Edited by Jean Anderson, MD

5£RVICe,y

A GUIDE TO THE

CLINICAL CARE OF

WOMEN WITH

2000

Preliminary

Edition

r
Please send your

comments

criticisms

corrections

suggested changes, and

other guidance

to one of the addresses below. Be sure to include in your

letter/note an address (fax, e-mail, or postal) where you can

be reached for follow-up.

This Guide is a

PRELIMINARY EDITION.

We need YOUR HELP

to make the

NEXT EDITION

as useful as possible!

Translation Partners Needed

Write to us if you can help us find partners to help us have

this Guide translated into your native language. For

Instance, provide us with a contact who works with translation in your country's Ministry of Health, or tell us about a

group at a medical school that translates medical texts.

Send Us Your Comments

E-mail: womencare@hrsa.gov

Fax to the attention of "Womencare": 301-443-0791 (USA)

Postal address: Womencare

Parklawn Building, Room 11A-33

5600 Fishers Lane

Rockville, Maryland 20857

USA

Note that this and subsequent editions of

A Guide to the Clinical Care of Women with HIV

will be available online.

Go to the HIV/AIDS Bureau Web site

and click on the publication Women's Guide'.

http://www.hrsa.gov/hab
^rA GUIDE TO TH

CLINICAL CAR

WOMEN win

2000

Preliminary

Edition

Edited by Jean Anderson, MD

U.S, Deoartment of Health & Human Services HIVAIPS

1

Health Resources & Services Administration
KC

(,'>7

Some of the information contained in this

Guide may cite the use of a particular drug

in a dosage, for an indication, or in a manner

other than recommended. Therefore, the

manufacturer's package inserts should be

consulted for complete prescribing information.

This Guide contains information relating to general principles of medical care which should not be construed as specific instructions for

individual patients. Recommendations for HIV care change frequendy, so the care provider is cautioned that this preliminary edition is dated

May, 2000. To find updated information, consult the listings in Chapter XV on Resources.

For the most current HIV/AIDS treatment guidelines, contact the

AIDS Treatment Information Service (ATIS):

United States & Canada: 1-800-HIV-0440

Fax number: 1-301-519-6616

TTY: 1-888-480-3739

International: 1-301-519-0459

Mailing Address: HIV/AIDS Treatment Information Service

P.O. Box 6303

Rockville, MD 20849-6303

Web site: http:/ /hivatis.org

E-mail: atis@hivatis.org

Send Us Your Comments

E-mail: womencare@hrsa.gov

Fax to the attention o/" "Womencare": 301-443-0791 (USA)

Postal address: Womencare

Parklawn Building, Room 11A-33

5600 Fishers Lane

Rockville, Maryland 20857

USA

Note that this and subsequent editions of

A Guide to the Clinical Care of Women with HIV

will be available online.

Go to the HIV/AIDS Bureau Web site

and click on the publication Women's Guide'.

http://www.hrsa.gov/hab
A Guide to the Clinical Care ofWomen with HJV

is dedicated to Donna M. Davis, who died in June 1999.

She worked to improve the lives of women

both in the U.S. and globally.
ACKNOWLEDGEMENTS

A number of people made this Guide possible. Joan HoUoway’s vision provided the framework for the Guide 's inception and development. Magda

Barini-Garcia, MD, the Project Officer, skillfully shepherded and oversaw the

project. Helen Schietinger, the Project Manager, coordinated the entire process

masterfully and brought it to fruition. Others whose work was essential

include staff from HRSA’s HIV/AIDS Burearu, Tom Flavin and Brad Read of

the Office of Communications, and Carole McGeehan of the DHHS Program Support Center’s Media Arts Branch. Carole’s work on design, layout,

and final production of the Guide was artful and invaluable.

For sale by the U.S. Government Printing Office

Superintendent of Documents, Mail Stop: SSOP, Washington, DC 20402-9328

ISBN 0-16-050394-9

ISBN 0-16-050394-9

90000

9 780 60 503948
CONTRIBUTING AUTHORS

Silvia M Abularach, MD, MPH

Assistant Professor

Division of Gynecologic Oncology

Johns Hopkins School of Medicine

Baltimore, MD

Carla S. Alexander, MD

Assistant Professor of Medicine

University of Maryland School of Medicine

Baltimore, MD

Jean Anderson, MD

Associate Professor

Gynecology AND Obstetrics

Johns Hopkins School of Medicine

Baltimore, MD

Barbara Aranda-Naranjo, PhD, RN, FAAN

Chief, Demonstration Project Developmentand Evaluation Branch

HIV/AIDS Bureau, Health Resources and Services Administration

Rockville, MD

Patricia Barditch-Crovo, MD

Assistant Professor

Division of Infectious Diseases

TheJohns Hopkins School of Medicine

Baltimore, MD

Victoria A Cargill, MD, MSCE

Office of AIDS Research

National Institutes of Health

Bethesda, MD

Laura Cheever, MD

Chief, HIVEducation Branch

HIV/AIDS Bureau, Health Resources and Services Administration

Rockville, MD

Connie Celum, MD, MPH

Associate Professor of Medicine

University of Washington

Seattle, WA

Rachel Davis, RN

Clinic Coordinator

South Texas EamilyAIDS Network

University of Texas Health Science Center

San Antonio, TX

Judith Feinberg, MD

Professor of Medicine

University of Cincinnati College of Medicine

Cincinnati, Ohio
Henry L. Francis, M.D.

Director, Center on AIDS and Other Medical Consequences of Drug Abuse

(CAMCODA)

National Institute on Drug Abuse

Bethesda, MD

Donna Futterman, MD

Associate Professor of Pediatrics

Albert Einstein College of Medicine

Bronx, NY

Ruth Greenblatt, MD

Professor of Medicine, Epidemiology and Biostatistics University of California at San Francisco

San Francisco, CA

Nancy A. Hessol, MSPH

Department of Medicine

University of California, San Francisco

San Francisco, CA

Joyce Seiko Kobayashi, M.D.

Associate Professor

University of Colorado Health Sciences Center

Denver, Colorado

Rani Lewis, MD

Associate Professor

Department of Obstetrics and Gynecology

Vanderbilt University Medical Center

Nashville, TN

Janine Maenza, MD

Acting Assistant Professor, Medicine.

Division of Allergyand Infectious Diseases

University of Washington

Seattle, WA

Paul Pham, PharmD

Research Associate

Division of Infectious Disease

Johns Hopkins University

Baltimore, MD

Chia C Wang, MD, MS

University of Washington

Seattle, WA
TABLE OF CONTENTS

Forward

Joseph F. O’Neill, MD, MPH ix

Introduction

Jean Anderson, MD xi

I: Epidemiology and Natural History of

HIV Infection in Women

Ruth M Greenblatt, MD and Nancy A Hessol, MSPH 1

II: Approach to the Patient

Jean Anderson, MD 35

III: Prevention of HIV

Chia Wang, MD, MS and Connie Celum, MD, MPH 43

IV: Primary Medical Care

Judith Feinberg, MD andJanine Maenza, MD 79

V: Adherence to HIV Therapies

Laura WCheever, MD 139

VI: Gynecologic Problems

Silvia Abularach, MD, MPHandJean Anderson, MD 149

Color Plates 195

VII: HIV AND Reproduction

Jean Anderson, MD 211

VIII: Psychosocial and Cultural Considerations

Barbara Aranda-Naranjo PhD, RN and Rachel Davis, RN 269

IX: Psychiatric Issues

Joyce Kobayashi, MD 283

X: Substance Abuse

Henry L Francis, MD and Victoria A Cargill, MD, MSCE 307

XI: Adolescents

Donna Futterman, MD 329

XII: Palliative Care and End-of-life Care

Carla Alexander, MD 343

XIII: Occupational Exposure

Rani Lewis, MD 377

XIV: Pharmacologic Considerations in

HIV-infected Pregnant Patients

Paul Pham, PharmD and Patricia Barditch-Crovo, MD 395

XV: Resources 457

Index 471

us. Department of Health and Human Services, Health Resources and Services ADMiNis'iRAnoN, HIV/AIDS Bi 'ri ai ' y

Forward

Joseph F O’Neill, MD, MPH

Dear Colleagues:

The Ryan White CARE Act program of the Health Resources and Services

Administration is pleased to make this Guide available to clinicians caring for

women living with HIV/AIDS. We believe it is the first comprehensive clinical

manual on this topic, and the need for such a guide has never been greater.

The World Health Organization estimates that the number of people living

with HIV/AIDS is rapidly approaching 50 million, and that women constitute

45%—50% of the total. Already, in several regions of the world, more than

half of the people living with HIV/AIDS are women. But these statistics tell only part of the story. In addition to facing unique clinical issues, women liv- ing with HIV/AIDS are often challenged by social isolation, poverty, discrimination, and lack of access to quality health care.

Please note that this Guide for the care of women has been written almost

entirely by women. This is testimony to the enormous contribution that

women have made in the battle against HIV/AIDS on every front and in

every community across the globe. However, no medical guide can stand alone

in assuring that women will receive the best treatment available. In addition to

furthering our clinical knowledge, we must commit ourselves to addressing the

myriad social and economic issues that hamper effective prevention and access

to care for seropositive women.

Regard this preliminary edition as “our” Guide. It belongs to the global

community of clinicians who struggle daily with HIV/AIDS, caring for people

with competence, compassion and equality. Your comments, criticisms and

suggestions are needed to shape this manual into a clinical tool that will be of

maximum utility to all of us. Throughout the Guide you will find requests for

your input. Please respond by post, fax, or e-mail. And, if you can, suggest

partners who can help have this Guide translated into the many languages of

“our” community.

We all owe a debt of gratitude to John G. Bartlett, M.D. His guide, 1999

Medical Management ofHIVInfection was the inspiration and template for this

volume. He graciously allowed us to adapt many of the charts and algorithms

for this book.

us. Department of Health and Human Services, Health Resources and Services Administr.vhon, 1 1 IV/AIDS Hi 'ri.m IX
A Guidi- to ini' Ci.iNicAi, Carr oi' Women wrni HIV

I'onvard

Finally, I want offer my personal thanks to the editor, Jean Anderson, M.D.,

for her dreless dedication and perseverance in creating this Guide. Her efforts

have made a profound change possible. This Guide., I believe, will mark a turning point in significantly improving the care of women living with HIV/AIDS.

Cordially,

Joseph F. O’Neill, MD, MPH

Director, HIV/AIDS Bureau

Health Resources and Services Administration,

U.S. Department oe Health and Human Servlces

Send Us Your Comments

E-mail: womencare@hrsa.gov

Fax to the attention of "Womencare": 301-443-0791 (USA)

Postal address: Womencare

Parklawn Building, Room 11A-33

5600 Fishers Lane

Rockville, Maryland 20857

USA

Note that this and subsequent editions of

A Guide to the Clinical Care of Women with HIV

will be available online.

Go to the HIV/AIDS Bureau Web site

and click on the publication Women's Guide'.

http://www.hrsa.gov/hab

X US. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
Introduction

Jean Anderson, MD

Despite the dramatic advances made in understanding the natural history of

HIV disease and the development of effective antiretroviral therapies, the

AIDS epidemic continues to grow. And that growth has displayed some disturbing trends. HIV/AIDS morbidity and mortality increasingly impact the

poor, the disenfranchised, and the young. Women are traditionally over-represented in these groups.

The growing number of women living with HIV/AIDS is a dominant fea- ture of the evolving epidemic. In addition, because they are often diagnosed

later and generally have poorer access to care and medications, women tend to

have higher viral loads and lower CD4 counts. Women living with HIV/AIDS

also must contend with vulnerability related to reproductive issues and domestic violence. Finally, women living with HIV/AIDS are usually relied upon to

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

are also HIV-positive.

For these, and other reasons, a manual addressing the primary care needs

unique to women with HIV infection is long overdue. This manual represents an attempt to fill this gap. Our target audiences are clinicians who provide

primary care to women. This Guide might also be of interest to individuals

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

HIV/AIDS.

The book you have in your hands is a preliminary edition, a work in

progress, and we welcome your comments and suggestions. Please send

any feedback to the postal, fax, or e-mail addresses found throughout the

book and on the inside covers. We are particularly eager for this Guide to be translated into other languages. Please let us know if you can help or

suggest partners.

This preliminary edition is focused primarily on the problems facing

HIV-infected women in the developed nations, primarily the US. Our goal

is that in future editions of this Guide we can take a more global perspective

and address the care of women with HIV/AIDS in both developed and

developing nations.

us. Department of Health and Human Services, He/\lth Resourcf.s and Sfirvicfis Admini.s-ih.viion, HIV/AIDS Hi hi \r XI
A ('lUIOB TO rilli Cl.lNlCAI. CaRIL Ol'- WOMI'N WI l Il HIV

Introduction

I want to offer my personal thanks to Helen Schietinger and Magda BariniGarda for their championing this Guide throughout its development, displaying enormous tact, tenacity, and attention to detail. Without them, this manual

would never have been published.

Finally, we want to acknowledge the women with HIV/AIDS who have

been the inspiration for this manual. Their strength is celebrated and their

struggle is not forgotten. We offer this Guide as a tribute to them, and to the

providers who have taken on this struggle and made it their own.

Jean Anderson, MD

Editor

xii us. Department of He/\lth and Human Services, Health Resources /\nd Services Administr/\tion, HIV/AIDS Bureau
I. Epidemiology and Natural History of

HIV Infection in Women

Ruth M. Greenblatt, MD and Nancy A. Hessoly MSPH

I. INTRODUCTION

The successful introduction and spread of the human immunodeficiency virus

(HIV) into the global human population has occurred for many reasons. The

discovery and wide spread use of penicillin and other antibiotics meant that

there was treatment and cure for most sexually transmitted diseases. The existence of these new drugs changed how people perceived risks associated with

sexual activity. Soldiers in World War II increasingly used prophylactics and the

subsequent development of hormonal contraceptives hastened the pace of

change in sexual practices, as prevention of pregnancy became a real possibility. Lifestyles also were changing: people were moving into regions that were

previously uninhabited by man and long distance travel became easier and was much more common, allowing for more social migration and sexual mixing.

Although the virus may have first been introduced to humans earlier in the

20th century (most likely contracted from infected animals), it was in the

1970’s that wider dissemination occurred.

For industrialized countries, the first evidence of the AIDS epidemic was among groups of individuals who shared a common exposure risk. In the

United States, sexually active homosexual men were among the first to present

with manifestations of HIV disease, followed by recipients of blood or blood

products, then injection drug users, and ultimately children of mothers at risk. Women have represented an increasing proportion of reported AIDS cases in

the United States, accounting for 23% of adult cases from July 1998—June

1999. (CDC, 1999) Eighty percent of AIDS cases in women are in African

Americans and Hispanics, as compared to 61% of cases in men.

In developing countries, the AIDS epidemic manifested itself c|uite differently, both because the signs and symptoms were harder to identify due

to other competing causes of morbidity and mortality and because the epidemic did not seem to be limited to “high-risk” groups and, instead, was

more generalized. Worldwide, women now represent 43% of all adults living

with HIV and AIDS (Table 1-1, next page) and this proportion had been

steadily increasing over time. (UNAIDS, 1998)

This chapter reviews the epidemiology of HIV/AIDS: beginning with how

HIV is transmitted and the variables involved; the natural history of I II

V

infection in women, both without treatment and in the era of higlilv actiw

us. Dep.vrtment of Health and Human Services, Healih Rilsourcics \nd Si-rvice-s Admini.vih vnnr,. I ll\ / Ml )^ Hi . i 1
A Ciiuni' TO Till': (j.iNicAi. C\ri; oi' Womi;n with llIV

I epidemiology and Natural History of HIV Infection in Women

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2 us. Department of Health and Hunun Services, Health Resourctcs and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

antiretroviral therapy (HAART); and concludes with future issues regarding

the HIV/AIDS epidemic.

II. HIV TRANSMISSION

Fipidemiological studies have demonstrated that HIV is transmitted by three

primary routes: sexual, parenteral (blood-born), and perinatal. Virtually all cases of HIV transmission can be attributed to these exposure categories.

Transmission rates from the infected host to the uninfected recipient vary by

both mode of transmission and the specific circumstances. Since HIV is a relatively large virus, has a short half-Ufe in vitro, and can only live in primates,

HIV cannot be transmitted from causal (i.e. hugging or shaking hands) or surface (i.e. toilet seats) contact or from insect bites.

A. MODES OF TRANSMISSION

Sexual transmission of HIV from an infected partner to an uninfected partner can occur through male-to-female, female-to-male, male-to-male, and femaleto-female sexual contact. Worldwide, sexual transmission of HIV is the predominant mode of transmission. (Quinn, 1996) Among U.S. women with

AIDS, sexual transmission constitutes 40% of reported cases as of June 1999.

(CDC, 1 999) This 40% is probably and underestimate when you take into consideration that a large proportion of the women with AIDS who report no

identifiable risk (an additional 1 5% of AIDS cases in women) are acmaUy also

infected via sexual transmission. While receptive rectal and vaginal intercourse

appear to present the greatest risk of infection (approximately 0.1—3% and

0.1 -0.2%, respectively, per episode), insertive intercourse (both rectal and vaginal) have also been associated with HIV infection (approximately 0.06% and

0.1%, respectively, per episode). (Vittinghoff, 1999; Mastro, 1996) In addition,

there have been a few case reports of male-to-male transmission from receptive oral intercourse with an HIV-infected male partner (approximately 0.04%

per contact) and female-to-female transmission from oral-vaginal, oral-anal, and

digital intercourse. (Marmor, 1986; Monini, 1996; Monxon, 1987; Perry, 1989;

Rich, 1993; Sabatini, 1983)

Parenteral transmission of HIV has occurred in recipients of blood and

blood products, either through transfusion (estimated 95% risk of infection

from transfusion of a single unit of HIV-infected whole blood — (CDC,

1998)) or clotting factors, in intravenous or injection drug users through the

sharing of needles (approximately 0.67% risk per exposure (Kaplan, 1992)),

and in health care workers through needle sticks (approximately 0.4% risk per

exposure, depending on the size and location of the inoculum (Tokar, 1 993))

and less commonly mucous membrane exposure. (Hessol, 1989) Among

cumulatively reported AIDS cases in U.S. women through June 1999, 42%

had injection drug use as their exposure risk and 3% receipt of blood, blood

products, or tissue. (CDC, 1999) Parenteral transmission patterns vary by

U.S. Department of Health and Human Services, Health Rilsources and Servicils ADMiNi.s'i'R.vnoN, I II\7AIDS 3
A CJUIOli TO I'lll'. (j.lNlCAl. (^MUC Ol' WoMl'N wri'ii HIV

F.pidcmiology and Natural History of HIV Infection in Women

geographic region due to social and economic factors. For instance, in regions

where the prevalence of HIV infection is higher, the risk of occupational or nosocomial transmission of HIV is increased over regions where there is lower prevalence. (Consten, 1995) The transmission risk is therefore related to the prevalence of HIV in the population as well as the frequency of exposure

to infected body fluids and organs and the method of exposure. (Fraser, 1995)

In addition, many developing countries that have a high prevalence of HIV

infection also lack the resources to implement universal precautions adequately

(Gilks, 1998) and may experience a greater amount of transfusion-associated

HIV transmission due to a lack of HIV antibody screening in some areas, a higher residual risk of contamination in blood supplies despite antibody

screening (McFarland, 1997), and high rates of transfusion in some groups

of patients.

Perinatal transmission can occur in utero, during labor and delivery, or post-partum through breast-feeding. (Gwinn, 1996) Perinatal transmission

rates average 25—30% (Blanche, 1989), but vary by maternal stage of disease, use of antiviral therapy, duration of ruptured membranes, practice of breastfeeding, as well as other factors. In the U.S. as of June 1999, 91% of cumulative pediatric AIDS cases were attributed to perinatal transmission. (CDC,

1999) More information on perinatal transmission can be found in Chapter

VII on HIV and Reproduction.

B. FACTORS FACILITATING TRANSMISSION

Transmission of HIV infection can be influenced by several factors, including

characteristics of the HIV-infected host, the recipient, and the quantity and

infectivity of the virus. A summary of factors affecting sexual transmission of

HIV is presented in Table 1-2.

Infectiousness of the Host

There is an association between the quantity of virus transmitted and the risk

of HIV infection. (Roques, 1993) Several studies have found that HIVinfected persons may be more likely to transmit the infection when viral replication is high, both during the initial stage of infection (Palasanthiran, 1993)

and at more advanced stages of HIV disease. (Laga, 1989) People with high

blood viral load are more likely to transmit HIV to recipients of blood, their

sexual partners, and their offspring. (Vernazza, 1999; Quinn, 2000) HIV has

been quantified in semen (Coombs, 1998; Speck, 1999; Vernazza, 1997) and

detected in female genital secretions (Ghys, 1997; Mostad, 1998), and virus in

these locations may facilitate transmission. However, the association between

infectivity and disease stage is not absolute; HIV-infected women may transmit

virus to a first-born child while not to a second-born child (deNartubim

1991), and temporal studies of semen from HIV-infected men demonstrate

waxing and waning viral titers over time. (Krieger, 1991; Tindall, 1992)

4

us. Department of FIe.\lth and Hunwn Services, He,vlth Resources and Services AoMiNisnunoN, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

Table 1

- 2 : Biologic and Host-related Factors Affecting Sexual

Transmission of HIV

Biologic Factor

Host-related Infectivity Factors

HIV Concentration

IN GenitalSecretions

Infectiousness

(Transmission)

Susceptibility

(Acquisition)

Mutation of chemokinereceptor gene

?• 9•

Late stage of HIV infection Jk. Not applicable

Primary HIV infection Jk. Not applicable

Antiretroviral therapy ?

Local infection Jk. Jk. k. k

Presence of cervical

ectopy? k k

Presence of foreskin? 9• jk. Jk Jk

Method of contraception

Barrier Not applicable

’''

Hormonal contraceptives Jk

Spermicidal agents 9• ^9 k

Intrauterine devices 9• 9• k k

Menstration 9• k

Factors that lower

cervicovaginal pH? ? ? ^9

Immune activation jk. k

Genital tract trauma? jk Jk k k

Pregnancy ^9•

The degrees of positivity (^Xo and negativity (''to of the associations are

indicated with arrows, with three arrows indicating a very strong association. The symbol ^

denotes that there is evidence in support of both a positive and negative association. A question

mark ( ? ) indicates an unknown or hypothesized association that is not currently supported

by data. Source: Royce, 1997.

Factors that decrease viral titers, including anti-retroviral therapy, may

decrease but not eliminate the risk of HIV transmission. (Hamed, 1993)

Zidovudine has been shown to reduce vertical transmission from mothers to

their fetus even when administered late in pregnancy or during labor. (CDC,

1998) (See Chapter VII on HIV and Reproduction) Individuals receiving antiretroviral therapy have also shown reduced transmission rates of HIV to their sex partners. (Musicco, 1994) Several studies have suggested that anti-retroviral

treatment reduces detection of HIV in female genital secretions (Ciu Uvin,

1998) and the concentration of HIV in semen. (Gilliam, 1997; Gupta, 1997)

Providers counseling patients on treatment should be clear that precautions to prevent transmission of the virus should be maintained since not all treatment

us. Department of Health and Hum.-\n Services, Health Rfsources and Services Adminis-ih.viion, I ll\'/ AIDS IIvki.m 5
A CJuioi-: ro riiii Ci.inicai. C\ri; oI' WomivN wrni FllV

r.pidcmiology and Natural History of HIV Infection in Women

reduce infectiousness and transmissions have been reported among individuals

with undetectable HIV RNA levels. (The European Collaborative Study

Group, 1999)

Factors which increase the risk of exposure to blood, such as genital ulcer

disease (Cameron, 1989; Plummer, 1991), trauma during sexual contact (Marmot, 1986), and menstruation of an HIV-infected woman during sexual contact (The European Collaborative Study Group, 1992; Nair, 1993; St. Louis,

1993) may all increase the risk of transmission.

Method of contraception also affects the likelihood of HIV transmission.

(Daly, 1994) There is overwhelming evidence that the correct and consistent use of latex condoms protect both men and women against HIV. However,

because of methodologic difficulties in studies of contraceptive use and HIV

transmission, it remains unclear whether the use of hormonal contraceptives,

lUDs and spermicides alter the risk of HIV transmission.

Susceptibility of the Recipient

Similarly, characteristics of the uninfected individual may increase the likeli- hood of infection for a given exposure to HIV. Specifically, inflammation or

disruption of the genital or rectal mucosa (which can occur with sexually

transmitted diseases and trauma), and lack of circumcision in heterosexual

men may increase the risk of infection. (Cameron, 1989; Moses, 1994; Quinn,

2000) Sex during menstruation may increase women’s risk of acquiring HIV

infection (Laz2arin, 1991) as may bleeding during sexual intercourse. (Seidlin,

1993) In women, both uclerative and non-uclerative sexually transmitted dis- eases have been shown to be risk factors for getting infected with HIV. (Laga,

1993; Plummer, 1991) Cervical ectopy has been identified as a risk factor for

acquisition of HIV infection in some (Nicolosi, 1994; Plourde, 1994) but not

aU (Mati, 1994) studies that have evaluated this condition. There is also some

evidence that changes in the vaginal flora, as characterized by bacterial vaginosis, may facilitate acquisition of HIV. (Sewankambo, 1997)

Non-barrier contraceptive methods have also been investigated in association with risk of HIV transmission but the results are inconclusive. The most

frequently studied methods of contraception have been oral contraceptives,

injectable hormones, intrauterine devices, and nonoxynol-9. (Daly, 1994; Plummer, 1998) (See Chapter III on Prevention) Traditional vaginal agents, used in

African women for sexual enhancement and self-treatment of vaginal symptoms, has also been investigated as a potential cofactor for HIV transmission.

(DaUabetta, 1995) For many of these studies, limitations of the study design

preclude any definitive conclusions.

There is increasing evidence that host genetic or immunologic factors may

protect against HIV infection. This has been investigated in cohort studies of

Nairobi sex workers (Willerford, 1993) and in United States homosexual men

(Dean, 1996), both of who remained uninfected despite multiple sexual expo6

US. Department of Health and Human Services, Health Resources and Services Administraiion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

sures t(3 HIV. Individuals who are homozygous for a nuU allele of CCR5 are

relatively resistant to sexually transmitted infection with HIV, indicating an

important, though not absolute, role for this receptor in viral transmission.

1 lowever, homozygous CCR5 mutations were not found among 14 hemophiliacs who remained uninfected with HIV after being inoculated repeatedly with

HIV contaminated Factor VIII concentrate from plasma during 1980-1985.

(Zagury, 1998) In this study, investigators found an over production of betachemokines in most of the uninfected individuals.

Viral Properties

Several viral factors have been proposed to play a role in the transmissibility of

HIV. These include phenotypic characteristics (e.g., envelope proteins required

for transmission), genetic factors that control the replicative capacity and “fit- ness” of the virus, and resistance to antiviral drugs. (Vernazza, 1999)

Envelope sequences can define viral quasispecies that have been phenotypically arranged according to their ability to induce syncytia formation in

infected T-cells. (Paxton, 1998) It appears that the most commonly transmitted

phenot}q)e is the non-syncytia-inducing (NSI), M-tropic viral strain, which is frequently found in those who have been recently infected. During the course of HIV infection the development of a more cytopathic, syncytia-inducing

(SI), T-tropic viral phenotype can be found and this is often a precursor to the

development of AIDS. While some researchers have suggested that NSI isolates of HIV are preferentially transmitted (Roos, 1992), others have not been

able to show preferential transmission of this isolate. (Albert, 1995)

Envelope sequences can also be used to define viral subtypes, or clades,

and these subtypes may also influence the transmissibility of HIV. The distri- bution of HIV subtypes differ according to geographic region, with A, C, D,

and E predominant in sub-Saharan Africa and Asia and B predominant in the

United States, the Caribbean, South America, and Western Europe. (Hu, 1996)

In one study, subtype E is reported to have greater tropism for Langerhans’

cells than subtype B (Soto-Ramirez, 1996) and may have a greater per contact

transmissibility.

Lastly, the transmission characteristics of a viral strain that is resistant to

certain antiretroviral agents may differ from transmission of wild type virus.

More research is needed in this emerging field of therapy-resistant virus and

its characteristics.

III. NATURAL HISTORY AND HIV DISEASE PROGRESSION

The natural history of HIV infection in adults has been extensively documented in the medical literature. The impact of gender on the manifestations

and progression of HIV-disease is stiU being investigated. Concerns about

gender-based differences in the course of HIV infection were expressed early

us. Department of Health and Human Services, Health Resourcf.s and Services AoMiNis'iRAnoN, HIV/.MDS Bi ri.m' 7
A (kuDi' I'o 'mi'. (j.iNic.M, C\Ki': oi' Wom1 ';n wrni I IIV

I'.pidcniiology and Natural History of HIV Infccdon in Women

in the epidemic. In most industrialized countries, women tended to have lower

income, be un- or under-insured for health care, know less about HIV, more

likely to be Black or Hispanic, and to have a personal or partner history of

injection drug or cocaine use. Women also appeared to have more rapid progression of illness than men and to present with a different constellation of

opportunistic conditions than men. When sophisticated statistical methods

were applied that controlled for the tendency of women to receive less care, and to present with more advanced disease, gender-based differences in HIV

disease course appeared to lessen. More recently, however, with better measures of viral activity and infirmity, the issue of gender-based differences in

rate of disease course and virologic parameters has again been raised. These

new observations have prompted active research into the impact of gender,

hormones and demographic factors on the outcome of HIV infection.

HIV infects and induces cell death in a variety of human cell Hnes. T-helper

lymphocytes (also known as CD4 cells) are a major target of viral infection,

and circulating CD4-ceUs become steadily depleted from peripheral blood in

most untreated infected persons. Thus quantification of CD4-cells in blood is a rather simple way of determining cumulative immunologic damage due to HIV. Profound CD4-ceU depletion is unusual in persons who do not have

HIV infection and are usually iatrogenic or associated with severe illnesses,

such as chemotherapy-induced leukopenia. (Aldrich, 2000) Other immunological parameters become altered with HIV-disease progression, and though

often used for research purposes, they tend to be more difficult to measure and less reliable or more costly.

Untreated HIV infection is a chronic illness that progresses through characteristic clinical stages; AIDS is an endpoint of HIV infection, resulting from

severe immunological damage, loss of an effective immune response to specific opportunistic pathogens and tumors. AIDS is diagnosed by the occur- rence of these specific infections and cancers or by CD4-celI depletion to less than 200/mmk

A. STAGING

HIV can cause a wide range of symptoms and clinical conditions that reflect

varying level of immunological injury and different predisposing factors. Certain conditions tend to occur in association with each other and at specific

CD4 cell counts. Staging systems for HIV-disease facilitate clinical evaluation

and planning therapeutic interventions, help determine the individual level of

infirmity, and give prognostic information. Untreated HIV infection is a chronic illness that progresses through characteristic clinical stages that can be

used to describe infirmity. Several groups have produced organized staging

systems to facilitate clinical evaluation and planning therapeutic interventions.

In industrialized countries, the most widely used system for classifying HIV

infection and AIDS in adults and adolescents was published by the United

States Centers for Disease Control in 1993. (CDC, 1992)

8

us. Dei’.\rtment of He.\lth and HumN Services, Health Resources and Services AdministR/\tion, HIV/AIDS Bureau
A Guide to the Clinic.\l C.\re of Women with

Epidemiology and Natural Plistor)' of HW Infection in Women

Table 1-3: 1993 Revised Classification System for HIV Infection

AND Expanded Surveillance Case Definition for AIDS

Among Adults and Adolescents

CD4 CELL CATEGORY CuNiCAL Category A CuNiCAL Category B CuNicAL Category C

1 500 cells/mm^ A1 B1 Cl

2. 200-499 cells/mm^ A2 B2 C2

3. < 200 cells/mm^ A3 B3 C3

Category A Conditions Category B Conditions Category C CoNomoNS

No symptoms

Acute HIV infection

(resolves)

Generalized

lymphadenopathy

Bacillary

angiomatosis

Oropharyngeal

candidiasis

Vulvovaginal

candidiasis:

persistent, frequent,

or poorly responsive

to therapy

Cervical intraepithelial

neoplasia II or III Constitutional

symptoms: fever,

diarrhea > 1 month

Oral hairy leuko

plakia

Herpes zoster: multiple episodes

or involving > 1 dermotome

Idiopathic

thrombocytopenic

purpura

Listeriosis

Pelvic inflammatory

disease: particularly

if complicated by

tubo-ovarian

abscess

Peripheral

neuropathy

Candidiasis of bronchi,

trachea, lungs or esophagus

Invasive cervical cancer Coccidioidomycosis

,

disseminated or extrapulmonary

Cryptococcosis,

extrapulmonary

Cryptosporidiosis, (intestinal

infection > 1 month duration)

Cytomegalovirus disease

(excluding liver, spleen or lymph nodes)

HIV-related encephalopathy

Herpes simplex: chronic ulcer > 1 month duration, or

bronchitis, pneumonitis, or esophagitis

Histoplasmosis: disseminated

or extrapulmonary

Isosporiasis: > 1 month's

duration

Kaposi's sarcoma

Burkitt's lymphoma

Immunoblastic lymphoma

Primary lymphoma of the

brain

MAC* or M. kansasii:

disseminated or extrapulmonary

M. TB: any site Mycobacterium: other species

or unknown species,

disseminated or extrapulmonary

Pneumocystis carinii

pneumonia

Recurrent pneumonia

Progressive multifocal

leukoencephalopathy

Salmonella septicemia,

recurrent Toxoplasmosis of the brain

Source: CDC, 1992. Wasting syndrome due to HIV

US. Department OF HE.u.TH.\NDHiaL\NSERMCES,HE.\LTH Resources AND Services Administration. HIV/AIDs Hi > 9
A C'lUii:)!' TO riiH (j.inicai. Caric oi' Womi;n with HIV

Epidemiology and Namral History of HIV Infection in Women

The case definition (Table 1-3) begins first with confirmation of HIV

infection either via serologic testing (combination of a screening method such

as enzyme immunoassay and more specific confirmatory test such as Western

blot), or direct detection of HIV in patient tissue by viral culture, antigen

detection or other test such as polymerase chain reaction (PCR). The definition of each stage of illness is then based on two types of information;

peripheral blood CD4 cell counts and clinical manifestations. CD4 cell counts

are placed in three strata, ranging from relatively normal (> 500 cells/ mm^) to severe CD4 depletion (< 200 cells/mm^).

The clinical manifestations of HIV infection are also placed in three strata,

generally in accordance with the level of immunologic dysfunction associated

with the various conditions. (Table 1-3) Category A includes persons who have

minimal clinical findings, clinical findings that do not indicate immune injury

(including absence of symptoms), generalized lymphadenopathy or resolved

acute HIV infection. Category B includes conditions that indicate the presence

of a defect in cell-mediated immunity or conditions that appear to be worsened

by HIV infection. Category C includes conditions that are considered AIDS

defining, even in the absence of a CD4 cell count less than 200 cell/ mm^.

(CDC, 1992) The addition of specific laboratory measures such as plasma HIV

RNA level, improves prognostic value even after the occurrence of Category C

conditions. (Lyles, 1999)

Developing World

The CDC criteria require diagnostic testing and case confirmation methods

that may not be available in developing countries, so several other sets of criteria have been proposed for these regions. Since lymphocyte subset quantitation is not widely available in many countries, the Global Program on AIDS of

the World Health Organization (WH.O.) proposed a clinically based staging

system that is more broadly applicable than the CDC system. (W.H.O., 1993)

The system uses clinical historical data, laboratory measures (optional) and

indices of physical activity to assess level of infirmity to establish four strata that are summarized in Table 1-4. Laboratory measures include a single assess- ment absolute CD4 cell count, with the option of replacing this test with total

lymphocyte count, each of which are placed in three strata. CD4 cell count is a better prognostic indicator than total lymphocyte count, but the two results

correlate well. (Brettle, 1993)

Clinical history and functional measures are placed in four categories that

range from asymptomatic to severe disease. In general, when compared with

the CDC stages, the WH.O. system requires less diagnostic test data and fewer

direct observations. The definition includes broader categories for conditions

that may vary by region (e.g., disseminated infections with endemic mycoses

which are common in South East Asian AIDS patients but not in the United

States or Europe). The inclusion of performance scale measures permits

quantitative clinical assessment that is not dependent on laboratory resources.

10 us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure/\u
A Guide to the Cunic\l C\re of Women with HTV

Epidemiology and Natural History of HW Infection in Women

Table 1-4: The World Health Organization Clinical HIV Staging

System and Proposed Modifications

Laboratory Component CuNiCAL Group

CD4 i

CELL COUNT ^

Total

-^LYMPHOCYTE COUNT 1 2 3 4

a ^500 ^2000 A1 A2 A3 A4

B 200-499 1000-1999 B1 B2 B3 B4

C < 200 < 1000 Cl C2 C3 C4

CuNfCAL Stage CuNicAL History

Performance

Scale Criteria Proposed Modifications

One:

Asymptomatic

1. Asymptomatic

infection

2. Persistent generalized

lymphadenopathy

3. Acute retroviral

infection

Normal

functional level

in performance

scales

none

Two:

Mild

Disease

1. Unintentional weight

loss less than 10% of

body weight

2. Minor

mucocutaneous

manifestations

3. Herpes zoster within

the previous 5 years

4. Recurrent upper

respiratory infections

Performance

scale level at which

symptoms are present but

patients are almost fully

ambulatory

1. Substitution of weight

loss with BMI of

19-21kg/m^*

2. Specify addition

of acute oral or

genital ulcers as one of the minor

mucocutaneous

manifestations*

3. ESR <65mm/hr

defines Kigali stage II

4. ESR > 65 mm/hr

defines Kigali stage ill

Three:

Moderate

Disease

1. Unintentional weight

loss greater than 10%

of body weight

2. Chronic diarrhea **

3. Prolonged

intermittent or constant fever **

4. Oral candidiasis

5. Oral hairy leukoplakia

6. Pulmonary

tuberculosis

developing within the

previous year

7. Severe bacterial

infections

8. Chronic vulvovaginal

candidiasis** or poorly responsive to therapy

Performance

scale level at which patients

remain in bed < 50% of

daytime, but more than

normal

1. Suggest exclusion of

oral candidiasis and

pulmonary

tuberculosis*

2. Recommend

substitution of

weight loss with

BMI <19 kg/m^*

3. Differentiation of

ambulatory vs

hospitalized patients

improved correlation

with laboratory

markers (Kassa, 1999)

4. ESR <65mm/hr

defines Kigali stage II

5. ESR > 65 mm/hr

defines Kigali stage III

Table continues . .

.

US. Department of He.alth and Human Services, Health Resources and Services ,\DMiNisrR,\TiON, HU'/AIDS Bi riai' 11
A C'tUIDH to Tim Cl.lNICAL CARI' oi' WOMF.N WITH HIV

Epidemiology and NaUiral History of HIV Infection in Women

Table 1-4: The World Health Organization Clinical HIV Staging

System and Proposed Modifications (continued)

CuNtCAL Stage CuNiCAL History

Performance

Scale Criteria Proposed Modifications

Four:

Severe

Disease

1. HIV wasting

syndrome defined as unexplained weight

loss > 10% and either

chronic diarrhea** or chronic weakness**

and unexplained

fever

2. Pneumocystis carinii pneumonia

3. CNS toxoplasmosis

4. Chronic cryptosporidial diarrhea**

5. Chronic isosporiasis

with diarrhea **

6. Extrapulmonary

cryptococcosis

7. Cytomegalovirus

disease affecting

organs other than the

liver, spleen or lymph

nodes

8. Visceral or chronic**

mucocutaneous

herpes simplex virus

infection

9. Progressive

multifocal

leukoencephalopathy

10. Any disseminated

endemic mycosis

11. Candidiasis of the

esophagus, trachea,

bronchi or lungs

12. Disseminated atypic

Mycobacterium sp. Infection

13. Nontyphoidal Salmonella septicemia

14. Extrapulmonary

tuberculosis

15. Lymphoma

16. Kaposi's sarcoma

17. HIV-related

encephalopathy

Performance

scale at level which patients

remain in bed more than 50%

of daytime

1. Addition of oral candidiasis

2. Substitution of

weight loss with

BMI <19 kg/m^*

3. Addition of chronic**

oral or genital ulcer

4. Addition of

pulmonary

tuberculosis

5. ESR > 65mm/hr

defines Kigali stage III

6. Addition of positive

HIV serology***

7. Addition of invasive

cervical cancer***

* Lifson, 1995. ** > 1 month duration *** De Cock, 1993. Source: W.H.O., 1993.

12 us. Department of Health and Human Services, Hf^^lth Resources and Services Administr-vtion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

The four clinical stages in the WH.O. system correlated well with CD4 cell counts and HIV RNA levels in a study of 750 Ethiopians (included 336

women) by Kassa and others. (Kassa, 1999) Other studies of patient populations have also demonstrated correlation of WH.O. clinical stage with CD4

cell count and clinical outcome. (Morgan, 1997; Morgan, 1998; Schechter,

1 995) WTen compared with the CDC staging, the WH.O. clinical stages

demonstrated a high degree of specificity, but a lower level of sensitivity

(35-65%) for HIV infection. (Gallant, 1993; Gallant, 1992) In particular all of

the systems for disease staging are not perfectly sensitive and specific for HIV

infection, but can be improved by the addition of HIV serologies. (Ankrah,

1994; DeCock, 1991) Modifications (Table 1-4) have been proposed that

improve the prognostic accuracy of the WH.O. system. Based on observations

made in a study of AIDS mortality among Rwandan women, Lifson and colleagues proposed minor modifications of clinical history definitions, replacement of body mass index (BMI) (weight(in kg) divided by height (in m^)) for

weight loss and use of erythrocyte sedimentation rate (ESR) as a laboratory

indicator of infirmity. (Lifson, 1995) BMI was significantly better at predicting

mortality than percentage of body weight lost over two measurements taken

in one year. Both ESR and hematocrit were highly predictive of mortality over

a 36 month period of observation. (Lifson, 1995)

Other HIV-disease classifications, such as the Caracas definition proposed

by the Pan American Health Organization (Rabeneck, 1996; Weniger, 1992)

have been proposed but have not been evaluated as extensively as the CDC

and WH.O. systems.

