophylaxis, 89–92

risk factors, 99

and substance use, 106

transmission case studies, 95–96

transmission potential, 22

vertical transmission prevention, 98–

100

HIV care characteristics, 135

hope, 127

hospice care, 126

HSV. see herpes simplex virus (HSV)

hyperemesis gravidarum, 101

hyperglycemia, 45, 101

hyperlactatemia, 44

hypogonadism, 62

hypoxemia, 68

I

immunization, 33

immunologic failure, 31–32

infants, 16, 101

infections, 16

insulin resistance

and ART, 39

monitoring, 40

protease inhibitors, 45

treatment recommendations, 41

intensification, 32

interdisciplinary approach

care model, 134–136

patient benefits, 18

practice integration, 155

intermittent therapy, 34

internet, 151–154

intrauterine devices, 98

intregrated model of care, 123–124

J

journals, 151–152

K

Kaposi sarcoma (KS), 68, 73–74

L

laboratory tests

abnormal values, 77–82

HCV exposure, 92–93

initial contact, 16–17

pregnant women, 100

for STDs, 23–24

for substance abuse, 106

lactic acidosis

and ART, 39

case studies, 48, 65

drug cause, 55

monitoring, 40

overview, 43–44

during pregnancy, 101

lipid abnormalities, 39–42

lipodystrophy. see fat redistribution

liver function tests, 79

lymphoma, 72, 74

M

maintenance medications, 109

malignancies

and HIV infection, 68, 73–74

psychiatric symptoms, 115

malnutrition, 61–62

manic depressive illness, 117

MCMD. see minor cognitive-motor 

disorder (MCMD)

meningitis, 72

mental health, 109, 115

minor cognitive-motor disorder (MCMD), 

116

minorities, 5

mitochondria, 44

molluscum contagiosum, 60

mood disorders, 117
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

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

index

mother-to-child-transmission (MTCT), 

98–100

mouth lesions, 60–61

MTCT. see mother-to-child-transmission 

(MTCT)

myalgia, 62

Mycobacterium avium complex 

(MAC), 67, 70

mycobacterium tuberculosis, 67, 72–73

myopathy, 62

myositis, 65

N

nausea, 56–57

nephropathy, 82

neuropathic pain, 58

neutropenia, 78

New York State AIDS Institute, 135

NNRTIs (non-nucleoside reverse 

transcriptase inhibitors). 

see Index of Drugs

NRTIs (nucleoside reverse transcriptase 

inhibitors). see Index of Drugs

nucleosides. see Index of Drugs

non-Hodgkin lymphoma, 68, 74

nonoccupational exposure PEP, 88–89

notification

of at-risk partners, 16

elements of, 24

treatment considerations, 7–8

O

occupational exposure PEP, 86–88

opportunistic disease, 67–68, 115

opportunistic infection, 67–68

oral candidiasis, 60–61

osteoporosis

ART, 45

monitoring, 40

treatment recommendations, 41

P

pain management, 110, 125

palliative care, 123–126

pancreatitis, 55

patient care challenges, 5

patient education

clinical setting, 136

gaps in, 21

resources, 8–9

patient evaluation, 13–18

patient readiness, 51

patient recruitment, 133

PDAs. see personal digital assistants

PEP. see postexposure prophylaxis

perinatal care, 100–102

periodontal disease, 61

persistence, 33

personal digital assistants (PDAs), 154

personality disorders, 117

pets, 16

phenotypic resistance, 32

physical exam, 55

PIs (protease inhibitors). see Index of 

Drugs

Plan-Do-Study-Act cycle, 144–145

Pneumocystis jiroveci (carinii) pneumonia 

(PCP)

management, 57, 68–69

risk factors, 67

pneumonia, 57

pneumothorax, 68

POSIT. see Problem Oriented Screening 

Instrument for Teenagers

postexposure prophylaxis (PEP)

case studies, 95–96

hepatitis B, 92–93

HIV, 89–92

nonoccupational, 22, 88–89

occupational, 86–88

overview, 85

See	page	165	for	

Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 163

index

PPD test, 77, 78

pregnancy

HBV PEP, 92

HIV PEP, 89

MTCT prevention, 98–100

perinatal care, 100–101

planning for, 97

prevention of HIV

in clinical practice, 26

interventions, 23–26

patient education, 15–16

rationale, 21–22

Problem Oriented Screening Instrument 

for Teenagers (POSIT), 107

pruritus, 59

psychosis, 116–117

psychotherapy, 120

public health, 7–8

pulmonary symptoms, 57

pulse therapy, 34

Q

quality improvement

data collection, 143

integrated practice, 155

overview, 141–143

R

relapses, 108, 109

renal disease, 82

resistance mutation, 91

resistance testing, 32–33

resources

direct contact, 149–151

electronic, 152–154

written materials, 151–152

respect, 133

retinitis, 70, 71

risk assessment

gaps in, 21

patient education, 15

patient review, 10–11

question samples, 23

RPR test, 78

rural practice, 151

Ryan White Care Act (RWCA), 133, 134

S

scabies, 59

schizohrenia, 117

seborrheic dermatitis, 60

self image, 6

serum lactate, 44

sexual assault, 89

sexual orientation, 6–7, 10

sexually transmitted diseases (STDs)

and HIV PEP, 88

initial screening, 15, 17

laboratory tests, 23–24

and substance abuse, 109

shingles, 59–60

side effects, 31–32

sinus disease, 57

spermicides, 98

SPIKES mnemonic, 127

spirituality, 127

staff attitude, 133

staff training, 138

statin drugs, 41–42

STD. see sexually transmitted diseases

Stevens-Johnson syndrome, 55

STI. see structured treatment interruption

stigma, 5, 6–7

stress, 129

structured treatment interruption (STI), 33
A Guide to Primary Care of People with HIV/AIDS