B. UNTREATED NATURAL HISTORY

Primary or Acute Infection

Acute HIV infection is a transient symptomatic Hness that can be identified in

40—90% of cases of new HIV infection. It is characterized by a high rate of

HIV replication, high titers of virus in blood and lymphoid organs (up to several million copies of HIV RNA per mm^ of plasma), and initiation of an

HlV-specific immune response. The amount of virus present in blood and tis- sues begins to fall after appearance of cytotoxic (“killer”) lymphocytes that

specifically react with HIV antigens; the vigor of this response varies among

individuals and is associated with subsequent rate of disease progression. (Cao,

1995) A pool of persistently infected CD4 cells (“latent reservoirs”) emerges

early in the course of HIV infection and persists indefinitely. (Chun, 1998)

Symptoms have been identified from 5—30 days after a recognized exposure

to HIV. (Schacker, 1998) The signs and symptoms of acute HIV infection are not specific; fever, fatigue, rash, headache, lymphadenopathy, pharyngitis, mild

gastrointestinal upset, night sweats, aseptic meningitis and oral ulcerations are most frequently reported. Because the clinical signs of acute HIV infection

resemble those of many acute viral illnesses, the correct diagnosis is often

us. Department of Health and Human Services, Health Resources and Services Admini.s-i-rahon, HI\'/AIDS Biiri.m' 13
A CJuiDi; TO niH Ci.inicai. Caric oi’ W()mi:n with HIV

P.pidcmiology and Natural Hi.story of HIV Infection in Women

missed. Because early treatment at the time of acute infection may be especially beneficial (See Chapter IV on Primary Medical Care), early suspicion of

and evaluation for HIV infection should be encouraged. (Kahn, 1998)

Established Infection

Regardless of whether the syndrome of acute HIV infection is recognized or

not, after the HIV-specific immunological response begins to control the

intensity of viremia, a so-called “viral set-point” is established, which varies

by individual. With exceedingly rare exceptions, the immunological response to HIV does not eliminate infection, but rather establishes a steady state between

viral replication and elimination. (Henrad, 1995) A variable level of viremia is attained, which can be measured via quantification of the number of copies of

HIV RNA present in blood (viral load). Although the viral load within the

first 120 days of HIV infection is not of prognostic value (Schacker, 1998), in

most patients a relatively stable viral load is attained after recovery from acute

infection, and this viral set point is highly predictive of the rate of future progression of illness, at least as determined in studies that were largely focused

on men. In the case of a high viral load set point (i.e. values ranging up from

40,000 copies per mm^) more rapid decline in CD4 cell counts and more rapid occurrence of Clinical Class B and C conditions will occur. Some individuals

have viral load set points that are low (below 500 copies per mm^), which indi- cates a better prognosis; no evidence of progression (CD4 cell depletion or

HIV-diseases) is seen for long periods of time in a small subset of patients

(see section on long-term progression, below). The viral set point is likely

influenced by several factors such as presence of other infections at the time

of HIV exposure, genetic characteristics (particularly the type of HIV binding

receptors present on lymphocytes), viral characteristics, age and perhaps gender (see below). (Kahn, 1998)

During the period of clinical stability acute illnesses and other events that can stimulate the immune system, such as influenza, herpes simplex outbreaks,

and tuberculosis as well as routine vaccinations, have been demonstrated to

result in 10—1000 fold increases in viral load; these increases are transient and

most often resolve within two months. (Stanley, 1996; Staprans, 1995) Thus,

determination of viral load for prognostic purposes should not be done during

or shortly after an acute illness.

For most HIV-infected persons, viral quasispecies evolve overtime. Transition for the non-syncytia-inducing macrophage-tropic viral strains, that are commonly present after transmission to syncytia-inducing T-lymphocyte tropic

strains occurs in many hosts. While variation of viral quasispecies with time is usual, the mechanism by which this process occurs has not been defined.

However, transitions in viral quasispecies and cellular tropism has been

observed to coincide with key cUnical events such as CD4 cell depletion and

development of symptomatic illness. These virologic changes may reflect evolution of a virus that is tailored to an individuaTs immune response or other

14 us. Department of Health and Human Services, Health Resources and Services Administr/\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Epidemiology and Namral History of HIV Infection in Women

genetic characteristics. Interventions that prevent evolution of quasispecies in

a host may yield effective therapies in the future.

The HIV RNA level in tissues does not correlate in a linear fashion with

blood levels, so even in patients with undetectable plasma HIV RNA, intracellular and tissue HIV RNA can stiU be detected with more sophisticated techniques. (Hockett, 1 999) Thus HIV replication continues at varying pace among

infected persons, even those who can control viremia well.

HIV is also frequently present in the genital tract (Fiore, 1999; Iverson,

1998), where expression of inflammatory mediators, and lymphocyte receptors

differ from blood and may influence the rate of viral replication and numbers

of virions present. (Anderson, 1998; Hladik, 1999) While the quantities of

HIV present in cervicovaginal fluid are generally similar to blood (Hart, 1999;

Shaheen, 1999), they differ in some individuals. The finding that HIV isolates

from the lower genital tract can have different genotypic markers than blood

isolates from a single host (DiStefano, 1999; Shaheen, 1999), supports the concept that the lower genital tract sometimes functions as a separate virologic

compartment.

Time Course

In most studies of seroconverters, (persons for whom the date of the HIV

infection can be estimated), 50—60% of adults will be diagnosed with an AIDS-defining condition within 10 years of infection (for the pre-HAART

treatment era). Forty-eight percent of seroconverters die (due to any cause)

after 10 years of infection. Increasing age is the factor most consistently associated with rate of progression and death in most groups of patients studied

to date. (AUoum, 1998; UK Register of HIV Seroconverters Steering Committee, 1998; Pezzott, 1999; Prins, 1999) Date of infection also influences time

from infection to an AIDS diagnosis, at least in some locations, demonstrating

that even in the pre-HAART era, improvements in treatment resulted in tangible benefits. (Webber, 1998)

Laboratory Indicators and Predictors

A large number of laboratory tests have been evaluated as prognostic indicators in HIV infection. For the most part, the tests can be divided into three

groups: A. measures of HIV replication, B. measures of immune function and

C. measures of inflammation. Group A is specific to HIV infection. Group B,

when indicating severe CD4 cell depletion is relatively specific to HIV infection and Group C are generally not specific to HIV infection. Table 1-5, on

the following page, summarizes these laboratory measures, outcomes, their

advantages and disadvantages. HIV RNA quantitation, performed on fresh or

fresh-frozen plasma or serum, is a powerful and accurate prognostic indicator

in HIV infection, and is uniquely useful in determining response to antiretroviral therapy. (Saag, 1996) In general the best measures of prognosis and staging include combinations of HIV RNA level, CD4 cell count and perhaps

us. Department of Health and Human Services, Health Resources and Services AoMiNis'i'RAnoN, HIV/AIDS Hi ri;.« 15
A CJuini' TO Till' (J.INICAI. (]A1 U- ()!• WoMl'N Will I HIV

I 'epidemiology and Natural History of HIV Infection in Women

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16 us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinic.\l Care of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

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lymphocyte function (cytotoxic lymphocyte response to HIV). (Spijkerman, 1997; Vlahov, 1998)

Long Term Non-progressors

In untreated adults the median time

from HIV infection to AIDS in developed countries is 8-10 years. However, approximately 8—15% of HIV

infected persons (most studies focus

on men) remain symptom free for

much longer periods of time , a phenomenon that has been named longterm survival (LTS). Among these

individuals who remain clinically sta- ble without treatment for 5—8 years, two groups can be discerned, those

who have stable CD4 cell counts and

those who have low CD4 cell counts,

but no AIDS defining conditions.

(Schrager, 1994) Several factors have

been found to be associated with

long-term survival including host

characteristics such as the presence of

specific anti-HIV cytotoxic lymphocyte responses, and viral characteristics such as defective genes and gene

products. (Kirchhoff, 1995) LTS

patients tend to have consistently

lower levels of HIV RNA after the

period of acute infection suggesting

better control of viral replication.

(Vesanen, 1996) For example viral

growth in peripheral mononuclear

cells taken from LTS was markedly

less than in PBMCs taken from

healthy HIV-uninfected donors. (Cao,

1995)

Gender Effects

In general the predictors of the rate of HIV-disease progression and survival among women are the same as in men. CD4 cell count depletion and

higher HIV RNA level are strong pre

U.S. Department of Health and Human Services, Health Resourcft; and Servici-s ADMiNis-ncvnoN, HI\7AID,s Hi : i 17

I,

Epidemiology

AND

Natural

History
A GuIDF. lO IHF. Cl.lNlCAl, CaRI- Ol- W'OMFN WI TH Hl\'

Epidemiology and Namral History of HI\’ Infection in Women

18 us. Dep.\ktment of He.\lth and Human Sermces, He.\lth Resources ,\nd Sermces ^\dministration, HRV-AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

us, Department of He.alth and Human Services, Health Resources and Services ADMiNiSTR,vnoN, HIV/AIDS Bi'ri-ai' 19
A CJuiDi' ro iiiH (j.iNicAi. (].\Kr. oi' Womi;n wrni HIV

Epidemiology and Natural History of Hl\' Infection in Women

dictors of progression and survival in women. (Anastos, 1996b) Several recent

reports, however, describe gender-based differences in HIV RNA level and in rate of CD4 cell depletion; women had HIV RNA levels that were 30-50%

lower than men who had comparable CD4 cell counts. (Bush, 1996; Evans,

1997; Farzadegan, 1998) Similar results occurred when analysis was restricted to seroconverters or when HIV culture was used to quantify viremia rather than

RNA assays. QLyles, 1998; Sterling, 1999) Intuitively, lower levels of circulating

HIV RNA, which suggest lower steady state level of viremia, should be associated with better outcome. However, the findings of several recent studies suggest that the lower HIV RNA level does not provide benefit to women. Women

experienced more rapid CD4 cell depletion and faster progression to AIDS and

death than men at similar HIV-RNA levels, even when race and age were taken

into consideration. (Anastos, 1999a; Farzadegan, 1998)

Determination of the effect of gender on the rate of progression, time

until occurrence of an AIDS defining condition and death is a complicated

process. Unless the date of HIV infection can be established, duration of

infection becomes a significant unknown factor in studies. In addition, particularly in developed countries, HIV-infected women and men differ by more

than just their gender. Women tend to have lower income, be members of

minority ethnic groups, have been born in Africa, have used injection drugs or

cocaine, or to have a sexual partner who has done so, all of which are risk fac- tors for poor health in general. In most studies women have shorter duration

of infection prior to AIDS and death than men, but these differences tend to disappear when CD4 ceU count and drug use are taken into consideration.

(Alioum, 1998; UK Register of HIV Seronconverters Steering COmmittee,

1998; Pezzotti, 1999; Santoro-Lopes, 1998) Several studies have reported an

excess proportion of infections or deaths due to bacterial infection, often

pneumonia (Feldman, 1999), among women compared with men. (Melnich,

1994; Weisser, 1998)

A summary of factors that influence disease progression is shown in

Table 1-6.

C NATURAL HISTORYINHAARTERA

Industrialized Countries

In countries that are able to provide highly affective antiretroviral treatments

(HAART), HIV-associated morbidity and mortality have declined significantly.

(Michales, 1998; MiUer, 1999a; Miller 1999b; PaleUa, 1998; Pezotti, 1999) (See

Primar}^ Medical Care in Chapter IV for more information). These population

findings, based on regional surveillance systems, were preceded by a multitude

of clinical trials that demonstrated clinical and virologic benefits of HAART.

(Bartlett, 1996; CoUier, 1996; Deeks, 1997; Hammer, 1997) Despite the promise and documented benefits of HAART, clinical progression continues to occur among recipients, particularly among persons who received antiretroviral

20 us. Department of He.alth and Human Services, He.\lth Resources .\nd Services .\dministr.ation, HIAV-UDS Bureau
A Guide to the Clinical C.lre of Women with HIV

Epidemiology and Natural History of HIV Infection in Women

treatment prior to initiation of HAART. (Ledergerber, 1999) Viral resistance

to I lAART components can occur via several mechanisms, which for the most

part involve mutation of viral target proteins. (Richman, 1996; Schapiro, 1999)

I'he emergence of antiretroviral resistance is a function of several factors:

prior treatment, pre-treatment level of viremia, drug levels (adherence to medication regimens, bioavailability of medications, adequate dosing) and specifics

of the regimen. (Guilick, 1998; Ledergerber, 1999; Shafer, 1998) Multiple daily

doses, side effects and in some cases, dietary restrictions aggravate the problem of achieving optimal drug levels since protease inhibitor agents are relativ-^ely poorly bioavailable. Suppression of viral replication and prevention of

resistance are directly related to level of antiretroviral drug. Persistent viral

replication provides opportunity of occurrence of resistance mutations, and

selective pressure to support continued presence of such mutants. (Condra,

1998; Feinberg, 1997; Wong, 1997) Besides clinical treatment failure, emergence of antiretroviral resistance is now associated with transmission of resistant virus to previously uninfected persons, a finding that could portend

significant limits to the effectiveness of these treatments in populations over

long periods of time. (Boden, 1999; Brodine, 1999; Yerly, 1999)

Developing Countries

The high cost of antiretroviral drugs and the need for clinical and laboratory

services for monitoring response to and efficacy of these treatments has

greatly restricted provision of PIAART in the developing world. Thus the

reductions in morbidity and gains in survival in FlIV patients that have been

demonstrated in many industrialized countries do not extend to developing

countries in which the majority of HIV cases worldwide occur. A consensus

statement regarding provision of these therapies has been released based on

meetings held in Dakar and Abidjan during 1997. The key recommendations

of conference participants include: efforts must be made to expand provision

of ART, ART only makes sense in the setting of effective AIDS control programs, funding must be sustained to provide uninterrupted treatment and continuity of care, care providers must be trained in use of the treatments and

basic patient rights, resources for assessment of efficacy and tolerance must be

available, sentinel monitoring for resistance pattern determination should be

available, 3-drug combination regimens should be used when possible, treat- ment of pregnant women to prevent perinatal transmission must be a priority,

and new drug development should focus on less costly medications. (International AIDS Society, 1 999)

V. FUTURE ISSUES

A. GLOBAL IMPACT

The HIV/AIDS epidemic continues to spread without full control in any

country. Over forty million people have been infected worldwide. By the end

us. Department of Health and Human Services, Health Resources and Skrvktls .\DMiNis-i-R,vn<)N, HI\7.\IDS Huri-.M' 21
A ('jUII)f. to tmf: Cunicai. Carf. of Womi:n wrm HIV

F.pidcmiology and Namral History of HIV Infection in Women

of 1998, the United Nations Program on AIDS (UNAIDS) estimated that

33.4 million people were living with HIV, a figure which includes 13.8 million

adult women (UNAIDS, 1998) (Table 1-1, page 2). In 1998 it is estimated that

5.8 million new HIV infections occurred of with 2.1 million of these occurring in women. After steady increases of the prevalence of disease among

women during the 1990s, currently 43% of aU persons over the age of 15

years living with HIV are women. Globally, AIDS is now the fourth leading cause of mortality; 2.5 million deaths have been attributable to AIDS, of

which 900,000 occurred in women. The notable improvements in AIDS mortality reported in North America and Europe, in association with the introduction of highly active combination antiretroviral therapies, do not extend to

most of the world’s cases which occur in regions in which this expensive type

of treatment is not available.

More than 95% of HIV-infected people live in the developing world, most

in Sub-Saharan Africa. Seventy percent of infections that occurred during

1998 took place in this epicenter. The region has also experienced 83% of aU

AIDS deaths. Unfortunately prior projections of the epidemic course in

Southern Africa underestimated the incidence of infection by half. (Balter,

1998) Improved data have revealed that the prevalence rates in southern Africa

are staggering; 20—26% of adults (aged 15—49 years) are infected; in some

regions 20—50% of pregnant women are infected and are likely to transmit

infection to 1/3 of their offspring. The declining mortality rate, and population growth taking place in other regions cannot be extended to Sub-Saharan

Africa, due to the extent of AIDS mortality. (Bongaarts, 1998) AIDS has now

surpassed malaria as the leading cause of death in this region. (Balter, 1999)

Life expectancy will fall from 64 to 47 years by 2015. AIDS will cost, on an

average, 1 7

years of life expectancy in the 9 Sub-Saharan countries with a > 10% prevalence of HIV infection among adults. The child mortality rates in

this region are also elevated by AIDS; rates are approximately double that

expected without the HIV epidemic. (UNAIDS, 1998) Within one year 2,400

Zimbabweans will succumb to AIDS per week, many in the prime of life, many leaving dependent children as orphans (up to 1 in 5 children are likely to

become orphans). The United States Surgeon General, David Satcher, notes

that “the progress of decades of work immunizing children, controlling dis- eases, and improving nutrition is being negated by HFV.” (Satcher, 1999)

In Asia, the epidemic has a mixed pattern that includes countries with slow

growth in HIV prevalence, countries with some success in control efforts and

regions that appear to be experiencing explosive epidemics. Currently 7 million

Asians are infected with HIV. Rapidly accelerating epidemics are possible in

China, Cambodia, Vietnam and India. While urban areas were initially of

greatest concern in many countries, recent information has revealed very

active epidemics in specific rural areas (up to 2% of the general population),

which are hosts to large proportions of the region’s population.

22 us. Department of Health and Human Services, Health Resources and Services Administr.'\tion, HIV/AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

Epidemiology and Natural Plistory of HIV Infection in Women

While the outlook for AIDS in Asia is bleak, there is also cause for hope.

Growth of the epidemic in the Philippines is notably slow. (Jacobs, 1999)

Thailand has been successful in reducing the incidence of infection in sentinel

population groups (such as members of the military and pregnant women)

using a combination of good surveillance, effective policy response, implementation of educational and condom promotion programs. The incidence of

I II V infection among pregnant women in Thailand has dropped from a peak

of 2.4% in 1995 to 1.7% in 1997. (Phoolchareon, 1998) However ongoing

political upheaval and cuts to the national HIV prevention budget may modify

this pattern of success in the near future.

In the Americas the epidemic continues to grow in specific subgroups. In

the United States, as summarized earlier in this chapter, the highest incidence

of infection is occurring among poor women, particularly among women of

color. In Mexico the incidence of infection among men who have sex with

men continues high, while in Brazil and the Caribbean heterosexual transmission is increasing. At surveillance sites in the Dominican Republic and Haiti

the prevalence of HIV infection among pregnant women has reached 8%.

(UNAIDS, 1998)

Rapid spread of infection among injection drug users in Eastern Europe

and Central Asia likely to foreshadow a large number of cases among women

and increasing prevalence of perinatal transmission. The introduction of HIV

into these high-risk populations has been paralleled by tremendous increases

in the incidence of syphilis and other sexually transmitted diseases. (GoUub,

1999)

B. CONTAINING THE EPIDEMIC

Control of the HIV epidemic should be a worldwide health priority. Complex

interactions of social, economic and cultural factors have preceded AIDS with

epidemics of other sexually transmitted diseases, and now hinder control of

HIV itself. Global disparities in economic status have limited efforts to control

sexually transmitted diseases that are much simpler to diagnose and treat than

HIV. The effect of limited monetary resources are compounded by stigmatization of HIV and sexually transmitted diseases that effect willingness to seek

care, social support of afflicted individuals and health policy decision making.

Traditional cultural values regarding the role of women also tends to intensify

the problems. Lack of acceptance of the right of women to make decisions

about child bearing and work outside the home limit options for individuals

who wish to reduce risk of infection via sexual exposures. Economic independence is a crucial factor enabling women to make some decisions themselves. The options for employment outside of sex work, for divorced or widowed women, in many societies are quite restricted. These fundamental

values may directly conflict with efforts to empower women to avoid risk of

HIV and other sexually transmitted diseases.

us. Department of Health and Human Services, Health Resourci-s and Service.s .VDMiNi.s-i'RAnoN, IIIV/.MDS Ki ri m 23
A C'lLiiDi-'. ro riiF. ('i.inicai, (Ivri-: of \X’omf:n wmi HIV

I Epidemiology and Namral History of HIV Infection in Women

To control the HIV epidemic, societies need to make deep commitments

that may require an uncomfortable loss of highly valued cultural norms. Without social acceptance and encouragement, behaviorally mediated risk reduction

strategies may not assume full efficacy. Vaccination is, at present, an optimal

but unavailable solution. The prospects for development of an effective vaccine in the near future are not promising. Thus we have good cause to fear for

the effects of HIV on women worldwide, and to increase our attention to this

enormous problem as we enter the twenty-first century and the third decade

of the HIV pandemic.

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Hum Retrovirol, 5(12): 1212—1223, 1992.

W.H.O. International Collaborating Group for the Study of the WH.O. Staging. Proposed “World Health Organization Staging System for HIV-Infection and Disease’:

preliminary testing by an international collaborative cross-sectional study. AIDS, 7: 711-718, 1993.

Willerford, DM, Bwayo, JJ, Hensel, M, et al. Human immunodeficiency virus infection

among high-risk seronegative prostimtes in lAArohl. J Infiect Dis, 167(6): 1414—7,

1993.

Winkler, C, Modi, W, Smith, MW, et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. Science, 279: 389—393, 1998.

Wong, JK, Gunthard, HF, HavUr, DV, et al. Reduction of HIV-1 in blood and lymph

nodes following potent antiretroviral therapy and the virologic correlates of treat- ment failure. Proc Natl Acad Sci, USA, 94: 12574—12579, 1997.

Yerly, S, Kaiser, L, Race, E, et al. Transmission of antiretroviral-drug-resistant HIV-1

variants. Lancet, 354: 729-733, 1999.

Zagury, D, Lachgar, A, Chams, V, et al. C-C chemokines, pivotal in protection against

HIV type 1 infection. Proc Natl Acad Sci USA, 95(1): 3857-61, 1998.

Zimmerman, PA, Buckler-White, A, Alkhatib, G, et al. Inherited resistance to I II\’-1

conferred by an inactivating mutation in CC chemokine receptor 5: studies in pop

ulations with contrasting clinical phenotypes, defined racial background, and c|uan

tified risk. Molecular Med, 3(1): 23—36, 1997.

us. Department of Heai.th and Human Services, Health Ri-sourcils and Servicics ADMiNis-i-R.vnoN, I IIV/AIDS Hi ri m 33
This Guide is a

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II. Approach to the Patient

Jean Anderson, MD

The woman with HIV infection is indistinguishable from most women seen in

primary care today. Women with HIV cover the spectrum of age, color, geography, educadon, cultural background, and income level, and have aU of the

health and lifestyle concerns any other woman has, in addition to those related

to HIV She is often asymptomatic, and may not know she is infected. She is frequently a mother and a caretaker for other family members. The issues most

important to her will be those shaped by her personal circumstances — HIV is part of these circumstances, but her own perception of how big a part will

vary from woman to woman and from time to time. The health care providerpatient relationship begins with where the individual woman is. To be most

effective, it must become a partnership, based on mutual trust and respect.

This chapter reviews general guidelines for interaction with aU patients,

highlighting points that are particularly relevant to women with HIV infection,

and provides an overview of the initial and ongoing medical and psychosocial

evaluation.

I. GENERAL GUIDELINES

A. COMMUNICATION

The initial interaction of patient and provider should begin with introductions

and from there, it should be highlighted with communication that is clear and

nonjudgmental. Language and terminology used should be sensitive, inoffensive, and easily understandable to the individual patient. This will vary depending on the patient’s age, cultural background and level of education.

Translation will be needed for women unable to adequately understand or

express themselves in the language of the medical provider.

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

including questions about behavior and treatment adherence, and the woman

should be given permission to be honest and to acknowledge failure in terms

of relapse or nonadherence. She should be given adequate time and opportunity to ask questions and express concerns. Women undergoing gynecologic exams often feel special anxiety, vulnerability, embarrassment, or simply fear of discomfort or the discovery of pathology. It is important to adequately prepare her verbally for the exam and

us. Department of Health and Human Services, Health Resources and Services Admini.s-i-ra-hon, HIV/AIDS Buri;.m- 35
A Cuioi' ro rill'. Cmnicai, CarI' oh Womi;n wrni HIV

Approach to the Patient

visually as well, if possible, showing her charts, models, or equipment (such as specula), which may demystify the whole process. Explain what will be done

and why, as well as the degree of discomfort to be expected. During the exam

tell her what you are going to do before doing it, describe what is seen or felt, reassure when findings are normal.

Do not underestimate the importance of nonverbal communication. Facial

expression and body posture are often far more articulate than words, and the

most effective providers are sensitive to these cues and use their own body

language with care. Maintaining frequent eye contact encourages the patient’s

candor, builds rapport and trust, helps allay embarrassment and fear, and conveys your interest and attention.

Patients should be given written instructions on how to reach their

providers when there are problems or questions and to make appointments.

Whenever possible, written information about HIV and its treatment, as well as other health issues, should be available to supplement face-to-face

discussions.

B. RESPECT

Every person deserves respect. Do not be condescending or patronizing.

Under no circumstances should a patient ever be treated as a sexual object,

particularly when assessing risk behaviors or performing the pelvic exam. Although different circumstances may dictate different levels of formality,

addressing the patient by her first name (without her express consent) or, especially, by terms of familiarity (e.g. honey, dear) is usually inappropriate and

often offensive.

Respect for the individual includes respect for her beliefs and values. Use

of complimentary therapies among HIV-infected individuals is common

and should be respected, not ridiculed, even while discouraging potentially

harmful remedies and emphasizing the proven effectiveness of currently

recommended regimens.

C SENSITIVITY

Sensitivity is essential to gather and impart important information, to foster

trust, and to insure ongoing follow-up. It requires attention to how words are used, questions are asked, and to a great deal that is unspoken. Responding to

a patient’s fear, anxiety, denial, or anger is inevitably part of the health

provider’s role and requires consideration of more than a disease process, but

of a whole person and the entire context of her life. Any chronic and life- threatening disease carries with it an enormous burden of vulnerability and

loss of control. Anything the provider can do to give back some control to the

woman will help ease that burden. The importance of adherence to antiretroviral regimens for optimal effectiveness and to reduce the development of

drug resistance has been well established. Allowing the patient to be involved

36 us. DliPARTMENT OF HEALTH AND HUMAN SERVICES, He.\LTH RESOURCES AND SERVICES ADMINISTRATION, HIV/AIDS BUREAU
A Guide to the Clinical Care of Women with

Apprt)ach to the Patient

in choosing her treatment regimen will allow her values and lifestyle (job

schedule, etc) to be considered and is believed to enhance adherence. Understanding her cultural background enhances your sensitivity. For example,

involvement of the patient’s spouse or mother during visits may be particularly

important and reassuring for Hispanic women.

D. CONFIDENTIALITY

Confidentiality is a major cornerstone of the therapeutic relationship. It carries

special meaning for HIV-infected individuals who have experienced discrimination in the workplace and other settings; stigmatization; and occasional

abandonment by friends or family. HIV-positive women may be particularly

\oilnerable to these effects because of lower economic status, cultural traditions and general societal beliefs about the role of women, minority status,

and child-care or other caretaking responsibilities. Information about a

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

strictly confidential by providers and shared only with the express permission

(if the woman herself At the same time she should be encouraged and

assisted in disclosing her status to others who need to know, i.e. sexual part- ners and health care providers.

II. THE EVALUATION OF THE HIV-INFECTED WOMAN

A. TEAMAPPROACH

Because of the medical and social complexity of HIV disease, a team

approach to the care of women with HIV is essential. Expertise needed

includes HIV medical expertise (including management of antiretroviral regimens), gynecology, nursing, counseling, and social service assistance/case

management. Throughout the course of HIV infection, multidisciplinary medical collaborations should be available for evaluation and management of the

varied medical problems associated with HIV. The use of peer counselors may

be especially helpful as women deal with negotiating safer sexual practices,

contraception and other reproductive concerns, medication adherence, and

other issues where similar cultural background and personal experience with

HIV may facilitate education and candid discussion.

B. HIVEXPERIENCE

Care by a medical provider with HIV experience is one of the few specific

factors that has been shown to prolong the life of HIV-infected individuals

(Laine, 1998; Kitahata, 1996). This is increasingly important as antiretroviral

treatment becomes steadily more complicated and recommendations change

on an almost monthly basis. Awareness of drug interactions and strategies

to avoid the development of antiretroviral resistance are but two issues that

have a significant impact on both the short- and long-term health of the

us. Department OF Health and Human Services, He.u,th Resource-s and Services ADMiNis-iR vnoN, IIIX’/AIDS Hi ri .m 37
A CiUlOH TO TIIF, Cl.lNlCAl, CARF. OF' WOMFIN WI TH HIV

Approach to the Patient

HIV-positive individual. Primary providers with litde or no HIV experience

should Link with providers with HIV expertise to provide optimal care by

referral or regular consultation. Current USPHS treatment guidelines, several

as living documents with regular online updating, can be accessed at http:/ /www.hivatis.org. The Health Resources and Services Administration

also supports the AIDS Education and Training Centers warmline (1-800-933-

3413), which is a resource for clinical providers needing expert consultation.

C. CULTURAL SETTING/BACKGROUND

The ability to give optimal patient care depends on an understanding of where

the patient “begins,” her traditions and beliefs. These affect her understanding

of health and disease and her acceptance of conventional medical treatment,

as well as possible reliance on alternative or complementary therapies. These

also affect her view of herself as a woman, her role and responsibilities in

society, and issues related to childbearing and contraception. The role of cultural sensitivity in the care of HIV-positive women will be more fully

addressed in Chapter VIII on Psychosocial and Cultural Considerations.

D. SPLRITUALLTY

The spiritual dimension of a person’s life encompasses their beliefs and values

and what gives their Life meaning and a sense of wholeness. (Puchalski, 1999)

Spirituality is important throughout life, during both health and illness, and an

individual’s beliefs and values can have a profound effect on the way they view

illness and its treatment. Some women may view HIV as a punishment and

this belief may lessen her acceptance of treatment or may put her at risk of

nonadherence. Major spiritual questions which often arise during illness are: What gives my life meaning?

Why is this thing happening to me?

How will I survive this loss?

What will happen to me when life ends?

It is important that the health care provider consider spirituality as an

important component of physical, emotional, and mental health and assess the

woman’s beliefs and learn what is important to her. The spiritual history should

include specific questions about the patient’s faith or beliefs; the importance

and influence of these in her life; her involvement in a spiritual or religious

community and its importance to her; and how the health care provider can

help address these issues as part of her health care. Spirituality should be

addressed as an ongoing issue, and referrals to ministers, priests, rabbis, other

spiritual guides or similar community resources can be an important component of care. The provider’s own spiritual beliefs can be a source of strength

personally and can enhance the patient-provider relationship, but should not be

imposed on the patient-her own beliefs should be respected.

38 us. Department of Health .wd Human Services, Health Resources and Services Administr-ation, HIV/AIDS Bureau
A Guide to the Clinic.\l C.\re of Women with

Approach to the Patient

E. IDENTIFYING SUPPORT SYSTEMS/DISCLOSURE

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

support system should be identified and reinforced and updated information

about this support system should be obtained at each \tisit. To whom has

she disclosed her HIV status and what was the response? Many HIV-positive

women experience feelings of guilt and shame, or are fearful of violence or abandonment, and so are reluctant to trust anyone with knowledge

of their infection or their feelings about it. Their sense of isolation is harmful to both their physical and emotional well-being, and may result

in avoiding clinic visits and nonadherence with drug therapy. The use of peer advocates or support groups may offer additional support for

many women with HIV.

Special issues involve disclosure to sexual partners, children, and other

health care proHders. Disclosure to those individuals who may be at risk for

transmission of HIV from the patient should be encouraged and barriers to

disclosure, such as fear of \tiolence, should be identified and addressed. The

proHder should offer assistance with disclosure when appropriate. Disclosure

of a mother’s HIV status to her children, who may or may not be infected

themselves, is a personal decision and should be honored. The provider

should discuss the various considerations in this decision and offer assistance,

if needed.

E MEDICAL EVALUATION

Initial Evaluation

The initial evaluation of an HIV-infected woman should include a comprehensive medical assessment, including a detailed HIV history: date of

diagnosis, possible routes of exposure, HIV-related symptoms or opportunistic infections, previous antiretro\tiral or prophylactic therapies, disclosure

history and support systems (see above). Prior antiretroHral treatments

should be documented in as much depth as possible, including specific

medications, length of treatment, side effects or complications, response,

and adherence. Current employment, relationship stams and childcare

responsibilities, insurance status, and drug and alcohol abuse must all be

considered in decision-making about further therapeutic regimens. A comprehensive gynecologic histor}" should be obtained, including menstrual history,

sexual practices, contraception and condom use history, previous sexually

transmitted and other genital tract infections, prior abnormal pap smears,

and other gynecologic illnesses or symptoms. The initial physical examination

should include a baseline pelvic exam with pap smear and other studies

as needed based on history and physical findings. Various studies (Anderson,

1989; Frankel, 1997; Ivlinkoff, 1999) have found that both prevalence and

incidence of gynecologic problems are high in HIV-infected women throughout their disease course.

us. Dep.\rtment of Health ,\nd Hunl\n Services, He.\lth Resourcfis and Servio-s Administr-viion, HI\7-MDS Bi ri .m 39
A Gl ide to the Climcaj Care: or Women wtih H1\'

Approach to the Patient

Tliis initial assessment should take place over several closely-spaced visits. Tltis will allow the woman and her clinical care team to become familiar witii one anotlier and to begin to develop the trust and partnership that will form

die foundation of her ongoing care. Tliis is particularly important for the

woman widi newly diagnosed who is often struggling with the shock,

fear, denial and despair that accompany the discovery of a life-threatening Ul- ness; she should be given the opportunit}’ to assimilate information about

and her own clinical status in small bites.

Follow-up Visits

Follow-up Atisits should be scheduled at inter\*als based on the woman’s

HR" clinical, immunologic, and Atirologic stams; other medical or comorbid

conditions, including substance abuse or mental illness; and other indiHdual

needs for counseling or psychosocial support. CD4 cell counts and HR’^

RXA levels should be monitored at 3—1 month inteiA'als and more often

if results suggest inadequate or failing therapeutic response, or with development of clinical signs or stTnptoms. At each inteiwal Hsit the woman should

be questioned about new stTnptoms, side effects/adherence with medications,

and psychosocial issues and concerns. Last menstrual period should be

documented, as well as current sexual actiAip', and interval use of condoms

and contraception. Risk behaHors should be reassessed at regular inteiw'als,

since sexual and drug use patterns may vary, and safe practices should be

reinforced. Pehic examination should be repeated at least annually, and

more frequently with histon’ of abnormal pap smears, unsafe sexual practices,

exposure to STDs, or development of gtm signs or symptoms. STD screening

should be performed wLen the patient reports recent or ongoing high-risk

sexual activity. Pehic examination everv six months may be considered in

w'omen with clinically advanced disease, low’ CD4 cell counts, and/or high

Airal loads since their incidence of certain HR-related gtmecologic problems

may be increased. The medical and gynecologic evaluation of the HRinfected woman is described in more detail in Chapter R^ on Primary’

Medical Care and Chapter ^T on Gynecologic Problems.

G. FAMILY-CENTERED CARE

HR" is a disease of families. Not only may the woman be infected, but her

husband or parmer and children may also be Ring with HR". Even w’hen

other family members are not infected, they are deeply affected by the pres- ence of chronic and life-threatening illness within the family, possible fears of

transmission of infection, and often stigma. The HR"-positive w’oman may

neglect her own care while proHding care to sick family members or to her

children. The proHder should encourage all HR"-positive family members to

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

woman, by proHding information and education about HR" and updates on

the woman’s condition (with her permission), and by assistance in identifring

support systems for the entire family.

40 C.S. Dep.\ktment of He-\lth .\nd Hum.\n Sermces, He.\lth Resources .\nd Sermces Administr.\tiok, HW/AIDS Bure\u
A Guide to the Clinical Care of Women with HIV

Approach to the Patient

H. EDUCATIONAND COUNSELING

Despite the dramatic advances in therapy, decreases in mortality and hospitalizations, and overall improvement in quality of life, HIV remains a life-threatening and often life-ending disease with no cure on the horizon. For women it

is often enveloped by poverty; isolation; person, partner, or community drug

use; and the competing priorities of children and family. Not dissimilar to diabetes, modern management of HIV disease requires a basic understanding of

1 II V infection and an intense personal involvement in one’s own care — taking multiple medications on fairly strict schedules, food requirements, recognizing and managing side effects, etc. UnUke most other chronic medical

conditions, HIV-positive individuals remain infectious for the rest of their

lives and must learn about and become empowered to change behaviors that

put themselves or others at risk. This learning process is ongoing and life-long

and recjuires continuous reinforcement. It should aim to correct misconceptions and myths and should recognize that relapses in unsafe sexual or drugusing behaviors and at least episodic problems with adherence are the norm

rather than the exception. Peer advocates (HIV-affected women from similar

cultural backgrounds) can be effective members of the clinical team to help

educate patients, advocate for them, and provide counseling as needed.

I. ACCESS TO CARE

A recent report from the HIV Cost and Services Utilization Study (HCSUS),

using a national sample representative of the adult US population infected

with HIV and in ongoing care, found significant variations in service utilization and receipt of medication. Women were more likely than men to use the

Emergency Department and to be hospitalized and were less likely to have

received antiretroviral therapy including a protease inhibitor or nonnucleoside

reverse transcriptase inhibitor by early 1998. Other predictors for poor access

to care included racial or ethnic minority status and lack of insurance (Shapiro,

1999). If women with HIV are to benefit equally from the advances in understanding and management of this infection, attention must be paid at the individual, community, and societal level to the factors hindering equal access to

care: stigma and isolation; lack of empowerment; competing concerns (e.g.

food, housing, care for other family members); childcare; transportation; insur- ance; violence against women, and many more.

REFERENCES

Anderson J, Horn J, King R, et al. Selected gynecologic issues in women with 1 11\^

infection. Int Conf AIDS 1989 June 4—9; 5: 760 (abst # Th.D.P.lO).

Frankel R, Selwyn P, Mezger J, Andrews S. High prevalence of gynecologic disease

among hospitalized women with human immunodeficiency virus infection. Clin

Infect Dis 25 (3):706-712, 1997.

us. Department of Hf.,\lth and Human Services, Health Resourcfls and Services Admini.s-|-r.vi-ion. I IIV/AIDS Hi 're. m 41
A C'.uioi'. TO rill' ('i.iNiCAi. CaiU': or WomI':n wrni I IIV Approach to the Patient

Kitahata M, Koepsell T, Deyo R, et al. l^hysicians’ experience with the acquired immunodeficiency syndrome as a factor in patients’ survival. NEnglJ Med

(ll):701-706, 1996.

Laine C, Markson L, McKee L. The relationship of clinic experience with advanced

HIV and survival of women with AIDS. AIDS 12: 417^24, 1998.

Minkoff HL, Eisenberger-Matityahu D, Feldman J, Burk R, Clarke L. Prevalence and

incidence of gynecologic disorders among women infected with human immunodeficency virus. Am J Obstet Gynecol 180 (4):824—836,1999.

Puchalski CM et al. FICA. A spiritual J Palliative Care 1999 (in press).

Shapiro MF, Morton SC, McCaffrey DF, et al. Variations in the care of HIV-infected

adults in the United States: Results for the HIV Cost and Services Utiiizarion

Study. JAMA 281(24):2305-2315, 1999.

42 us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
III. Prevention of HIV

Chia Wang, MD, MS and Connie Celum, MD, MPH

I. INTRODUCTION

Two decades into the human immunodeficiency virus (HIV) epidemic, scientists and clinicians on both the biomedical and behavioral fronts continue to

be faced with daunting challenges. While scientists have made progress in vaccine development and in understanding the complexities of the viral-host

immune response, the prospect of highly effective, widely available biomedical

preventative measures are stiU in developmental stages. Thus, there remains a

critical need to identify and implement effective behavioral strategies and to

more effectively address the complex forces that fuel the heterosexual HIV

epidemic, including poverty, migration of populations, social and cultural disruption, gender discrimination, and stigma about STDs and HIV.

Many of the measures that women can take to prevent acquisition of STDs

and HIV have been known for the past decade: abstaining from intercourse,

selecting low-risk parmers, negotiating partner monogamy and male condom

use. However, the high rates of incident HIV infections among women in

many parts of the world and the rising incidence among women in the United

States is a testament to prevention barriers facing women in heterosexual relationships. Women often are unaware of their partners’ infection status or level

of risk, and in many cases, are unable to negotiate sexual safety. Importantly,

in many parts of the world, prevalence figures suggest that girls are exposed

to HIV earlier than boys (UNAIDS, 1999). Young girls are often emotionally

immature, economically disadvantaged, and socially inexperienced, making

them vulnerable to sexual relationships that may expose them to HIV and to

other sexually transmitted infections that can potentiate HIV transmission.

Women in economically disadvantaged nations and in socially marginalized

groups in the industrialized world may have less access to medical care for

treatment of STDs and contraception, and may also not feel empowered to

negotiate for condom use, abstinence, or monogamy within their sexual rela- tionships. Thus, culturaUy-sensitive interventions that target both behavioral

and biologic risk factors for HIV are necessary to reduce transmission to

women and girls.

This chapter discusses issues regarding HIV testing, including risk assess- ment and pre- and post-test counseling, and then goes on to review models of

behavioral intervention strategies for HIV prevention, published behavioral

us. Department of Health and Human Services, Health Resources and Serv'ices .VjMiNis'i'R.vnoN, HIV/.\IDS Buri-.mi 43
A Ciumi' I'o Till'. (j.iNicAi. (^\R^: or Womt.n wrni 1 IIV

Prevention of HI\'

intervention trials, and some practical aspects of counseling women on how to reduce sexual risk behavior. Biologic cofactors that may increase risk and thus

may be targets for intervention are briefly examined. Finally, new approaches

to HIV and STD prevention, including microbicides, vaccines, and postexposure antiviral medication are reviewed. The important issues of substance

abuse and strategies for changing drug use behavior are not addressed in this

chapter, but are reviewed extensively in Chapter X.

II. RISK ASSESSMENT FOR STD/HIV INFECTIONS

Unprotected sex increases a woman’s risk of HIV infection, based in

large part on her partner(s)’ risk behaviors.

Just as most people would find celibacy an impractical means of reducing

sexual risk, many individuals may find changing other specific sex behaviors

difficult or unacceptable. While some sexual behaviors may be less “mainstream” than others, it is important to remember that participation in such

behaviors does not necessarily reflect a lack of morals or willpower, but

rather different perceptions of enjoyable and common sex behavior. Furthermore, sexually active women may not realize that they are practicing

behaviors that put them at risk for HIV infection. Because of the heteroge- neous nature of sexual practices, individual risk assessment is crucial in any

attempt to reduce risk of HIV by changing sex behavior. In pre-and posttest HIV counseling, individual risk assessment provides a framework in

which to conduct further behavioral intervention and identifies patients

appropriate for HIV and STD screening. Guidelines for physicians and

other care practitioners recommend that HIV and STD risk assessment

be conducted for every patient; however, most primary care physicians do

not routinely incorporate questions about sexual behavior into routine

patient care.

Clinician discomfort and fear of embarrassing or offending the

patient when discussing sex are impediments to conducting effective

risk assessment.

In such circumstances, the clinician may find it more acceptable to “frame”

the discussion by explaining the routine nature of such questions, thus

demonstrating that the patient is not singled out because of mannerisms,

’appearance, or ethnicity. One approach may be to emphasize the importance role of this information for patient care: “To be able to provide

the best care for you today, we need to understand your risk for certain

infections by talking about your sexual practices.” Another may be to

allude to the universality of many concerns: “Many women find it difficult

to get their men to wear condoms; has this been a problem for you?”

(Curtis, 1999)

44 us. Department of Health and Human Services, Health Resources and Services Administrahon, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Prevention of HIV

As with any type of medical history taking, open-ended questions

probably serve as the most effective means of eliciting information

when taking a sexual history.

Language should be clear, easy to understand, nonoffensive, and nonjudgemental. Many clinicians prefer closed-ended questions when they are functioning under time pressures. In such cases, a questionnaire that the patient

completes in the waiting room may be a preferred tool. Whenever possible,

however, clinician-patient interaction serves as the ideal forum for sexual

risk assessment.

Many clinicians are not familiar with risk factors for HIV infection

specifically relevant to women.

Risk factors for HIV infection in male homosexuals and intravenous drug

users have been well described. In contrast, factors that may increase risk in

women, such as a history of unwanted pregnancy, or an incarcerated sex

partner, are less specific, and less well recognized. While some risk factors

for women can be derived from epidemiologic studies, such as history of

“high-risk STDs” (i.e. gonorrhea or syphilis), crack cocaine use, and intra- venous drug use, some women are at risk through monogamous partner

relationships with their HIV-infected husbands. Therefore, identifying risk

behaviors in women requires a careful and skilled clinician. In many cases, a low threshold for recommending HIV testing is necessary. Important risk

topic areas to cover are listed in Table 3-1.