Index of Topics

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

index

substance abuse

adherence, 54

assessment, 105–107

brain changes, 109

DSM-IV definition, 107

HIV transmission, 22

medication policy, 136

pain management, 110

psychiatric symptoms, 115

treatment, 107–109

support groups, 7

support services, 137

syphilis, 77

T

therapeutic drug monitoring (TDM), 33

therapeutic failure, 31–32

thrombocytopenia, 78

thrush, 60

Title III requirements, 134

toxic epidermal necrolysis, 55

toxoplasma titer test, 78

toxoplasmic encephalitis, 72

toxoplasmosis, 16, 67

transplantation, 82

travel, 16

treatment failure, 33

triglycerides, 41–42

tuberculosis

management, 72–73

and substance abuse, 110

testing, 77

U

ulcers (cutaneous), 59–60

ulcers (oral), 61

V

VDRL test, 78

vertical transmission, 98–100

viral load, 15, 30, 78

viral resistance, 49

virologic failure

cause, 31

dealing with, 32

regimen choice, 38

vitritis, 71

W

warmline, 151

wasting, 61–62

websites, 152–154
A Guide to Primary Care of People with HIV/AIDS

Index of Drugs

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 165

index

A

abacavir (ABC)

hypersensitivity reaction, 55

liver function, 80

side effects, 56

adefovir dipivoxil, 81

amitriptyline, 119

amprenavir (APV), 56, 98

antibiotics, 56

antidepressants, 118-119

antipsychotics, 118

antiretroviral therapy

adherence benefit, 49

antidepressant interactions, 119

case studies, 36-38

contraceptive interactions, 98

goals, 29

hepatotoxicity, 79

HIV prevention, 22

initial regimens, 30-31

metabolic complications, 39-45

OI incidence, 68

patient education, 8

PEP, 85-92

post-lactic acidosis, 44

during pregnancy, 101

prenatal exposure, 101

psychiatric symptoms, 115

regimen change, 31-32

starting criteria, 29-30

and substance abuse treatment, 111-112

symptoms management, 55

and vertical transmission, 99

anxiolytics, 120

APV. see amprenavir (APV)

ART. see antiretroviral therapy

atazanavir (ATV)

lipid levels, 42

liver function, 80

side effects, 56

atovaquone, 69

AZT. see zidovudine (AZT)

B

buprenorphine, 109

bupropion, 119

C

citalopram, 119

clindamycin, 69

clomipramine, 119

D

dapsone, 69, 101

ddC. see zalcitabine

ddI. see didanosine

desipramine, 119

didanosine (ddI)

hyperlactatemia, 44

liver function, 80

in PEP, 91

side effects, 56

doxepin, 119

d4T. see stavudine

See	page	159	for	

Index	of	Topics Index	of	Drugs
A Guide to Primary Care of People with HIV/AIDS

Index of Drugs

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

index

E

efavirenz (EFV)

and contraceptive interactions, 98

liver function, 80

during pregnancy, 98, 101

side effects, 56

emtricitabine (FTC)

HBV treatment, 81

liver function, 80

side effects, 56

enfuvirtide (ENF, T-20), 30

F

FAPV. see fosamprenavir

fibric acid derivatives, 42

fluoxetine, 119

fluvoxamine, 119

fosamprenavir (FAPV), 56, 98

FTC. see emtricitabine

fusion inhibitors, 30

I

impramine, 119

indinavir (IDV)

liver function, 80

renal insufficiency, 82

side effects, 56

interferon, 82

L

lamivudine (3TC)

HBV treatment, 81

liver function, 80

side effects, 56

lopinavir (LPV), 56, 98

M

methadone, 111-112

methamphetamines, 112

mirtazepine, 119

N

nefazodone, 119

nelfinavir (NFV)

and contraceptive interactions, 98

diarrhea, 63

side effects, 56

nevirapine (NVP)

and contraceptive interactions, 98

lipid levels, 42

liver function, 80

in PEP, 91

side effects, 56

NFV. see nelfinavir (NFV)

NNRTIs (non-nucleoside reverse 

transcriptase inhibitors). see also

specific drugs

initial regimens, 30-31

liver function, 80

metabolic complications, 39

nortriptyline, 119

NRTIs (nucleoside reverse transcriptase 

inhibitors). see also specific drugs

hyperlactatemia, 44

liver function, 80

metabolic complications, 39

side effects, 56

nucleosides, 30

NVP. see nevirapine

See	page	159	for	

Index	of	Topics
A Guide to Primary Care of People with HIV/AIDS

Index of Drugs

U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau 167

index

P

paroxetine, 119

pentamidine, 69

PIs (protease inhibitors)

diarrhea, 63

glucose metabolism, 45

initial regimens, 30

lipid abnormalities, 40

liver function, 80

metabolic complications, 39

methamphetamine interaction, 112

nausea, 56

during pregnancy, 101

primaquine, 69

R

ribavirin, 82

ritonavir (RTV)

contraceptive interactions, 98

lipid abnormalities, 40

side effects, 56

S

selective serotonin reuptake inhibitors 

(SSRI), 112

sertraline, 119

stavudine (d4T)

hyperlactatemia, 44

lipid levels, 42

lipodystrophy, 43

liver function, 80

in PEP, 91

side effects, 56

T

3TC. see lamivudine

tenofovir (TDF)

lipid levels, 42

liver function, 80

side effects, 56

TMP-SMX, 69

trazodone, 119

trimetrexate, 69

V

venlafaxine, 119

Z

zalcitabine (ddC)

oral ulcers, 61

polyneuropathy, 58

side effects, 56

zidovudine (AZT, ZDV)

liver function, 80

myopathy, 62

during pregnancy, 99-100