Table 3-1 : Risk Assessment for STD/HIV for Women

Number of sex partners in the previous year , and lifetime:

Sex with: Qmen, Qwomen, or aboth

History of abnormal pap smear: Qyes, or Qno

History of sexually transmitted disease: Qyes, or Qno

History of using: Qintravenous drugs, Qsharing needles, use of crystal methamphetamines, or Gcrack cocaine

History of a sex partner who was incarcerated: Gyes, or Gno

History of alcohol abuse: Gyes, or Gno

History of feeling that the sex partner puts the patient at risk: Gyes, or Gno

How does the woman protect herself from AIDS?

How does the woman protect herself from unplanned pregnancy?

Is there anything else that she feels she should mention to ensure good medical care?

us. Departnientof Health and Human Services, Health Resources and Services Administr.mion, HIX'/.MDS Hi rihi 45
A CJuini; TO Till- Ci.iNiCAi. CarI' oi- Womi:n wrm HIV

Prevention of F IIV

III. HIV COUNSELING AND TESTING

There are clear benefits to HIV testing.

For a woman, knowledge of her serostatus is essential to prevent vertical

transmission to her infant and horizontal transmission to her partners, and

to seek medical care for herself With the proven efficacy of several periparmm antiviral regimens to reduce vertical transmission rates and medical

therapy to improve survival among HIV-infected individuals, there are even

stronger reasons to urge sexually active women to seek HIV testing for

themselves and their partners.

Screening strategies range from mandatory screening of pregnant

women to selective screening of high-risk women.

Selective screening strategies have targeted intravenous drug users, STD

clinic attendees, and economically-disadvantaged individuals (Ades, 1999).

The advantage of selective screening is cost-savings, particularly in lowprevalence parts of the world. Many experts favor a universal recommendation for HIV screening, at least for pregnant women. The advantage of

universal screening is not only increased detection rates, but perhaps also

increased test acceptance. Universal screening removes the stigma of HIV

testing by eliminating any targeted testing based on sexual orientation,

socioeconomic status, or race. When HIV testing is stigmatized, women in

high-risk groups may be reluctant to identify themselves. On the other

hand, the cost of universal HIV testing is significantly higher than voluntary, selective screening strategies, and there are both practical and ethical

issues in implementing universal screening, even in perinatal care.

A. PRE- AND POSTTESTHIV COUNSELING

The counseling that occurs before and after HIV testing has three

principal goals (Celum, 1999):

1 . to provide counseling about risk reduction for HIV-negative persons;

2. to identify HIV-infected persons for chnical interventions; and

3. to provide counseling to HIV-positive persons about potential

transmission.

The components of HIV pre-test and post-test counseling are outlined in Table 3-2

Pre-test counseling should include discussion about the basic facts of HIV

infection, the acquired ifnmunodeficiency syndrome (AIDS), and HIV testing. However, in most situations, emphasis should be placed less on didactic

material than on individualized discussion of risk and risk-reduction unless

the patient has very limited understanding of HIV/AIDS. Post-test counseling should reinforce these concepts in the context of the test result. Regardless of the test result, resources and referrals for the patient and/or

their parmer, should be provided. For patients at risk for domestic violence,

the potential domestic turmoil that a positive test result can elicit should be

46 us. DeparTMent of Health and Human Services, He,\lth Resources and Services ADMiNisTR^moN, HIV/AIDS BurFjW
A Guide to the Clinical Care of Women with HIV

Prevention of HIV

Table 3-2: Components of HIV Pre- and Post-test Counseling

Pre-test Counseling

Assess understanding of HIV transmission and natural history; psychological

stability; social support; impact of a positive result Discuss likelihood and meaning of positive, negative, and indeterminate test results*

Discuss provisions made at the site for confidentiality. (In the United States, some

states have name-based reporting of HIV, and clients should be informed about

the availability of anonymous testing)

Ensure that follow-up is available

Emphasize the importance of obtaining test results

Discuss risk reduction plan and referral to other services

Obtain informed consent for HIV antibody testing

* For patients who identify a high-risk exposure, the clinician should explain that tests are generally positive within 3 months of exposure. Therefore, repeat testing should be

recommended 3 months after exposure, if the initial test is negative.

Post-test Counseling

Ensure that the client is ready to receive results

Disclose and interpret results: • For HIV seronegative persons:

Readdress and reinforce risk reduction plan

Discuss the need for repeat testing for those with recent (< 3 months)

exposure or ongoing risk behavior • For persons with indeterminate HIV- 1 Western blots:

Discuss prevalence of and risk factors for indeterminate

For persons with p24 bands and persons with high risk behavior:

Discuss the possibility of acute HIV infection and need for

repeat testing in 1,3, and 6 months

Perform HIV polymerase chain reaction, if available, to confirm

infection status and determine viral load • For HIV seropositive persons: > Differentiate between being HIV-infected and having AIDS

Emphasize the importance of early clinical intervention, if available,

and make medical referral, if necessary

Counsel patient that he/she is HIV positive and discuss ways to avoid

transmitting HIV to others

Assess need for psychological support and provide referral, if necessary and if available

Assess possibility of domestic violence and provide referral, if necessary and if available

Ensure that the patient has follow-up

emphasized. This issue will be further addressed in the section on ethnic

and gender considerations.

Make use of an opportunity to provide client-centered counseling

Any time spent with the patient, however short, provides an opportunity

for the clinician to conduct individualized counseling about recognizing and

reducing high-risk sexual behaviors. Patients who present with concerns or symptoms of sexually transmitted diseases (STDs) are usually also at risk or

us. Department of He,vlth and Human Services, Health Resources and Services Adminestra'iion, HIV/AIDS Bi'ri-.m 47
A (iiJioi' TO Tin: Ci.iNicAi, (L\ri: ()!• WoMi-N wrm HIV

Prevention ot HIV

concerned about risk for STD, including HIV. In the context of a negative

HIV test, the post-test counseling session provides a valuable opportunity

to develop a risk reduction plan in a woman who has identified herself as someone who concerned about risk and may be at high risk. Many clini- cians may find it effective to deliver the negative test result in the context of

a “second chance,” thus emphasizing that current behaviors are unsafe and

can be changed.

B. RAPID TESTS

Rapid tests are a good alternative in certain circumstances.

After aU, HIV testing is only of value if patients return for their test results

and post-test counseling. Many testing programs in the United States use an

initial enzyme-linked immunosorbent assay (ELISA) with confirmation

through Western blot (WB). In less developed areas, two ELISAs run in

sequence are often used. With both protocols, the patient is required to return to clinic one to two weeks after testing for results. In 1995, 25% of

persons testing HIV-positive and 33% of persons testing HIV negative at pubUcly funded HIV testing sites in the U.S. failed to return for test results

(CDC, 1998d). Similar low return rates have been described in Nairobi,

Kenya, and in other parts of the world.

Rapid testing for HIV would result in substantial cost savings and cir- cumvent patient no-show rates. At least 1 0 rapid tests, defined as tests requiring less than two hours, are currently available internationally,

although only one test (Single Use Diagnostic System HIV-1 Test) is approved for use in the United States (See Chapter IV on Primary Care)

(Kassler, 1997; Spielberg, 1996). The WH.O. has developed alternative test- ing strategies using sequential rapid tests, thus obviating the need for expensive and delayed confirmatory testing. Some tests require as little as five

minutes and are easy to perform in the field. Most tests are 95% to 100%

sensitive and specific. In the United States, the CDC has published recommendations that cHents receive the results of rapid HIV tests on the day of

testing. Patients who test negative can be given a definitive negative result

without a return visit. For patients who test positive, it is recommended that

they be informed that their screening test was positive, and that they should

return to receive a confirmed test result. In the United States, rapid testing is most appropriate in areas of high

prevalence where clinic return rates are low (STD clinics. Emergency

departments) or an HIV diagnosis wiU influence immediate management

decisions (post-exposure prophylaxis, unknown HIV status in a pregnant

woman presenting to Labor & Delivery). In many ways, rapid testing is most appropriate in economically disadvantaged countries where HIV sero- prevalence is high, laboratory resources are limited, and patient travel to and

from clinic may be very inconvenient.

48 us. Department of Health and Hum,\n Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Prevention of HW

Rapid tests may result in unwanted test results

Critics of rapid testing for HIV are concerned about the ability to provide

appropriate counseling outside the framework of two visits for pre- and posttest counseling. Importantly, the prompt sequence of events associated with

rapid testing may not give the patient enough time to digest counseling information. However, for many women in areas where rapid tests are likely to be

used, rapid testing presents several difficulties. Women may find it difficult to decline an unwanted test, sometimes related to a cultural injunction against

refusing a test offered by a health care worker perceived as an authority figure. furthermore, women may fear that refusing HIV testing may result in

not receiHng other health care services offered by the clinic. Therefore, availability of rapid tests may result in subtle coercion of a woman to consent to HIV testing. Informal surveys in the context of HIV research in Kenya have

revealed that many women feel that an interval of one week between testing

and results is ideal. In some cases, failure to return to clinic for HIV test

results may reflect a desire not to have had the test in the first place.

C IMPACT OF HIV COUNSELING AND TESTING ON

PREVENTION

What is the e\tidence that HIV testing may change risk behavior? The literature

in this area is difficult to synthesize, largely because of evolving counseling

practices, varying lengths of foUow-up, and lack of a well-defined endpoint. In one large prospective study the incidence of STDs was determined for

patients who received HIV testing and counseling at a public STD clinic in

Baltimore. Both HIV positive and negative patients demonstrated high rates of

STDs 6 to 23 months after receiving HIV test results and posttest counseling

(Zenilman, 1992). In another study, the incidence of gonorrhea was measured

after receipt of HIV result and post-test counseling. HIV testing and counseling was associated with a moderate decreased in gonorrhea infection among

patients who tested positive for the virus, but with a slight increase in incidence in patients who tested negative (Otten, 1993). These findings suggest

that learning of a positive HIV test result may have a modest effect on sexual

risk-taking. The studies also raise important concerns about the effectiveness

of HIV testing and counseling in impacting sexual risk-taking, and about

potential disinhibition after receiving a negative test result.

Results from a smdy of discordant couples in Zaire were more promising;

among 149 discordant couples who voluntarily attended an HIV counseling

center, HIV testing and post-test counseling resulted in a increase in consistent

condom use from less than 5% to more than 70% (Kamenga, 1991). During

100 person years of foUow-up, incidence of new HIV infections was only 3%.

The difference between these results and the results obtained in Baltimore and

Nhami may reflect varying levels of baseline HIV knowledge, the differences

between individuals in long-term relationships versus casual relationships, and

cultural and geographic influences.

us. Dep-\rtment of Health and Hunlan Services, He.alth Resources and Services Adminisikaiion, lll\7Ains Hi ri.m’ 49
A CJuini': ro Tin; Cj.inicai, (^'\lll; oi- Womi;n wnii HIV

Prcvcnrion of HIY

IV. BEHAVIORAL INTERVENTION MODELS

The Health Belief Model, the Social Cognitive Theory, the Theory of

Reasoned Action, and the Stages of Change Theory (Bandura, 1996;

Fishbein 1999) have been developed to explain determinants of human

behavior change. These models all have in common the theory that perceived risks and benefits of behavioral change predict the likelihood of

behavior change as well as can guide the approach to behavioral interventions. These models are described and contrasted in Table 3-3.

The AIDS Risk Reduction Model (ARRM) integrates the concepts of

the above-mentioned theoretical models into a framework providing information, motivation, and behavioral skills specific to AIDS risk reduction

(Catania, 1990) (Fisher, 1992). With this model, counselors help patients to

identify sexual behaviors that put them at risk for acquiring HIV, formulate

plans to change these behaviors, and take action to reaU2e these plans.

The Stage of Change (SOC) behavioral theory proposes that the

process of behavioral change occurs along a continuum of five fundamental stages (Table 3-3) (Coury-Doniger, 1999). The stages can be used to tai- lor the counselor’s approach to an individual by assessing where an

individual is on that continuum for a specific behavior. For example, an

individual with multiple partners who sees no need to use condoms consisTable 3-3: Behavioral Theories Relevant to Sexual Risk Reduction

Counseling

Health Beuef Model

Adopting health-protective behavior depends on a person feeling personally

threatened by a disease with serious negative consequences, and must feel that the

benefits of making the behavior change will be outweigh the costs of not changing.

Social Cognitive Theory

Adopting health-protective behavior depends on a person believing that he or she

has the ability to change (self-efficacy) and that the benefits of making the behavior

change will outweigh the costs of not changing.

Theory of Reasoned Action

Adopting health-protective behavior depends on a person's strength of intention to perform that behavior. The strength of the intention is based on the person's overall

positive or negative attitude towards performing the behavior, based on perceived

outcomes, as well as whether the person believes that important family members

and friends believe that he or she should alter behavior.

Stages of Change

Adoption of new behavior involves five distinct stages:

1. Precontemplative Does not see need to do target behavior

2. Contemplative Sees a need to do target behavior,

but is ambivalent

3. Ready for Action Ready to do target behavior soon,

or has already started

4. Action Doing target behavior consistently 3-6 months

5. Maintenance Doing target behavior consistently > 6 months

50 us. Department of He.\lth and Hunun Services, Hii.\i,TH Resourcf.s and Services Administrahon, HIV/AIDS Bure,\u
A Guide to the Clinical Care of Women with HIV

Prevention of

tently would be in the Precontemplative stage. In contrast, a woman in a mutually monogamous relationship who sees the need to know her partner’s HIV status, but fears angering her parmer by this request, would be in

the Acdon stage. A counselor’s approach to these two patients would be

different. For the first individual, counseling directed at recognition of risk

would be most appropriate, while for the second woman, communication

and goal-setting skills should be emphasized. Importantly, individuals do

not always move forwards linearly along this continuum, but may “relapse”

and move forwards and backwards between the stages. At the Rochester

STD clinic, clinicians who have formally incorporated the SOC in their risk

assessment and counseling of STD clients report a high degree of satisfaction with the SOC model as a diagnostic tool that guides their specific

counseling interventions with a client.

V. PUBLISHED BEHAVIORAL INTERVENTION TRIALS

Several well-designed randomized controlled trials have been conducted to

assess the efficacy of various behavioral intervention strategies, and most conclude that such interventions result in decreased sexual risk-taking, primarily

unprotected sex, and in some studies, STD and HIV incidence. In contrast to

didactic education sessions, behavioral interventions focus on recognizing risk

and formulating effective risk reduction strategies. Knowledge alone does not

motivate change. To translate this concept into an issue many of us have experienced, consider the issue of weight reduction and diet modification. Despite

widespread knowledge about the adverse health effects of eating fatty foods,

adhering to a diet is notoriously difficult. Similarly, knowledge about STDs and

HIV is not enough to implement change in sexual behavior.

Randomized controlled studies using STD incidence as an outcome provide objective evidence of health-related endpoints, thus representing the

most valid measurement of an intervention’s efficacy. Five such trials have

been published in the past few years examining the efficacy of behavioral

intervention strategies using STD incidence as an outcome measure. (Table

3-4) tMI five studies used similar intervention approaches incorporating education, motivation, and development of a concrete plan for behavioral change.

Sessions were structured as individual or group counseling.

Behavioral interventions can lead to lower rates of STD acquisition

As shown in Table 3-4, results of these studies varied. The discrepancy in

reported outcomes may be related to several factors. The sample sizes of

the NIMH study (NIMH, 1998) and CDC-funded Project RESPECT

(Kamb, 1998) study were large, providing excellent ability to detect even a modest effect of the intervention. In the San Francisco study (Boyer, 1997),

for example, the sample size provided only 45% power to detect the

approximate 20% change in STD incidence detected in the RESPIiCT

study. However, an appreciable effect of the intervention was detected in

us. DeP.^RTMENT of HE.U.TH .\ND HUALW SERVICES, HiULTH RESOURCES AND SERVICE.S AD.MINI.STR.\TI0N, HIW AIDS B' Rl M 51
A (iuiDH K) If Hi Cj.iNicAi. Cari: (ji- Womi:n van I I ilV

Prevention of HIV

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52 us. DfiPARi-MiiN'r oi' HfiAi.rn and Human Skrvk.hs, Hi;ai;;h RiisouRCus and SiiRvicus Administrahon, HI\'/AIDS Burhau
A Guide to the Clinical Care of Women with HIV

Prevention of HIV

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the San Antonio study (Shain,

1999) despite a sample size of

only 617. In this study, ethnic-specific tools and counselors were

used, thus perhaps enhancing the

effect of the intervention. Indeed,

in this study, a 49% decreased

STD incidence was detected after

12 months, compared to a 20%

decrease reported in the

RESPECT study. Finally, adher- ence to behavioral session schedule and follow-up with STD exam

are crucial elements affecting

study validity. The NIMH,

RESPECT, and San Antonio

studies all reported higher adher- ence rates and follow-up rates compared to the Houston (Branson, 1998) and San Antonio studies, thus providing increased

ability to measure the effective- ness of the intervention.

Even brief (two 20 minute)

counseling sessions can

result in lower STD rates

and can be incorporated

into clinical settings

The 20 minute Project RESPECT

counseling sessions may be most

applicable to busy practitioners

interested in conducting effective

behavioral counseling. This study

demonstrated that individual

“brief” counseling, involving two

sessions of 20 minutes each, was

as effective in reducing STD incidence as “enhanced” four one

hour sessions. Both intervention

arms, the two 20 minute and four

one hour counseling sessions, were superior to a didactic

message. The first of the two

brief 20-minute sessions focused

on recognizing HIV risk and barUS. Depari-munt of Health and Human Services, Health Risources and Services ADMiNisTRAnos, HIN'/.MliS Hi rim 53
A CJUlOli TO rUH (j.INlCAl, CAIU', oi' WOMI'N WITH HIV

Prevention of HIV

riers to risk reduction. After working with the client to agree on an achievable risk reduction plan, the counselors concluded the sessions by identifying a small risk-reduction step which could be achieved before the second

session. At the second session, counselors reviewed progress and barriers in

achieving the behavioral goal, and helped to clients to arrive at a long-term

risk reduction plan. Although the four one-hour “enhanced” sessions also

included recognizing risk and formulating risk reduction plans, more energy

was focused on key theoretical behavioral elements such as self-efficacy,

attitudes, and social norms underlying risk behavior. The fact that the brief

two 20 minute counseling sessions demonstrated equivalent efficacy to four

hours of counseling is encouraging to practitioners who would like to integrate effective HIV counseling into busy clinical settings.

VI. PRACTICAL ASPECTS OF COUNSELING PATIENTS

ABOUT SEXUAL RISK REDUCTION

All of this information may seem overwhelming to the health care provider

who has no special training in behavioral theory. However, the underlying

principle is one that can be applied by any practitioner in any setting: counseling should be individualized to the person receiving the counseling. Any

attempt to accomplish individualization of approach would be superior to

simply providing a didactic message. Some practical aspects of counseling are

listed in Table 3-5 and discussed below.

Focus the counseling session

The cornerstone of the counseling session is to focus the session on the

patient’s recent sexual activities, their perception of their risk, and motivation to reduce their risk of HIV/STD exposure, redirecting the patient to

this topic whenever necessary. Clinicians and counselors may become distracted by providing excessive information about scientific data and principles in response to patient questioning. Such information is probably more

effectively dispensed in pamphlet form or by referral to other patient information sources. In addition, women at risk for STDs including HIV fre- quently come to clinic with multiple complicating issues, including poverty,

domestic violence, substance abuse, and child care problems. Often the

counselor begins to feel responsible for addressing aU of these issues and

Table 3- 5 : Practical Aspects of Counseling

Focus the counseling session on risk reduction topics

Listen and react to the patient Don't stick to a practiced script

Avoid over-ambitious risk reduction plans; focus on realistic goals

Give the patient a written documentation of the risk reduction plan

Use culturally sensitive and ethnic-specific language and terminology, when

available and appropriate

Consider issues specifically relevant to women

54 us. Department of Health and Human Services, HE/U,th Resources and Services ADMiNiSTR,moN, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with

Prevention of

Table 3- 6 : Appropriate Risk Reduction Topics

Enhance self-perception of risk • Identify risk behavior • Assess level of concern

• Identify ambivalent feelings about risk Explore specifics of most recent risk • Identify specific risk details • Assess patient acceptable risk level • Address ability to communicate with partner • Identify situations that make the patient vulnerable to risk • Identify triggers of high-risk behavior • Assess patterns of risk behavior

Review previous risk reduction experience • Identify successful attempts at risk reduction • Identify obstacles to risk reduction

Synthesize risk patterns • Summarize and reflect patient risk • Address rish in context of patient's life • Convey concerns and urgency regarding risk • Support and encourage the patient to action

Source-. Adapted from Kamb ML, Fishbein M, Douglas JM, et. al. Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted disease: a randomized controlled \x\a\.JAMA 280:1161-1167, 1998.

discouraged by the fact that many of them seem so insurmountable. Furthermore, the patient may be uncomfortable discussing her own risk, and

may therefore be emotionally invested in distracting the counselor from that

subject. For these reasons, it is important for the counselor to remember

that the goal during the limited interaction period with the woman is to

directly address, and hopefully impact, risky sexual behaTnor. Some appropriate topics are listed in Table 3-6. Other longstanding issues may not be

easily solvable, and may be more appropriately referred to a social worker,

substance abuse counselor, or mental health counselor.

Listen and react

At the same time, it is important to listen and react to the patient. It

is a human quality that we enjoy talking and thinking about ourselves.

A counseling technique of summarizing patient’s descriptions and viewpoints about her risk is an extremely effective communication tool. In an effort to be non-judgmental, counselors may find themselves nodding

supportively to just about any statement that the patient may make. Instead,

sometimes direct and clear feedback from the counselor about self- destructive behavior may communicate more effectively the importance of

reducing risk (Figure 3-1). For example, if a patient is describing an evening

during which she had sex with multiple men while using crack cocaine, it may be more appropriate for the counselor to respond with emphasis that

such behavior is dangerous. It would also be important to explore the

us. Dep.\rtment of He-U-th .\nd Sermces, He.vl.th Resources .\nd Services Administration, HHV-AIDS Buril\u 55
A Ck ini^ TO nn-; Ci.imcai. Cari-; oi- NX'omi-a w ith Hl\'

Prevention ot Hl\'

emotional or physical needs leading to such risky sexual behavior and to

identif}' potential alternatives to fulfilling such needs.

Don’t stick to a practiced script

In an effort to focus, some counselors may restrict themselves to a practiced script and thus squander opportunities to effectively impact risk

beha\tior. Specific counseling scenarios a pro\tider might encounter are described below: • references to suicide: “I could have killed myself” • self-deprecating comments: “I was so stupid” • over-acceptance of risk: “Even if I would have known he was HIVpositive, I wouldn’t have used a condom”

• inappropriate beha\tior: giggling, putting feet up on the table

Such statements are usually pleas from patients for a direct and honest

response, and taking such opportunities to acknowledge and problem-solve

risk}" beha\tior is important in establishing the objectives of the session.

Inappropriate patient behaHor such as excessive giggling, angry postures, or demonstrations of boredom, should also elicit comment and questions

from the counselor. Overlooking such behaVor in an effort to be professional, pohte, or focused detracts from the ability to communicate.

Avoid over-ambitious risk reduction plans

The most common error made by counselors is to develop an over-ambitious risk reduction goal, particularly during sessions in which good rapport

has been developed. In many cases, counselors may comtince themselves

that the woman has acknowledged her risk to such a degree that she is now

ready to eliminate any subsequent episodes of unprotected sex. Such goals

are likely unrealistic. Beha\ioral specialists favor extremely concrete goals,

such as “On Friday night I am going to ask my partner to wear a condom.”

Even modest goals, such as stopping at a drug store and purchasing con- doms on the way home from the session, may be suggested. Other possible

goals are Listed in Table 3-7 on the following page.

Put it in writing

Furnishing written documentation of patient goals reinforces verbal

instructions and pro\tides additional motivation.

Use time wisely

The question then remains: what amount of time is necessar\" to effect a behaHoral interv-ention? The Project RESPECT study demonstrated successful interv^ention with two 20 minute sessions within 10 days of each

other. An ongoing follow-up study, RESPECT 2, compares a single 1 hour

Hsit with rapid HIV testing to the two 20 minute sessions. In busy clinics,

where care for genital tract infections and other medical problems may be

occurring simultaneously with patient counseling, clinicians may not feel that they have sufficient time to counsel effectively. However, in many

56 U.S. DEP.MmtENT OF HE.\LTH and HU.M.FN Sermces, He.\lth Rrsources and Sermces ,\DNnNISmvnON, HA'/.\IDS Bure.\u
A Guide to the Clinical Care of Women with HIV

Prevention of HIV

Figure 3-1 : Listen and React to the Patient

React to what a woman tells you. Use words and body language to

express yourself.

Instead of .. .

Try . . .

us. Dep.\rtment of Hr\lth .\nd Hliman Services, He.u.th Resources ,\nd Services .\DMiNiM"R.vnoN, H1\'/A1DS Bureau 57
A Glide to the Cunical Care of Women vlith HR’

Prevention of HIV

Table 3 - 7 : Examples of Concrete Individualized Risk

Reduction Plans

Type of Plan Description

1 . Patient will talk about HIV/STD

concern/risk to partner[friends

Disclosure or communication with partner

Disclosure or communication with peers

Disclosure or communication with others

2. Patient plans to get

herself tested or have partners tested

for HIV/S TDs prior

to having sex

Patient will test herself again to ensure uninfected

Have partner tested for HIV/STD

Use condoms until partner tested for HIV/STD

Abstain from sex until partner tested for HIV/STD

3. Patient plans to reduce,

change, or eliminate

at-risk partner(s)

Break up with high risk partner(s)

Eliminate a particular type of high risk partner

(prostitute, anonymous partner)

Patient will have fewer partners

4. Patient will change

the type of partners

she has

Patient will get to know partners better before

having sex

Patient will remain monogamous with one partner (3 months)

Patient will abstain from sex (3 months)

5. Patient plans to change use of

alcohol and drugs

Decrease/eliminate alcohol/drug use when having sex

Generally decrease/eliminate a specific drug/alcohol

Change venue where use needles/drugs/alcohol

Do not share needles (exchange or obtain new)

Clean needles or only share with known negative

partner

6. Patient plans to increase condom

use or increase

situations that she

uses condoms

Talk to partner(s) about using condoms

Buy condoms or have them more available

Sex with condoms more often

Use condoms with all partners (vaginal/anal sex)

Use with all non-main partner (vaginal/anal sex)

Use condoms with main partner (vaginal/anal sex)

7. Patient plans to change

the kind of sex she

win have

Have oral sex instead of vaginal or anal sex Have mutual masturbation or petting (no penetrative

sex)

8. Patient plans to make

changes in the situation

she is in that are associated with

risk behavior

Eliminate going to particularly risky place (bar-park)

Reduce number of times going to particularly risky

place

Substitute behavior — go to . . . gym, movies, etc

Source: Adapted from Kamb ML, Rshbein M, Douglas JM, et. al. Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted disease: A randomized controlled trial. JAMA 280:1161-1167, 1998 and from Beth Dillon, Project

RESPECT training materials.

58 USl Dep.uitmest of He.ilth .vmj Hum-vs Seimces, He.uth Resovsces ,\nx> Sekntces .\dmimstr-\tios, HRVAIDS Bl-re-u;
A Guide to the Clintc\l Care of Women 'stth

Prevention of HT\^

(MM-N, patients spend much more time waiting in the reception area or in the

exam room than they actually do with the clinician. Optimizing use of

patient time bv providing educational materials during waiting periods may

allow the clinician to limit the amount of didactic information dispensed in

clinic and to spend more time in interactive behaxtioral modification. A self- assessment of the counseling session will allow clinicians to measure their

counseling skills. Cioals for the counseling session include exploring behax'-

lors most associated with risk, identifying a reasonable risk reduction plan,

and assessing the patient support system. A reasonable checklist for a behavioral intervention session is listed in Table 3-8.

Table 3-8: A Checklist for the Behavioral Intervention

Counseling Session

j Explored behaviors most associated with risk j Identified behaviors most amenable to change

j Identified reasonable change step

J Developed the change step into a plan for action

J Problem-solved obstacles to the plan

J Confirmed with patient that the plan is reasonable

J Assessed patient's support system

J Identified referral resource, if necessary and available

J Reviewed date, time, and goals for next visit J Recognized behavior change as a challenge

Source: Adapted from Kamb ML, Fishbein M, Douglas JM, et. al. Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted disease: a randomized controlled trial. JAMA 280:1 161-1 167, 1998 and from Beth Dillon, Project

RESPECT training materials.

VII. ETHNIC AND GENDER CONSIDERATIONS IN RISK

REDUCTION COUNSELING

Language, visual materials, and descriptive terms sensitive to specific

cultures and ethnicities may be important in improving communication techniques.

Ethnographic data from the San Antonio smdy found that African-American w'omen in their study population displayed an emphasis on infectious

disease prevention, referring to sharing eating utensils as “eating behind”

and sharing needles as “fixing behind.” The authors suggested that use of

terms such as haying sex “behind” someone might be an effective means

of communicating the concept of unsafe sexual practices in their smdv

population. In contrast, people of Asian background often conceptualize

the human body of being made up of “hot” and “cold” components and

may think of disease processes such as STDs as “hot”. Referring to a con- dom as “cold” may emphasize the effectiveness of such prev^entatiy'e measures. Finally, some studies have shoxvn that the use of visual tools enhances

verbal communication in Spanish. It is important to recognize, however.

us. Department of Health .and Hi alan Seratces, Health Resoit$ces .and Seratces .\D.\nNTSTR.AT!ON, HI\' AIDS Bi rf 59
A Gl ide to the Cumcai. Cari-: oe Women with HH'

Prevenrion of HI\

tliat such colloquialisms or culmral preferences may vary between regions,

socio-economic strata, and religions. If used in die wrong setting,

approaches designed for one etiiic group may offend anotiier, and detract

from the counselor’s abilip' to communicate. In the absence of a yalidated

communication tool, the counselor should take tiieir cues from the patient.

Some counseling concerns are particularly relevant to women.

In many economically-disadvantaged areas of the world, poverti' engenders

oppression of women. When education and jobs are scarce, many

economies preferentially educate and employ men, thus leaiting women

financially dependent on their husbands, imlnerable to “sugar daddies,” and

bartering sex for food and clothing either in informal relationships or in a structured brothel setting. Many cultures sanction a family structure in

which the mother of the husband lives in the home and is responsible for

directing household activities and ensuring the well-being of her son. Many

cultures also may place more value on men than on women, and may

mythologize male prowess and discourage condom use. Finally, many societies do not recognize the legal rights of women in custody battles, thus

leaving women tied to their husbands if they v^ish to remain with their children. In conditions in which w'omen are economically and emotionally

dependent on men, women often neglect their basic human rights. Such

barriers may be extremely daunting to counselors, and the temptation may

be to attempt to debunk societal inequalities or to degenerate into a “malebashing” session. In such cases, the basic tenets of behavioral counseling

should be recalled; focus on risk and tailor the session to the readiness of

the woman for behavioral change. Clear, feasible risk reduction plans should

be formulated, usually involving self-education about risk and recognition

of responsibility to reduce risk.

Unfortunately, the issue of domestic violence may also need to be

addressed.

Domestic violence continues to be a prev^alent problem, affecting 20—30% of

households in the United States and possibly even higher numbers in other

parts of the world. A smdy of HR" testing of w'omen in Nairobi, Kenya,

has produced some disturbing results. Out of 243 women informed that

they were HR" positiv'e, only 66 (27%) informed their parmer of their result

Of these 66, 11 (!"’%) were chased from the home, 7 (11%) were beaten,

and 1 (1%) committed suicide. X^hen the testing protocol was changed to informing women that remrning for HR" test results was optional, only onethird of women returned for their results (Temmerman, 1995).

Fear of domestic violence may also impede a woman’s ability to assert her

rights in a relationship to reduce her risk of HR" infection. Counselors

must realize that such fear may be entirely reasonable, and that counseling

patients about domestic violence may be beyond their area of expertise.

N^thenever possible, appropriate patients should be referred to domestic violence centers. At the same time, counselors can help patients formulate risk

60 us DEP.urrvEST of He.m.th .vsd Services, He.u.th Resochces ,\nd Services Ad-vcmstb-vtios HIV/.VIDS Bcre.ve
A Glide to the Clinical C.\re of Women \xtth HI\"

Prevention of

reduction plans in the setting of domestic violence. The counselor must

approach the issue of HIV testing while mentioning and indeed when

appropriate, emphasizing, the possibilitv' of domestic violence and social

stigma. W hile counselors must encourage disclosure in order to avoid the

potential of infecting an uninfected partner, they must remember that the

safety of the patient is their first priority. Unformnately, only initiation of

widespread testing and recognition of seroprevalence will succeed in destigmatizing 1 11\^ infection. Meanwhile, on the individual level, care must be

taken to help the woman identify ways to reduce her risk of physical harm

and excessive emotional stress while at the same time initiating the process

of recognizing and reducing risk behavior.

VIII. SEXUALLY TRANSMITTED DISEASES AND THE

RISK OF HIV INFECTION

Genital tract infections increase susceptibility to HIV infection

The fact that STDs are important cofactors for HIV infection has been

well-established by prospective studies examining risk factors for sero- conv'ersion in high-risk populations. In such studies, the increased risk

for HIV-1 acquisition in women with genital ulcer diseases and gonococcal

and chlamydial cervicitis has been estimated at tw’O to four abov^e baseline.

Women with Candida and trichomonal vaginitis hav^e been estimated to

hav'e an approximately two to three times increased risk abov^e baseline

(I.aga, 1993).

Bacterial vaginosis may also increase susceptibility to HIV infection

In an important recent study in Malawi, bacterial v’-aginosis w^as showm to be

a significant risk factor for HR^ seroconversion in pregnant women attending an antenatal clinic. In this study, bacterial v^aginosis (defined by v^aginal

pH > 4.5, homogeneous v^aginal discharge, absence of other etiologic

agents of cervicitis or v'aginitis, presence of clue cells, and positive amine

odor) w’as a prevalent condition, affecting 30% of w’omen. Presence of BV

at the enrollment exam w’as associated with a three- to four-fold increased

risk of HIV seroconv^ersion ov^er the median 2.5 years of foUow’-up (Taha,

1998). An association between bacterial vaginosis and HI\^-1 seroconv^ersion

has also been reported in a study of nonpregnant w^omen; women with bacterial vaginosis in the 60 days before HW testing were 1.4 times more likely to hav'e incident HIV infection than women without genital infections (multivariate p=.07) (iMartin, 1998).

Syndromic management of STDs decreased HIV acquisition rates,

but mass treatment of STDS did not in two different community

randomized trials

From these studies, one can conclude that a healthy genital tract reduces

a woman’s susceptibility to HIV infection. This conclusion was further

us. Dep.\ftment of He.\lth and Hum.\n Sermces, He.\lth Resources .\nd Seruces Ad.ministr.\tion, HIVV.VIDS Bure.\u 61
A (kllDI', TO llll- (J.INICAI, (^\RI' Ol- WoMliN WITH HIV

Prcvcnrion of HIV

solidified by the results of a community-based randomized trial conducted

in Mwanza, Tanzania demonstrating that syndromic management of STDs

resulted in a 40 percent reduction in HIV-1 seroconversion in the intervention communities (Hayes, 1995; Mayaud, 1997). In contrast, a randomized

controlled trial of mass antibiotic treatment conducted during almost the

same time period in Rakai, Uganda, failed to demonstrate a reduction in

HIV seroincidence (Wawer, 1999). The reason for the difference in findings

in these two trials testing a STD intervention is Likely related to the stage of

the epidemic in the two locations. In Mwanza, the baseline prevalence of

HIV was only 4%, indicating an early phase of the epidemic. In comparison, the Rakai study was conducted in a population with a baseline prevalence of 16%, indicating a more mature epidemic. Experts feel that the core group of high-risk individuals crucial to epidemic transmission was already

saturated in Rakai, thus minimizing the impact of the intervention. The

Rakai intervention also did not address genital herpes which was the most

common cause of genital ulcer disease in the Rakai communities. The disparate findings of these studies emphasize the complexities of the association between HIV and cofactors affecting transmission.

How should we counsel women at risk for STDs and HIV?

Important issues in counseling women at risk for STDs and HIV are presented in Table 3-9. Reducing the prevalence and incidence of STDs should

reduce the susceptibility to HIV transmission. Measures to reduce STDs

include female and male condom use, seeking early diagnosis and treatment

of genital tract symptoms, and frequent STD screening and should be a part of HIV prevention in the U.S. as well as in developing countries (CDC,

1998b). Infections such as yeast vaginitis and bacterial vaginosis are not sexually transmitted, but arise from disruption of a woman’s genital tract flora. For this reason, these infections are often under-emphasized in programs to

diagnose and treat genital tract infections. However, these are prevalent

conditions, and studies have shown that both yeast vaginitis and bacterial

vaginosis may increase risk of HIV acquisition. Clinicians should diagnose

and have a low threshold to treat both bacterial vaginosis and Candida

vaginitis in women with high-risk sexual behavior. Douching may increase

the risk of developing bacterial vaginosis or pelvic inflammatory disease.

Table 3-9 : Measures to Reduce Sexually Transmitted Diseases

(STDs)

Encourage male and female condom use Encourage seeking medical care early for diagnosis and treatment of genital tract symptoms

Routine screening for genital tract infections, including chlamydia cervicitis, yeast

vaginitis, and bacterial vaginosis among sexually active women

Discourage douching

Educate women about risk factors for yeast vaginitis

Teach how to recognize genital herpes recurrences and prodromes and offer

antiviral treatment to shorten or suppress recurrences

62 U.S. Dkp.^rtment of Hk,u,th .\nd Human Services, Health Resource.s and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Prevention of HIV

Douching has no therapeutic benefit and should be strongly discouraged.

Preventable risk factors for Candida vaginitis include uncontrolled diabetes

mellitus, antibiotics, and high-estrogen oral contraceptives. Other possible

risk factors that are less well-documented include wearing poorly ventilated

clothing, use of low-estrogen oral contraceptives, frequent swimming, feminine hygiene sprays, and use of spermicidal jelly.

Finally, many studies have shown that genital ulcer diseases (i.e., syphilis,

chancroid, and genital herpes) are important co-factors for HIV transmission. Women with a history of genital herpes or with serologic evidence

of HSV-2 infection should be taught how to recognize prodromes and

recurrences. Suppressive herpes antiviral therapy should be considered in

women with frequent recurrences who report high-risk sexual behavior

(CDC, 1998a).

IX. CONDOMS AND PREVENTION OF HIV INFECTION

Readers of history may know that decorative pende covers have been mentioned in Eg}q)tian writings as far back as 1350 BC. In 1564, the Italian

anatomist, Fallopius, described the concept of a penile barrier for the prevention of venereal disease. The famous romancer, Casanova, is said to have protected himself with sheets of sheep intestine. Since that time, technology has

allowed the production of latex male condoms, and more recentiy,

poljmrethane male condoms and female condoms. Important issues to discuss

while counseling women on use of male and female condoms are listed in

Table 3-10, on the following page, and discussed below.

A. MALE CONDOMS

Male condoms prevent transmission of many STDs

The literature on the role of barrier contraception as protection against

STDs is vast and the reported degree of protection against specific STDs

varies from paper to paper. A distillation of available data produces the

conclusion that, of available barrier methods that have been adequately

tested, latex male condoms provide substantial protection against infection

with HIV and most other STDs, and are currentiy the most reliable protective measure. Most studies describe a seven- to eight-fold decrease in risk of

HIV-1 seroconversion for people who use condoms consistentiy. Some

have reported no seroconversions at all among consistent despite repeated

coital exposure (CarUn, 1995). In terms of other STDs, male condoms may

be less reliably protective against transmission of herpes and human papilloma viruses.

Latex male condoms must be stored and used properly

Male condom failures are more likely caused by post-manufacture defects

secondary to latex deterioration than to manufacturing defects. Latex male

us. Department of Health and Human Services, Health Resources and Servicf.s Administr/Viion, HIV/AIDS Hureau 63
A CuMoi'. ro rill- (j.inicai, (^\Kl•: or Womi-n wrrii 1 IIV

Prevention of 1 IIV

Table 3-10: Important Issues for Patients Being Counseled on

Condom Use

Store in a coot, dry place, such as a bedroom drawer

• Avoid excessive humidity, such as in a bathroom

• Avoid excessive heat, such as in a wallet carried in a trouser pocket • Avoid exposure to direct sunlight

Use appropriate spermicide or lubricating jelly • Mineral-oil containing compounds, such as petroleum jelly, cooking oils, shortening, or lotions, can weaken latex Use male condom properly • Use male condom at the onset of male arousal, even before penetration • Make sure that the male condom is unrolled to extend completely to the

penis base • Use enough lubrication to prevent excessive friction that might lead to breakage • Hold the male condom at the base during withdrawal to prevent slippage

Use female condom properly • The inner ring must be placed completely onto the cervix or the condom

may twist • Additional lubrication may be needed to prevent the condom from twisting • Care must be taken not to insert the penis between the condom and vaginal

wall • The outer ring may need to be held in place to keep the condom from

slipping into the vagina or anus • During anal intercourse, the insertive partner may have to keep thrusts

shallow, because the condom is not as long as the rectum. It also might be

advisable to remove the inner ring for anal sex to reduce likelihood of rectal bleeding.

condoms have proved impermeable to HIV in vitro. In contrast, natural

membrane (“skin”) condoms have been shown to be permeable to small

amounts of HIV and other infectious agents, and are not recommended for

disease prevention. Transmission of HIV that occurs with use of latex male

condoms is likely due to technical failures or improper usage rather than to

manufacturing defects. Since 1987, the Food and Drug Administration

(FDA) in the United States has maintained a high level of quality by limiting the number of defective condoms to four per 1000 count batch.

Patients should be counseled that stored male condoms should be replaced

often, as temperature, light, and animal pests all can contribute to latex

deterioration and decreased effectiveness. In clinical studies, breakage rates range from 0.5% to 7% (Stratton, 1993). Studies reporting higher breakage

rates tended to include populations from under-developed areas or those

who participated in anal intercourse.

Male condoms must also be used properly in order to be effective.

Using oil-based lubricating materials such as petroleum jelly, cooking oils,

shortening, or lotions during intercourse weakens latex and promotes

breakage. Common errors that patients should be cautioned about include

delaying condom use until just prior to full penetration, failure to extend

64 us. Department of HE.\LrH and Hum,\n Services, Health Resources and Services Administration, HIV/AIDS Bure/\u
A Guide to the Cuntc.\l C.\re of Women \xtth HR"

Prevention of HR

the condom all the way to the penis base, insufficient application of

a water-based lubricant, and failure to hold the condom at the base

during withdrawal.

Polyurethane male condoms may be a future alternative

Acceptabilit}' of male condom use is limited by complaints of decreased

male sensitivit)’ and limitation of sexual enjoyment by both men and

women. Pohiirethane has been hailed as an attractive alternative to latex

because of increased tensile strength that should, theoretically, allow" for a thinner condom wall translating into increased penile sensation. A male

polyurethane condom, Avanti, has been popular since its introduction in

late 1994, but after increasing numbers of complaints of condom breakage,

the manufacturers have changed specifications to produce a thicker condom

labeled “Intended for Latex Sensitive Condom Users Only.” Breakage rates,

patient acceptability’, and the abikty’ of this product to protect against STD

and HIV infection are yet to be demonstrated.

B. FEMALE CONDOMS

Also made of pohairethane, the female condom has been available for use in

the United States since 1993 (Bounds, 1997) and offers women more control over use than with the male condom. The female condom is a sheath, closed

at one end, with flexible rings at both ends (Figure 3-2 on the following page).

The de\ice is inserted into the vagina by compressing the closed-end ring and

pushing against the cer\ix, w’-hile the outer ring covers the labia (Figure 3-3 on

the following page). Only one female condom is currently available, marketed

under the name “Reality’” in the United States and Canada and “Femidom” in

other parts of the w’orld. Dmited data are available on the efficacy’ of the

female condom in preventing HIA^ and STDs, although most experts have

extrapolated from the data on male latex and poly’urethane condoms to conclude that, if used properly’, female condoms would be impermeable to most

viruses and other micro-organisms. In a study sponsored by’ the United

Nations Programme on HIV/AIDS (UNAIDS), female commercial sex w’orkers in Thailand w’ere randomized into a group instructed to consistently use male condoms, and a group given the option to use female condoms if the

male refused to w’ear a condom (Fontanet, 1998). Both groups reported universal male or female condom use rates of approximately’ 97%, although 9%

of the w’omen in the “option group” used the female condom. Before introduction of the female condom, w’omen in the study’ population w’ere experiencing an average of tw’O STDs per y’ear (trichomoniasis, chlamy’dial infection,

gonococcal infection, genital ulcer disease). This rate w’as surprisingly high,

particularly given the high rate of reported condom use, and may be due to overreporting of condom use (given the Thai 100% condom use policy) or STDs acquired from their husbands or nonpaying partners. Nevertheless, the

group randomized to the option to use either ty’pe of condom demonstrated a 24% decrease in the incidence of STD compared to the male condom only

us. Dep.\rtment of He.\lth .\nd Hu^L\N Sermces, He,\lth Resources ,\nd Services .Vn.MiNi.smAnos. MI\'/.\IDS Bi k. v 65
A Cii'iiM'; I'o nu- (j inicai. (2ari; oi' Womi:n with HIV

Prevention of HIV

Figure 3-2: The Female Condom

group. Importantly, female condoms were reportedly well accepted both by

the women and their clients. Condom tears occurred less frequendy with the

female condom than the male condom.

C ACCEPTABILITY OFMALEAND FEMALE CONDOMS

Factors influencing condom use are presented in Table 3-11. These factors are complex, and often differ between men and women. Surveys have shown that

both men and women are influenced by perceived social norms and attitudes

about condom use, and by the recognition that condoms may prevent STDs.

Ability to obtain condoms without excessive cost or embarrassment, ease of

using the condom, and preservation of pleasurable sexual sensation are clearly

66 us. Dewrtment of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Prevention of HIV

Figure 3-3: Female Condom Insertion and Positioning

Step 1

Inner ring is squeezed

for insertion.

Step 2

Sheath is inserted,

similarly to a tampon.

Steps

Inner ring is pushed

up as far as it can go

with index finger.

Step 4

Female condom is in place

Source: Adapted from Reality brand female condom literature.

us. Dkp.\rtment of He.\lth and Human Services, He,vlth Resource,s and Services Adminis-i-rai-ion, HIV/AIDS Buri-imi 67
A Ciuini; I'o riii'. (Iunicai. Cari-; oI' WomI'N wmi HIV

Prevention of Hl\'

concerns for both men and women. Acceptability of the male condom for

both men and women is increased by normal appearance and feel, lack of odor,

lack of slippage, the presence of a reservoir tip, and spermicidal lubrication.

Men may be more likely to use the male condom if they feel that the woman

may perceive them as being more sensitive and caring if they do so. Women, on

the other hand, have complained that the interruption of foreplay negatively

affects the acceptability of the male condom. For the female condom, both

men and women have complained about the aesthetic appearance of the external ring, and the noise during intercourse. The fact that the female condom is made of polyurethane and not latex may increase its acceptability, particularly

Table 3-11: Factors Associated with Condom Use and Non-use

Condoms in General Important to Men Important to Women

Negative image of condom use

associated with disease, promiscuity,

and distrust of sex partner

Actual and perceived social norms

governing condom use

Perceived ability to protect against

sexually transmitted diseases

Ease of obtaining or purchase

Ease of putting on or in Slippage during intercourse

Adequate lubrication

Sensation during intercourse

Male Condoms Important to Men Important to Women

Normal appearance and feel m m

Lack of odor

Reservoir tip

Spermicide coating

Interruption of foreplay

Inferior contraceptive method

Perception that partner may believe user is sensitive and caring

Female Condoms Important to Men Important to Women

Aesthetic appearance of external ring

Noise during intercourse

Polyurethane material

Interruption of foreplay

Female controlled device

Inferior contraceptive method

Source: Adapted from Grady WR, Klepinger DH, Nelson-Wally A. Contraceptive characteristics: the perceptions and priorities of men and women. Fam Plann Perspect 1999;31:168-75.

68 us. Dep.^rtment of Health and Human Services, Hem.th Rilsources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinic.\l C.\re of Women with HIV

Prevention of HIV

among latcx-allcrgic users. Women have reported that inserting the female con- dom interrupts foreplay. Interestingly, in several surveys, more women have said

that they would be likely to use the female condom again than have said that

they liked using it, suggesting that women may be willing to sacrifice comfort

anil pleasure during sex for protection against STDs and pregnancy. Many

women have also strongly expressed a preference for a female-controlled device

to prevent STDs, h'inally, in surveys, pregnancy prevention is more important to

women than to men, and most women feel that both the male and female con- dom may be inferior to other contraceptive methods. (Grady, 1999)

X. OTHER FORMS OF CONTRACEPTION AND THE RISK

OF HIV INFECTION

The role of hormonal contraceptives in HIV transmission is

controversial

The association between hormonal contraception and HIV infection has

been the subject of controversy. Because of the unique considerations that

contribute to contraceptive choice, a chnical trial randomizing a woman to

contraception or placebo is probably not feasible. Thus, although many

studies presenting data on the association have been published, all are population surveys or observational studies. The reported effects of oral contraceptives on HIV susceptibility are widely divergent, ranging from

protective, to no effect, to an increased risk. A meta-analysis on the subject

reported that the use of oral contraceptives may be associated with a small

increased risk of HIV infection (Wang, 1999). When the results of all 28

published studies were combined, a pooled odds ratio of 1.2 (95% Cl 0.99-

1.42) was found. This pooled risk estimate increased with increasing study

qualit}', suggesting that a true association, albeit small, does exist. In addition, two cross-sectional studies and two prospective studies have reported

that w'omen using depo medroxyprogesterone acetate (Depo-Provera) are at increased risk of HIV infection. In a study conducted in Mombasa, Kenya,

commercial sex workers (n=779) were followed for a median of 224 days;

in multivariate analysis, women using Depo-Provera demonstrated two

times increased risk of HIV seroconversion (Martin, 1998). Insufficient data

exist on other hormonal contraceptive methods to reach a conclusion about

the effect on a woman’s susceptibility to HIV

Barrier contraceptives other than condoms

Other forms of barrier contraception, such as the diaphragm and the cervical cap, do not cover the vagina, and therefore would not be expected to

proHde substantial protection against HIV infection, although the

diaphragm with nonoxynol-9 containing spermicide has been associated

with a modest decrease in bacterial STDs. N-9 spermicides alone provide

modest protection against bacterial STDs but no apparent effect on HIV in randomized chnical trials despite evidence of in vitro activity against 1 1 IV.

us. Dep.\rtment of He.\lth .\nd Human Services, Health Resourcf.s ,\nd Services Adminisir.\tion, I II\7.MDS Bi 're m' 69
A CiuiDi': TO mi: Ci.imcai. Carh oI' Women vnni HIV

Prevention of HI\'

Furthermore, N-9 spermicides have been associated with chemical irritation or epithelial disruption in the lower genital tract at higher doses of N-9 or uith frequent use, raising concerns that these women may be at increased

risk for HIV transmission if they use spermicides only. The use of spermicides alone should be discouraged in at-risk women and the potential benefits (lubrication, possible increase in protection if the condom breaks) and

risks of spermicide use with condoms should be discussed. Intrauterine

devices (lUDs) have been associated with an increased risk of pelvic

inflammatory disease, especially around the time of insertion. A two- to threefold increased risk of HIV infection in women who use lUDs has

been reported (Kappa, 1994). The foreign body reaction induced in the

endometrium by an lUD, with accompanying inflammation, ulceration, and

thinning, as well as generally longer and heavier menses (which may

increase risk bidirectionally), provide a easily-conceived biologic basis for

increased susceptibility to HIV infection.

Sterilization and prevention of HIV infection

Female sterilization by tubal ligation has no effect on male-to-female HIV

transmission. Early penile withdrawal, while theoretically reducing the

innoculum size, has not been studied and should not be recommended.

While the exact effect of vasectomy on the ability to transmit HIV from

male to female is unknown, HIV has been cultured from the ejaculate of

vasectomized men (Anderson, 1991).

Contraception and prevention of infection are separate issues

The issue of contraception for sexually active, reproductive age women, is obviously complex. The importance of preventing unwanted pregnancies is

clear. Any counselor working with women is familiar with the issue of controlling and planning family size while taking into account economic factors,

maternal health, and social pressures. Hormonal contraception is one of the

most effective means to prevent pregnancy. The message conveyed to

Table 3-12: Contraception and prevention of HIV-1 infection

Method May Increase Risk*

No Effect or CoNFUCTiNG Data*

Protective —

Strong Evidence

Male condom

Female condom

Intrauterine device

Diaphragm

Cervical cap

Tubal ligation

Vasectomy

Early penile withdrawal

Oral contraceptives

Depo-Provera

* Counsel that condoms should be used to prevent HIV-1 infection

70 us. DEP.Mri'ME.NT OF AND HUMAN SERVICES, HEALTH RESOURCES AND SERVICES ADMINISTR-OTON, HIWAIDS BUREAU
A Guide to the Clinical Care of Women with HIV

Prevention of

womc-n must be that contraception and protection against STDs, including

HIV, are separate considerations. For women who choose to use hormonal

contraception, counselors must emphasize that male and female condoms

are the only means to prevent STD transmission

'I'he effectiveness of various contraceptive methods in reducing risk of

MIX' infection is summarized in Table 3-12.

XI. NEW APPROACHES TO HIV AND STD PREVENTION:

MICROBICIDES, VACCINES, AND POST-EXPOSURE

PROPHYLAXIS

(liven the difficulties that many women encounter in negotiating condom use, other prevention strategies under the control of women have been sought,

such as topical microbicides. XXTrile microbicides have generated considerable

enthusiasm, progress in this area has been relatively slow. Most of the research

in microbicides over the past 10 years has focused on safety and efficacy of

nonoxynol 9 (N-9). The findings have not been consistent across all studies,

complicated by different concentrations and formulations of N-9 used, insufficient sample size, and differing frequency of condom use by the women studied. Data on N-9 are weU-summarized in a recent meta-analysis (Roddy, 1998a).

In general, the data available from randomized trials do not support

significant efficacy of N-9 against HIV (Roddy, 1998a).

Current efficacy trials of N-9 by UNAIDS and HFVNET will hopefully answer remaining questions about whether the lack of efficacy of N-9 in

vivo was due to high condom use or too low a dose of N-9.

While the concept of topical microbicides is promising, the process

to developing and testing new microbicidal products for safety, and

ultimately efficacy in preventing HIV, in clinical trials will take a number of years

New topical microbicidal products in early clinical trials include broad-spectrum microbicides (such as natural lactobacilli, buffering products such as BufferGel, and surfactants such as C31G), inhibitors of viral entr)^ and cell fusion (such as PC503 which has activity against HIV, HSV, and C. tra- chomatis; and PR02000) and inhibitors of HIV replication (such as nucleotide reverse transcriptase inhibitors such as PMPA). Many challenges

face the study of topical microbicides, including the standardization of in

\titro exposure assays for meaningful and consistent comparisons of activities of different compounds against HIV and other STDs and identification

of placebos that have similar viscosity and pH to the active ingredient.

Vaccines hold the most promise for protecting the largest number of

HIV infections transmitted sexually, perinatally, or through drug use. However, no HIV-1 vaccine with proven efficacy currently exists, and the

necessary components of an immunogen that can induce protection against

us. DEP.«TMENT of HE.VLTH .WD HUMAN SERVICES, HE-ALTH RESOURCES ANT) SERVICES ADMINISTR-ATION, HIV/.\IDS BuRI-.AU 71
A duiDi': TO iiii-. (j.iNicAi. oi' WoMi'N wnii HIV

Prevention of Hl\'

HlV-1 infection are poorly understood. Clues have emerged from dissecting

the properties of immunity that correspond to protection against other

pathogens, and more particularly in vaccine studies in the related SIV/HIV

primate models. In addition, persons demonstrating unusual control of

HIV-1 infection, e.g., those repeatedly exposed to HIV-1 without overt

infection, HIV-1 long-term non-progressors, and HIV-2-infected persons,

may have acquired a unique host defense against HIV that merits induction

by vaccination.

Our understanding of the mechanism of action of other effective viral

vaccines and HIV pathogenesis is guiding HIV vaccine development. Most

licensed vaccines prime host immunity to control initial infection more efficiently, rather than to provide sterilizing immunity. Protection is commonly

mediated by induction of antibodies that block infection, which allows time

for antigen-specific T cells to mature and overtake any cells that do become

infected. HIV-1 preferentially targets T helper cells, and either destroys

them or establishes latent infection; a vaccine must restrict HIV-1 “seeding”

and reemergence over time. HIV-1 is not easily neutralized by antibody, so

that mimicking the largely safe recombinant protein strategy for Hepatitis B

virus vaccines is less apt to be successful with HIV-1. HIV-1 transmission occurs predominantly by sexual contact; thus, protection may require both

mucosal as well as systemic immunity.

Most experts believe that regimens priming both the cellular and

humoral immune arms are the best candidates for protection, based

on strong evidence in both experimental and human viral infections.

HIV vaccines that can stimulate a cellular immune response include poorly

replicating viral or bacterial vectors expressing HIV gene products, such as poxviruses, vaccinia and avipox. These products (e.g., the canarypox vector

with gag, nef, and env genes) can elicit CD8+ cytotoxic T cell responses in

approximately one-third of volunteers. Macaque studies suggest that the

less virulent, modified vaccinia Ankara (MVA) recombinant may induce even stronger T cell responses, and its safety profile from previous use

internationally looks quite good. Other recombinant vectors containing

HIV-1 gene inserts that hold promise for clinical testing include Venezuelan

equine encephalitis virus, adenovirus, poliovirus, and bacterial vectors (e.g.,

salmonella or listeria), but these as yet have not reached phase I testing.

DNA vaccines may have promise, based on studies in the macaque model

for SIV in which CD4+ and CD8+ T cell immunity and low-level antibodies were elicited. DNA vaccines are stable and will not require continuous

cold storage, and may be more readily altered as the pool of viruses in the

infected transmitting populations evolve, but immunogenicity has not been

optimal at up to 3 mg doses.

Building upon these insights, vaccine development has ensued and several

strategies have been tested in the phase I/II setting. Of the vaccine regimens tested thus far in HIV-1 high-risk populations, no single approach is

72 us. Department of HealTM and Human Services, Heai.to Resource.s and Services Administr,\tion, HIV/AIDS Bureau
A Guide to the Clinical C\re of Women with HR

Prevention of HR"

devoid of “breakthrough” infections. Clinical trials to test vaccine efficacy

are expensive and large scale and have not as yet been endorsed except by

private industry (VaxGen) which is testing the efficacy of a bivalent gpl20

vaccination approach in Xorth America and Thailand. At present, among

the agents available and demonstrating acceptable safeR* in phase II trials,

the next vaccine candidates to move to efficacy trials are likely to be a multivalent vaccine regimen with a canartyiox vector prime and subunit gpI20

boost, which induce neutralizing and non-neutralizing antibodies primarily

recognizing the variable envelope regions of strains closely similar to that of

the immunogen and cytotoxic T cells. An intermediate-sized efficacy trial in

the next several years may answer w'hether the potenc}' of antibodies and

frequency of antigen-specific T cells elicited by the canan-pox prime-gpl20

boost is adequate for protection.

Post-exposure prophylaxis (PEP) is a method which may reduce the

likelihood of HFV infection after a high-risk exposure.

Theoretically, PEP may either prevent establishment of infection or prevent

new infection while allowing clearance of already infected cells. The rationale for PEP with sexual exposure is that the probabdit}’ of infection after a

single exposure w’as similar to needlestick exposures (i.e., 0.1—3% for unprotected receptive anal intercourse or 0.1—0.2% for vaginal intercourse)

(USPHS, 1998; Katz 1997, 1998). Animal models indicate that PEP may be

effective, particularly w'hen used within 24-48 hours of exposure with

potent antiretro^iral agents. The data for efficac)" of antiretroxirals for

occupational exposure primarily is derived from a case-control study, in

which health care workers who took zidoxmdine after needlesticks had an 80% lower likelihood of being infected, but which may suffer biases due to

the case-control design. This study has been criticized because of its retro- spective nature, small number of cases, and other potential sources of bias.

There are also reported cases in w^hich ZDV failed to prevent HI\^ infection in health care workers. However, no prospective studies have assessed

the efficacy of PEP for either occupational or sexual exposures due to ethical and pragmatic considerations in conducting a randomized trial of PEP.

Thus, the risks and benefits of PEP for sexual exposure remain uncertain.

Efficacy of PEP is likely to be influenced by time to initiation of treatment,

duration of treatment, size of inoculum, and drug characteristics.

IndiHdual proHders who are approached by anxious patients who have

recentiy had a high risk sexual exposure must w'eigh the likelihood of HI\'

infection in the contact, antiretroxfiral treatment histon- if the contact is knowm to be infected, specific nature and timing of the exposure

(since initiation of PEP within 48 hours may be important) and possible

risks of drug toxicity or side effects in choosing whether to use PEP and

w’hich drugs to prescribe. The CDC guidelines recommend Rvo drugs (generally zidoxaidine or staxaidine and lamixaidine) for four w’eeks for most

cases of occupational exposure, and this approach has been adopted bv

many proxiders w'hen selecting a regimen for “sexual PEP.” (CDC, 1998c).

us. Dep.\stsjent of He.uth .\nd HuiU-S Ser\ices, He.uth Resources .usd Sermces .\D.\nNismuTioN, HI\’ .MDS Bi rj ' 73
A CJUIDI' lO rui' (J.INICAI. C;.\RI' Ul' WoMKN WITH HIV

Prevention of HIV

The source partner’s likelihood of resistant virus, based on treatment history, stage of disease, and viral load can be factored into the choice of a PEP regimen. Other considerations should include evaluation for other

STDs, emergency contraception when appropriate, and possible indication

for hepatitis B vaccination. Informed consent is recommended when

administering PEP.

PEP should not be administered routinely, with exposures at low risk of

transmission, or when care is sought after 72 hours from the time of exposure. Situations in which PEP should be considered include condom breakage with serodiscordant couples and sexual assault. PEP is not a substitute

for risk reduction and should not be considered a form of primary HIV

prevention. Individuals presenting for possible PEP should have reinforcement of the importance of initiating, resuming, or improving risk reduction

activities. Providers are requested to report non-occupational PEP use to a national registry maintained by the CDC at (877) 488 1737 or http://www.hivpepregistry.org.

XII. CONCLUSIONS

Prevention of HIV remains a critical priority, particularly midst increasing

complacency related to enthusiasm about more effective treatments for HIV.

The most effective available strategies for prevention are HIV counseling and

testing, behavioral interventions to reduce risk-taking, and condoms. Syndromic STD treatment has been shown to reduce HIV incidence in a large

community-randomized trial, and ongoing studies are assessing other STD

interventions. Topical microbicides may provide a prevention strategy directly

under the control of women, although nonoxynol-9 has not been shown to have significant efficacy against HIV transmission in commercially available

spermicidal concentrations. New microbicide products are early in pre-cUnical

and clinical trials testing. Several HIV vaccines are also currently in clinical

trials, ranging from phase I safety and immunogenicity studies to phase III efficacy trials of a recombinant gpl20 subunit HIV vaccine. Lastly, post-exposure prophylaxis is occasionally being prescribed for high-risk exposures,

although there is very limited data on safety and efficacy. While these new

strategies are being tested for their efficacy to prevent HIV infection,

providers must continue to conduct risk assessments to identify women at risk

for HIV and assist women in reducing their risk through setting achievable

risk reduction plans.

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A Guide to the Clinical Care of Women with HIV

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76 us. Department of He.\lth and Hu.man Servicfs, Heai,th Resources and Services Administration, HtV/AIDS Bureau
A Guide to the Clinic.\l Care of Women with HIV

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us Dep.vrtment of He,u.th and Hum.\n Services, Health Resources .\nt) Services ADMiNisTR.vnoN. HI\7-\1DS Buri au 77
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IV. Primary Medical Care

Judith Feinberg, MD andJanine Maenza, MD

I. INTRODUCTION

No field in medicine today is moving as swifdy as that of HIV/AIDS. The

speed at which new developments occur and the rapidity with which they are superseded by newer data is nothing short of breathtaking. As a consequence,

most studies are typically out of date at the time of publication. Because of

the rapid turnover of key information, this chapter will focus on the essential

principles of care for the HIV-infected woman. ‘Cutting-edge’ treatment

strategies that are currendy being studied will be mentioned but will not be

described in detail. To be truly useful, we will indicate the general directions in

which this field is moving and how to access updated information.

Several studies have demonstrated that positive clinical outcomes are a function of the clinician’s experience in caring for HIV-infected individuals.

(Kitahata, 1996) Nonspeciahsts are urged to seek expert advice and consultation whenever there is any question about the best way to manage a specific

patient. This is especially important in the setting of antiretroviral treatment

failure and in advanced HIV disease when patients are vulnerable to multiple

simultaneous oppormnistic processes.

There is as yet no compelling evidence that the clinical course of HIV

infection in women differs significantly from that of men, with the obvious

exception of the associated gynecological conditions and obstetrical issues

which are described elsewhere. (Chapters VI and VII) Although recent data

have indicated that women may have lower HIV viral loads than men with an

equivalent degree of immunosuppression, no differences in overall survival or

complication-free survival have been demonstrated. At present, the approach

to management of HIV-infected women and men is the same. With prolonged

survival now possible, general preventive strategies and health maintenance,

such as smoking cessation, control of hypertension, minimizing cardiovascular

risk factors and routine screening for malignancy (cervical, breast, colon) are

all part of routine care for HIV-seropositive adults.

us. Department of Health and Human Services, He/\lth Resources and Servicf^ Admini.s-i-raiion, HIV/AIDS Buri-.m' 79
A C'lLiioi', lo Till'; (j.iNiCAi, C\Ki; oi' WomI'IN wrm HIV

Primary Medical Care

II. INITIAL EVALUATION

A. HISTORY

A comprehensive database is valuable to the primary caregiver in assessing the

patient’s current status and in formulating a management plan. It is critical to remember that most patients are anxious and frightened at their initial encounter for HIV care; the ability to empathize, to share knowledge without

being patronizing, to provide reassurance and to remain non-judgmental are

essential to gaining the patient’s trust and to obtaining accurate information

(see Chapter II: Approach to the Patient.) In addition to aU the usual aspects

of history-taking, the following areas are of particular importance in HIV dis- ease and deserve special attention.

HIV diagnosis: When did you first test positive for HIV? Why were you

tested? This neutral, open-ended start permits the patient to raise issues

around HIV risk behaviors and possible route(s) of transmission, including

sexual partners and practices and alcohol/drug use behaviors. Was the

patient ever tested for HIV before? If prior test(s) were negative, it is valuable to assess whether HIV has been relatively recently acquired by looking

for evidence of the acute seroconversion syndrome within the past 6—9

months. These symptoms are classically those of seronegative mononucleosis — fever, aches, pharyngitis, lymphadenopathy and frequently rash,

although the range of possible clinical manifestations of acute HIV infection is very broad.

HIV treatment history: If the patient has already been treated for HIV

disease, then it is extremely valuable to know the patientt’s pre-therapy

CD4 cell count and HIV viral load and specific treatment history. What

was her prior antiretroviral therapy, including duration, any difficulties

with adherence, response to therapy, adverse effects experienced and

history of treatment-limiting intolerance to any agent? It is important to determine what, if any, obstacles she has experienced in taking antiretroviral therapy as prescribed. (See Chapter V on Adherence) Has she

had any HIV-associated diagnoses and was she treated for these conditions?

Has she taken any OI prophylaxis? Has she ever been hospitalized? For

an HIV-related problem?

History of sexually transmitted diseases and other infectious dis- eases: including syphilis, gonorrhea, herpes simplex, pelvic inflammatory

disease, anogenital warts; tuberculosis (PPD status, exposure to active case, prior prophylaxis or treatment for active disease); hepatitis A, B or C; prior

vaccinations, including those for childhood illnesses, hepatitis A and/or B,

pneumococcal infection and influenza; history of chicken pox or shingles;

complete gynecologic history (See Chapter VI on Gynecologic Problems),

including most recent evaluation, Pap smear and results.

80 us. Departmf.nt of He,u,th and Human Services, He,u.th Resources and Services Administr/VHON, HIV/AIDS Bureau
A Guide to the Climc\l C.\re of omex with PKA

Primarv Medical Care

History of other medical diagnoses: with particular attention to ht’pertension, npe II diabetes, cardiovascular disease, premalignant or malignant

conditions.

Sexual practices: including use of condoms (male and/or female versions)

and/or other forms of birth control, consistenc}' of use; number of current partners and their stams (if known); histor}’^ of trading sex (oral or intercourse) for drugs or money; histon' of anal sex.

Presence of HIV-associated signs and symptoms: fatigue, h mphadenopathy, weight loss, skin problems, bacterial pneumonia, thrush

(oral, vaginal), as well as signs/ symptoms more ppical of advanced HW

disease, including, fevers, night sweats, persistent diarrhea, severe headache,

respiratory symptoms (especially progressive dyspnea on exertion and

cough, whether productive or non-productive), mental status changes, difficulrs' swallowing, midline substernal discomfort with swallowing, and visual

changes, particularly the presence of floaters or Tusual field deficits.

Mental health history: past and current problems, evidence of depression

(trouble sleeping, early awakening, change in appetite, loss of interest in

usual acti\ities, anhedonia).

Family history: age and health of children, including test results if performed; HIV in other familjT members; other medical diagnoses, especially hypertension, type II diabetes, cardiovascular disease, malignancy^ in

family members.

Medications taken regularly: including prescription and over-the-counter

remedies; history- of and attitude to regular medication use; use of alternative

(non-traditional) medications for or other conditions; drug allergies.

Social history: place of birth, w'here patient w-as raisedd, w^here and with

whom patient lives and relationship to others in the household; childcare

responsibilities; history- of domestic Holence; pets, especially reptiles (risk of

salmonellosis) and kittens (risk of toxoplasmosis); extent of formal education; occupational history- and potential toxic exposures; travel history-; cigarette, alcohol and illicit drug use in the past or continuing; misuse of

prescription medications.

Sources of support: To w-hom has the patient disclosed her diagnosis and

w’hat w-ere their reactions? Are there friends or family- to w-hom disclosure seems possible either now or perhaps in the future? Are other family members HR^-positive? Are family or friends able to care for the patientt’s children in the event of ihness? Does she have a job and, if so, does it provide

health insurance?

Just as important as the information that the clinician obtains in the history-taking process is the information about HR'’ disease that is shared with

the patient. Counseling and education are important elements of the therapeutic bond with the caregiver, but because this entails an enormous

U.S. Department of He.mth .\ntd Hunl\n Sermces, Heuth Resources .\nt> Services .\DNnNTsTR.moN. Hr\7 AIDS Bi ri 81
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Primary Medical ('are

amount of information, it is best broached initially and then reintroduced

and reinforced at appropriate intervals.

Many patients are in a state of shock following diagnosis, or may be suffering from situational depression or fear of their partner’s response. Be

kind. Be patient. Schedule enough time (1 hour) for the initial visit. Make

sure the patient knows your purpose is to support her and care for her.

Another key bond is the one between the patient and the office/ clinic nurse, which should be encouraged. Ensure that she has a path to reach you

or the nurse for any questions, complaints, or symptomatic therapy, especially when starting antiretroviral therapy.

It is important to convey information in lay language at a level of complexity appropriate to the patient’s level of comprehension (remembering

that formal educational levels may not necessarily correlate with the

patient’s ability to understand complicated medical concepts). These include

the following areas: HIV pathogenesis: What are CD4 lymphocytes and why are they important? How does HIV infection affect CD4 cells??

Natural history of HIV disease: How is “AIDS” different from “HIV

infection” (or “HIV disease”)? What is the typical time course between

acquisition of HIV and the development of HIV-associated problems?

AIDS?

Monitoring the activity of HIV disease: What do CD4 cell counts and

HIV viral load tests measure? How are they used, and how often will they

be repeated?

Goals of HIV disease management: to maintain or improve the patient’s

immune system, control HIV replication; avoiding or minimizing side

effects of medications; preventive care (vaccinations, OI prophylaxis, periodic Pap smears, other appropriate screening tests).

Principles of HIV treatment: describe the available viral targets and

classes of drugs used, and the value of combination therapy in preserving

health and prolonging life.

Preventing spread of HIV infection: notifying sexual partners and drug

use contacts, safer sexual practices, safer needle use including needle

exchange programs, ready availability of bleach in the household for cleaning up blood, appropriate wound care for accidental injuries, reassurance about the difficulty of transmitting HIV to casual contacts and to family

members even in the close context of everyday family life.

Last, because a diagnosis of HIV infection remains a chronic, Ufe-threatening disease and still carries a social stigma, the clinician plays a key role in

exploring mental health and psychosocial needs, helping the patient identify

potential sources of support, and referring the patient for additional medical,

psychiatric and/or social serHces.

82 us. Dep.xrtment of HriALTH AND Human Services, Health Resources and Services Administra'hon, HIV/AIDS Bureau
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B. PHYSICAL EXAMINATION

The examination may yield clues to specific HIV-associated conditions. Vital

signs should be tracked carefully, particularly temperature and weight. The discovery of hypertension, largely ignored in the past, should trigger appropriate

attempts at control, including weight loss, reduction of salt intake and medication if necessary. Special attention should be paid to the following areas.

General: evidence of wasting, often prominent at the temples; fat redistribution syndromes including the development of a buffalo hump, enlarged

breasts and truncal obesity which may coexist with or be separate fromm

marked subcutaneous fat loss in the extremities, face and buttocks.

Eyes: The conjunctival surfaces should be examined for the purplish spots

of Kaposii’s sarcoma (KS) and for petechiae. Fundoscopy may reveal “cotton wool”spots (microinfarcts of the retinal nerve fiber layer due to occlusion of retinal capillaries). These must be differentiated from the typical

‘eggs and ketchup’ appearance of the infiltrates and hemorrhages caused by

cytomegalo\tirus (CMV) retinitis in patients with very advanced HIV dis- ease; visual field deficits are common in CMV retinitis and may be uncovered with simple field testing by confrontation.

Oropharynx: Oral examination often yields the earliest physical evidence

of HIV infection with thrush (white plaques on buccal mucosa or posterior

pharynx that are readily scraped with a tongue blade) and oral hairy leukoplakia (furry white plaques most often found on the lateral margins of the

tongue which cannot be scraped off); purpUsh spots or plaques on mucosal

surfaces, including the area under the tongue, typically indicate Kaposu’s sarcoma but may also be consistent with bacillary angiomatosis. No examination of an HIV-infected person, regardless of disease stage, should be

considered complete without a careful assessment of the oropharynx.

Lymph nodes: Non-tender or rniriimaUy tender generali2ed adenopathy

may wax and wane and most often is related to HIV infection itself, but

may also indicate lymphoma. Regional adenopathy is more frequently associated with local pathology, such as intrathoracic adenopathy in tuberculosis or abdominal adenopathy in disseminated Mycobacterium avium complex

(MAC) infection. Extremely tender lymph nodes should trigger an evaluation for the etiology.

Lungs: fine dry “cellophane” rales are classic for Pneumocystis carinii

pneumonia (PCP), but are a late finding and may be absent.

Hepatosplenomegaly: Organomegaly typically reflects disseminated infection with MAC, TB or histoplasmosis, or may be a sign of lymphoma.

Pelvic examination: • External genitaUa/perineum: sores or ulcers are usually indicative

of sexually transmitted diseases, especially herpes simplex virus (1 ISV)

or syphilis. In very immunosuppressed patients, ulcers may be caused

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by other opportunistic pathogens, such as CMV, or may represent

aphthous ulcers. Condyloma acuminata may appear as small fleshy

papules or may be exuberant, florid growths reaching several centimeters in diameter; other HPV-associated lesions may be recognized only

with magnification and/or application of acetic acid. Raised and pigmented lesions may represent premalignant changes (vulvar intraepithelial neoplasia). • Speculum and bimanual pelvic examination: abnormal vaginal discharge can be caused by various forms of vaginitis (yeast, bacterial

vaginosis, or trichomoniasis) or cervicitis. Pap smears should be

obtained to rule out cervical dysplasia. Cervical motion, uterine, and

adnexal tenderness suggest possible pelvic inflammatory disease (PID).

(Gynecologic exam is discussed in detail in Chapter VI.)

Neurologic: Motor deficits may reflect space-occupying lesions of the central nervous system such as toxoplasmosis, CNS lymphoma and progressive

multifocal leukoencephalopathy (PML), or may be due to neurosyphilis.

Symmetrical, distal sensory deficits (especially decrease or loss of vibratory or proprioceptive sensation), p’pically affecting the feet more than the

hands, indicate peripheral neuropathy, which may be due to HIV itself or to

drug toxicity from the dideoxy nucleoside analogues. Poor short-term memory, diminished concentration and sensorimotor retardation are the hall- marks of AIDS dementia complex (HIV encephalopathy). Dysphoric mood

or flat affect may reveal depression.

Skin: Like the oropharynx, careful examination of the skin often yields

early clues about HIV infection, and should be performed regularly. Early

manifestations include pruritic papular eruptions that may be bacterial folliculitis, eosinophilic folliculitis or scabies. Pearly papules, often with central

umbilication, are p^ical of moUuscum contagiosum. A painful vesicular

rash may be HSV but in a dermatomal distribution is usually shingles (Varicella zoster virus). Seborrheic dermatitis may be severe and appears as scaly,

erythematous areas on the face, especially the nasolabial fold and eyebrows,

or may be confined to the scalp and hairline. Psoriasis is another common

scaling lesion. Purplish macules or plaques may be either KS or bacillary

angiomatosis, similar to their appearance on mucosal surfaces; however, in

dark-skinned individuals, KS may appear more brown than purple.

III. LABORATORY TESTING

A. INITIAL DIAGNOSIS

HIV infection is usually diagnosed by serologic tests which detect antibody to the virus. Infection may also be detected by nucleic acid based assays that

either measure the number of copies of the virus in plasma (RNA PCR) or

84 us. Dep.\rtment of He.\i,th and Human Services, Resources and Services Administration, HrV'/AIDS Bure.au
A Guide to the Clinic\l Care of Women with HIV

Primary Medical Care

tlutcxf the virus in cells (DNA). Informed consent, with pre- and post-test

counseling, is legally mandatory for performing HIV serologic tests in most

locations, and should be performed at all times when the test is offered.

Serology: The most common method of HIV detection is with an ELISA

test for screening, followed by confirmation with a Western blot. For a positive Western blot, the CDC and Association of State and Territorial Public

I lealth Laboratory Directors (ASTPHLD) require a band pattern indicating

antibodies to two of the following proteins: p24, gp41, and gpl20/160. A

serologic test may be reported as positive if the ELISA is positive and

Western blot criteria are met. The test may also be reported as indeterminate if the ELISA is positive, but only a single band is detected by Western

blot. Serologic tests generally become positive 3—12 weeks after infection

occurs. The interpretation of an indeterminate test during this window

period may be clarified by the use of a quantitative virology assay with a PCR-based technique, (see Below) An indeterminate test may reflect the

process of seroconversion, but may also be a constant finding in an uninfected individual. Causes of indeterminate results include: • seroconversion; • advanced HIV infection with decreased titers of p24 antibodies; • HIV-2 (more common in West Africa); • HIV subtype O (distinct from the more common subtypes A-I, collectively known as M) or non-clade B strains; • autoantibodies due to autoimmune or collagen-vascular diseases or malignancy; • cross-reactive aUoantibodies from pregnancy, blood transfusions, or organ transplantation; and • previous receipt of an experimental HIV vaccine.

The window period prior to seroconversion, agammaglobulinemia, and

HIV subtype O are possible causes of false negative results. ELISA assays are now available which detect HIV-2 and some ELISAs

are designed to detect both HIV-1 and HIV-2; Western blot detection of

HIV-2 remains inconsistent on standard assays, but there are also specific

HIV-2 Western blots to confirm reactive HIV-2 ELISAs.

Accuracy of HIV serologic testing is quite high (with > 99% sensitivity

and specificity), but the predictive value of a positive or negative test depends on the seroprevalence of HIV in the patient population. In a low

prevalence population, the rate of false positive results of combined ELISA

and Western blot testing is < .001%. The frequency of indeterminate results

in a low prevalence population is .02%.

Viral detection; • Nucleic acid amplification: May be used to clarify the diagnosis of

HIV infection in acute infection, during the window period (after

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Primar)' Medical Care

exposure, prior to seroconversion), when serologic tests are indeterminant, or with neonatal infection.

plasma HIV-RNA: routinely used to monitor the course and

treatment of HIV infection. (See below) The three most common

techniques are RT-PCR, a branched DNA (bDNA) technique, and

nucleic acid sequence-based amplification (NASBA). These tests report the number of copies of virus per mL of plasma. The

assays are considered equally reliable, but vary somewhat in lower

levels of detection and dynamic range. Lower limits of detection

for standard tests are 400 copies/ml, but ultrasensitive assays are now available which can detect as few as 20-50 copies/ml. Sensitivity is 90—95% overall, but is increased to 98—100% with CD4

counts < 200/mm\ False positive rates are 2—3%, usually with low

HIV RNA titers. (Rich, 1999)

DNA PCR: a qualitative test used to detect intracellular virus, and

primarily used for viral detection with neonatal infection and with

indeterminant serology. Sensitivity is > 99% at all stages of infection and specificity is approximately 98%. • Viral isolation: qualitative or quantitative cultures are used primarily

for diagnosis in neonatal HIV infection, and for more in-depth viral

analysis. The procedure is expensive and labor intensive. Sensitivity is 95-100%.

Alternative tests: • Home testing: Home Access Express Test is the only available home

test for HIV as of April, 2000. Filter paper with a blood sample

obtained with a lancet is mailed in to a laboratory in a coded, anonymous process. Dried blood samples are tested by the same ELISA

and Western blot tests used on venous blood. Sensitivity and specificity approach 100%. Results are provided by phone (a recorded

message for those with negative results, counseling for those with

positive results). • Rapid tests: There are three available tests that provide results in

about 10 minutes: SUDS, Recombigen, and Genie. Sensitivity

approaches 100%; specificity is also > 99%, but positive results should

be confirmed with standard serology. Rapid tests may prove useful in

STD clinics or emergency rooms (where patients often do not return

for tests results) or on labor and delivery wards for high-risk pregnant

women who have not previously been tested. • Saliva test: The OraSure test uses ELISA and Western blot testing

to detect antibodies to HIV in saliva. Sensitivity and specificity are

similar to that with standard serology. This test is useful for people

with poor venous access or those who want HIV testing, but refuse

blood tests.

86 us. Department of Health and Hunl\n Ser\'ices, Health Rf.sources .umd Services Adminlstration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

• Urine test: The only currently available urine test (Calypte HIV-1

Urine IvIA) is licensed for screening only and must be administered

b\- a physician; a positive result requires confirmation by another

method.

B. BASELINE LABORATORYEVALUATION

After the diagnosis of HIV has been confirmed, a baseline laboratory evaluation is needed to establish the stage of disease, as well as exposure to other

infectious diseases. In addition, routine tests of hematology, chemistry, and

lipid profiles are needed at baseline, as HIV and other concomitant illness may

affect these values, and detected abnormalities may also have an impact on the

choice of therapy for the individual patient.

CD4 lymphocyte count: The hallmark of HIV infection is the progressive

decline in CD4+ (helper) T lymphocytes. Normal laboratory ranges for

(iD4 lymphocyte counts are usually 500 to 1400/mm^. CD4 counts may

drop precipitously at the time of primary HIV infection, and then usually

rebound to near-baseline levels. The natural history of HIV then involves a progressive loss of CD4 cells, averaging 30—60 ceUs/year. (See Figure 4-1 on

the following page) The risk of oppormnistic infections increases with

declining counts. (See Chapter I, Epidemiology and Natural History)

Knowledge of the baseline CD4 count is of vital importance in assessing

the patient: staging of HIV infection (See Table 1-3 in Chapter I) as well as recommendations for antiretroviral treatment (see section IV.C) and prophylaxis against specific opportunistic infections (see section VA) are based

on the degree of immunosuppression as quantified by the CD4 count.

Many factors may cause variability in the CD4 count. These include;

inter-laboratory variations;

seasonal and diurnal variation (lowest levels at noon, highest in the

evening)

the use of corticosteroids (decreases values)

intercurrent illness (decreases values)

HTLV-1 co-infection (increases values).

In addition, since the CD4 count is a value derived by determining the

percentage of white blood cells that are lymphocytes, and then the percentage of lymphocytes that are CD4 receptor-positive, there may be variation

in other WBC compartments (as may occur in pregnancy) that leads to variations in the CD4 count. Because the CD4 percentage is the directly measured value and the absolute CD4 count is the calculated one, it is more

useful and accurate to focus on the CD4 percentage to assess trends in this

important parameter.

us. Demrtment of He.\lth and Human Services, He^\lth Resources and Services ADMiNis-niAnoN, HIWAIDS Bi ri.m 87
A (Uiini’ TO rill'. (j.iNicAi CarI'. op VC'omi'.n wiiii I IIV

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88 us. DEPAR'ncfENT OF HK,\LTH AND HUMAN SERVICES, HEALTH RESOURCES .\ND SERVICES AdMINISITLCTION, HIV/AIDS BuRILCU
A Guide to the Clinic.\l C\re of Women with HIV

Primary Medical Care

US. Dep.wtment of He,\lth .and Human Services, He.\lth Resources and SERVicia; .•\DMiNis-iR.vnoN, HIX'/AIDS Hi rim 89
A C^uioi-: IX) 1H1-: ('i.inicm. Cari; oi-' Womrn with HIV

Primary Medical ('are

Table 4-1: Indications for Plasma HIV RNA Testing*

CuNiCAL Indication Information Use

Syndrome consistent with

acute HIV infection

Establishes diagnosis

when HIV antibody test is negative or indeterminate

Diagnosis**

Initial evaluation of newly

diagnosed HIV infection

Baseline viral load "set point"Decision to start or defer

therapy

Every 3-4 months in patients not on therapyChanges in viral load Decision to start therapy

2-8 weeks after initiation of antiretroviral therapy

Initial assessment of drug

efficacy

Decision to continue or change therapy

3-4 months after start of

therapy

Maximal effect of therapy Decision to continue or change therapy

Every 3-4 months in patients on therapyDurability of antiretroviral effect Decision to continue or change therapy

Clinical event or significant

decline in CD4-I-T cells Association with changingor stable viral load

Decision to continue,

initiate, or change therapy

* Acute illness (e.g., bacterial pneumonia, tuberculosis, HSV, PCP, etc.) and immunizations can cause increase in plasma HIV RNA for 2-4 weeks; viral load testing should not be performed

during this time. Plasma HIV RNA results should usually be verified with a repeat determination

before starting or making changes in therapy.

** Diagnosis of HIV infection made by HIV RNA testing should be confirmed by standard methods such as Western blot serology performed 2-4 months after the initial indeterminate or negative test.

Source: U.S. DHHS, Jan. 28, 2000.

Quantitative virology/Viral load assays: The HIV RNA level or “viral

load” is also of pivotal importance in assessing the HIV-infected patient.

Whereas the CD4 count indicates the current degree of immunosuppression, the Aoral load indicates the rapidity with which the disease is likely

to progress: higher viral loads have repeatedly been shown to be associated

with a more rapid rate of disease progression. (See Figure 4-2 on page 87.)

The most commonly used methods to quantify HIV RNA are RT- PCR,

bDNA, and NASBA techniques (see Viral Detection section above). Standard tests have lower Umits of detection of 400 copies/ml, but current

ultrasensitive assays can detect as few as 20 copies/ml. Although results of

different viral load assays correlate, absolute values differ and there is no

standard multiplication factor to translate between results in the different

assays. Therefore, the same assay should be used to follow an individual

patient longitudinally. Intra-person variability on viral load assays is < 0.5

log, but this degree of variability is important to consider when deterrnining

clinical significance of a reported change in viral load values for an individual patient.

Indications for plasma HIV RNA testing are shown in Table 4-1. It is also critical to repeat any HIV RNA result that is being used as the basis for a change in patient management.

90 us. DEPARniENT OF HEALTH AND HUMAN SERVICES, HEALTH RESOURCES AND SERVICES ADMINISTRATION, HTV'/AIDS BURE-VU
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

Hematology and Chemistry Panels: The effects of HIV and related

infections may involve hematologic, renal, or hepatic abnormalities. A complete blood count is necessary at baseline in order to evaluate for leukopenia, anemia, and thrombocytopenia. In addition, the total white count and

lymphocyte count are needed in order to calculate an absolute CD4 count.

A chemistry panel that includes an evaluation of renal and hepatic function

is also necessary: HIV-associated nephropathy may be indicated by elevations in BUN/creatinine, and the effects of viral hepatitis, alcohol, or medications may cause abnormalities of Uver function tests. Any of these

findings provide important information in their own right, but will also

have an impact on the patient’s options for antiretroviral therapy.

Other serologies: • Syphilis: High rates of co-infection with other STDs necessitate routine syphilis serology in all HIV-infected patients. A reactive non-treponemal assay (RPR or VDRL) must be confirmed with the

treponemal-specific FTA or MTPA. CSF evaluation is indicated in

HIV-infected persons with latent syphilis, treatment failure (when a non-treponemal test does not decline four- fold within 6—12 months

after treatment), and those patients with neurologic signs or symptoms. • Toxoplasmosis: Serologic evidence of latent toxoplasmosis infection,

as detected by Toxoplasma gondii IgG, may be relevant for decisions on

prophylaxis, evaluation of neurologic symptoms in patients with

advanced immunosuppression, and avoidance of exposure in those

who have not been previously infected. There is great worldwide variation in the prevalence of latent toxoplasma infection: in the U.S. the

rate is approximately 30%. • Cytomegalovirus (CMV): Latent CMV infection is present in the

majority of HIV-infected adults. Knowledge of CMV antibody status

is most useful in guiding the medical provider to the use of CMVnegative blood products if transfusions are required. • Varicella: In patients who do not have a known history of chicken

pox or of shingles, varicella serology should be obtained. The knowledge that a patient is varicella IgG-negative is important in the event

of a subsequent exposure: post-exposure prophylaxis with varicella

immune globulin could then be given. • Hepatitis: Hepatitis A serology is not routinely performed, but given

the newly available vaccine for those who are not immune, such testing

may be appropriate to determine vaccine candidates. Hepatitis B

serologies should be performed routinely: hepatitis B surface antigen

(HBsag) and hepatitis B core and surface antibodies (anti-HBc and

I anti-HBs) allow determination of active hepatitis (HBsag-positive) and

of those who are not immune to hepatitis B (anti-HBc-negative, antiHBs-negative). Hepatitis B vaccination is then recommended in those

who are not immune; and antiviral therapy, such as lamivudine (which

us. DeparTMent OF He,\lth and Human Services, Hilu.th Resourcf.s and Services Adminis-irmion, m\7.\IDS Bi rim 91
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l^rimarv Medical (iare

Table 4-2: Laboratory Tests for Hepatitis Viruses

Hepatitis Virus Laboratory Test Interpretation

A anti-HAV IgM recent HAV infection

anti-HAV IgG immunity to HAV

B Hbsag current (acute or chronic) HBV

infection

Hbeag current HBV infection with high risk of infectivity

anti-HBc past or present HBV infection

anti-HBs immunity to HBV (past infection or

after vaccination)

C anti-HCV IgG (ELISA) past or present HCV infection

anti-HCV IgG (RIBA) confirms HCV ELISA

HCV RNA current HCV infection

has anti-hepatitis B activity), can be considered in those who are Hbsag-positive. Hepatitis C serology (anti-HCV IgG) is also routinely

recommended. Recombinant immunoblot assays (RIBA) for HCV are

also useful: both to confirm the diagnosis if a screening ELISA is positive and to clarify it if a first generation ELISA test is negative. HCV

RNA, as detected by RT-PCR or bDNA assay, allows determination of

active HCV infection. Knowledge of hepatitis C antibody status is needed to guide therapeutic decision for possible HCV treatment, and

may also be relevant for decisions regarding antiretroviral therapy and

other potentially hepatotoxic agents, as well as frequency of assess- ment of LFTs during such therapy. (See Table 4-2)

Tuberculosis: A baseline PPD should be obtained in aU patients who do

not have a history of a positive PPD in the past.

G6PD: A relative deficiency of glucose-6-phosphate dehydrogenase may be

found in up to 2% of African-American women and an absoute deficiency

is occasionally found in women of Mediterranean descent. Absolute G6PD

deficiency predisposes to hemolytic anemia upon exposure to certain medications, including several that are commonly used in HIV treatment: dapsone, sulfonamides, primaquine. A relative deficiency is not usually clinically

significant. Baseline testing in selected patients is helpful so that these

agents may be safely administered at a later date without needing to determine G6PD levels at that point.

Lipid Profile: Many antiretroviral agents have been associated with the

development of hypertriglyceridemia and hypercholesterolemia. A baseline

fasting lipid profile should be performed to determine total cholesterol,

triglycerides, HDL, and LDL levels prior to the initiation of any antiretroviral therapy.

92 us. Department of Health and Hum.\n Services, Health Resources and Services Administrahon, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HW

Primary Medical Care

Table 4-3: Baseline Laboratory Evaluation

Summary: Baseline Laboratory Evaluation

j Confirm HIV diagnosis (usually with ELISA and Western blot)

j CD4 count

j Viral load

J Chemistry panel: including liver and renal function

J Hematology panel: including WBC differential

ij Lipid profile: total cholesterol, HDL, LDL, triglycerides

Serologies: Syphilis, Toxoplasmosis, CMV, VZV (if no history of chicken pox or

shingles). Hepatitis A, Hepatitis B, Hepatitis C

ij PPD

IJ G6PD (in selected patients)

(J Pap Smear/STD screening

Pap smear/STD screening: A Pap smear should be obtained, and testing

done for gonorrhea and Chlamydia.

C INTERVAL MONITORING

In an asymptomatic patient not on antiretroviral therapy with a high

(> 500/ mm’) CD4 count, follow-up every six months may be appropriate. For

those patients who are symptomatic and/or receiving antiretroviral therapy,

visits should occur at least every 3 months. For those who have just initiated or changed antiretroviral therapy, follow-up in 4—6 weeks may be appropriate.

Laboratory evaluation at each of these visits should routinely include the fol- lowing: complete blood count with differential, CD4 lymphocyte count, and

viral load. Chemistry panels may be done less frequently (every six months) in

a patient with prior normal values who remains clinically stable.

Hematology and chemistry values are needed to monitor possible medication toxicities, complications of HIV, and other possible illnesses. The CD4

count and viral load allow assessment of disease progression and effects of

antiretroviral therapy. In following the CD4 count over time, it is important to

recognize the causes of variability discussed above. Use of the CD4 percentage, rather than absolute CD4 count, may help eliminate some of this variability in order to clarify CD4 response to medications. In interpreting viral load

changes over time, the variability of tests results must be noted: .3-.5 log. In a patient who has previously had a viral load below the limit of detection of the

assay being used (“undetectable”), who now has quantifiable virus, a repeat

test should be performed as soon as possible, rather than waiting until routinely scheduled follow-up.

The frequency with which Upid profiles are checked will vary by individual

patient characteristics. In patients not taking antiretroviral therapy, a baseline

lipid profile should be done with the initial evaluation or prior to the initiation

of antiretroviral therapy. The profile should include total cholesterol, HDL,

LDL, and triglycerides. If the baseline is normal, there is no need for interval

us. Department OF Health and Hum/\n Services, Health RESouRCFii and Servicics ADMiNi.s-m.vnoN^HIV/AIDS Hi'ri .m 93
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Figure 4-3: Patient Intake Flow Sheet

Name Provider/Attending

History # D.O.B. Phone

Dates HIV+ AIDS AIDS Reported

1st Visit Psychosocial evaluation Immunizations

(dates)

Pneumovax dT (q lOyr)

Hep B

vaccine #1 #2 #3 G6PD

Serologies HBsAg HBsAb HCV Toxo CMV VZV

Year PPR

PPD

Pap smear

Ophtho exam

Flu vaccine

Advance Directives Family/Contacts Case Manager Home Care

Date Wgt CD4 RNA Antiretrovirals Other Meds Diagnoses, S/Es, Comments

Source: Johns Hopkins Outpatient HIV Clinic. Reprinted with permission.

94 us. Department of Health and Hum^\n Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

monitoring beyond that which would be done in an HIV uninfected adult. In

patients taking combination antiretroviral therapy, general guidelines are:

1

. get a baseline lipid profile (fasting) prior to initiation of therapy;

2. follow total cholesterol with routine chemistry panels;

3. obtain a complete fasting lipid profile annually or if the total cholesterol begins to increase on routine testing; and

4. follow complete lipid profiles every three—six months for patients in

whom a lipid abnormality has been detected, both prior to initiation of

any antihyperUpidemic therapy and once such therapy has been started.

Recommendations for management of hyperlipidemia may be found at http:/ /www.americanheart.org.

Annual monitoring of syphilis serology for reactivation or new infection is generally recommended. PPDs should also be checked annually.

Baseline data and interval monitoring may be followed by the use of a flow

sheet such as the one developed at the Johns Hopkins Outpatient HIV Clinic.

(Irigure 4-3)

IV. ANTIRETROVIRAL THERAPY

A. GENERAL PRINCIPLES

There are three characteristics of HIV infection that have significant implications for antiretroviral therapy:

1. between the time of initial infection and the development of clinical

disease there is progressive immunosuppression as evidenced by a decline in CD4 lymphocyte counts;

2. viral replication is extremely rapid: the half-life of HIV in plasma is

less than 48 hours and there is turnover of up to 1 billion virions per

day (Ho, 1995); and

3. HIV has a high degree of inherent genetic mutability: mutations that

may confer resistance to antiretroviral therapy arise rapidly.

Thus, there is a rationale for initiation of antiretroviral therapy prior to the onset of symptoms (i.e. to prevent immunosuppression), and therapy must

be maintained to prevent viral replication. Strategies of antiretroviral therapy

have therefore evolved to prevent the development of viral resistance. Although

monotherapy with any of the antiretroviral agents will increase

CD4 count, the clinical benefit of such therapy is very limited, largely due to the

development of viral resistance. Combination antiretroviral therapy has been

shown to have superior effectiveness in controlling viral replication and in limiting the emergence of resistant virus. These effects translate into greater clinical

benefit: combination therapy reduces the risk of HIV progression and of death.

In addition, patients with levels of circulating virus that are below 400—500

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copies/mL (the limit of detection in the past few years), but greater than 20-50

copies/mL (the limit of detection in the newest generation of tests) will experi- ence virologic failure sooner that those with viral loads that are below 20—50

copies/mL. (Raboud, 1998) Therefore, achievement of the lowest possible viral

load should be a guiding principle in tlie selection of a treatment regimen.

The specific combination of antiretroviral therapy selected for an individual patient needs to take into account many factors. These include the specific

side effects, dosing schedules, drug-drug interactions of different medications,

as well as prior history of antiretroviral therapy. See Chapter XIV on Pharmacologic Considerations in HIV-infected Pregnant Patients for information on

Hv\ART in pregnancy and Chapter XV on Resources for sources of complete

updated information on antiretroviral therapy.

B. ANTIRETROVIRAL AGENTS

Nucleoside Analogs

Nucleoside analog reverse transcriptase inhibitors (NRTIs) were the first class

of agents shown to be effective in the treatment of HIV infection. The target

enzyme for this group of drugs is HIV reverse transcriptase, an RNA-dependent DNA polymerase. (See Figure 4-4)

Figure 4-4: Sites of Action of Antiretroviral Agents

1. Site OF Action OF NRTIs: Incorporate into DNA

2. Site of Action ofNNRT/s: Bind to reverse transcriptase

3. Site of Action of Pis: Bind to protease to inhibit viral protein cleavage and

therefore release of virus from cell

HIV

RNA

Reverse

Transcriptase

Cell CD4 Cell Nucleus

DNA

HIV DNA incorporated

into cellular DNA

Protease

96 us. Di-;p.\rtment oi' Health and Human Services, Health Resources and Services ADMiNisnuvnoN, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

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Table 4-4: Nucleoside Analog Reverse Transcriptase Inhibitors

Generic Name Trade Name Standard Dosing Common Side Effects

zidovudine (AZT) Retrovir 200 mg tid or 300 mg bid

(2-6 pills/d)

anemia, nausea,

headache

didanosine (ddl) Videx 200 mg bid or 400 mg qd

(125 mg bid if < 60kg)

(4 pills/d)

Gl symptoms (diarrhea),

peripheral neuropathy,

pancreatitis

zalcitibine (ddC) Hivid 0.75 mg tid (3 pills/d)

peripheral neuropathy,

pancreatitis

stavudine (d4T) Zerit 40 mg bid

(30 mg bid if < 60kg)

(2 pills/d)

peripheral neuropathy,

pancreatitis

lamivudine (3TC) Epivir 150 mg bid

(2 pills/d)

headache

lamivudine/

zidovudine

Combivir 1 pill bid as for 3TC and ZDV

abacavir (ABC) Ziagen 300 mg bid

(2 pills/d)

hypersensitivity*, rash,

Gl symptoms

* 3-4% of patients will develop a hypersensitivity reaction to abacavir with symptoms that include

fever, rash, myalgias. Re-challenge with abacavir after development of a hypersensitivity reaction may be life-threatening, and should never be done.

There are six NRTIs currently licensed in the U.S.: zidovudine (AZT),

didanosine (ddl), zalcitibine (ddC), stavudine (d4T), lamivudine (3TC),

and abacavir. (See Table 4-4)

In addition to the side effects listed for each medication, lactic acidosis

with hepatic steatosis is a rare, but potentially life-threatening toxicity with the use of NRTIs.

Non-nucleoside Reverse Transcriptase Inhibitors

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) noncompetitively

inhibit HIV reverse transcriptase by binding to a site distant from the

enzyme’s active site. There are three NNRTIS currently available in the U.S.: nevirapine, delavirdine, and efavirenz. (See Table 4-5)

Table 4-5: Non-nucleoside Reverse Transcriptase Inhibitors

Generic Name Trade Name Standard Dosing Common Side Effects

nevirapine Virammune 200 mg qd x 14d,

then 200 mg bid

(2 pills/d)

Rash

delavirdine Rescriptor 400 mg tid (12 pills/d)

Rash

efavirenz Sustiva 600 mg qd

(qhs administration

may limit CNS side

effects)

(3 pills/d)

Headache, dizziness,

cognitive effects, rash

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Table 4-6: Protease Inhibitors

Generic Name Trade Name Standard Dosing Common Side Effects

saquinavir

(hard gel

capsules)

Invirase 600 mg tid (9 pills/d)

diarrhea, nausea,

abdominal discomfort

saquinavir

(soft gel

capsules)

Fortovase 1200 mg tid (18 pills/d)

diarrhea, nausea, abdominal discomfort

ritonavir Norvir 600 mg bid

(12 pills/d)

nausea, abdominal

discomfort, circumoral

paresthesias,

hypertriglyceridemia

indinavir Crixivan 800 mg q8h

(6 pills/d)

nephrolithiasis,

Gl symptoms

nelfinavir Viracept 750 mg tid (or 1250 mg bid)

(9-10 pills/d)

diarrhea

amprenavir Agenerase 1200 mg bid

(16 pills/d)

Gl symptoms, rash

Protease Inhibitors

Protease inhibitors (Pis) prevent maturation of Anrus protein by competitively

inhibiting HIV protease, an enz}-me essential for Antal protein cleaA^age. VTien

this enzyme is blocked, immature, non-infectious Anrus particles are produced.

The other important properties AA’hich protease inhibitors share include their

limited central nerA-ous system penetration, and their metabolism by the C}nochrome P450 enzyme system and resultant multiple drug-drug interactions.

(See Table 4-6)

In addition to the medication-specific side effects listed here, there are a number of abnormalities associated with protease inhibitors as a class. Patients

taking protease inhibitors may deA^elop serum lipid abnormalities (h}y>erlipidemia, hA’pertriglyceridemia), redistribution of body fat (lipodystrophy),

and/or glucose intolerance.

Lipodystrophy (Fat Redistribution Syndromes)

A dramatic increase in body shape changes has led some investigators to

belieA'e that some antiretroAtiral drugs may be associated Avith redistribution of

body fat as AA-eU. Protease inhibitors, which may certainly produce h}y)ertr}"glyceridemia, were the first agents associated Avith this syndrome, but other

drug classes haA’-e recently been implicated as well, such as the nucleoside ana- log d4T (staAmdine). HoweA-er, the etiolog}" of this syndrome (or syndromes) is unknoAAm. VCbmen seem particularly prone to deA^eloping truncal obesity

(increased abdominal girth, increased breast size). Some patients may primarily

lose subcutaneous fat in the face, buttocks and extremities, and a subset may

haA^e both fat loss and fat gain in different areas. Abnormal fatp" deposits,

which may be disfiguring, haAx been reported in the neck and the dorsocervti98 U.S. Der«tmest of Health and Human Sermces, Hem,th Resources ,\nd Serntces Administration, HIV/AIDS Bureau
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Primarv Medical Care

cal area (“buffalo hump”), although cortisol levels are normal. These body

shape changes may or may not be accompanied by the development of htyierlipidemia and/or diabetes mellitus. Our current level of understanding of

these syndromes and what causes them is fairly rudimentar}".

It may be useful to obtain some standard measurements, such as rninimum

waist, maximum hips and neck circumference at an early visit, before antiretroviral therapy is started. It is important to question the patient at regular intervals about any perceived changes in body shape or changes in clothing and

brassiere size, and anthropomorphic measurements may be repeated to document any changes. As yet there is no specific antidote to this poorly understood phenomenon.

Detailed descriptions of medications, drug-drug interactions, and medication use in pregnancy may be found in Chapter XIV on Pharmacologic Considerations in HIV-infected Pregnant Patients.

C TREATMENT GUIDELINES

The Department of Health and Human SerVces (DHHS) Panel on Clinical

Practices for Treatment of HIV Infection updates treatment guidelines on an ongoing basis. Updated recommendations are available at; http:/ /www.

hivatis.org. The guidelines detail indications for therapy in chronically

infected patients, recommendations for initial therapy, considerations for

changes in therapy, and possible regimens for such changes. (See Table 4-7)

Table 4- 7 : Indications for Initiation of Antiretroviral Therapy in

THE Chronically HIV-Infected Patient

CuNiCAL Category CD4 COUNT / HIV RNA Recommendation

Symptomatic Any Value Treat Asymptomatic CD4 < 500/mmi or HIV RNA > 10,000 (bDNA), or > 20,000 (RT-PCR)

offer treatment, with strength

of recommendation based on

prognosis for disease-free

survival and willingness of

patient to accept therapy

Asymptomatic CD4 > 500/mm^ and

HIV RNA < 10,000 (bDNA), or < 20,000 (RT- PCR)

many experts would delay

therapy and observe,

others would treat

Source: Adapted from DHHS Guidelines, Jan 28, 2000.

As indicated in this table, the strength of the recommendation for therapy

in an as}’mptomatic patient must take into account prognosis for disease- free

surxtival and the willingness of the patient to take, and adhere to therapy. (See

Chapter V on Adherence) Prognosis for disease-free surVval may be determined by utilizing the table in Table 4-8 (on the following page). In these considerations the potential benefits and risks of initiating therapy should be

considered and reviewed with the patient.

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Table 4-8: Risk of Progression to AIDS Defining Illness

IN A Cohort of Homosexual Men Predicted by

Baseline CD4 + T Cell Count and Viral Load’

CD4 ^350

Plasma Viral Load (copies/ml)^

% AIDS

(AIDS-defining complication)^

bDNA RT-PCR n 3 YEARS 6 YEARS 9 YEARS < 500 < 1,500 4 — — —

501 — 3,000 1,500 — 7,000 30 0 18.8 30.6

3,001 — 10,000 7,001 — 20,000 51 8.0 42.2 65.6

10,001 — 30,000 20,001 — 55,000 73 40.1 72.9 86.2 > 30,000 > 55,000 174 72.9 92.7 95.6

CD4 351 — 500

Plasma Viral Load (copies/ml)

% AIDS

(AIDS-defining complication)

bDNA RT-PCR n 3 YEARS 6 YEARS 9 YEARS < 500 < 1,500 — — — —

501 — 3,000 1,500 — 7,000 47 4.4 22.1 46.9

3,001 — 10,000 7,001 — 20,000 105 5.9 39.8 60.7

10,001 — 30,000 20,001 — 55,000 121 15.1 57.2 78.6 > 30,000 > 55,000 121 47.9 77.7 94.4

CD4 > 500

Plasma Viral Load (copies/ml)

% AIDS

(AIDS-defining complication)

bDNA RT-PCR n 3 YEARS 6 YEARS 9 YEARS

< 500 < 1,500 110 1.0 5.0 10.7

501 — 3,000 1,500 — 7,000 180 2.3 14.9 33.2

3,001 — 10,000 7,001 — 20,000 237 7.2 25.9 50.3

10,001 — 30,000 20,001 — 55,000 202 14.6 47.7 70.6 > 30,000 > 55,000 141 32.6 66.8 76.3

' Data from the Multi-Center AIDS Cohort Study (MACS). (Mellors, 1996)

^ MACS numbers reflect plasma HIV RNA values obtained by bDNA testing. RT-PCR values are consistently 2 - 2.5 fold higher than bDNA values, as indicated.

^ In this study AIDS was defined according to the 1987 CDC definition and does not include asymptomatic individuals with CD4-I- T cells < 200mm^

‘ Too few subjects were in the category to provide a reliable estimate of AIDS risk. Source: U.S. DHHS, Jan. 28, 2000.

Among the benefits of therapy are: prevention of progressive immunosuppression by control of viral

load;

delayed progression of clinical disease/progression to AIDS;

prolongation of Ufe; and

possible decreased risk of transmission. (Quinn, 2000)

The risks of initiation of therapy include:

a decrease in quahty of life associated with adverse drug effects and

inconvenience of dosing;

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limitations of future options for therapy if resistance develops to current agents;

unknown long-term toxicity of therapy;

unknown duration of effectiveness of therapy; and

possible transmission of drug-resistant virus.

Recommendations for Initial Treatment Regimens

Recommendations for antiretroviral treatment continue to evolve with the

development of new medications and additional data from clinical trials. The

most recent guidelines from the DHHS are shown in Table 4-9 on the following page.

Although these guidelines illustrate generally recommended regimens, nonspecialists should consider expert consultation regarding initiation of a specific

regimen whenever there is any question about patient management.

The regimens Listed in the preferred category are all considered highly

active antiretroviral therapy or HAART. Although there are multiple possible

1 1 AART regimens, a comparison of several different example regimens will

illustrate the principles used in selecting a regimen for a specific patient.

One possible HAART regimen is: AZT + 3TC + nelfinavir. This regimen

could all be taken on a twice-daily basis, which may help with adherence, and

the total pill burden is moderate: AZT and 3TC may be taken in combination

as Combivir (1 pill bid) and nelfinavir requires 5 pills twice a day. In a patient

with significant bone marrow suppression, the provider may wish to avoid

AZT, and might instead select ddl + d4T + nelfinavir or d4T + 3TC+ nelfinavir. It is also possible to take a HAART regimen that does not utilize a protease inhibitor, such as: 2 NRTIs and efavirenz. In this example, the piU

burden is lower than with Pl-containing regimens (efavirenz is taken as 3 pills once a day), reductions in viral load are comparable to those with Pl-containing regimens, and the potential class-specific side effects of protease inhibitors

(e.g. lipid abnormalities) may be avoided, but the long-term effectiveness of an NNRTI-based regimen has been less well studied.

In addition to regimens designated as HAART, there may be instances in

which alternative regimens are utilized. Such situations may occur, for example, when a patient states that she will only take a limited number of pills a day. Options for alternative regimens include AZT + 3TC + Abacavir. This

regimen only requires 4 pills a day (Combivir bid, abacavir bid) and utilizes

only NRTIs thus preserving both the NNRTIs and Pis for future regimens.

Another possible alternative regimen containing only NRTIs is ddl + hydrox3mrea, with or without a second NRTI. Hydroxyurea is not incorporated into

most standardized guidelines, and has no antiretroviral activity on its own, but

has been shown to increase the efficacy of ddl. It has most commonly been

used in patients who have exhausted all standard regimens. There are recent

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Table 4-9: Recommended Antiretroviral Agents for Initial

Treatment of Established HIV Infection

This table provides a guide to the use of available treatment regimens for individuals with no prior or limited experience on HIV therapy. In accordance with

the established goals of HIV therapy, priority is given to regimens in which clinical

trials data suggest the following: sustained suppression of HIV plasma RNA

(particularly in patients with high baseline viral load) and sustained increase in CD4+ T cell count (in most cases over 48 weeks), and favorable clinical outcome

(i.e. delayed progression to AIDS and death). Particular emphasis is given to regimens that have been compared directly with other regimens that perform

sufficiently well with regard to these parameters to be included in the "strongly

recommended" category. Additional consideration is given to the regimen's pill burden, dosing frequency, food requirements, convenience, toxicity, and drug

interaction profile compared with other regimens.

It is important to note that all antiretroviral agents, including those in the 'Strongly

Recommended' category, have potentially serious toxic and adverse events

associated with their use. The reader is strongly encouraged to consult Chapter XIV on Pharmacologic Considerations in HIV-infected Pregnant Patients while

formulating an antiretroviral regimen.

Antiretroviral drug regimens are comprised of one choice each from

columns A and B. Drugs are listed in alphabetical, not priority order. Column A Column B

Strongly Recommended Efavirenz Stavudine -i- Lamivudine

Indinavir Stavudine -I- Didanosine

Nelfinavir Zidovudine -I- Lamivudine

Ritonavir -I- Saquinavir Zidovudine -i- Didanosine

(SGC* or HGC*)

Column A Column B

Recommended as an Abacavir Didanosine -I- Lamivudine

Alternative Amprenavir Zidovudine -I- Zalcitabine

Delavirdine

Nelfinavir -I- Saquinavir-SGC

Nevirapine

Ritonavir

Saquinavir-SGC

No Recommendation; Hydroxyurea in combination with other

Insufficient Data** antiretroviral drugs

Ritonavir + Indinavir

Ritonavir -i- Nelfinavir

Column A Column B

Not Recommended; Saquinavir-HGC^ Stavudine -i- Zidovudine

Should Not Be Offered Zalcitabine -l- Lamivudine

(All monotherapies whether

Zalcitabine + Stavudine

from column A or B***)

Zalcitabine -i- Didanosine

* Saquinavir-SGC, soft-gel capsule (Fortovase): Saquinavir-HGC, hard-gel capsule (Invirase). ** This category includes drugs or combinations for which information is too limited to allow a recommendation for or against use. *** Zidovudine monotherapy may be considered for prophylactic use in pregnant women with low viral load and high CD4 -f- T cell counts to prevent perinatal transmission, as discussed in Chapter VII on HIV and Reproduction.

' Use of Saquinavir-HGC (Invirase) is not recommended, except in combination with ritonavir.

Source: U.S. DHHS, Jan. 28, 2000.

US. DepartmisNT of He.\lth and Human Services, Heai.th Resources and Services Administr,\tion, HIV/AIDS Bureau
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concerns, however, about enhanced NRTI toxicity with hydroxyurea that may

cause serious, and even life-threatening, pancreatitis. The role of hydroxyurea

will likely be better defined after additional safety information is available.

Recommendations for Antiretroviral Therapy in the

Treatment-experienced Patient

'file need for a change in antiretroviral therapy most commonly arises in two

situati(jns: medication toxicity and lack of therapeutic efficacy.

1 . When the need to change therapy arises due to medication toxicity, it may be possible to simply change one component of a regimen. If the

toxicity occurs in a regimen that has provided effective virologic control,

the goal would be to continue effective therapy by changing the component that causes toxicity. For example, in a patient taking an effective

regimen of AZT/3TC/PI, the development of anemia could be attributed to AZT. A different NRTI that does not commonly cause bone

marrow suppression (e.g. d4T) could be substituted. The similar toxicities of certain agents must be remembered when making such changes:

for example, in a patient taking ddl, the development of peripheral neuropathy, would not be expected to be alleviated by substituting d4T.

There are other situations in which the toxicity is not as easily attributed to a single component of a regimen (e.g. rash, GI symptoms). In

these instances, a “drug hoUday” (temporary discontinuation) of the

entire regimen may be necessary to allow symptoms to resolve, and a new regimen initiated with some change in components. With the

exception of abacavir, which has caused hypersensitivity reactions

(and should never be re-instituted after symptoms of such a reaction),

re-initiation of antiretroviral therapy would not be expected to be

associated with any increase in side effects.

2. Changes in regimen for lack of efficacy may be triggered by evidence

of clinical progression, progressive decline in CD4 count, and, most

commonly, for virologic “failure.” Virologic failure is apparent when a regimen has failed to provide suppression to below the level of assay

detection in 4—6 months after initiation, or when a patient with previously undetectable virus has a rebound to detectable levels. In these cir- cumstances, (i.e. where viral load values will be used to determine a change in patient management), the test should always be repeated

before a regimen change is made. Although some patients may derive

continued clinical benefit and a sustained CD4 increase despite a detectable viral load, the possibility of development of viral resistance

should lead the clinician to consider a change in regimen. The fact that

continued exposure to an ineffective regimen will allow continued \aral

replication, and therefore the opportunity for development of additional resistance mutations, provides a rationale for changing therapy in

this situation. Increased viral resistance may also lead to cross-resistance

to other drugs in the same medication class, and therefore lower

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chances of effectiveness of any future regimen. It is particularly important that the clinician use caution in this setting to avoid changing to an even more complicated regimen in a patient who is demonstrating virologic failure due to difficulty with adherence. (See Chapter V on Adherence) In some circumstances, (e.g. prior exposure to multiple

medications) it may not be possible for the clinician to constmet a new

regimen diat is effective, and some experts choose to continue a virologically failing, but weU-tolerated, regimen under these circumstances

When a regimen is changed for lack of efficacy, the goal is to use medications which are “new” to the patient to decrease the likelihood

of viral resistance. A general principle is that all medications should be

changed at the same time, and that a minimum of two new agents be

utilized. If there are two previously unused NRTIs that can be used

together, these should be part of a new regimen. There is significant

cross-resistance among NNRTIs, although efavirenz may sometimes

be used after delavirdine or nevirapine, depending on which mutations

have arisen; only resistance testing will enable the clinician to know

when this is possible. If an NNRTI was not used initially, it would be

beneficial to include one in a second regimen. For Pis, there are some

resistance mutations which are common to several agents in the class,

and others which may be distinct for an individual agent. In general, it

is has proven more effective to salvage a failing PI regimen, by using a second regimen that contains a combination of two new Pis, rather

than just substituting one PI for another. (Hall, 1999; Tebas, 1999)

Recommendations for regimen changes may also be found at: http:/ /www.hivatis.org. Testing for resistance mutations may also

be a crucial factor when deciding on a regimen change. (See “Resistance Testing” below)

“Intensification” is a concept that some patients with a decrease in

viral load, but not complete viral suppression, from an initial regimen

may benefit from the early addition of just a single new agent. This

may also refer to the situation where a first rebound occurs after complete viral suppression. In these patients, low levels of detectable virus

(e.g. < 5000 c/mL) are present. This may be a unique situation where

it may be reasonable to add only a single medication, or to change only

a portion of the combination. However, it is important to realize that

Table 4- 10 : Indications for Consideration of Change in Therapy

Failure to suppress HIV RNA to undetectable levels within 4-6 months of initial therapy

Repeated detection of virus after initial suppression to undetectable levels Increase (^3X) from lowest HIV RNA (not due to other factors such as intercurrent

illness, vaccination)

Medication side effects/toxicity

May also consider with: persistently declining CD4 counts and/or clinical deterioration

U.S. Df.partment of Health and Human Services, Health Resources and Services ADMiNisTR,vnoN, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

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at the present time “intensification” represents an unproven hypothesis

that is being evaluated in ongoing clinical trials. A summar}^ of situations in which a change of therapy should be

considered is shown in Table 4-10.

Resistance Testing

T'here are nvo main techniques to assess the development of viral resistance to

antiretroviral therapy. Phenop^ic assays directly determine the amount of a medication required to inhibit HIV. These assays are not yet licensed for clinical

use, and commercial availabilip^ is limited. Genotypic assays determine changes

in the nucleotide sequences of the genes that code for the protease and reverse

transcriptase en;^ymes. Interpretations of genotypic results require knowledge

of which specific changes are associated with resistance. Results are reported as

a string of three pieces of information or each mutation detected:

1 . wild-p'pe amino acid;

2. codon involved; and

3. amino acid coded for by mutated codon.

Figure 4-5 on the following page shows the mutations known to be associated with resistance to specific agents. (Hirsch, 1998) Updated listings of

mutations and associated resistance can be found at: http:/ /hiv-web.lanl.gov

or http:/ /WWW.viral-resistance.com.

Both phenoppic and genotypic assays are difficult to perform if the viral

copy number is less than 1000 c/ml. Their utility is also limited by an inability to detect resistant virus that makes up less than 20% of the total viral burden

in a sample. It is also critical to recogni2e that these assays will only reliably

detect mutations conferring resistance to medications the patient is taking at the time the assay is performed: samples from patients who are off therapy at the time of resistance testing are Ukely to show reversion to wild-type

(sensitive) virus as the predominant circulating viral strain. Thus, resistance test- ing is insensitive to mutations secondary to selective pressure that is no longer

present after a change in regimen. Virions with these mutations likely stiU exist

as a small percentage of circulating virus and may lead to cUnical resistance if inactive drugs that test “sensitive” but are vulnerable to these resistance mutations are used; current assays will not detect their presence. A comparison of

genotypic and phenotypic assays is shown in the Table 4-11 on page 105.

At least two studies have shown that patients for whom genotypic analysis

is done prior to a change in antiretroviral therapy have a better virologic

response to the new regimen than do patients in whom a change in therapy is based soley on antiretroviral history. (Durant, 1999; Baxter, 1999) Resistance

testing may be useful in:

1. assessing NRTI resistance/cross-resistance in patients with virologic

failure on a NRTI-containing regimen (e.g., to look for mutations associated with pan-NRTI-resistance)

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Figure 4-5: Mutations Associated with Resistance to Specific

Agents

NRTls

AZT

ddl

ddC

3TC

d4T

4l|r70 210 1

II 219

215

65 L

|74 184

65 1 1 174

69

75

184

184 I

ABC 62

Muftipie NRTls

74 115 184

103

Pis

RTV

SQV 10

10 20 24 CO CNI 54 63 71| I 7382I 84 90

20 32 36 46 54 63 71 00 90

33

1 _ d[54T63 71 7382 84 bo

NFR 301361 46 63 71 77 84 90 1 88

APV 10 46 50 84

47

Mutations in the reverse transcriptase and protease genes that have been

associated with drug resistance are depicted above. Bold lines represent

major mutations, while thin lines indicate secondary mutations. Dotted

lines represent mutations that have been identified in vitro though have

not been associated with resistance in clinical isolates. Resistance

mutations, along with more complete sequencing data, can be found at http://www.viral-resistance.com and at http://hiv-web.lanl.gov.

Source: Erbelding, 1999. (Adapted from JAMA 279(24) 1984-91, June 24,1998.)

106 us DE7.utno.T OF He.\lih .O.T) Seimces, He-Uth Resocsces -vnd Sei\tces .Mwonistratjon, Hn'/AIDS Bcee-u:
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Table 4-11: Comparison of Genotypic and Phenotypic Assays

Type of Assay Advantages Disadvantages

Genotypic easier to perform more widely available more rapid

only measures susceptibility

indirectly

prior knowledge of mutations

associated with resistance

required

must have HIV RNA

> 1000 c/ml

will not detect mutations if in less than 20% of total viral particles

Phenotypic measures susceptibility

directly

allows assessment of

cross-resistance

complex assay: harder to perform, slower time to

results, and less widely

available

must have HIV RNA

> 1000 c/ml

will not detect mutations if in less than 20% of total

viral particles

clinically significant breakpoints for susceptibility/

resistance not yet defined

2. Assessing cross-resistance betu’een NXRTIs

3. defining presence/ extent of PI resistance in those with virologic failure

on a Pl-containing regimen

4. determining if there is drug-resistance in a patient with acute HR" w'ho

is considering antiretro^iral therapy. (See “Treatment of Acutre

Infection” below.)

Patients with pan-sensitive ^irus in the face of virologic failure should

be questioned carefully, but non-judgmentaUy, about their medicationtaking behaviors.

D. TREATMENT OFACUTE HIVINFECTION

In order to be able to consider treatment of acute HR^ infection, the clinician

must first recognixe its presence. In more than half of aU patients who

acquire HR^ infection, there are clinical symptoms two to six wrecks after

the exposure. The symptoms van* in severit}', but commonly include fever,

h-mphadenopathy, fatigue, rash, myalgias, and phanmgitis — a symptom complex that mimics mononucleosis. HR^ antibodies will not yet be present at this

point, but techniques that detect \iral nucleic acids (see “Initial Diagnosis”

above) wiU confirm the diagnosis: a negative or indeterminate antibody test in

conjunction with a positive HR^ RNA or HR^ DNA test is diagnostic of

acute HR^ infection. It is important to note, how^ever, that a low level of HR'

RNA (e.g. < 5000 c/ml) may be a false positive result, and should be repeated.

U.S. Der\rtment of He-Uth .vnd Hum.\n Sermces, He-U-TH Resoi-rces -Vnd Services .\dminl-tr.\tion. HI\' \IDS B< 107
\ Ck iDi: 111 rm Ci.isu \i. Cark oi W'omi.n with H1 \’

Frimarv Medical Care

(Rich, 1 999) In addition, an HIV DNA assay could be performed to clarif)’ the

diagnosis: this should almost always be positive in an infected person, regardless of RNA level. Relatively recent infection may also be diagnosed in a patient with negative HIV serologies in the previous 6—9 months and a first positive result, even in the absence of a seroconversion syndrome.

The benefits of treating acute HIV infection are not completely defined.

The rationale for early treatment is that there will be early suppression of

Airemia, which may preser\'e CD4 cell number/ function including HIV-specific CD4 cells. There are also risks associated with early treatment: these

include the toxicities of the medications used and the possibility of the early

development of resistance. These unanswered questions about risks and benefits of early therapy should be addressed with the patient; enrollment in clini- cal trials and obsen^ational studies of acute HIV should be considered. In

treating acute HW, it is always important to use a three- or four-drug regimen

that w’ould be expected to proAtide complete Atiral suppression. In addition,

after considering the source of exposure and local epidemiologic information,

genotA’pic resistance testing may proA^e useful in this setting. In acute HIV

infection, the patient’s predominant Aims will be the strain that AA^as transmitted, without reA'ersion to the AAild-tAq>e (pan-sensitiA^e) Aims seen in chronically

infected patients \A^ho haA^e stopped treatment. The potential risks and benefits

of treating acute HIV are summari2ed in Table 4-12.

Table 4- 12 : Risks and Benefits of Early Initiation of

Antiretroviral Therapy in the Asymptomatic

HIV-Infected Patient

Potential

Benefits

Control of viral replication and mutation; reduction of viral burden

Prevention of progressive immunodeficiency; potential maintenance

or reconstruction of a normal immune system

Delayed progression to AIDS and prolongation of life Decreased risk of selection of resistant virus

Decreased risk of drug toxicity

Possible decreased risk of viral transmission

Potential

Risks

Reduction in quality of life from adverse drug effects and

inconvenience of current maximally suppressive regimens

Earlier development of drug resistance

Transmission of drug resistant virus

Limitation in future choices of antiretroviral agents due to development of resistance

Unknown long term toxicity of antiretroviral drugs

Unknown duration of effectiveness of current antiretroviral therapies

Source: U.S. DHHS, Jan. 28, 2000.

Post-exposure Prophylaxis

See Chapter XIII on Occupational Exposure.

U.S. Deructment of He_\lth ,\.st) Sermces, He-Uth Resources .\nd Services Administr-vtion, HIAV-AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

Treatment in Pregnancy

( iukldincs for optimal antiretroviral therapy in pregnancy are the same as those for non-pregnant adults. (See above) Particular concerns for fetal exposure to medications and for strategies to reduce the risk of viral transmission

must also be considered. Please see Chapter VII on HIV and Reproduction.

Information is also provided at: http://www.hivatis.org.

Immune-Based Therapy

'Therapy to augment the immune response to HIV may be possible through

the use of HIV vaccines or cytokines, such as interleukin-2. Such strategies to

enhance the control of HIV already provided by antiretroviral medications are being assessed in clinical trials, but are not part of current standard care.

Alternative/Complementary Therapy

Some patients may present with knowledge or questions about alternative or complementar}^ therapy, or may indicate that they are already taking such therapy. Specific complementar)’^ therapies change rapidly, and their use varies

widely with geography and patient demographics. For patients who do choose

such therapies it is important to make sure that agents that have overlapping

toxicides with a patient’s prescribed therapy are avoided, and that discussions

of alternative therapy are held in way that does not alienate the patient from

her involvement in medical care.

V. COMPLICATIONS: OPPORTUNISTIC DISEASES

The risk for various opportunistic processes — so called because they take

advantage of patients with a weakened immune system — is defined by the

total CD4 lymphocyte count. They include opportunistic infections (OIs) and

certain malignancies, and are similar to the diseases seen in other immunocompromised hosts such as recipients of soUd organ transplants. In fact,

AIDS was first recognized as a new entity by the characteristic pattern of

opportunistic diseasess — especially pneumocystis pneumonia and Kaposi’s sarcoma — that were being diagnosed in young, previously healthy gay men. The pattern and sequence of OIs that are seen as the total CD4 cell count

decreases is so reliable that in most cases the total CD4 cell count limits the

differential diagnosis. (See Table 4-13)

At total CD4 cell counts above 500, illnesses are rarely specifically associated

with the patient’s HIV serostatus. Non-Hodgkin’s lymphoma (NHL) and mucocutaneous KS are occasional exceptions; they can occur at varying CD4 cell counts, but are more frequently diagnosed at lower values. Infections that are virulent among HIV-seronegative individuals, such as tuberculosis and bacterial

pneumonia, may of course occur at any CD4 cell count but are increasingly

more common and more severe as the CD4 count declines. Between 200-500

us. Dep,\rtment of Health and Human Services, Health Resources and Services Admini.str.vtion, HIV/.\IDS Buru.mi 109
A Guini', TO rill' (j.inicai. (^akI'I oI' WomivN wi iii HIV

Primary Medical Care

Table 4-13: Correlation of Complications with CD4 Cell Counts

CD4 CELL COUNT* Infectious Complications Non-infectious" complications > 500/m Acute retroviral syndrome

Candidal vaginitis

Persistent generalized

lymphadenopathy (PGL)

Guillain-Barre syndrome

Myopathy

Aseptic meningitis

200-500/mm' Pneumococcal and other

bacterial pneumonia

Pulmonary TB

Herpes zoster Thrush

Candidal esophagitis

Cryptosporidiosis,

self-limited

Kaposi's sarcoma

Oral hairy leukoplakia

Cervical intraepithelial

neoplasia

Cervical cancer

B-cell lymphoma

Anemia

Mononeuronal multiplex

Idiopathic thrombocytopenic

purpura

Hodgkin's lymphoma

Lymphocytic interstitial pneumonitis < 200/mm' R carinii pneumonia

Disseminated/chronic

Herpes simplex

Toxoplasmosis

Cryptococcosis

Disseminated

histoplasmosis and

coccidioidomycosis

Cryptosporidiosis, chronic

Microsporidiosis

Miliary/extrapulmonary TB

Progressive multifocal

leukoencephalopathy (PML)

Candidal esophagitis

Wasting

Peripheral neuropathy

HIV-associated dementia

CNS lymphoma

Cardiomyopathy

Vacuolar myelopathy

Progressive polyradiculopathy

Immunoblastic lymphoma

< 50/mm' Disseminated CMV

Disseminated M. avium

complex

* Most complications occur with increased frequency at lower CD4 counts. ** Some conditions listed as "Non-infectious" are probably associated with transmissible microbes: examples are lymphoma (EBV) and cervical canver (HPV). Source: Bartlett, 1999. (Adapted from Arch Intern Med 1995; 155: 1537.)

cells, less serious HIV-associated problems begin to manifest themselves, such as oral hairy leukoplakia, various skin problems, shingles and oral or vaginal candidiasis (thmsh). Candida vaginitis, which is also common among women who

do not have HIV, may be the first indication of HIV infection. (Imam, 1990)

According to the 1993 version of the CDC case definition, AIDS may be

defined by a number of serious opportunistic illnesses or by a decline in the

total CD4 cell count below 200. (See Table 1-3 in Chapter I.) This CD4 ceU

count criterion acknowledges an important threshold for OI risk. Pneumocystis

us. Department of Health and Human Service-s, Health Resources and Services Administrahon, HIV/AIDS Burf„\u
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Priman' Medical Care

carinii pneumonia (PCP), the most common AIDS-defining OI and leading cause of death, is usually diagnosed as patients approach and drift below this

critical number of total CD4 cells. Other OIs, such as toxoplasmosis, cn^ptococcal meningitis and disseminated histoplasmosis, tend to occur as the CD4

cell count declines from less than 200 to below 100 cells. T)^icaUy, end-stage

illnesses such as CNS lymphoma, CMV end-organ disease and disseminated

.MAC, tend to occur at verj’ low CD4 cell counts, often less than 25 cells.

Antimicrobial therapy works in concert uith the individual’s immune sys- tem to clear infection. Before the advent of potent combination antiretro^tiral

therapy, HIV-associated opportunistic diseases could not be controlled without

ongoing suppressive therapy, because the patients’ immune function was too

weak to effect that control. Once an OI was diagnosed and treated acutely

(“induction” therapy, borrowing from the language of oncologt"), treatment

would be continued at lower “maintenance” levels or the OI would ine\itably

recur. “Cure” of OIs w"as not part of the vocabular}- of HIV disease management. With potent combination antiretro\iral therapy resulting in dramatic

improvement in CD4 cell counts and immune function, both prophylactic and

chronic suppressive therapies are being withdrawn successfully in responders.

This has opened an entirely new era in the care of people with advanced HIV

(\ide infra).

A. OI PROPHYLAXIS

One of the early significant advances in the management of HIV/AIDS was

the demonstration that chemoprophylaxis could prevent PCP and thereby

improve sur\ival. Prior to the development of potent combination antiretro\iral therapy an important focus of the clinical research effort was to identify

effective prophylactic agents for the other common OIs. The success of this

research w^as in part responsible for the slowing of the death rate from AIDS

that w’as first apparent near the end of 1995, just before the era of potent

combination antiretro\iraI therapy began. Recommendations for prophylaxis

for specific OIs depend on a number of factors: the CD4 threshold that

defines the greatest risk, the overall effectiveness of a given approach, the risk

of resistance development, the presence of pregnancy, toxicity and cost. The

USPHS/IDSA guidelines for OI prophylaxis are updated periodically to

reflect the most current understanding of disease risk and prevention. (Current recommendations for initiating OI prophylaxis can be found at http://www.hivatis.org, or in 1999 Medical Management ofHIVInfection by

John Bartlett, listed in the Resources Appendix.) (USPHS, 1999)

B. PRESENTATIONAND MANAGEMENT OF THE MOST

COMMON COMPLICATIONS OFADVANCED HIV

DISEASE (AIDS)

Summaries are presented below. However, specific agents and dosing regimens

for acute conditions and secondaty opportunistic infection prophylaxis.

us. Dep.\rtment of He.\lth .\nd Hum.\n Sermces, He.\lth Resource.*; .\nd Sermces .\D.MiNi;rrR.\TioN. HI\7AIDS Burf.m 111
A C'.uioi' ro Till' Ci.iNiCAi. (L\rI' oI' Womhn wri'ii HIV

Primary Medical Care

respectively, can be found at http:/ /www.hivatis.org, or in the 1999 Medical

Management ofHIVInfection by John Bartlett. See Table 4-14 for primary prophylaxis of the most common OIs.

Table 4- 14 : Prophylaxis to Prevent First Episode of Opportunistic

Disease in Adults and Adolescents Infected with

Human Immunodeficiency Virus

Pathogen

Preventive Regimens

Indication First Choice Alternatives

/. Strongly Recommended As Standard of Care

Pneumocystis

carinii'

CD4-I- count < 200/(1 L or oropharyngeal

candidiasis

Trimethoprimsulfamethoxazole

(TMP-SMZ), 1 DS

po q.d. (Al)

TMP-SMZ, 1 SS po

q.d. (Al)

Dapsone, 50 mg po

b.i.d. or 100 mg po

q.d. (Bl); dapsone,

50 mg po q.d. plus

pyrimethamine, 50

mg po q.w. plus

leucovorin, 25 mg

po q.w. (Bl); dapsone, 200 mg

po plus

pyrimethamine, 75

mg po plus

leucovorin, 25 mg

po q.w. (Bl); aerosolized

pentamidine, 300

mg q.m. via

Respirgard IITM nebulizer (Bl); atovaquone, 1500

mg po q.d. (Bl); TMP-SMZ, 1 DS po

t.i.w. (Bl)

Mycobacterium

tuberculosis

Isoniazid-sensitive^

TST reaction

>5mm

or prior positive

TST result without

treatment or contact with case of active

tuberculosis

Isoniazid, 300 mg

po plus pyridoxine,

50 mg po q.d. x 9

mo (All) or

isoniazid, 900 mg

po plus pyridoxine,

100 mg po b.i.w. x

9 mo (Bl); rifampin,

600 mg plus pyra- zinamide, 20 mg/kg

po q.d. X 2 mo (Al)

Rifabutin 300 mg

po q.d. plus

pyrazinamide, 20

mg/kg po q.d. x 2 mo (BIN); rifampin

600 mg po q.d. x 4

mo (Bill)

Isoniazid-resistant Same; high

probability of

exposure to isoniazid-resistant

tuberculosis

Rifampin 600 mg

plus pyrazinamide,

20 mg/kg po q.d. x

2 mo (Al)

Rifabutin, 300 mg

plus pyrazinamide

20 mg/kg po q.d. x

2 mo (Bill); rifampin, 600 mg po

q.d. X 4 mo (Bill); Rifabutin, 300 mg

po q.d. X 4 mo (CHI)

Table continues . . .

us. Department of Health and Human Services, Health Resources and Services Administra-hon, HIV/AIDS Bureau
A Guide TO THE Clinical Care of Women with HIV

Primary Medical Care

Table 4-14: Prophylaxis to Prevent First Episode of Opportunistic

Disease in Adults and Adolescents Infected with

Human Immunodeficiency Virus (continued)

Pathogen

Preventive Regimens

Indication First Choice Alternatives

Multidrug-(isoniazid

and rifampin)

resistant

Same; high

probability of

exposure to multidrug-resistant

tuberculosis

Choice of drugs

requires

consultation with

public health

authorities

None

Toxoplasma gondiT IgG antibody to Toxoplasma and

CD4-I count

<100/|tL

TMP-SMZ, 1 DS po

q.d. (All) TMP-SMZ, 1 SS po

q.d. (BIN): dapsone,

50 mg po q.d. p/«s

pyrimethamine, 50

mg po q.w. plus

leukovorin, 25 mg

po q.w. (Bl); ato- vaquone, 1500 mg

po q.d. with or without pyrimethamine, 25 mg po q.d.

plus leukovorin, 10

mg po q.d. (CHI)

Mycobacterium

avium complex'’

CD4-I count

<50/pL

Azithromycin,

1,200 mg po q.w.,

(Al) or clarithromycin, 500

mg po b.i.d. (Al)

Rifabutin, 300 mg

po q.d. (Bl); azithromycin, 1,200

mg po q.w. plus

rifabutin, 300 mg

po q.d. (Cl)

Varicella zoster

virus (VZV)

Significant ex- posure to chickenpox or shingles for

patients who have no history of either

condition or, if available, negative

antibody to VZV

Varicella zoster immune globulin

(VZIG), 5 vials (1.25

mL each) im,

administered <96 h

after exposure,

ideally within 48 h

(AMI)

//. Generally Recommended

Streptococcus

pneumoniae^

All patients Pneumococcal

vaccine, 0.5 mL im

(CD4-I >200/pL

[Bll]; CD4+

< 200/p L [Clll])- might reimmunize if initial immunization was given when

CD4-I <200/pL and

if CD4-I increases

to > 200/p L on

HAART(CIII)

None

Hepatitis B virus® All susceptible

(anti-HBc-negative)

patients

Hepatitis B vaccine:

3 doses (Bll) None

Table continues . . .

us. Department of Health and Human Services, Health Resources and Servicrs ADMiNisncvnoN, I ll\7AIDS Ruri-..\i 113
A CiiiiDi' IX) ini': Ci.iNic.u. C\m- oi' Womi:n vvnii HIV

Primary Medical Care

Table 4-14 Prophylaxis to Prevent First Episode of Opportunistic

Disease in Adults and Adolescents Infected with

Human Immunodeficiency Virus (continued)

Pathogen

Preventive Regimens

Indication First Choice Alternatives

Influenza virus® All patients

(annually, before

influenza season)

Whole or split

virus, 0.5 mL im/yr

(BIN)

Rimantadine, 100

mg po b.i.d. (Clll), or amantadine, 100

mg po b.i.d. (Clll)

Hepatitis A virus® All susceptible

(anti-HAV-negative)

patients with

chronic hepatitis C

Hepatitis A

vaccine: two doses

(Bill)

None

///. Not routinely indicated

Bacteria Neutropenia Granulocytecolony-stimulating

factor (G-CSF), 5-10

pg/kg sc q.d. x 2-4

w or granulocytemacrophage

colony-stimulating

factor (GM-CSF),

250 pg/m^ iv over 2 h q.d. X 2-4 w (Cll)

None

Cryptococcus

neoformans’

CD4h- count

<50/pL

Fluconazole, 100-

200 mg po q.d. (Cl) Itraconazole, 200mg po q.d. (Clll)

Histoplasma

capsulatum’

CD4-F count

<100/pL, endennic

geographic area

Itraconazole

capsule, 200 mg po

q.d. (Cl)

None

Cytomegalovirus

(CMV)®

CD4-F count

<50/|iL and CMV

antibody positivity

Oral ganciclovir, 1 g po t.i.d. (Cl) None

NOTES: Information included in these guidelines might not represent Food and Drug Administration (FDA) approval or approved labeling for the particular products or indications in question.

Specifically, the terms "safe" and "effective" might not be synonymous with the FDA-defined legal

standards for product approval. The Respirgard IITM nebulizer is manufactured by Marquest,

Englewood, Colorado.

Letters and roman numerals in parentheses after regimens indicate the strength of the recommendation and the quality of evidence supporting it. Categories reflecting the quality of evidence forming the basis for recommendations regarding the use of a product or measure for the prevention of opportunistic infection in HIV-infected persons: 1 — Evidence from at least one

properly randomized, controlled trial; II — Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center), or from multiple time-series studies or dramatic results from uncontrolled experiments; III — Evidence from opinions of respected authorities based on clinical experience,

descriptive studies, or reports of expert committees.

Categories reflecting the strength of each recommendation for or against the use of a product or measure for the prevention of opportunistic infection in HIV-infected persons: A — Both strong

evidence and substantial clinical benefit support a recommendation for use; B — Moderate

evidence—or strong evidence for only limited benefit—supports a recommendation for use; C —

Poor evidence supports a recommendation for or against use; D — Moderate evidence supports a recommendation against use; E — Good evidence supports a recommendation against use. ABBREVIATIONS: Anti-HBc = antibody to hepatitis B core antigen; b.i.w.= twice a week; DS =

double-strength tablet; HAART = highly active antiretroviral therapy; HAV = hepatitis A virus; HIV = human immunodeficiency virus; im = intramuscular; iv = intravenous; po = by mouth; q.d. =

daily; q.m. = monthly; q.w. = weekly; SS= single-strength tablet; t.i.w. = three times a week;

TMP-SMZ = trimethoprim-sulfamethoxazole; sc = subcutaneous; and TST = tuberculin skin test.

Table continues ...

US. Department of Health and Hum.\n Services, Hilklth Resources and Services Administtloton, HIX'/AIDS Burelw
A Guide to the Clinicul C\re of Women with HR"

Priman- Medical Care

Table 4-14: Prophylaxis to Prevent First Episode of Opportunistic

Disease in Adults and Adolescents Infected with

Human Immunodeficiency Virus (continued)

Prophylaxis should also be considered for persons with a CD4+ percentage of <14%, for persons

with a history of an AIDS-defining illness, and possibly for those with CD4+ counts >200 but <250 cells/pL. TMP-SMZ also reduces the frequency of toxoplasmosis and some bacterial

infections. Patients receiving dapsone should be tested for glucose-6 phosphate dehydrogenase

deficiency. A dosage of 50 mg q.d. is probably less effective than that of 100 mg q.d. The

efficacy of parenteral pentamidine (e.g., 4 mg/kg/month) is uncertain. Fansidar (sulfadoxinepyrimethamine) is rarely used because of severe hypersensitivity reactions. Patients who are being administered therapy for toxoplasmosis with sulfadiazine-pyrimethamine are protected

against Pneumocystis carinii pneumonia and do not need additional prophylaxis against PCP

Directly observed therapy is recommended for isoniazid, 900 mg b.i.w.; isoniazid regimens should

include pyridoxine to prevent peripheral neuropathy. Rifampin should not be administered

concurrently with protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Rifabutin should not be given with hard-gel saquinavir or delavirdine; caution is also advised when the drug is coadministered with soft-gel saquinavir. Rifabutin may be administered at a reduced dose

(150 mg q.d.) with indinavir, nelfinavir, or amprenavir; at a reduced dose of 150 mg q.o.d. (or 150

mg three times weekly) with ritonavir; or at an increased dose (450 mg q.d.) with efavirenz; information is lacking regarding coadministration of rifabutin with nevirapine. Exposure to multidrug-resistant tuberculosis might require prophylaxis with two drugs; consult public health

authorities. Possible regimens include pyrazinamide plus either ethambutol or a fluoroquinolone.

’ Protection against toxoplasmosis is provided by TMP-SMZ, dapsone plus pyrimethamine, and

possibly by atovaquone. Atovaquone may be used with or without pyrimethamine.

Pyrimethamine alone probably provides little, if any, protection.

' See footnote 2 regarding use of rifabutin with protease inhibitors or nonnucleoside reverse

transcriptase inhibitors. Vaccination should be offered to persons who have a CD4-F T-lymphocyte count <200 cells/pL,

although the efficacy might be diminished. Revaccination 5 years after the first dose or sooner if the initial immunization was given when the CD4-F count was <200 cells/|LiL and the CD4-F count

has increased to >200 cells/pL on HAART is considered optional. Some authorities are concerned that immunizations might stimulate the replication of HIV. However, one study

showed no adverse effect of pneumococcal vaccination on patient survival (McNaghten AD,

Hanson DL, Jones JL, Dworkin MS, Ward JW, and the Adult/Adolescent Spectrum of Disease

Group. Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on

survival after AIDS diagnosis. AIDS 1999 [in press]).

® These immunizations or chemoprophylactic regimens do not target pathogens traditionally

classified as opportunistic but should be considered for use in HIV-infected patients as indicated. Data are inadequate concerning clinical benefit of these vaccines in this population, although it is logical to assume that those patients who develop antibody responses will derive some

protection. Some authorities are concerned that immunizations might stimulate HIV replication,

although for influenza vaccination, a large observational study of HIV-infected persons in clinical care showed no adverse effect of this vaccine, including multiple doses, on patient survival (J. Ward, CDC, personal communication). Hepatitis B vaccine has been recommended for all children and adolescents and for all adults with risk factors for hepatitis B virus (HBV). Rimantadine and

amantadine are appropriate during outbreaks of influenza A. Because of the theoretical concern

that increases in HIV plasma RNA following vaccination during pregnancy might increase the risk of perinatal transmission of HIV, providers may wish to defer vaccination until after antiretroviral therapy is initiated. For additional information regarding vaccination against hepatitis A and B and

vaccination and antiviral therapy against influenza see CDC. Prevention of hepatitis A through

active or passive immunization; recommendations of the Advisory Committee on Immunization

Practices (ACIP). MMWR 1996;45(No. RR-15); CDC. Hepatitis B virus: a comprehensive strategy

for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR

1991;40(No. RR-13); and CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999; 48(No. RR-4).

’ In a few unusual occupational or other circumstances, prophylaxis should be considered;

consult a specialist.

® Acyclovir is not protective against CMV. Valacyclovir is not recommended because of an

unexplained trend toward increased mortality observed in persons with AIDS who were being

administered this drug for prevention of CMV disease. Source: Gross PA, Barrett TL, Dellinger P, et al. Purpose of quality standards for infectious diseases.

Clin Infect Dis 1994;18:421. Also: CDC. USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus: A

Summary. United States, July 1995. MMWR 44 (RR-8), 1995.

us. Dep.^rtment of He.\lth .\nd Hunlw Services, He.\lth Re-sourcis .\nd Servici-.s .\DMiNis-|'R.\n()\, HU’/.MDS Hi ri.m’ 115
A C'lUIDl'. IX) ini': ('UNICAI Cxui'-. Ol' WoMI'.N WITH I IIV

Primary Medical (^arc

Pneumocystis Carinii Pneumonia (PCP)

The diagnosis of PCP can be challenging and recjuires a heightened index of

suspicion. Although there are “classic” symptoms, findings on exam and chest

X-ray manifestations, the presentation of PCP can be subtle and nonspecific.

The classic triad of fever, exertional dyspnea and nonproductive cough occurs

in only half of cases, although almost all have at least two of the following:

fever, cough, dyspnea, lactate dehydrogenase greater than 460 U/L or an arterial partial pressure of oxygen (Pa02) less than 75 mmHg. A careful history

may reveal long-standing exertional dyspnea that has worsened incrementally over weeks to months. Physical exam findings are also nonspecific. Fine

dry“cellophane” rales may be heard or auscultation may be entirely normal. In

2—6%, PCP may present as spontaneous pneumothorax. The classic X-ray

findings are diffuse interstitial or perihilar infiltrates, but a wide range of X-ray

abnormalities is possible and radiography is normal in over one-third of cases. Extrapulmonary pneumocystosis is uncommon. PCP is suggested by oxygen

desaturation with exercise, easily measured in the office or clinic with a pulse

oximeter. This is particularly useful when symptoms are minimal, the patient

does not appear acutely ill, and the chest x-ray is unimpressive. Severity of ill- ness is indicated by hypoxemia or a widened alveolar to arterial oxygen differ- ence ([A-a]D02) on blood gas analysis.

Many diseases may have a similar presentation, including mycobacterial,

fungal, viral or bacterial pneumonias, heart failure, pulmonary KS and pulmonary emboli. The definitive diagnostic test requires bronchoalveolar lavage

of affected lung segments that is then concentrated and stained for Pneumocystis carinii organisms. Experienced sites can make a histologic diagnosis

from an induced sputum sample that is concentrated and stained, but this less- invasive, cheaper diagnostic test should not be attempted where expertise in

both obtaining and interpreting the smear is lacking.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatment

for PCP; intravenous or oral administration depends on the severity of the

episode. There are a number of alternative regimens for patients who experi- ence treatment-limiting toxicity or who fail to respond to TMP-SMX. PCP

should be treated for 21 days. After completing acute therapy, the patient

should begin routine daily PCP prophylaxis to prevent recurrence. Patients

with Pa02 less than 70 mm Hg or with an (A-a)D02 greater than 35 on room

air should receive adjunctive steroids, which have been shown to decrease the

incidence of ventilatory failure and death. A 21 day course of prednisone (40

mg twice daily for 5 days, then 20 mg twice daily for 5 days, followed by 20

mg once daily for 1 1 days) is the most popular and cost-effective approach.

Candidiasis

The appearance of mucosal candidiasis is often the first clinical indication of

impaired T cell immunity in HIV-infected individuals. While oral and vaginal

thrush are almost ubiquitous and Candida esophagitis is the second most comU.S. Department of Health and Human Services, HE(\lth Resources and Services Administr,\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

mon ()l after candidemia and tissue-invasive disease are rare. Pharyngitis

may be asymptomatic or may cause dysphagia. White plaques can be easily

scraped from the pharynx or buccal mucosa; severe cases will involve the

tongue, gums and lips. Vaginitis causes a thick white discharge, pruritus and

sometimes dyspareunia, and has a similar appearance on speculum exam.

Intense erythema may be the most prominent finding in some patients with

either pharyngitis or vaginitis. Scrapings will be KOH positive by microscopic

exam and will grow readily in culture. These forms of candidiasis may be

treated with topical or oral antifungals; topical agents are more cost-effective,

and avoid the risk of systemic side effects or drug interactions.

Candida esophagitis is a more serious infection that may result in significant weight loss because of odynophagia. Esophagitis should be considered

when the patient describes midline substernal chest discomfort with swallowing instead of pain limited to the throat. It may occur in the absence of

oropharyngeal thrush, and can be diagnosed by endoscopy or by barium swallow. Topical agents should not be used for esophagitis. Oral fluconazole, 200

mg once daily for 10 days, is the treatment of choice.

Prolonged usage of oral azoles such as fluconazole can result in resistant

candidiasis, so it is important to avoid chronic usage. Most experts try to use

topical antifungals or intermittent courses of azole drugs, whenever possible.

Prophylaxis for vaginal candidiasis with topical antifungals should be considered when systemic antibiotics are given. Some patients with fluconazoleresistant esophagitis may respond to itraconazole, especially the cyclodextrin

solution, or to oral amphotericin B solution. However, most patients with

resistant infection will require IV amphotericin for relief

Cryptococcal Meningitis

Cr)^tococcal meningitis may present as nothing more than the worst headache

of the patient’s Ufe. Fever is common but meningismus may be minimal or

absent. Altered mental stams and elevated intracranial pressure above 180 mm

of water portend a poorer prognosis. Cranial nerve deficits and seizures are only seen in patients who present very late in the course of their infection and

are often antemortem events. The diagnosis is made by detection of cryptococcal capsular antigen in the cerebrospinal fluid (CSF); relying upon a positive India ink stain that demonstrates the organism’s thick capsule is too

insensitive. Cryptococcus neoformans may also be cultured from blood and

CSF. CT or MRI scans may reveal basilar inflammation, and in patients with

intracranial hypertension, the ventricles may be enlarged. Very mild cases may

be treated from the outset with oral fluconazole, 400 mg once daily for 1

0

weeks, followed by chronic suppressive therapy (200 mg once daily). Most

experts prefer using intravenous amphotericin B at a dose of 0.7-1. 0 mg/kg/d

for the first two weeks, with or without flucytosine, and then switching to flu- conazole as described above if the patient is responding. Intracranial hypertension can be managed with frequent lumbar punctures to remove large volumes

us. Department of Health and Human Services, HealTM Resources and Services Admini.str.viion, HI\7AIDS Bi rem 117
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Prirruirv Medical Care

of CSF (20-30 ml at a time). Serum cr^-ptococcal antigen may occasionally be

positive before the onset of headache. It may also be detectable when extra- meningeal infection occurs, and in the evaluation of a fever of unknown origin. In these situations, oral fluconazole is appropriate therapy.

Toxoplasmosis

Toxoplasmosis manifests almost exclusively as an encephalitis in AIDS

patients. The patient presents with a neurologic deficit and classically one or more ring-enhancing space-occup}ing lesions can be seen on CT or MRI scan. How’ever, the radiographic appearance of the lesions is not pathognomonic

and may mimic other processes such as primary CNS lymphoma. Because

serology may be negative and because it is often difficult to obtain a brain

biopsy for a definitive diagnosis, the standard approach is a diagnostic trial of

anti-toxoplasma therapy with pyrimethamine and sulfadiazine for at least two

w^eeks. Both clinical and radiographic improvement should be e\tident in

response to therapy if the patient has toxoplasmic encephalitis (TE). CHndamycin may be substimted for sulfidiazine if it is poorly tolerated. Although

TE in AIDS patients results from reactivation of latent infection, a baseline

negative IgG test for T. gondii does not exclude the diagnosis, and seronegative patients will routinely receive a trial of therapy regardless of their serostatus. For this reason, and because PCP prophylaxis with TMP/SMX will also

prevent TE, obtaining a toxo IgG may not be very cost-effective. A situation

w’here knowledge of toxo serostatus is helpful is when a patient cannot toler- ate TIMP/SMX prophylaxis; in this case pyrimethamine should be added to second-line PCP prophylaxis with dapsone in order to pro\tide protection

from TE as well.

Herpes Simplex Virus

HIV-infected indi\iduals may have recurrent genital HSV that can be suppressed with oral anti\ixal drugs such as acyclovir, valaciclo\tir and famciclovir.

Both treatment and prophylaxis of HSV may require higher doses and, in the

case of treatment, longer administration than is required in the management of

HIV-negative patients; this is particularly the case in women with more

advanced immunosuppression, (see Chapter VI on Gynecologic Problems)

Definitive diagnosis is usually made by culturing HSV from the base of the

lesions, although experienced clinicians will often rely on p’pical appearance,

distribution and symptoms. V('Iien patients develop severe mucocutaneous

lesions or ulcers that persist for more than 4 weeks, this unusually persistent

form of HSV is considered an AJDS-defining illness. Similar to fluconazoleresistant candidiasis, injudicious chronic use of antiherpes drugs may result in

drug-resistant infection, which in this case requires treatment with intravenous

foscarnet. Varicella zoster \tirus, a related member of the herpes\tirus family, causes shingles which responds to higher doses of antiherpes drugs than those

needed for HSV. Shingles can be exquisitely painful and patients may have prolonged post-herpetic neuralgia. Secondar}" bacterial infection may occur, so it is

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important to keep the lesions clean and to use topical or systemic antibiotics as needed. (Control of pruritus and pain is essential for patient comfort. Drugresistant V/V has also been reported and is also treated with IV foscarnet.

Cytomegalovirus

Cytomegalovirus (CiMV) causes retinitis in 80-85% of AIDS patients with

end-organ (iMV disease. Gastrointestinal disease anywhere from the mouth to

the anus is diagnosed in another 12-15%. Other diagnoses, such as encephalitis and pneumonitis, are uncommon (~1%). CMV retinitis can cause visual

loss, and untreated, progresses inexorably to blindness. Because retinitis is a necrotizing process, with effective antiviral treatment the lesions become quiescent and atrophic, but the affected areas do not regain function. Retinitis near critical structures such as the macula or optic nerve may cause cata- strophic visual loss even when the total infected area is small. Patients may be

completely asymptomatic, or may complain of floaters (due to inflammatory

debris), diminished acuity or visual field defects when the lesion(s) is (are) in

the periphery. Diagnosis is made by visual inspection of the entire retina using

dilated indirect ophthalmoscopy by an experienced ophthalmologist. Extensive

disease may lead to retinal detachment which may require surgical repair.

Treatment is usually begun with intravenous ganciclovir, foscarnet or cidofovir

for 2-3 weeks, followed by chronic suppression with either less frequent IV

doses or oral ganciclovir. Chronic use of these agents requires the placement

of an indwelling catheter for ease of administration, or IV therapy can be

used briefly until an intraocular device can be inserted surgically that slowly

releases small amounts of ganciclovir directly into the vitreous. Because CMV

is a systemic infection with viremia, patients who receive the ganciclovir

implant also need chronic suppressive therapy with oral ganciclovir to prevent

the development of extraocular CMV disease. CJVIV can become resistant to

antiVrals. Refractory disease is often treated with intraocular injections, which,

like the ganciclovir implant, deliver high concentrations of drug to the site of

active \tiral replication. End-organ disease at nonocular sites is treated with 2-3

weeks of intravenous induction therapy. There is no clear agreement that

CMV disease at sites outside the eye requires chronic maintenance therapy, but

with the availabiLity of oral ganciclo\ir it seems reasonable to provide continued anti-CMV treatment.

Disseminated Mycobacterium Avium Complex (MAC)

Like CMV, disseminated MAC is one of the OIs that appears at end-stage dis- ease, when the total CD4 cell count is extremely low. It presents non-specifically with fever, weight loss, diarrhea, anemia and sometimes abdominal

discomfort due to organomegaly and impressive intraabdominal lymphadenopathy. Mycobacterial blood culture provides a definitive diagnosis.

Combination oral antimicrobial therapy is required and should include, at a minimum, an azalide (azithromycin or clarithromycin) and ethambutol, 1 5-25

mg/kg/day. Other drugs, such as ciprofloxacin and amikacin, have been used

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but do not routinely provide much additional benefit; clofazimine has been

shown to have an adverse effect on survival and should not be used.

Tuberculosis (TB)

There is a bi-directional interaction between Mycobacterium tuberculosis and

HIV; each facilitates acquisition of the other, so it is critical to assess all HIVinfected patients for active TB and to test all patients with active TB for HIV

Because TB is virulent enough to cause disease in patients with intact immune

systems, it may occur in HIV-infected individuals who still have high CD4 cell counts. TB is especially virulent in HIV seropositive individuals. Aspects of

this virulence include the high frequency of positive blood cultures and of

disseminated (miliary) infection. However, standard combination antimicrobial

therapy is effective as long as the patient is adherent and the acquired strain is not multidrug resistant. It is essential to provide directly observed therapy

(DOT) to ensure an adequate course of treatment and conversion of positive

sputum cultures to negative. Until susceptibilities are known, aU HIV-infected

patients should be treated initially with at least 3 drugs expected to be active

according to local susceptibility patterns. Subsequently, when the results of

susceptibility testing are available, therapy for drug-sensitive infection can usually be narrowed to 2 agents (isoniazid and rifampin). Clinicians should work

closely with their local health department to ensure that patients receive DOT,

and to track and limit the spread of TB, especially resistant strains. All close

contacts — especially young children — must be evaluated for TB so they

may be treated promptly for active disease or given prophylaxis as indicated.

Cryptosporidiosis and Microsporidiosis

These enteric protozoa can cause debilitating diarrhea and weight loss in

patients with advanced HIV disease. Diagnosis is made by special stool stains.

Unfortunately there is no effective therapy (except for Septatis intestinalis,

which may respond to albendazole), so care is supportive. Every effort should

be made to optimize the patient’s antiretroviral therapy, as there are reported

cases of clinical resolution (and even clearing of the organism from stool)

with potent combinatiuon antiretroviral therapy. Patients may develop severe dehydration due to voluminous watery diarrhea. In addition to volume repletion, attempts at slowing the diarrhea should be made as follows by adding

(not substituting) each additional agent in a stepwise manner: 1) diphenoxylate or loperamide, increased to their maximum dose, plus 2) tincture of opium or

paregoric, with the dose titrated gradually until the desired effect is achieved,

and, if additional control is needed, 3) parenteral somatostatin.

Peripheral Neuropathy

Distal, symmetrical polyneuropathy, typically affecting the feet more than the

hands, may result from use of the neurotoxic dideoxy nucleoside analogues

(didanosine, stavudine, zalcitabine) and much less commonly from dapsone, or

us. Dep.\rtment of Health and Human Services, Health Rf.sources and Services Administilwion, HIV/AIDS Burilw
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may be a consequence of advanced HIV disease itself. Most patients present

with paresthesias and/or numbness, but some experience pain that can be disabling. b!,xaminadon reveals slow or absent ankle jerks, diminished vibratory

and proprioceptive responses in both feet, and in patients whose primary

complaint is pain, discomfort sometimes even with Hght touch. If drug toxicity is suspected, the offending agent(s) should be discontinued immediately

and replaced. If this is accomplished quickly enough, symptoms may resolve

entirely. W^hen the nerve damage is not attributable to anti-HIV therapy or does not resolve after drug discontinuation, supportive care may be offered.

Non-steroidal antiinflammatory drugs; agents useful in chronic pain syndromes such as amitrjqDtiiine, phenytoin, or carbamazepine; the neurotransmitter inhibitor gabapentin; mexilitene; and in refractory cases, long-acting

narcotics, all have a role in the management of dysesthesias and pain due to

peripheral neuropathy.

AIDS Dementia Complex (ADC)/HIV Encephalopathy

In the pre-HAART era, frank dementia was the AIDS-defining illness in up to

10% of patients. The initial manifestations may be subtle, and can be uncovered by questioning the patient carefuUy about short-term memory loss and

difficulty concentrating. Useful questions about the latter include the ability to

balance a checkbook or to make change. In some patients, a depressed affect

may be a prominent finding, and in others, unexplained seizures may bring the

patient to medical attention. Psychomotor retardation — slowing of the

impulses that match actions to thoughts and intentions — is another hallmark

of ADC. CT and MRI scans show diffuse cortical loss with prominent sulci

(“walnut sign”). A good sense of the patienmt’s level of intellectual functioning can often be obtained at the bedside. In subtle or difficult cases, especially

when there is a prior history of depression or subnormal IQ, the patient can be referred for a battery of neuropsychological tests that may clearly demonstrate the losses characteristic of ADC. There is no specific treatment for

ADC other than effective antiretroviral therapy. Patients may demonstrate a remarkable degree of recovery with antiretroviral therapy even when they

present with advanced dementia, so it is valuable to attempt treatment of aU

patients, even those initially referred for nursing home care. It may be particularly useful to include agents that achieve good CSF levels.

Wasting Syndrome ("Slim Disease")

Weight loss is common in HIV disease, especially in its advanced stages, but the

Centers for Disease Control surveillance definition of wasting syndrome specifically refers to involuntary weight loss that exceeds 10% of the patient’s baseline weight in the presence of diarrhea (>2 loose stools per day) or chronic

weakness and documented fever (intermittent or constant) for at least 30 days

that is not attributable to a condition other than HIV itself Typically wasting

syndrome is accompanied by loss of muscle mass, for example in the temporal

areas, and complaints of generalized fatigue and modest weakness. In severe

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A GulDl' TO ini' Cl.lNlCAl. CaRI; of WOMliN WI TH HIV

Primary Medical ('arc

cases the serum albumin level will be very low. Wasting can accompany any of

the typical end-stage illnesses, such as disseminated MAC, or may occur by

itself in the absence of any evident concomitant illness. Loss of weight, and

especially, of lean body mass, portends poorer survival. Appetite stimulants,

such as the progestin megestrol acetate or the marijuana derivative dronabinol,

may be used although weight gain with these agents typically consists of fat and water, rather than an increase in lean body mass. However, the psychological benefit of an improved appetite and some weight gain cannot be underestimated, even if the gain is primarily fat. Recombinant human growth hormone

has been used with some short-term success for improvement in lean body

mass, but it is very expensive and must be given parenterally. Other approaches

include enteral and parenteral feedings, anabolic steroids such as nandrolone or oxandrolone, and thalidomide or pentoxifyline for cytokine suppression. Men

with symptoms of hypogonadism often respond to testosterone replacement,

but this approach has not been evaluated in women.

Kaposi's Sarcoma (KS)

Kaposi’s sarcoma is an endothelial cell tumor that, along with PCP, was the harbinger of the AIDS epidemic. It primarily affects gay and bisexual men, and is

fairly uncommon among injecting drug users and women. It is most likely

caused by human herpesvirus-8 (HHV-8). KS can occur at a range of total

CD4 cell counts, but prognosis is poorer at lower values. Most commonly it is limited to mucocutaneous surfaces, where it is a cosmetic problem but not a threat to health. KS of the GI mucosa is very vascular and may lead to slow,

chronic blood loss. When it involves the lymphatic system, KS can cause massive edema and woody induration, especially of the lower extremities; such

patients are prone to severe, recurrent episodes of cellulitus. KS may also

invade the viscera, especially lung parenchyma. Experienced clinicians can generally diagnose mucocutaneous KS by inspection, but a punch biopsy showing

typical spindle-shaped cells is easy to obtain and is definitive. GI and bronchial

mucosal lesions are also diagnosed by inspection; bronchial lesions may bleed

profusely and are generally not biopsied for that reason. Visceral KS, which

may occur in the absence of mucocutaneous disease, requires a tissue diagnosis.

Mucocutaneous KS may be treated with a number of local modalities

including intralesional vincristine or vinblastine, radiation and topical retinoids.

Gastrointestinal lesions can be cauterized endoscopicaUy. Visceral disease

requires systemic chemotherapy, with single cytotoxic agents or combinations.

Systemic Lymphoma

Several different types of lymphoma occur at increased frequency among

HIV-infected individuals. These too may occur at any CD4 cell count although once again prognosis is worse at lower absolute numbers of CD4 cells. HIV

seropositive patients may develop Hodgkin’s disease, immunoblastic lymphoma and Burkitt’s lymphoma as well as less common forms, but the most

U.S. Department of Health and Human Services, HfjMth Resources and Services AdministR/\tion, HIV/AIDS Bure^w
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

common type is an aggressive non-Hodgkin B cell lymphoma. There is a marked tendency for extranodal presentations, and AIDS patients have been

described with NHL at a range of unusual sites. AIDS-associated lymphoma is diagnosed and staged in the same manner as in seronegative patients, and the

same types of combination chemotherapy are used. However, HIV-infected

jsatients may require somewhat lower doses or aggressive support with GCSF

Ijecause t)f their baseline bone marrow fragility.

Central Nervous System (CNS) Lymphoma

(iNS lymphoma occurs at total CD4 ceU counts well under 100 cells and is a

typical end-stage complication. Definitive diagnosis is made by brain biopsy or

(iSh’ cytology in the presence of a space-occupying lesion(s) on CT or MRI

scan. A presumptive diagnosis may sometimes be made by nuclear SPECT

scan. Because brain biopsy may be difficult to obtain, patients who fail a trial of therapy for toxoplasmosis are often assumed to have CNS lymphoma.

There is no effective cytotoxic chemotherapy for this disease, and irradiation is considered palliative. Survival after a diagnosis of CNS lymphoma is usually

limited, on the order of a few months.

Progressive Multifocal Leukoencephalopathy (PML)

PML is another end-stage complication of HIV disease, usually presenting as a focal neurologic deficit(s). It is caused by the JC virus, which can be detected

by PCR performed on CSR MRI scan of the brain demonstrate involvement

of the white matter that can be focal or fairly diffuse, but is not associated

with either mass effect or surrounding edema. Most commonly it affects areas adjacent to the cortex, but lesions can located anywhere. Definitive diagnosis

is made by brain biopsy or positive PCR, which is highly specific in the appropriate clinical context. Where these diagnostic modalities are unavailable, the

t}'pical MRI picture usually suffices. There is no specific proven therapy for

this condition, although there are a number of case reports describing clinical

remission in patients begun on potent combination antiretroviral therapy. In

the pre-HAART era, survival was very limited, but now there are patients alive

more than a year after diagnosis.

Chronic Hepatitis B and C

Many of the same behaviors that put women at risk of acquiring HIV also

result in hepatitis B and/or C infection. Both hepatitis B and C may become

chronic, resulting in hepatocyte destruction that is manifested as intermittent

transaminase elevation (especially ALT), and ultimately to fibrosis, scarring and

end-stage Uver disease. ALT levels may wax and wane, and may only be modestly elevated. Coinfection with viral hepatitis and HIV results in higher hepatitis B and C viral loads. Conversely, hepatitis C has been associated with

acceleration of HIV disease, although hepatitis B has not. Branched-chain

DNA (bDNA) tests for either form of hepatitis are more suitable for follow-up

us. Department of Health and Human Services, Health Resources and Services Adminis-i-r.\tion, HIV/AIDS Bureau 123
A CJiuni' lo 'mi': Ci.inicai, Caiu; oi' WomI'N wrm HIV

Primarv Medical (iare

Figure 4- 6 : Guidelines For Use of Erythropoietin in the Anemic

HIV Patient

Goals of Therapy

• Resolution of Anemia:

Hgb >12g/dLor Hct >36%

Increased energy, activity, and

overall quality of life for

patients, prolonged survival

Reduced need for transfusion

* If Hgb > 15g/dL at any point, hold EPO and restart when Hgb < 12g/dL, using dose reduced by

10,000/week.

** During dose adjustment phase, hemoglobin should be monitored every 2-4 weeks. Allow at lease 4 weeks to assess response to dose changes. Source: Joel Gallant, MD.

us. DEPAimKENT OF HEALTH AND HUNLVN SERVICES, HEALTH RESOURCES AND SERVICES ADMINISTRATION, HIV/AIDS BUREAU
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

of coinfccted patients than PCR-based tests, which may be too sensitive. Both

entities are treatable, and specific therapy should be considered to prevent or

delay cirrhosis and liver failure. Hepatitis B responds to treatment with 3TC

(lamivudine) and some investigational agents. Hepatitis C may respond to sys- temic alpha interferon, and better stiU, to a combination of interferon and ribavirin, although only a minority of patients achieve solid success rates.

Anemia

Modest anemia (>9-10 g/dL) is a hallmark of chronic HIV infection and may

be complicated by menstrual losses in women of child-bearing age. Severe

anemia (<9 g/dL) may occur as part of certain opportunistic diseases, especially MAC, disseminated histoplasmosis and lymphoma, and may also be the

result of drug toxicity. Although severe anemia has been shown to be associated with a poorer prognosis for survival in a number of studies, diagnosis

and treatment of the opportunistic process is often sufficient to improve ane- mia in these cases.

Patients who are symptomatic with exertional dyspnea and dizziness can

be transfused acutely. Most HIV-infected patients become anemic gradually,

and unconsciously limit their activities to control symptoms. These individuals can be managed with changes of antiretroviral or OI therapies known to be

toxic to red blood cells, such as AZT (zidovudine) and trimethoprim-sulfamethoxazole. In patients refractory to conservative management, red blood

cell production can be stimulated by using recombinant erythropoietin along

with sufficient iron replacement to stimulate production of new red cells. (See Figure 4-6)

C OPPORTUNISTIC DISEASE IN THE HAARTERA

The impact of highly active antiretroviral therapy on the natural history of

opportunistic diseases has been profound, and the clinician must be familiar

with at least the broad outline of these changes. There may be sufficient

immune restoration that even patients with end-stage disease may become

capable of mounting an inflammatory response to opportunistic pathogens.

This can result in the atypical development of an acute OI in the first couple of

months after initiating potent combination therapy, after CD4 cell counts have

begun to improve. These cases may be marked by focal symptoms, such as the

acute development of a tender, enlarged lymph node with negative blood cul- tures in the case of MAC lymphadenitis, where in the pre-HAART era the t)y>ical presentation would have been diffuse, with widespread nontender

adenopathy and high-grade mycobacteremia. This seemingly paradoxical development of an OI with rising CD4 cell counts is likely due to an inflammatory

response to an OI that was subcUnical when HAART was begun.

Just as initial presentations may be altered as the result of HAART, continued disease activity may also be modified. Patients who recover pathogenspecific immunity in addition to the overall increase in CD4 cells may be able

us. Department of He.\lth and Human Services, Hf..\lth Resources and Servicrs Adminls-iration, HIV/AIDS Buri-iau 125
A (lUlOH TO I'HF. ('I.INIOU. C\RF Ol- WOMFN WITH HIV

Primary Medical (Lire

to discontinue chronic suppressive (maintenance) therapy, because the patient’s

immune system is now capable of containing the infection. Thus far this has

been best demonstrated for discontinuing chronic suppression for CMV retinitis. However, there is no reason to think that other OIs will behave differently

and multiple clinical trials are currently in progress. Last, patients with previously untreatable opportunistic processes, such as PML or cryptosporidiosis,

have had clinical remissions after initiating HAART.

A number of studies have shown that patients receiving primary prophylaxis for PCP and MAC are at very low risk of developing these OIs if prophylaxis is withdrawn after total CD4 cell counts have improved above the

threshold levels for risk of a specific OI for at least 3-6 months. Most of

these studies have been performed among patients with reasonably well-controUed HIV viral loads, with the majority undetectable or at most, less than

10,000 copies. The 1999 revision of the USPHS guidelines on OI prophylaxis

describe the data and rationale for discontinuing suppressive therapy and prophylaxis in the appropriate patient. These guidelines are likely to be revised in

the near future, so it is wise to check the AIDS Treatment Information Service

Web site listed in Chapter XV on Resources.

VI. ALGORITHMS FOR DIAGNOSIS AND MANAGEMENT

OF SYMPTOMS

Figure 4-7: Fever of Unknown Origin in Patients with AIDS

Figure 4-8: Acute Diarrhea in Patients with AIDS

Figure 4-9: Chronic Diarrhea (CD4 Count < 300/mm^)

Figure 4-10: Cough, Fever, Dyspnea

Figure 4-11: Headache in Patients with Aids

Figure 4-12: Advanced HIV Infection Plus Altered Status, New Seizures,

Headache (Severe or Persistent), or Focal Neurologic Deficits

Figure 4-13: Lower Extremity Symptoms: Weakness and Numbness

Figure 4-14: Lower Extremity Symptoms: Pain

Figure 4-15: Lower Extremity Symptoms: Pain and Numbness

Figure 4-16: Odynophagia in Patients with AIDS

us. Demrtment OI- Health and Human Services, He,\lth Resources and Services Administration, HIV/AIDS Bure.\u
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us. Department of Health and Human Services, Health Resourcf.s and Serviqls Administraiion, HrV'/AIDS Bureau 127
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A Guide to the Clinical Care of Women with HIV

Primary Medical Care

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Primary Medical ('arc

Figure 4-12: Advanced HIV Infection Plus Altered Status, New

Seizures, Headache (Severe or Persistent), or Focal

Neurologic Deficits

CT scan with contrast or MRI

(MRI with gadolinium preferred)

Toxoplasmosis serology, serum

cryptococcal antigen, serum VDRL

Results of imaging

Multiple

enhancing

lesions

Atypical lesions for toxoplasmosisNo lesions

Empiric treatment

for toxoplasmosis

No response

clinically and/or by

MRI at 2 weeks

Source: Bartlett, 1999.

Periventricular

lesions, rapid onset

encephalopathy

CMV treatment if CSF shows CMV

by PCR or culture

Other

lesions

Brain biopsy

(stereotactic)

Viral culture

(HSV and CMV)

FA stain for HSV

Immune peroxidase

stain for SV40 (PML)

Lumbar

puncture

Cell count, protein,

glucose VDRL

Cryptococcal antigen

Cytology (lymphoma)

rarely positive

Experimental: PCR for Toxoplasma,

CMV, JC virus

(PML), EBV

(lymphoma)

PML: HAART and

consider SC

alpha interferon

us. Department of Health and Human Services, He,alth Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

Figure 4-13: Lower Extremity Symptoms: Weakness and Numbness

Source: Maenza, 2000.

Figure 4-14: Lower Extremity Symptoms: Pain

Source: Maenza, 2000.

us. Dep.\rtment of Health and Human Services, Health Resources and Services ADMiNiSTR.vnoN, HIW.MDS Buri:ai: 135
A CililDI'. lO llll', (J.INICAI, (].\KI' ()! \X'()MI-N Wmi HIV

Primary Medical (^arc

Figure 4-15: Lower Extremity Symptoms; Pain and Numbness

Source: Maenza, 2000.

us. Dep.^rtment of He.u,th ,\nd Human Services, HE/\lth Resources and Services Administration, HIV/AIDS Bure/\u
A Guide to the Clinical Care of Women with HIV

Primary Medical Care

Figure 4-16: Odynophagia in Patients with AIDS

Evaluation

1. Medication or food related

2. Gastroesophageal reflux disease:

(heartburn ± regurgitation and

dysphagia)

3. Opportunistic infection or tumor

Common: Candida sp. Less common: HSV, CMV, idiopathic

(aphthous)

Rare: TB, M. avium, histophasmosis,

PCP, Cryptosporidia, Kaposi's

sarcoma, lymphoma

Source: Bartlett, 1999.

us. Department of Health and Human Services, Health Resources and Services Adminis-i-r.vhon, HIN’/MDS Burilm 137
A C'lUlDl' TO TUF. Cl.INlCAI. CART. OT WOMHN Wi l l I HIV

Primary Medical (iare

REFERENCES

Bartlett JG. Medical Management ofHIVInfection. Baltimore, MD: Johns Hopkins University; 1999.

Baxter j, Mayers D, Wentworth D, et al. A pilot study of the short-term effects of anti- retroviral management based on plasma genotypic antiretroviral resistance testing

in patients failing antiretroviral treatment f[.B8]. 6th Conference on Retroviruses

and Opportunistic Infections, Chicago, IL, 1999.

Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy:

the VIRADAPT randomized controlled trial. Lancet 'iS'i: 2195-9, 1999.

Erbelding Emily J, Resistance Testing: A Primer for Clinicians. The Hopkins HIVReport.

11(3):1-12. May 1999.

Fauci A, Pantaleo D, Stanley S, Weismann D. Immunopathogenic mechanisms of HIV

infection. Annals ofInternal Medicine 124: 654-3, 1996.

Hall C, Raines C, Barnett S, Moore R, Gallant J. Efficacy of salvage regimens containing

ritonavir and saquinavir after failure of single protease-inhibitor containing regi- mens. AIDS 13: 1207-12, 1999.

Hanson DL, Chusy, Farizo KM, Ward JW, and the Adult and Adolescent Spectrum of

HIV Disease Project. Distribution of CD4+T Lymphocytes a+ diagnosis of

Acquired Immunodeficiency Syndrome — defining and other Human Immunodeficiency-related Illnesses. Arch Intern Med 155:1537, July 24, 1995.

Hirsch MS, Conway B, D’Aquila RT, et al. Antiretroviral drug resistance testing in adults with HIV infection: implications for cUnical management. International AIDS

Society - USA Panel. /.4AM 279 (24): 1984-91, 1998.

Ho D, Neumann A, Perelson A, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123-6, 1995.

Imam N, Carpenter CC, Mayer KH, Fisher A, Stein M, Danforth SB. Hierarchical pat- tern of mucosal Candida infections in HIV-seropositive women. Am J Med 89(2):

142-6, 1990.

Kitahata MM, Koepsell TD, Deyo RA, Maxwell CL, Dodge WT, Wagner EH. Physicians’ experience with the acquired immunodeficiency syndrome as a factor in patients’ survival. NEnglJ Med 334: 701-6,1996.

Mellors JW, Rinaldo CR, Gupta P, White RM, Todd JA, Kingsley LA. Prognosis in HIV1 infection predicted by the quantity of virus in plasma. Science 272:1167—1170,

1996.

Quinn TC, Mawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission

of human immunodeficiency virus type 1. NEnglJ Med 342: 921-9, 2000.

Rich JD, Merriman NA, Mylonakis SE, Greenough T, Flanigan T, Mady B, Carpenter

CCJ. Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: A case

series. Ann Int Med 130 (1): 37-9, 1999.

Raboud J, Montaner J, Conway B, et al. Suppression of plasma viral load below 20

copies/ml is required to achieve a long term response to therapy. AIDS 12:1619-

24, 1998.

Tebas P, Patrick A, Kane E, et al. Virologic responses to a ritonavir-saquinavir containing regimen in patients who have previously failed nelfmavir. AIDS 13: F23-8,

1999.

U.S. Department of Health and Human Services, Guidelines for the Use ofAntiretroviral

Agents in HIV-Infected Adults and Adolescents, January, 2000.

USPHS/ISDA Guidelines for the prevention of oppormnistic infections in persons

infected with human immunodeficiency virus. MMWR 1999; 48:1—67.

us. Departoknt of Health and Human Services, HfjVlth Resources and Services ADMiNisriumoN, HIV/AIDS Burr/\u
V. Adherence to HIV Therapies

Laura W. Cheever, M.D.

I. INTRODUCTION

Adherence to HIV therapies is critical if patients are to achieve and maintain

undetectable viral loads and avoid preventable opportunistic infections. Initial

clinical trials of highly active antiretroviral therapy demonstrated that 80—90%

of patients receiving protease inhibitor therapy could achieve viral loads < 400

copies/ml. (Gulick, 1997) However, currendy in real world clinical practice

only 50% of patients achieve this goal. (Deeks, 1997; Lucas, 1999) The primary reason is nonadherence with therapy. Adherence with medications in any

chronic disease is a challenge for most patients. As a general rule, only 50% of

patients with chronic illnesses maintain “good adherence” (taking > 80% of

medication doses) over time. Patients with HIV infection have similar rates of

adherence. Unfortunately in this infection, “good adherence” is not good

enough, and the consequences of nonadherence are severe.

This chapter addresses the important issues regarding adherence with HIV

medications. Beyond this specific issue, there are other aspects of adherence

with medical care, including adherence with recommendations for laboratory

monitoring for toxicity and clinical response and adherence with appointment

keeping, that are also critical factors in successful HIV treatment.

II. THE UNFORGIVING NATURE OF HIV AND THE

MEDICATIONS TO TREAT IT

Adherence with medications is critical in HIV infections for several reasons

involving both the nature of the virus and the drugs to combat it. First, the

virus has a very high replication and mutation rate. If drug doses are intermittently missed, the virus quickly begins to replicate. In the presence of low levels of drug, viral mutations that confer drug resistance will thrive. Second, the

most potent drugs, both protease inhibitors and nonnucleoside reverse tran- scriptase inhibitors, have broad class resistance. That is, when resistance to one

drug in the class occurs, often resistance has developed to all the drugs in that

class. Thus, nonadherence to one regimen can result in virus resistant to many

antiretrovirals.

Finally, a patient needs to have near perfect adherence, as shown in Figure

5-1, to achieve an undetectable viral load necessary to prevent the developUS. Department of Health and Human Services, Health Resources and Services ADMiNis-ncvnoN, f ID'/A IDS Buriai 139
A ('iLiini'. 'I’o mi', ([uNic.M, (IarI' op WomI'N wrni 1 IIV

Atihcrcnce to Hl\' 'riicrapics

ment of resistant virus. (Patterson, 1 999) For most chronic diseases, 80%

adherence is considered “good adherence.” However, only 50% of patients

achieved undetectable viral load with this level of adherence.

Thus, in HIV infection, patients must have exceptionally high levels of

adherence to therapy to prevent the emergence of resistant virus. Additionally,

unlike other chronic diseases, such as hypertension, if HIV-infected patients

are nonadherent, even for a few weeks, they may severely limit their future

treatment options due to broad class resistance.

III. PREDICTORS OF ADHERENCE

Adherence is a complex behavior. In analyzing predictors of adherence, it is important to consider factors related to the patient, the treatment regimen, the

doctor-patient relationship, and the system of medical care. There are several

patient related factors that are consistently predictive of adherence or nonadherence among HIV infected individuals. Depression and active substance

abuse (including alcohol, cocaine, or heroin) correlate with nonadherence,

whereas the patient’s belief that they can both make HIV medication regimens

fit into their life and be adherent with the regimen is predictive of adherence.

(Table 5-1, Cheever, 1999) In addition, one of the best predictors of adher- ence is adherence with previous therapy.

In most chronic diseases, demographic characteristics, such as sex, race, income, education, and age are not predictive of adherence. (Haynes, 1979)

However, in the initial studies of these factors of HIV-infected patients, the

data are inconclusive. In the HIV Cost and Services Utilization Study

(HCSUS), a national probability sample survey, the investigators found that

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Adherence to HIV Therapies

Table 5-1: Patient Factors Associated with Non-Adherence

Strongly Associated

Depression

Alcohol/substance abuse

Self Efficacy (Belief in one's ability to take medication as instructed)

Belief medications can be fit into their day

Understanding the relationship of viral resistance and adherence

Previous adherence

Inconsistently Associated

Sex (F<M)*

Race (AA< W)

Age (younger < older)

Stage of disease (Patients with higher CD4 < Patients with lower CD4)

Not Generally Associated

Education, Income, Employment

HIV Risk Factor

Belief that medications will improve health or cause symptoms

* In studies where an association is found, females are less adherent than males.

women, African Americans, Hispanics, younger adults, and patients with

higher CD4 counts reported lower rates of adherence. (Wegner, 1999) Other

studies report conflicting results, and the relationship between these demographic variables and adherence needs further exploration.

In terms of the treatment regimen, adherence decreases as the number of

doses per day, piUs, or medications increase. Likewise, medications with food

restrictions are harder to take as directed. Length of time on therapy also

impacts medication adherence. Adherence tends to wane over time, which is a compelling reason to delay therapy until the risk of progression to AIDS is significant. Pharmacy and social work counseling of patients whenever

HAART is initiated or the regimen is changed can be helpful in ensuring that

patients understand dosing and side effects and can assist in developing strate- gies to avoid missing doses.

The doctor-patient relationship is also an important variable in adherence

and should not be overlooked. Several studies have shown that patients who

trust their doctor are more likely to adhere to therapy, including one new study

among HIV-infected patients. (Kaplan, 1999) Most medical providers believe

that they can predict which patient will be able to adhere to a medical regimen.

However, studies have repeatedly shown that physicians, nurse practitioners,

and nurses cannotpredict with reliability which patients will adhere to therapy. (Patterson, 1999) Table 5-2 lists the most common reason patients say they

miss their medication. (Eldred, 1998; Chesney, 1997) These reasons vary significantly from the reasons that providers site as reasons their patients miss

doses. (Gallant, 1998)

us. Department of He,\lth and Human Services, He.u,th Resourcf.s and Servicf.s Admini.s-ir,mion, HI\7AIDS Bi ri:au 141
A C'llllDl-: 1() THi; (j.lNlCAl. C\Ri; ()! WOMl'N WITH HIV

Adherence to HIV 'I’herapies

Table 5-2 : Reasons Patients Cite for Missing Medication

Did not have medication at the time of the dose

Simply "forgot" to take it Asleep at time of dose

Too busy at the time

Off usual daily schedule/routine

Ran out of medication

Using drugs/alcohol

Pills to difficult to take (too many, too big, schedule to complicated)

Didn't want to be reminded of HIV/AIDS

Didn't want to take pills in front of others

The system of care can impact adherence to a medication regimen. Situations that facilitate patients’ access to medication, in terms of refill requests,

reminders to refill medication, and mechanisms to obtain medications when

gaps in medication insurance occur, can significantly impact a patient’s ability to adhere. Similarly, systems that help patients overcome barriers to seeking

medical care, including problems with transportation, childcare, and paying for

services, also assist in the patient’s adhere efforts. Finally, patient education is a

critical part of improving adherence. Within the system of care, personnel and

resources need to be dedicated to this important endeavor.

IV. ADHERENCE IN SPECIAL POPULATIONS

A INCARCERATED PATIENTS

Incarcerated patients have unique challenges to medication adherence. Medical

regulations vary significantly among correctional systems, and these regulations

influence patients’ medication adherence. Correctional institutions may provide

directly observed therapy of each dose of medication which may result in

excellent medication adherence. On the other hand, lockdowns and other security concerns supercede medical concerns and may result in missed doses. In

correctional systems where HIV-infected inmates are identified and called by

name to receive medications, many patients forego treatment rather than risk

disclosure of their HIV infection. Additionally, the incarceration process itself provides many opportunities for potential disruption in access to medications.

Most patients do not immediately access their antiretroviral medication on

entry to the system or at times of transfer within the system. When patients are discharged from the penal system, they are provided with a limited supply of

medication; often patients run out of medication prior to establishing medical

care in their communities, resulting in nonadherence with their regimen.

B. HOMELESS PATIENTS

It is often assumed that homeless patients face insurmountable barriers to

adherence with medications. Certainly, homelessness itself creates many chains. Demrtment of Health and Hum,\n Services, Health Resources and Services Administr/OTOn, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Adherence to HIV Therapies

lenges to adherence. Additionally, many homeless patients have mental illness or substance abuse that may further contribute to non-adherence. However,

patients with homelessness can be successful in taking HAART. In a study of

homeless and marginally housed patients from San Francisco, 38% of the 32

homeless patients taking protease inhibitors had high levels of adherence.

(Bangsberg, 1999) However, the group appears to be highly selected since only

34 of 153 patients in this marginally housed cohort were prescribed HAART.

C CHILDRENAND ADOLESCENTS

Young children are dependent on the adults around them for their medication

adherence. As with many HIV-infected adults, HIV-infected children may be

in tenuous social situations due to poverty and unstable housing, in addition to

illness among their parents. In addition, many children are unable or unwilling

to swallow unpalatable medication or piUs, making dosing administration take

hours each day. In one study, children with extreme problems around medication taking had gastric tubes placed with improvement in adherence, viral load,

time necessary to administer doses, and interpersonal relationships with the

persons administering the medication. (Shingadia, 1 999) Adolescents who have

not disclosed their HIV status may miss doses because of lack of a private

place to take their medication. Furthermore, adolescence is a time of testing

limits and feelings of invulnerability, both of which may contribute to the likelihood of nonadherence.

V. MEASURING ADHERENCE

There are many methods to measure adherence including electronic devises,

piU counts, and drug assays. However, in clinical practice, the most efficient

method to measure adherence is simply to ask the patient. (Icovicks, 1 997)

When asked in a nonjudgmental way, most patients (80% in several studies) are truthful about their medication taking. (Sackett, 1976) To get the most reli- able information, patients should be given permission to have missed doses,

asked in a nonjudgmental way, and given a specific time frame. For example,

“Everyone misses doses some ofthe time. In the last 2 weeks, how many doses have

you missed?”

Pharmacy records can also give important information regarding adherence

when available to the clinical staff. Serum drug levels are now commercially

available. These are most useful when patients professing adherence are not

responding well to therapy; however, low drug levels may also be due to poor

absorption or drug-drug interactions as well as to nonadherence.

VI. IMPROVING ADHERENCE

Given the importance of adherence in HIV infection and the relatively low

rates of adherence in any chronic disease, it is of utmost importance to supUS. Department of Health and Human Services, Health Resourcf-s and Services Administratoin, HIV/ AIDS Bure.au 143
A Gl lDE TO THE CUN1C\L CaRE OF W''OMF_\ WITH Hl\'

Adherence to Hl\' Therapies

port et'forts to increase patient adherence. Although there is litde information

specific to HI\' infected indiAduals, manv interventions have been shown to increase adherence with pill taking in chronic disease. Most interventions only

have a modest effect on adherence. Those that work best are multifaceted

(working on more than one aspect of the pill taking behaAor) and repetitive

(ha\ing the inteiwention reapplied OA'er time). (Haynes, 1996; Roter, 1998) Also

with anriretroAiral medication, it is critical to start the intervention before nonadherence, and Airal resistance, have occurred.

In initiating a successful regimen, the most important thing to consider is whether the patient is ready to start antiretroAiral therapy. The patient is usually

the best judge of when to start therapy as long as they are w'ell informed

regarding the rigors of antiretroviral therapy and the consequences of nonadherence. Thus, a majority of patient education efforts should be made prior to

initiation of therapy. Gwen that the patient’s “first shot [of antiretrovirals] is . the best shot,” most patients benefit in the long run by delating therapy if they

are not readv to start. The urgencv of therapy increases as the CD4 count falls and the viral load increases. Manv physicians feel pressured by practice guidelines for starting therapy. The best time to start therapy is when the patient is

ready.

There are, however, a few “antiretroviral emergencies,” pregnancv* being

one of them. Clearly, for the pregnant woman, the cost benefit considerations

are different, as outlined in Chapter \TI on HP/ and Reproduction. In the

case of pregnant women, the time permitted for the patient to prepare to start therapy is considerably compressed. Thus, ev^en more intensive educational

efforts are needed in this population.

Patient education is clearly important, with high returns on the inv^estment

made prior to starting therpy. Group education generally w'orks better than

one on one education, probably because of the support and practical peer

advice that is shared. (Roter, 1998) Many patients resist groups, but many find

them beneficial if they can be convinced to go. Specific interventions to

improv'e adherence are outlined in Table 5-3.

Two controlled intervention trial s to improv'e adherence in the HIV-infected

population hav'e been presented. In a pharmacy based trial from Spain, patients

starting highly active therapy received education detailing the importance of

treatment, adherence, and side effects management. (KnobeL, 1998) They w^ere

engaged in tailoring the medication into their daily schedule and given a tele- phone number to call with problems. In follow up phone calls, the importance

of adherence was stressed, and patients were engaged in problem solving

around missed doses. At 48 weeks, in the interv-ention arm, 77% of patients were adherent with medication, compared with 52% in the control arm.

In a second controlled interventional trial, a nurse based interv^ention to improv'e adherence with PCP prophylaxis was also reported to be successful.

(Cheever, 1998) Patients in the intervention group received a 10 minute nurseUS DEP.urrMENT OF He-Uth ,\nd Hl'mvs SomcES, He.\lth Resocrces .\sx> Sebmces .\dmixistr.\tio>s HW/AIDS Bcre.\l'
A Guide to the Clinic.\l C.\re of Women \xtth

Adherence to HW Therapies

Table 5- 3 : Interventions to Improve Adherence

Intervention Comments

The Patient

Start when the

patient is ready

For pregnant women, the cost-benefit analysis of

treatment is different.

Treat substance

abuse and depression

prior to initiating antiviral therapy

If there is no antiretroviral emergency, patients with

active substance abuse and depression should have

these comorbidities addressed prior to initiation of

antiretrovirals.

Engage the patient in medication tailoring

Discuss with the patient in detail how the medications will

fit into their daily routine- i.e. when (and if ) meals are

eaten, what the patient does 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 education.

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 to 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 medical practice.

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

staff can provide support through office visits, home

visits, and telephone calls, especially in the first days

and weeks of antiretroviral therapy.

Use skill building

excercises

Have the patient use a trial of jellybeans in a pill box to accustom themselves to their pill taking schedule

prior to initiating therapy.

Address barriers to adherence

Have the patient 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 or pill boxes, can decrease missed doses due to simply

forgetting.

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

table. The Regimen

Simplify as much as

possible

Once or twice daily regimens are easiest for patients.

Use as few pills and medications as possible.

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

Tailor the regimen

to the patient's

lifestyle (and not the

patient's lifestyle to the regimen).

Ask the patient about her daily routine, comfort in taking medications in front of others and at work.

Construct a regimen that works for the patient.

Table continues . .

.

us. Dep.uitmentof He.\lth ,\nd Hunlw SER\acEs, Ha\LTH Resources ,\nd Services .\DMiNi.sTRAnoN, MIN’/.MDs Bi r: 145
A Gl ini TO THE Cl.lMTAL CaRE OF W ONIFA WITH HIV

Adherence to HI\' Therapies

Table 5-3: Interventions to Improve Adherence (continued)

Intervention Comments

The Regimen (continued)

Use pill boxes Use of pill boxes allows the patient a mechanism to carry her daily medication.

Pill boxes allow for patients to easily recognize when

they have missed a dose.

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

The Doctor-Patient Relationship

Develop a trusting

relationship

Rarely is initiation of antiretrovirals required at the first

visit. Invest in the doctor-patient relationship prior to

initiating therapy.

Ask about

adherence

Medical providers cannot predict adherence- you must

ask the patient.

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 the patient.

The System of Care

Maintain close

follow up at initiation of regimen.

Have telephone, office, or home contact with patient

within first few days of therapy to assess for side

effects and accurate understanding of regimen.

Develop patient

education program

Consider use of 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.

Source: Adapted from Cheever 1999.

based exit interview at the end of each regular clinic ATsit. During the exit

interview, the nurse discussed the importance of PCP prophylaxis, stressed the

importance of adherence, and engaged the patient in medication tailoring.

Median adherence in the inteiwention group was 78%, 16% better than among

the control group. More randomized trials are needed to define which interventions work best to improve adherence, and many are undeiAX'ay.

VII. CONCLUSION

Adherence with medications is critical in infection. VTieneA^er medications are prescribed, special emphasis needs to be placed on patient readiness

and adherence. Many types of inteiwentions can improve adherence, and it is

us. Der\stmest of He-UJH .\sd Hi.74-\s Services, He.\lih Resolrces .knd Sebmces .\r»flNism\Tios HI\7AIDS
A Guide to the Clinic.\l C,\re of Women with

Adherence to Therapies

vital that these are employed to give patients the best chance at an optimal

response to 111\' therapies.

REFERENCES

Ihingsberg I)R, Hecht 1*M, Charlebois EC, et al. Spontaneous adherence (ADH) audits

(SA A) predict viral suppression in the REACH cohort. Program and Abstracts of

the 6th (ionference on Retroviruses and Oppoitunisric Infections, Chicago.

Abstract 93, 1999.

(dieevcr 1A\’, Barnes Gl., Chaisson RE. A randomized educational intervention to improve adherence with medication. Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Abstract 1-178, 1998.

( iieev'er I AX', \\’u A\X'. Medication adherence among HIV infected patients: understanding the complex behavior of taking this complex therapy. Current Infectious Diseases Report 1: 401-407, 1999.

(hesney MA. New antiretroviral therapies: adherence challenges and strategies. -Abstracts of the 37th Interscience Conference on Antimicrobial Agents and

(Chemotherapy, Toronto, Canada. Evolving HW treatments: advances and the chal- lenge of adherence symposium. 1997.

Decks S, Loftus R, Cohen P, et al: Incidence and predictors of virologic failure to indi- navir (1D\^ and/or ritonavir (RTV) in an urban health clinic. Abstracts of the

37th Intcrscience Conference on Antimicrobial Agents and Chemotherapy,

Toronto, Canada, Abstract LB-2, 1997.

lildred LJ, Wu AW, Chaisson RE, et al. Adherence to antiretroviral and pneumocystis

prophylaxis in HIV disease. } Acquir Immune Defic Syndr Hum Retroviral

18:117-125, 1998.

Ciallant JE, Block DS. Adherence to antiretroviral regimens in HIV-infected patients:

results of a survey among physicians and patients. ofthe International Association ofPhysicians in AIDS Care, 1998.

Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and

lamivoidine in adults with human immunodeficiency virus infection and prior anti- retroviral therapy. NEnglJ Med 337: 734—739, 1997.

Haynes RB. Determinants of compliance: the disease and the mechanics of treatment. In Compliance in Health Care. Edited by Haynes RB, Sackett DL. Baltimore: Johns

Hopkins University Press 49—62, 1979

Haynes RB, McKibbon KA, Kanani R. Systematic review of randomized trials of inter- ventions to assist patients to follow prescriptions for medications. Lancet

348:383-86, 1996.

Icovicks J. Behavioral measures. Adherence to New HIV Therapies: a Research Conference. Washington, D.C. NIH Office of AIDS Research 15—18, 1997.

Kaplan A, Golin C, Beck K, et al. Adherence to protease inhibitor therapy and viral load. Program and Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago. Abstract 96, 1999.

Knobel H, Carmona A, Grau S, et al. Strategies to optimise adherence to highly active

antiretroviral treatment. Program and abstracts of the 12th World AIDS Conference, Geneva, Switzerland. Abstract 338/32322, 1998.

Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large

urban clinic: risk factors for virologic failure and adverse drug reactions Ann Intern 131:81- 87, 1999.

us. Dep.\rtment of He.\lth .wd Hum\n Services, He.\lth Resources .\nd Services Ad.ministr,\tion, HIV/.VIDS Bi re.m 147
A CiUlDI', TO THIC Cl.lNlCAl. C\R1‘ OI' WOMICN WllIl HIV

Adherence to HIV Therapies

Patterson D, Swindells S, Mohr J, et al. How much adherence is enough: a prospective

study of adherence to protease inhibitor therapy using MEMS Caps. Program and

Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections,

Chicago. Abstract 092, 1999.

Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient

compliance a meta-analysis. Medical Care 36:1138—1161, 1998.

Sackett DL, Haynes RB, Gibson ES, et al. Randomized clinical trial of strategies for improving medication compliance in primary hypertension. Lancet 1:1265—68,

1976

Shingadia D, Viand R, Dankner W, et al. Gastrostomy tube for Improvement of adher- ence with HAART in pediatric HIV patients. Program and Abstracts of the 6th

Conference on Retroviruses and Opportunistic Infections, Chicago. Abstract 436,

1999.

Wenger N, Gifford A, Liu H, et al. Patient characteristics and attimdes associated with

antiretroviral (AR) adherence. Program and Abstracts of the 6th Conference on

Retroviruses and Opportunistic Infections, Chicago. Abstract 98, 1999.

us. Department of Health and Human Services, He.\i,th Resources and Services Administration, HIV/AIDS Bure/\u
VI. Gynecologic Problems

Silvia Abularach, MD, MPHandJean Anderson, MD

I. INTRODUCTION

(rynecologic problems are common among HIV-positive women and are fre- quently present at the dme of initial presentation for evaluation and care. Minkoff et al found that 46.9% of 262 HIV-infected women had a least one

incident gynecologic condition with serial assessment. (Minkoff, 1999) In a study of women admitted to an inpatient AIDS serHce, although only 9%

were admitted with a primary gynecologic (gyn) problem, 83% had coexisting

gynecologic disease when evaluated. (Frankel, 1997) Some gynecologic issues

are unrelated to the patients’ serologic status, whereas others are directly

related to HIV disease and associated immunosuppression. StiU others are associated epidemiologicaUy with HIV because of common risk factors, such

as sexual beha\ior or substance abuse.

From july 1998 to June 1999, women accounted for 23% of the adult

AIDS cases and 32% of the adult cases of HIV infection reported in the

United States. (CDC, 1999) Moreover, women have had the greatest increase

in AIDS incidence in recent years when compared with other U.S. population

groups . With this background and the fact that HIV infection primarily

affects women during their reproductive years, gynecologic and reproductive

health care will play an increasingly important role in the overall care of the

HIV-infected w-oman. With improved longevity and quality of life, gynecologic

problems will be encountered more commonly or may be more prominent.

With these issues in mind, the goal of this chapter is to use a problemoriented approach in reviewing the most common gynecologic complaints

together with their differential diagnosis, evaluation, management, and relationship to HIV

II. ABNORMAL UTERINE BLEEDING/AMENORRHEA

A. WHATIS CONSIDERED 'ABNORMAL BLEEDING?

A normal menstrual period should occur ever)" 21 to 35 days and last between

2 and 6 days. The average blood loss during menses is 20 to 60 ml., but up to 14% of healthy women have blood loss greater than 80 ml and are more likely to be anemic because of this. (MisheU, 1997)

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Graecolc^c Problems

Amenorrhea represents a sort ot abnormal bleeding in that it is the lack of

menstruation. Primary- amenorrhea is defined as the absence of menses bv age

1 6. Secondan- amenorrhea is the absence of menses for a variable period of

time, for at least 3 months and usually sis months or longer, in a woman who

has preAouslv menstruated.

B. RELATIONSHIP TO HI\^DISEASE

Menstrual disorders are firequendy reported by HI\"-positive women. However,

controlled smdies have yielded conflicting evidence regarding whether HR" or HR -related immunosuppression exerts a clinicallv significant direct effect on

these reported disturbances (Shah, 1994; EUerbrock, 1996; Chirg^xin, 1996)

and more definitive smdies are needed.

In the setting of HR" infection menstrual disorders mav be related to con- founding variables, such as weight loss, chronic disease, substance abuse, and

progestational agents used for appetite stimulation or contraception. The

impact of antiretroviral therapv on menstruation has not been well smdied but

hypermenorrhea, or excessive menstrual blood loss, has been reported \\ith

ritonavir. ^"Nielsen, 1999) The effect of HR"-RXA levels on menstrual function is unknown.

C HISTORY

Characteristics of bleeding date of last menstrual period, duration and

frequency of menses, amount of bleeding (number of pads/tampons used

per dav); presence of clots or associated pain/cramping; duration of menstrual irregularities or amenorrhea; presence of intermenstrual or postcoital

bleeding

Other bleeding sources: gastrointestinal (GI) or bleeding from the urinary

tract versus a gyn source); history of easv bruising, nose or gum bleeds

History of gynecologic problems /other s\Tnptoms: abnormal Pap

smears; uterine fibroids or polyps; prior ectopic pregnancy, abnormal vaginal discharge

Medical history: riming

of diagnosis of HR" disease/AIDS and existing

comorbid conditions; clinical symptoms of HR"; CD4 count and viral load;

history of platelet disorders (thrombocytopenia is firequendy diagnosed in

HR" infection, particularly in individuals with more advanced stages of dis- ease (Sloand, 1992); medications; history of substance abuse

Sexual histotA*: last sexual intercourse and use of conuaception and

condoms

D. PHYSICAL EXAM

A careful and comprehensive abdominal and pelvic examination should be

performed The presence of abdominal tenderness or mass should be noted

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Gynecologic Problems

The external genitalia, vagina, and cervix should be inspected for evidence of

activ ely bleeding lesions (e.g., lacerations, condylomata, polyps) or inflammation. A bimanual and rectovaginal examination assess the presence of pelvic

teiulerness, enlarged uterus or other pelvic mass.

E. DIFFERENTIAL DIAGNOSIS

Pregnancy. Pregnancy must be considered in any woman of reproductive

age with irregular bleeding or amenorrhea. Pregnancy may be either

intrauterine or ectopic (usually tubal); bleeding with an intrauterine pregnancy may indicate threatened or incomplete abortion or miscarriage or a serious obstetrical complication in later pregnancy.

Anovulation. Anovoilation is the most common cause of abnormal uterine

bleeding among reproductive-aged women. Typically, the woman has a history of menstrual irregularity and may go several months with no bleeding,

followed by the onset of prolonged and heavy bleeding. Anovulatory bleeding is a diagnosis of exclusion and organic, systemic, and iatrogenic causes of bleeding must be ruled out. Anovulation and oligoovulation are more

common among perimenopausal women and adolescents soon after menarche.

Perimenopause. In addition to anovulation/oHgoovulation, women in the

perimenopause may have irregular bleeding because of declining estrogen

levels.

Uterine fibroids. Fibroids are common benign uterine tumors that are most often asymptomatic, but may cause heavy and/or prolonged periods.

Cancer. Malignant processes in every part of the female genital tract (vulva,

vagina, cervix, uterus, fallopian tubes, and ovaries) can potentially present

with abnormal bleeding; most common in postmenopausal women.

Genital Tract Infections. Cervicitis, vaginitis, endometritis, vulvitis, and

pehtic inflammatory disease may present with abnormal vaginal bleeding or

spotting. Associated symptoms, including pain/tenderness, discharge, fever,

and other signs and symptoms of infection, will aid in making the diagnosis. In very immunosuppressed patients, consider opportunistic processes,

including tuberculous or CMV endometritis.

Medical conditions. Thyroid disorders (hypothyroidism or hyperthyroidism), coagulopathy (including platelet disorders), cirrhosis, chronic ill- ness/wasting.

Substance abuse. Drug use (including methadone) can lead to disturbances of the hyptothalamic-pituitary axis, with resulting irregular bleeding

or amenorrhea.

Medications. Progestational agents, such as those used for contraception

(e.g., Depo Provera, Norplant) or for appetite stimulation (e.g., Megace) fre- quently cause irregular vaginal bleeding. Consider antiretroviral agents as a

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V

(lynccologic l^roblcms

potential cause of abnormal bleeding. Medications which can affect prolactin concentrations and possibly result in amenorrhea include psychotropic drugs (tricyclic antidepressants, pheothia2ines, opiates) and

metoclopramide.

R EVALUATION

The basic evaluation includes the following:

Pregnancy test (urine or serum): perform on all women with abnormal

bleeding/amenorrhea within reproductive age range

Laboratory tests:

1. CBC, platelet count

2. Thyroid stimulating hormone (TSH), prolactin levels — consider with any irregular bleeding/amenorrhea without apparent

cause

3. Follicle stimulating hormone (FSH), estradiol —with

oligomenorrhea/amenorrhea and/or signs /symptoms of

decreased estrogen production (hot flashes, vaginal atrophic

changes). These tests are particularly helpful in distinguishing

ovarian failure (low estradiol, high FSH) and hypothalamic amenorrhea (e.g., with wasting) (low estradiol, low/normal FSH)

4. Coagulation profile — if evidence of systemic bleeding, to rule

out coagulopathy

Cervical testing for gonorrhea and chlamydia

Pelvic ultrasound: with abnormal exam (uterine enlargement, adnexal

mass, significant tenderness)or positive pregnancy test Endometrial biopsy: indicated with postmenopausal bleeding, prolonged amenorrhea followed by onset of irregular or heavy bleeding, persistently irregular bleeding. It is helpful in diagnosing endometritis,

endometrial hyperplasia, and uterine cancer; endometrial tissue necessary

to diagnose CMV or TB endometritis-alert your pathologist if these are considerations

Pap smear: do not perform with active bleeding; if cervical lesion seen, biopsy is required.

Further evaluation or referral is indicated based on results of these tests, severity of the problem, and response to basic management.

G. MANAGEMENT

Management depends on the diagnosis and results of testing. All women with

a positive pregnancy test require referral to a specialist. If anovulatory bleeding is suspected, medical management may be attempted with oral contraceptive pills (OCPs) or cyclic progestins (medroxyprogesterone acetate 10 mg po

QD for 10—14 days each month); these therapies help restore regular menstruUS. Department of Health and Hum,\n Services, Health Resourcils and Services AdministR/VDOn, HIV/AIDS Buriuu
A Guide to the Clinic.\l C.\re of Women with

Gynecologic Problems

ation; reckice possible anemia; and protect the endometrium from prolonged

estrogenic stimulation, which can cause hj’perplasia or neoplasia. OCPs will

also provide effecdve contraception, but are contraindicated in heavy smokers

over the age of 35, with hypertension or other cardiovascular disease, and in

diabetics and women with markedly abnormal liver function.

W ith severe bleeding and anemia, pelvic mass, findings suspicious for

malignancy, or bleeding that is not resolved with conservative measures, referral is indicated.

III. ABNORMAL PAP SMEAR

In the setting of HIV infection 30—60% of pap smears exhibit cytologic

abnormalities and 15^0% have evidence of dy^splasia; these rates are ten to

eleven times greater than those observed among HIV-negative women.

(Maiman, 1998)

A. INTERRELATIONSHIP OE HIVAND HUMANPAPILLOMAVIRUS (HPV)

Human Papillomavirus (HPV) infection plays a causative role in genital

intraepithelial and invasive neoplasia. The spectrum of HPV disease

includes subclinical disease, classic genital warts and other HPV-related skin

lesions, lower genital tract intraepithelial neoplasia, and invasive cancers of

the lower genital tract. There are over 70 HPV subtypes, which are di\tided

into low; intermediate or high risk, based on oncogenic potential; nevertheless, numerous exceptions exist and “low-risk” HPV types have been

described in cerHcal carcinomas.

HPV is an extremely common infection; current evidence suggests that over 50% of sexually^ active adults have been infected with one or more

genital HPV types, but most HPV infections are transient. (Evander, 1995;

Ho, 1998) Studies have shown that HIV-infected women have higher prevalence of HPV (Sun, 1997; Shah, 1996; Palefsky, 1999; Minkoff, 1998);

longer persistence of HPV (Sun, 1997); higher likelihood of multiple HPV

subtypes (Brown, 1994); and greater prevalence of oncogenic subtypes

(IMinkoff, 1998; Uberti-Foppa, 1998) than in HIV-uninfected women.

In HIV-positive women the prevalence and persistence of HPV infection

increases with decreasing CD4 count and increasing HIV RNA levels

(Palefsky^, 1999) and some studies show that oncogenic HPV types may be

more common with lower CD4 counts and/or higher \tiral loads. (Minkoff,

1998; Tuque, 1999)

Sun et al (Sun, 1995) have suggested that the presence of immunosuppression shifts the ratio of latent: clinically expressed HPV infections from 8:1 in the general population to 3:1 in HIV-positive women with CD4

> 500/mm^ to 1:1 in HIV-positive women with CD4 < 200/mm\

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B. HIVAND CERVICAL DYSPLASIA

Abnormal cervical cytology is more common among HIV-infected women

and is associated with the presence of HPV infection and the degree of

immunesuppression . Both frequency and severity of abnormal pap smears and histologically documented dysplasia increase with declining CD4 counts

and have also been associated with higher HIV-RNA levels. (Shah, 1996;

Garzetti, 1995)

In HIV-positive women dyspasia is associated with more extensive cervical

involvement, and is more likely to involve other sites in the lower genital

tract, such as the vagina, vulva, and perianal region (Maiman, 1990; Petry,

1996; Korn, 1995; Williams, 1994; HiUemans, 1996) as compared to HIVnegative women.

Recent studies have shown increased incidence of oncogenic HPV types

(Minkoff, 1998) and increased incidence of biopsy proven cervical dysplasia

(EUerbrock, 2000) in HIV-positive women compared to HIV-negative controls. A French study found an increased Likelihood of progression of cervical abnormalities in HIV-positive women, although analysis was based on

pap smear results only. (Six, 1998) At the current time there is Uttle evidence for increased rates of progression to invasive cancer, particularly if adequate screening and treatment programs are in place.

C INVASIVE CERVICAL CANCER IN HIVDISEASE

In 1993, the CDC expanded the case definition of AIDS to include invasive

cervical cancer.

There is little evidence to date that HIV infection is having a significant

impact on cervical cancer rates. However, a review of New York City AIDS

surveillance data 1990—1995 found that the observed cervical cancer cases were 2—3x higher than the expected number of cases. (Chiasson, 1997) One

study reported a higher prevalence of invasive cervical cancer in HIV-positive as compared to HIV-negative hospitalized patients, particularly among

those aged 20 to 34 and among African-American and Hispanic women.

(Weber, 1998) Women with HIV and cervical cancer tend to be younger

and less immunosuppressed as compared to HIV-positive women with

other AIDS-indicator conditions.

HIV-positive women with invasive cervical cancer appear to present at more

advanced stages, may metastasize to unusual locations (e.g. psoas muscle,

clitoris, meningeal involvement), have poorer responses to standard therapy,

and have higher recurrences and death rates, as well as shorter intervals to recurrence or death, as compared to HIV-negative women of similar stage.

(Maiman, 1990; Klevens, 1996)

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D. SCREENING TESTS

A single pap smear is associated with false negative rates of 10-25%; accuracy is significantly improved with regular periodic screening. Controlled

studies have not demonstrated a decrease in sensiti\ity or specificity with

standard cer\ical cytologt^ in HIV-positive women as compared with HIVnegative controls. (Adachi, 1993; SpiniUo, 1998)

Newer pap smear screening techniques using liquid-based media appear to

increase sensiti\ity, decrease inadequate smears, and reduce, but do not

eliminate, false negative results; they also offer the possibility of direct HPV

testing on collected specimens. They are more expensive than conventional

pap tests; there are no current data examining the utility of these tests in

HIV-positive women.

HPV testing can identify both oncogenic and non-oncogenic ^iral Rq>es;

such testing may play an important role in the evaluation of women with

equivocal Pap smear results, (hlanos, 1999)

The role of HPV-DNA testing as an alternative or addition to the pap

smear in HIV-positive women is unknown. One small study found that

HIV-positive w^omen with normal paps and CD4 counts < 200/mm^ and

presence of HPV-DNA were more likely to have biopsy-proven abnormalities as compared to HIV-negative women or HIV-positive women with

higher CD4 counts. (Anderson, 1996) A recent German study examining

HPV-DNA testing as a primary screening method for cer\ical dysplasia in

Table 6-1: Pap Smear Report Format for Bethesda System

Statement on specimen adequacySatisfactory for interpretation

Less than optimal

Unsatisfactory

General categorization Within normal limits Other/descriptive diagnosis

Descriptive diagnoses Benign cellular changes (including infections)

Reactive and reparative cellular changes (including

inflammation)

Epithelial cell

' abnormalities

Atypical squamous cells of undetermined significance

(ASCUS)

Low-grade squamous intraepithelial lesion (SIL),

including HPV changes and mild dysplasia/CIN 1 High-grade squamous intraepithelial lesion, including

moderate and severe dysplasia, CIN 2, CIN 3, carcinoma in situ Squamous cell carcinoma

Glandular cell abnormalities

Nonepithelial

malignant

neoplasm

Specify

Hormonal

evaluation (vaginal smears only)

Specify

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94 HIV-positive women found that HPV-DXA testing identified high-grade

cerHcal dysplasia more accurately than pap smear. (Petty, 1999)

Pap smear results are reported according to the Bethesda System. (National

Cancer Instimte Workshop, 1989)

E. RECOMMENDATIONS FOR PAP SMEAR SCREENING AND

COLPOSCOPY (CDQ 1998):

Both the CDC and the Agency for Health Care Policy and Research recom- mend that HI\"^infected women have a complete g}'necologic evaluation,

including a Pap smear and pehic exam, as part of their initial evaluation.

A Pap smear should be obtained tv,ice in the first year after diagnosis of

HR" infection. If these results are normal, annual examinations are then

indicated.

More firequent Pap smears should be obtained: • \^ith preHous abnormal Pap smear • HPV infection • after treatment for cervical dysplasia • in women \iLith symptomatic HR’’ infection (including CD4 counts

< 200/mm^

The American College of Obstetricians and Gynecologists recommends

Pap smears every 3—4 months for the first year after treatment of preinvasive cer\tical lesions, followed by Pap smears every six months. (ACOG,

1993)

The role of anal cytology is currentiy under smdy.

Indications for colposcopy are outUned in Table 6-2.

Table 6- 2 : Indications for Colposcopy

Cytologic abnormality (atypia or greater, including ASCUS, AGCUS)

History of untreated abnormal Pap smear

Consider periodic colposcopy after treatment of cervical dysplasia

Consider with evidence of HPV infection

Consider screening colposcopy with CD4 < 200/mm^

Table 6- 3 : Suggested frequency of Pap smears

CuNiCAL Scenario Screening Frequency

Normal Pap One year

Symptomatic infection / CD4 < 200 6 months

ASCUS/LGSIL (evaluated and followed

without treatment)

4-6 months

Following treatment of preinvasive

lesions

3-4 months for first year, then 6 months

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ASCII'S (atypical squamous cells of undetermined significance) represents

the mildest cytologic abnormality in the Bethesda system; its significance,

however, v^aries tremendously among different cytopathologists and laboratories. Various studies have found underlying dysplasia in 10—60% of

women with ASCUS on pap. In a study of women with ASCUS, Wright

(Wright, 1996) found that HIV-positive women were approximately twice as

likely to have underlying dysplasia as compared to HIV-negative women; a recent cross-sectional analysis of 761 pap smears form HIV-positive women

found that 27% were diagnosed as ASCUS; 15% had underlying high-grade

dysplasia. (Holcomb, 1999) Immunesuppression did not appear to increase

the frequency of dysplasia associated with ASCUS on pap. In the general

population it is recommended that an initial report of ASCUS prompt

repeat pap smear and referral for colposcopy be made with a second

ASCiUS report. However, given the frequency of cervical abnormalities and

the possible increased likelihood of underlying dysplasia with ASCUS in the

setting of HIV infection, many experts prefer to proceed with colposcopic

evaluation with the initial report of atypical cells. The ability to do this may

be limited by availability of colposcopic equipment and trained colposcopists.

The risk of underlying pathology with a diagnosis of ACGUS (atypical

glandular cells of undetermined significance) is significant: 17—34% have

associated significant intraepithelial or invasive lesions. (Kennedy, 1996;

Duska, 1998; Korn, 1998) Colposcopy is indicated with any AGCUS on

pap, as well as endocervical and endometrial sampling.

Biopsies should be obtained at the time of colposcopy to confirm cytologic

abnormalities and/or if abnormal areas are visualized.

Because of the multicentric nature of lower genital tract intraepithelial neoplasia in the setting of immunesuppression, it is recommended that the

entire lower genital tract (vagina, vulva, and perianal region) be examined at the time of colposcopy.

R MANAGEMENT OF CERVICAL LESIONS

Management of abnormal pap smears is outlined in Table 6-4. Documentation

of a high grade cervical lesion requires treatment. Standard excisional or ablative treatment is recommended, although HIV-positive women have an

increased incidence of recurrence after treatment (over 50% recurrence rate),

correlated with degree of immunesuppression. (Fruchter, 1996; Holcomb,

1 999) Cryotherapy has had the highest rate of recurrences and should be

avoided, if other treatment methods are available.

Topical vaginal 5-fluorouracil (5-FU) cream (2 gm biweekly for six months) was shown to reduce recurrence rates after standard treatment for high-grade

cervical dysplasia in HIV-positive women in a recent clinical trial; over 1

8

months of foUow-up, 31% of women with observation only developed a

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Civnccologic Problems

Table 6-4: Recommended Management for Abnormal Pap Smears

Pap smear result Management

(based on histologic findings)

Severe inflammation Evaluate for infection; repeat Pap if inadequate

Atypia, ASCUS Colposcopy, biopsy if indicated; follow

with Pap Q6 months

Low grade squamous intraepithelial

lesion (LGSIL, LSIL, CIN 1) Colposcopy, biopsy if indicated; followwith Pap Q6 months; consider repeat

colposcopy annually

High grade squamous intraepithelial

lesion (HGSIL, HSIL, CIN 2 or 3, carcinoma in situ)

Colposcopy, biopsy; treat with loop

excision or conization

Invasive carcinoma Colposcopy with biopsy or conization;

treat with surgery or radiation (referral to gynecologic oncologist needed)

recurrent high-grade lesion as compared to 8% of women receiving 5-FU.

Disease recurred more slowly in women who had received antiretroviral therapy, as compared to those who were antiretroviral-naive. (Maiman, 1 999)

5-FU may play a role in secondary prophylaxis of preinvasive cervical

lesions in some cases. However, clinical experience with this therapy is too

limited to provide a recommendation for routine use. 5-FU may have significant mucosal toxicity and concerns have been raised about the potential for

increased risk for transmission of HIV or other STDs with this therapy.

The role of highly active antiretroviral therapy (HAART) and immune

reconstitution in the management of lower genital tract precancerous lesions

remains unclear. In one study use of HAART was associated with regression

of cervical lesions over a median foUow-up of 5 months. (Heard, 1998) However, Duerr and colleagues found no differences in pap smear results, HPV

acquisition or persistence, number of HPV types, or the amount of HPV

present after 6—12 months on HAART. (Duerr, 1998)

At the current time, HIV-positive women should continue to be followed

closely for evidence of lower genital tract neoplasia, regardless of antiretroviral therapy or viral load.

IV. GENITAL ULCERS

A. HISTORY

Duration and location of lesion(s); previous history of genital ulcers, syphilis, or genital herpes (HSV); associated symptoms (pain, pruritus,fever, etc.); medications and timing of ulcers relative to initiation of new medication; sexual

history (including condom use); and CD4 counts and HIV RNA levels.

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B. PHYSICAL EXAM

Dimensions and location of lesion(s); presence of pigmentation, edema, erythema, or induration; presence of associated exudate or tenderness; presence

of oral lesions; associated lymphadenopathy or rash.

C EVALUATION

1 . Syphilis serology or darkfield examination

2. Culture or antigen test for HSV

3. Biopsy — with unclear diagnosis, lack of response to treatment; consider

special stains, if indicated (CMV, AFB)

4. Culture for Haemophilus ducreyi — not widely available commercially;

diagnosis of chancroid generally made with typical cHnical presentation,

after excluding syphilis and HSV

D. DIEFERENTIAL DIAGNOSISAND MANAGEMENT

Infectious

Herpes Simplex Virus (HSV)

most prevalent infectious cause of genital ulcers in the U.S.

two distinct serotypes of HSV (HSV-1 and HSV-2), most cases of recur- rent genital herpes (60—95%) are caused by HSV-2

since the late 1970s, the seroprevalence of HSV-2 infection has increased

by 30%; infection is now detectable in 21.9% of people aged 12 or older

nationwide (Fleming, 1997)

ppicaUy lesions present as painful vesicles that ulcerate and heal without

scarring

primary infection often associated with systemic symptoms (fever, photophobia, headache); duration of lesions and viral shedding more prolonged with primary infection; after primary episode latency established

in sacral dorsal root ganglia

nonprimary first episode herpes occurs in individuals with antibodies to

HSV-1 or HSV-1 but no previous clinical symptoms of HSV; milder,

shorter episode

recurrent episodes occur at variable frequency; more localized lesions,

shorter duration as compared to first episodes (primary or nonprimary)

viral shedding and sexual transmission can occur during asymptomatic

periods

HIV-positive patients: • more frequent, prolonged, and/or severe episodes common with

progressive immunesuppression; lesions may be appical in appear- ance or location

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• viral shedding increases with declining CD4 counts (Augenbraun,

1995); may be more common in oral contraceptive or Depo-Provera

users and in women with severe vitamin A deficiency (Mostad,

2000); most viral shedding asymptomatic • HSV is associated with increased risk for HIV transmission/ acquisition (Heng, 1994)

Treatment: See Table 6-5.

Table 6-5: Recommended Management for HSV

Drug Dose

First clinical episode Acyclovir 400 mg po three times a day for 7-10 days

Acyclovir 200 mg po five times a day for 7-10 days

Famciclovir 250 mg po three times a day for 7-10 days

Valacyclovir 1 gm po twice a day for 7-10 days

Recurrent episodes Acyclovir 400 mg po three times a day for 5 days

Acyclovir 200 mg po five times a day for 5 days

Acyclovir 800 mg po twice a day for 5 days

Famciclovir 125 mg po twice a day for 5 days

Valacyclovir 500 mg po twice a day for 5 days

Daily suppressive

therapy

Acyclovir

Famciclovir

Valacyclovir

Valacyclovir

400 mg po twice a day

250 mg po twice a day

500 mg po once a day

1000 mg po once a day

Severe disease Acyclovir 5-10 mg/kg body weight IV every 8 hours

for 5-7 days or until clinical resolution is achieved

Acyclovir-resistant HSV Foscarnet 40 mg/kg body weight IV every 8 hours or 60 mg/kg IV every 12 hours for 3 weeks

topical

Cidofovir

gel 1%

applied to lesions once a day for 5

consecutive days

Source: CDC, 1998.

Syphilis

systemic disease caused by Treponema pallidum

definitive methods for diagnosing early syphilis are darkfield examination

and direct fluorescent antibody test of lesion exudate or tissue

presumptive diagnosis is possible using two types of serologic tests for

syphilis: VDRL or RPR (nontreponemal) and a confirmatory FTA-ABS

or MHA-TP (treponemal)

nontreponemal test antibody titers usually correlate with disease activity

and are used to assess treatment response

HIV-infected patients may have abnormal serologic test results (e.g,

unusually high titers, false negatives or delayed seroreactivity). However,

generally serologic tests can be interpreted in the usual manner. If clinical

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iMulings suggest syphilis but serology is nonreactive, biopsy, darkfield

examination, or direct fluorescent antibody staining of lesion material

sliould be considered. The clinical presentation of syphilis is very

variable at all stages; atypical manifestations may be seen in the setting

of 1 II V disease. Neurosyphilis should be considered in the differential

diagnosis of neurologic signs or symptoms in HIV-infected individuals

(CDC, 1998)

Treatment: See Table 6-6.

Table 6-6: Recommended Management for Syphilis

Stage Treatment

Primary and Secondary Syphilis and

Early Latent Syphilis

Benzathine penicillin G 2.4 million units

IM (single dose); additional treatment

recommended by some (i.e., three

weekly doses of penicillin)

If penicillin-allergic (non-pregnant

patients only)

Doxycycline 100 mg po twice a day for

2 weeks, OR tetracycline 500 mg po

four times a day for 2 weeks

Late Latent Syphilis or Syphilis of

Unknown Duration (including tertiary

syphilis)

Examination of the CSF must be

performed prior to initiation of treatment.

If the CSF examination is negative,

patients should be treated with 7.2

million units of benzathine penicillin G

(three weekly doses of 2.4 million units

each) IM

Neurosyphilis Aqueous crystalline penicillin G 18-24

million units a day (administered as 3-4 million units IV every 4 hours) for

10-14 days.

Administration of benzathine penicillin

2.4 million units IM after completion of

the IV regimen recommended by some. Recommended Follow-Up

Stage Follow-Up

Primary and secondary syphilis HIV-infected patients require clinical and

serologic evaluation for treatment

failure at 3, 6, 9, 12, and 24 months

after treatment. Treatment failures necessitate a CSF

examination and re-treatment (three

weekly doses of 2.4 million units of

benzathine penicillin G if CSF

examination is negative).

The latter regimen should also be

considered for patients whose titers do

not decrease fourfold within 6 to 12

months.

Table continues

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Ciynccologic Problems

Table 6-6: Recommended Management for Syphilis (continued)

Stage Treatment

Recommended Fouow-Up (continued)

Latent syphilis HIV-infected patients require clinical and

serologic evaluation at 6, 12, 18, and

24 months after treatment. The CSF examination should be repeated

and appropriate treatment instituted if clinical symptoms develop, titers rise fourfold, or if titers fail to decline

fourfold between the evaluations at 12 and 24 months.

Neurosyphilis CSF examination should be repeated

every six months until the cell count is normal.

Retreatment should be considered if the

cell count has not decreased after six months or if the CSF is not entirely

normal after two years.

Source: CDC, 1998.

Chancroid

caused by Haemophilus ducreyi

endemic in some areas of the United States; also occurs in discrete outbreaks

10% of patients with chancroid have coinfection with T. pallidum or HSV

initial presentation typically consists of a tender papule that becomes

pustular and then ulcerative; the ulcer is usually well demarcated, with

ragged undermined edges

probable diagnosis can be made if: the patient has one or more painful

ulcers, there is no evidence of T. pallidum or HSV infection, and the clinical presentation appearance of ulcers and regional lymphadenopathy is typical for chancroid . Response to treatment may be diminished in the HIV-infected patient:

may require longer courses of therapy, increased risk for treatment failure

Treatment: • Azithromycin 1 gm po (single dose), OR

• Ceftriaxone 250 mg IM (single dose), OR

• Ciprofloxacin 500 mg po twice a day for 3 days, OR

• Erj^thromycin base 500 mg po four times a day for 7 days. • Pdote

In HIV-positive patients use single dose therapies only if followup can be ensured;

Some experts recommend the 7-day erythromycin regimen in the

setting of HIV infection.

us. Departnient of Health .and Human Services, He.alth Resources .and Services Administration, HIV/AIDS Burilau
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Gynecologic Problems

Cytomegalovirus (CMV)

should be suspected in severely immunocompromised patients

diagnosis requires biopsy of lesion with immunohistochemical stains

cervical shedding of CMV is associated with low CD4 counts (Clarke,

1996)

Treatment: • Ganciclovir 5 mg/kg IV twice a day for 2—3 weeks, OR

• Foscarnet 60 mg/kg IV q

8 hours or 90 mg/kg q

12 hours for 2—3

weeks.

Other Infectious Causes of Genital Ulcers

Lymphogranuloma Venereum (LGV): rare in U.S.; associated with tender, usually unilateral inguinal or femoral lymphadenopathy, proctocolitis,

rectal fistulas/strictures; diagnosis with serology and exclusion of other

causes; treatment doxycycHne or erythromycin for 3 weeks; HIV-positive

individuals may require more prolonged treatment

Granuloma Inguinale (Donovanosis): rare in U.S.; painless, progressive

ulcers which bleed easily on contact, without regional lymphadenopathy;

diagnosis with biopsy or tissue crush preparation; treatment trimethoprim-sulfamethox-azole or doxycycline for 3 weeks or until all lesions

healed; CDC recommends adding aminoglycoside to regimen in HIVpositive patients

Tuberculosis (Giannacopoulos, 1998): genital TB is generally a secondary manifestation of primary (usually pulmonary) disease. In the United

States, the incidence of genital disease is < 1%. Diagnosis is established

by biopsy. Genital tuberculosis should be treated as is extrapulmonary

disease; expert consultation is necessary.

Inflammatory Conditions

Crohn’s Disease

This disease may be easily misdiagnosed since its principal clinical fea- tures (i.e., fever, abdominal pain, diarrhea, fatigability, weight loss) are often found in patients with HIV disease. Crohn’s Disease may also present with genital ulcers, rectal fissures, perirectal abscesses, or intestinal fistulas. Sigmoidoscopy or barium enema is essential in making this

diagnosis. Manage with expert consultation.

Behcet’s Syndrome

This is a multisystem disorder that presents with recurrent oral and genital ulcerations as well as uveitis, arthritis, and vasculitis. Vaginal ulcers are usually painless, whereas lesions on the external genitalia are generally

painful. Ulcers range between 2 and 10 mm in diameter, and they can be

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Clynccologic Problems

shallow or deep with a central yellowish necrotic base; either a single

lesion or crops of lesions may be evident. The diagnosis is established

based on the clinical presentation and biopsy. Treatment consists of topical or systemic corticosteroids.

Hidradenitis Suppurativa. (Droegemueller, 1997)

This condition is a chronic, refractory infection involving the skin, subcuta- neous tissues, and apocrine glands. Lesions are painful and are associated

with a foul-smeUing discharge. Eventually, a deep-seated chronic infection

of apocrine glands develops, with multiple draining abscesses and sinuses. A

biopsy is necessary to establish the diagnosis. In the early stages of disease,

treatment options include antibiotics, topical steroids, antiandrogens, and

isotretinoin. Treatment of advanced disease requires surgical intervention.

Neoplastic

any nonhealing genital ulcer must be biopsied to rule out a neoplastic

process

squamous cell carcinoma, basal ceU carcinoma, adenocarcinoma, melanoma,

lymphoma, Kaposi’s sarcoma

refer to oncologist

Drug Reaction

Has been described as rare side effect of treatment with ddC and foscarnet

Aphthous Genital Ulcerations (Anderson, 1996)

no specific etiology (typical or opportunistic organism) is identifiable

similar to aphthous ulcers seen in the gastrointestinal tract

most patients are significantly immunosuppressed (median CD4 count

50/mm^)

lesions can be painful, multiple, deep, and extensive (size 1 to 6 cm)

associated morbidity includes immobility, bleeding, and superinfection

most have been reported to be chronic and/or recurrent or relapsing

oroesophageal ulcers coexist in about one third of cases and one fifth were

associated with fistula formation

Treatment: • Consider empiric therapy for HSV. • If empiric therapy fails, systemic steroids (prednisone 40—60 mg/day

for 1—2 weeks, then taper) have been moderately successful.

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A Guide to the Clinical Care of Women with HIV

Gynecologic Problems

• Thalidomide (200 mg/day for 2—4 weeks) has been used in similar

ulcers in the oropharynx or esophagus with complete healing in

55—73% of these ulcers (Jacobson, 1999; Jacobson, 1997); there has

been similar success anecdotally in genital apththous ulcers. (Warning:

this drug is a powerful teratogen and should only be used in women of

reproducdve age after appropriate counseling and pregnancy testing

and in the setdng of reliable contracepdon or absdnence.)

Trauma

history of traumadc injury

consider possibility of sexual violence

V. VAGINAL DISCHARGE

A. HISTORY

Duration and characterisdcs of discharge, associated symptoms (e.g., pruritus,

malodor, burning, pelvic pain), sexual history (including condom and other

contracepdve use), history of sexually transmitted diseases, history of douching, recent andbiodc use, CD4 counts and HIV-RNA levels, medicadons.

B. PHYSICAL EXAM

Complete genital inspecdon and bimanual pelvic examinadon; document the

characterisdcs and amount of discharge as well as the presence of erythema,

edema, and tenderness.

C EVALUATION

saUne wet mount

10% potassium hydroxide (KOH) prep

vaginal pH determinadon

tesdng for gonorrhea and chlamydia

fungal culture, if indicated (signs/ symptoms of yeast infecdon with negadve findings on microscopy; chronic/recurrent yeast infecdons)

D. DIEEERENTIAL DIAGNOSISAND MANAGEMENT

Bacterial Vaginosis (BV)

most prevalent cause of vaginal discharge or malodor

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A CjUioI' to I'lii; (j.iNicAi. C\ui' oi' Womp.n with HIV

Gynecologic Problems

results from replacement of normal LMCtohacillus dominant vaginal flora with

increase in prevalence and concentration of mixed flora, including anaerobic bacteria, Gardnerella vaginalis, and Mycoplasma hominis

18^2% prevalence among HIV-infected women; no significant difference

as compared to HIV-negative controls and no difference by CD4 count

(Cu-Uvin, 1999; Greenblatt, 1999)

some studies suggest that BV or BV-associated organisms (or lack of vaginal

lactobacilli) may enhance HIV transmission (Olinger, 1999; Martin, 1999)

associated with increase in several obstetrical and gynecologic complications, including pelvic inflammatory disease (PID), post-abortal and

posthysterectomy infections, preterm labor

standard diagnosis by clinical criteria; requires three of the following:

1) a homogeneous grayish or yellowish discharge (may coat vaginal walls);

(2) clue cells on microscopic examination; (3) vaginal pH >4.5; (4) a positive whiff test (i.e., fishy odor of discharge before or after addition of

10% KOH)

Treatment: See Table 6-7.

Table 6-7 : Recommended Management for Bacterial Vaginosis

Metronidazole 500 mg po twice a day for 7 days

Clindamycin cream 2%, 5 gm intravaginally at bedtime for 7 days

Metronidazole gel 0.75%, 5 gm intravaginally twice a day for 5 days

Note: Clindamycin cream is oil-based and may weaken latex condoms and diaphragms.

Alternative regimens: Metronidazole 2 gm po

Clindamycin 300 mg po twice a day for 7 days

Source: CDC, 1998.

Vulvovaginal Candidiasis

Most commonly caused by Candida albicans-, the prevalence of infections due

to nonalbicans species is increasing

75% of all women will have at least one episode of candidiasis, and

40-45% will have two or more episodes; less than 5% of women experi- ence recurrent episodes of candidiasis

typical symptoms: thick, white discharge and pruritus; other symptoms

include vulvar burning, vaginal soreness, dyspareunia, and external dysuria

Prevalence among HIV-infected women is 3—1 5%; most studies suggest no

significant difference in prevalence of infection between relatively immunocompetent HIV-positive women and HIV-negative controls; several other

studies have found increasing infection rates with declining CD4 counts.

(Cu-Uvin, 1999; Duerr, 1997) HIV-positive women may have higher incidence of infection (El-Sadr, 1997)

us. Demrtment of Health and Human Services, Health Resources and Servicf.s Administr^ation, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Gynecologic Problems

Possible confounding factor for HIV-positive women is more frequent use of antibiodcs

M(jst smdies show increased rates of vaginal (also rectal, oral) colonization

in HIV-positive women, particularly with declining immune function; no data

on relationship between HIV-RNA levels and candidiasis or colonization

In HIV-positive women 26-27% of vaginal isolates are non-albicans strains

(NAS) (Schuman, 1998); available studies are conflicting re: proportion of

NAS in HIV-positive as compared to HIV-negative women; most common

is Torulopsis glabrata. No association found to date between strain diversity

and HIV progression

diagnosis is made by identifying budding yeast or pseudohyphae on a wet

mount or KOH prep or Gram stain of vaginal discharge; positive identification can also be accomplished by means of culture

Treatment regimens: See Table 6-8.

Table 6-8: Recommended Management for Vulvovaginal

Candidiasis

Topical Azoles

Butoconazole 2% cream 5 gm PV for 3 days*

Clotrimazole 1% cream 5 gm PV for 7-14 days*

Clotrimazole 100 mg vaginal tablet for 7 days

Clotrimazole 100 mg vaginal tablet, 2 tablets for 3 days

Clotrimazole 500 mg vaginal tablet x 1 Miconazole 2% cream 5 gm PV for 7 days*

Miconazole 200 mg vaginal suppository for 3 days*

Miconazole 100 mg vaginal suppository for 7 days*

Miconazole 1200 mg vaginal suppository x 1 Tioconazole 6.5% ointment 5 gm PV x 1*

Tioconazole 2% cream 5 gm PV for 3 days

Terconazole 0.4% cream 5 gm PV for 7 days

Terconazole 0.8% cream PV for 3 days

Terconazole 80 mg vaginal suppository for 3 days

* OTC.

Note: These creams are oil-based and may weaken latex condoms and diaphragms.

Oral agent*

Fluconazole 150 mg po x 1 * avoid concomitant use with terfenadine, astemizole, cisapride secondary to cardiotoxicity

Others

Nystatin 100,000 unit vaginal tablet, one tablet for 14 days (less effective)

1% Gentian violet applied to vagina 4 times at intervals of approximately 7 days*

Boric acid 600 mg intravaginal capsules BID for 2 weeks*

* may be useful in chronic/recurrent cases; gentian violet messy, causes mucosal exfoliation; encourage abstinence during treatment; reinforce condom use.

us. Department of Health and Human Services, HE,u;m Resources and Serntcils Administ-ration, HI\7AIDS Hi ki.m 167
A CJuiDii 1C) rill' (j.iNicAi. Cari', oi' Womkn with HIV

Gynecologic Problems

• Special considerations in HIV-positive women:

Topical therapies may be more effective when given for at least 7

days

Consider prophylactic use of topical antifungals when antibiotics are given

Randomized, placebo-controlled trial of fluconazole 200 mg po

weekly for prophylaxis of candidiasis in women with CD4

< 300/mm^ (median CD4 15/mm^): effective in preventing

oropharyngeal candidiasis (RR 0.50, p

< 0.001) and vaginal can-

(iidiasis (RR 0.64, p=0.05), but not esophageal candidiasis. (Schuman, 1997) Consider in selected cases with recurrent vaginal

candidiasis.

Recent study found that ritonavir and indinavir (and possibly

other protease inhibitors) strongly inhibited secretory aspartyl proteinase (proteolytic enzyme produced by pathogenic Candida

species, considered a virulence factor) activity and production in a dose-dependent fashion, and exerted a therapeutic effect in an

experimental model of vaginal candidiasis, with efficacy similar to

fluconazole. (Cassone, 1999) • Azole resistance:

Concerns have been raised about extensive use of oral azoles and promotion of azole resistance, possibly limiting use of these agents for

other HIV-related indications. Current information about development

of resistance is limited:

ACTG 816: annual incidence of clinical failure to fluconazole (persistence of oral candidiasis after 200 mg/da or higher dose for 14

days) 5.8% (median CD4 15/mm^); C. albicans primary etiology

CPCRA-randomized, placebo-controUed trial of fluconazole 200

mg weekly for prophylaxis of candidiasis (described above)

(median CD4 15/mm^): after median 29 months follow-up, flu- conazole resistance < 5% resistance in both fluconazole and

placebo groups (Schuman, 1997)

HIV Epidemiology Research Study (HERS): overall fluconazole

resistance rare among C. albicans isolates, but frequent in non-albi- cans isolates from vagina and oral cavity; fluconazole resistance

with non-albicans species more likely in HIV-positive women; not

significantly related to CD4 count. Resistance among non-albicans

species stable after 1 year of follow-up (Schuman, 1997)

1 39 isolates from vulvovaginal candidiasis in HIV-positive women:

95—98% susceptibility of C. albicans to fluconazole, itraconazole,

clotrimazole; Torulopsis glabrata-44% resistance to fluconazole,

72% resistance to itraconazole and clotrimazole. Twenty percent

us. Demktment of Health and Human Services, Health Resources and Services Administr.\tion, HrV'/AIDS Bure.\u
A Guide to the Climc.\l C.\re of Women with

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of 90 relapses/persistence were with same organism; emergence

of drug resistance was not observed between sequential isolates.

Twelve percent had recurrent infection with different strains or

species. (Id, 1997)

There are no current data to suggest that intermittent therapy

with a single dose of fluconazole increases development of azole

resistance. Similarly, weekly prophylaxis with fluconazole was associated with infrequent development of resistance, which was not significantly different from placebo recipients. Nevertheless, long-term

use of fluconazole may select for more resistant and difficult-to-treat

non-albicans species and should be used with caution. Further study

is needed. • Recurrent candidiasis (4 or more symptomatic episodes per year):

Evaluation:

1 . establish diagnosis —fungal culture may be needed

2. identify/ eliminate predisposing factors, if possible: uncontrolled diabetes, corticosteroid use, topical or systemic antibiotics, spermicides (conflicting data), tight-fitting synthetic

underwear, douching, pregnancy, immunesuppression

3. speciation/ susceptibilit}" testing

Management Options:

1 . longer duration of standard treatment regimen

2. chronic intermittent therapy (e.g., with perimenstrual

episodes)

3. restriction of orogenital/anogenital sexual contact (anecdotal

e\tidence only); double-blind, placebo-controUed trials of

topical therapy for male sexual partners showed no benefit

(Sobel, 1999)

4. possible role for boric acid vaginal capsules, gentian \tiolet

5. maintenance therapy: initial intensive regimen for 10—14 days

followed by a maintenance regimen for at least 6 months:

a. fluconazole* 1 00—200 mg po q week

b. itraconazole *50—100 mg po q week

c. clotrimazole 500 mg suppositor}" per vagina q week

d. ketoconazole *100 mg po q

day (associated with rare but

significant hepatotoxicity-monitor liver function; significant drug interactions with some antiretrovirals (see

Chapter XTV on Pharmacologic Considerations in HIVmfected Pregnant Patients )

6. immune reconstitution; potential benefit with protease

inhibitors

* Note: avoid concomitant use with terfenadine, astemizole, cisapride secondary

to cardiotoxicity.

us. Dep.\rtment of Hr\lth .\nd Human Sermces, He.\lth Resource.'; and Services .\DMiMsTR.moN. HIV/.MDS Bi m w 169
\ Gl ide to the Cunich. Care of Womf„\ with HI\'

GvTiecologic Problems

Trichomoniasis

Caused by Trichomonas vaginalis

HR -positive women: 5—23®'o prevalence; suidies have not shown increased

preA'alence as compared to HR -negatiA'e women; incidence in HR -positive

women o (Minkoff, 1999; SorAtiUo, 1998)

Clinical features: profuse, malodorous, often frothy, vellow-green discharge

and ATtlA'ar irritation; mav have urinarv svmptoms or dvspareunia; signs of

inflammation-A-aginal erythema, “strawberrv” vagina, cerATx witli punctate

hemorrhages; may be as\Tnptomatic in chronic cases

Diagnosis: saline wet mount (motile trichomonads seen in 50-70% culmre

+ cases); Pap smear (60—70% sensitiAtit}', false positiA’es not uncommon);

culture (95% sensitiAin'); DXA probes; monoclonal antibodies

T. A'aginalis cvsteine proteases degrade and render nonfunctional secretorA' leukocvte protease inliibitor, a substance thought to protect mucosal sur- faces from HR" transmission by inhibition of HR" protease actiAtitA' necessarv for infection of monocAtes and macrophages (Draper D, 1998)

Treatment (CDC,1998): • Metronidazole 2 gm po (single dose), OR

• Metronidazole 500 mg po tALTce a day for days. • yiote:

No change in treatment based on HR" stams

Sex parmers should be treated AATth the same regimen (> 90% cure

rates can be expected if parmer is treated simultaneously); inter- course should be aA'oided until therapy is complete and patient and

parmer are asvmptomatic

Topical metronidazole less effective

Metronidazole resistance is rare; organisms ALith decreased susceptibthtA’ usually respond to higher doses of metronidazole. If treat- ment failure occurs ALith either regimen, re-treat ALtith metronidazole

500 mg po tALtice a day for days. If treatment failure occurs repeatedly, treat AAith metronidazole 2 gm po once a day for 3—5 days.

Patients AAith documented infection (\A-ith reinfection excluded) who

haA'e not responded to these measures should be managed in consultation with an expert.

Gonorrhea (GC)

caused by ISieisseria gonorrhoeae

clinical presentation: commonly asymptomatic; A-aginal discharge may be

present; if tmtreated, 10—20% dcA-elop pehtic inflammatory disease (PID);

urethra is priman' site of colonization after hysterectomy and should be

us DeP.\KTME>.T of HE.U.TH .VND HlTCXN SeKMCES, HE-UTH RESOlltCES .VND Sermces Administr.\tic)k, HIA7-AIDS Bltieau
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sampled with culture or DNA probe for testing in these patients; GC may

also cause rectal infection, pharyngitis, and (rarely) disseminated infection

diagnosis: culture, DNA probe, polymerase chain reaction (PCR) or Hgase

chain reaction (I.CR). PCR/LCR can be used wnth cerGcal, urethral, or

urine specimens; mav detect gonorrhea and chlamydia simultaneous^; sensitivitv 93-98%, specificity > 99%; able to detect 15^0% more infections

than culmre (Hook, 1999)

prevalence/clinical presentation/ diagnosis/treatment in HW-positive

patients: no difference when compared to HIV-negative patients

Treatment (CDC,1998): • Cefixime 400 mg po (single dose), OR

• Ceftriaxone 125 mg IM (single dose), OR

• Ciprofloxacin 500 mg po (single dose), OR

• Ofloxacin 400 mg po (single dose). • Alternative regimen:

Spectinomycin 2 gm IM (single dose) • Xofe:

It is recommended that women be presumptively treated for

chlamydia, particularly in areas \tith high rates of coinfection,

absence of chlamydial testing, and/or when patient may not

return for results

Sex parmers should be treated for both gonorrhea and chlamydia

if their last sexual contact was within 60 days prior to the diagnosis or onset of stTnptoms. If a patient’s most recent sexual contact

occurred more than 60 days prior to the onset of symptoms, her

most recent parmer should be treated. Intercourse should be

avoided until treatment is completed and symptoms have resolved.

Culmre and susceptibility testing recommended after apparent

treatment failure with standard regimen

Avoid use of quinolones and tetracyclines in pregnane}"

Chlamydia

caused by Chlamydia trachomatis

clinical presentation: astiriptomatic infection common; abnormal discharge;

S}Tnptoms of urethritis; if untreated, 10—40% develop PID

diagnosis: culture (cell based), antigen detection, DNA probe, PCR/LCR

(90—100% sensitivity-see above) (Stamm, 1999)

prevalence/clinical presentation/diagnosis/treatment in HIV-positive

women: no differences as compared to HIV-negative women

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(lynccologic Problems

Treatment (CDC,1998): • A2ithromycin 1 gm po (single dose), OR

• Doxycycline 1 00 mg po twice a day for 7 days • Alternative regimens:

Erythromycin base 500 mg po four times a day for 7 days OR

Erythromycin ethylsuccinate 800 mg po four times a day for 7

days, OR

Ofloxacin 300 mg po twice a day for 7 days. • Note:

Recommendations for the management of sex partners are the

same as for gonorrhea (see above)

Avoid use of doxycycline or quinolones in pregnancy

Other

Atrophic vaginitis: related to estrogen deficiency; irritative symptoms, vaginal dryness, and dyspareunia; the vaginal epithelium appears thin and a watery discharge may be present; treat with either topical or oral estrogen.

Foreign body (retained tampon, toilet paper, etc.)

Local irritants (spermicides, vaginal medications, toilet paper dye, hygeine

sprays, soap, detergent, douches, etc.)

VI. PELVIC/ABDOMINAL PAIN

Abdominopelvic pain can be classified as acute, chronic, or cyclic. Acute pain

is typically sudden in onset and short in duration, whereas chronic pain is of at least six months’ duration. Cyclic pain is associated with the menstrual cycle.

A. HISTORY

Characteristics of pain: onset (rapid or gradual), character (crampy, colicky,

sharp or dull), location (generalized or localized pain) and duration; associated

symptoms: abnormal vaginal bleeding or discharge, gastrointestinal symptoms

(e.g., nausea/vomiting, anorexia, constipation, diarrhea), and urinary (e.g.,

dysuria, frequency, urgency, hematuria) symptoms, fever or chills; history of

other medical conditions; surgical history; gynecologic history: date of last menstrual period, use of contraception and condoms, history of STDs; medications; CD4 counts and HIV-RNA levels.

B, PHYSICAL EXAM

A complete set of vital signs should be obtained. The physical exam should

focus on abdominal and pelvic findings. A complete abdominal exam should

evaluate the presence and character of bowel sounds, distension, suprapubic

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or costovertebral angle tenderness, other abdominal tenderness (including

rebound and guarding) and presence of masses. The pelvic exam should determine the presence of abnormal bleeding or discharge; reproducibility and

location of tenderness (e.g., uterine, adnexal, or cervical motion tenderness);

presence of a palpable abdominal or pelvic mass should be ruled out. C EVALUATION

Pregnancy test

Laboratory tests: CBC with differential, sedimentation rate, chemistry panel,

others as indicated

Wet mount/STD testing

Urinalysis and urine culture

Stool studies (cultures, evaluation for ova and parasites, C. difficile toxin

assay) — if indicated by GI symptomatology

PeKde ultrasound, CT scans —if indicated

Blood cultures — bacteria, M. avium, if indicated

D. DIFFERENTIAL DIAGNOSISAND MANAGEMENT

Includes but not limited to: Pregnancy: refer

Pelvic Inflammatory Disease (PID): PID is an upper genital tract infection, usually polymicrobial in nature. Sexually transmitted organisms,

including N. gonorrhea and C. trachomatis, are implicated in most cases of

PID; bacterial vaginosis-associated organisms are also commonly present.

Symptoms may be virtually absent or mild and nonspecific (e.g., abnormal bleeding, dyspareunia, vaginal discharge; less commonly right upper

quadrant pleuritic pain secondary to perihepatitis). Current CDC

recommended criteria for diagnosis of PID are (CDC,1998): • Minimum criteria:

lower abdominal tenderness

adnexal tenderness

cervical motion tenderness

Because of difficulty in diagnosis and the potential for long-term

complications, empiric therapy should be initiated if these criteria are present and no other cause for symptoms is identified. • Additional criteria:

oral temperature > 101 F (> 38.3 C)

abnormal cervical or vaginal discharge

elevated er)rthrocyte sedimentation rate

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Ciynecologic Problems

elevated C-reactive protein

documented cervical gonorrhea or chlamydia infection

These criteria enhance specificity. • Definitive criteria:

endometritis on endometrial biopsy

tubo-ovarian complex or thickened fluid-filled tubes on trans- vaginal ultrasound

laparoscopic abnormalities consistent with PID

Warranted in patients who are severely ill and when diagnosis is uncertain. • PID in the HIV-positive woman: Several studies have found

increased seroprevalence of HIV in hospitalized PID patients.

(Hoegsberg, 1990; Sperling, 1991) A recent analysis of hysterctomy

specimens from HIV-positive women and HIV-negative women,

matched for surgical indication, found chronic endometritis twice as commonly in the HIV-positive specimens; some degree of abnormal uterine bleeding had occurred in all cases. (Kerr-Layton, 1998)

Moreover, the clinical presentation among these women may be

more severe or otherwise altered (e.g., lower WBC counts than HIVnegative women) (Barbosa, 1997; Kamenga, 1995; Cohen, 1998); in

African studies, more severe illness, including tubo-ovarian abscess,

and longer hospital stays were required with significant immunosuppression. The microbiology of infection and response to standard

antibiotic regimens are similar to HIV-uninfected women; however,

some studies have reported a greater need for surgical intervention.

(Korn, 1 993) CMV and tuberculosis may cause upper genital tract infection in rare cases and should be considered in appropriate clinical situations. Current CDC recommendations call for managing

immunosuppressed HIV-infected women with PID aggressively

with a parenteral regimen. A more recent study from Kenya found

similar efficacy of oral ambulatory therapy in HIV-positive and

HIV-negative women with PID. (Bukusi, 1999) Decisions about oral versus parenteral therapy should be individualized. • Treatment (CDC,1998):

Parenteral regimens:

A. Cefotetan 2 gm IV every 12 hours, PLUS

DoxycycUne 1 00 mg IV, OR

B. Cefoxitin 2 gm IV every 6 hours, PLUS

Doxycycline 100 mg IV, OR

C. Clindamycin 900 mg IV every 8 hours, PLUS

Gentamicin loading dose IV or IM (2 mg/kg of body

weight), followed by a maintenance dose (1.5 mg/kg) every

8 hours

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Oral regimens:

A. Ofloxacin 400 mg orally twice a day for 14 days, PLUS

Metronidazole 500 mg orally twice a day for 14 days, OR

B. Ceftriaxone 250 mg IM once, OR

C. Cefoxidn 2 gm IM plus Probenecid 1 gm orally in a

single dose concurrendy once, PLUS

Doxycycline 100 mg orally twice a day for 14 days.

b’or alternadve oral and parenteral regimens, please see the CDC 1998

Guidelines for Treatment of Sexually Transmitted Diseases.

(http:/ /www.hivatis.org)

Parenteral therapy may be discontinued 24 hours after there is evidence

of clinical improvement. Oral therapy with Doxycycline 100 mg every 12

hours (consider the addidon of Metronidazole 500 mg every 12 hours, pardcularly with presence of tubo-ovarian abscess) or Clindamycin 450 mg

four dmes a day should then be insdtuted to complete a 14-day treatment

course. Sexual partners of women diagnosed with PID should be evaluated

and treated if they have had sexual contact within the sixty days preceding

the onset of symptoms.

Table 6-9: Indications for Hospitalization in Patients with PID

Inadequate response to outpatient therapy

Uncertain diagnosis; surgical emergency cannot be excluded

Pregnancy

Inability to tolerate or follow outpatient regimen

Immunosuppression (low CD4 counts, clinical AIDS,on immunosuppressive drugs,

other significant co-morbidity

Tubo-ovarian abscess

or other evidence of severe illness, nausea and vomiting, or high fever

Ruptured/hemorrhagic ovarian cyst rupture: can cause acute abdominal pain; bleeding associated with rupture is usually self-limited but may

require surgical intervention.

Ovarian torsion: acute, severe, unilateral lower abdominal/pelvic pain,

often with history of previous similar episodes; palpable adnexal mass

usually present. Surgical intervention required.

Uterine leiomyomas (fibroids): may cause pain with rapid enlargement,

degeneration, or torsion; referral indicated

Endometriosis: cause of acute or chronic pain, usually includes secondary dysmenorrhea and/or dyspareunia; referral to gynecologic specialist

indicated if endometriosis suspected

Dysmenorrhea: affects about half of all menstruating women; cyclic

pain with menses. Primary dysmenorrhea is menstrual pain in the

absence of pelvic pathology; secondary dysmenorrhea is associated with

underlying pathology (such as endometriosis). Treatment of primary

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V

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dysmenorrhea consists of nonsteroidal antiinflammatory drugs

(NSAlDs) (80% effective) or OCPs (90% effective). Treatment of sec- ondary dysmenorrhea is directed at the specific underlying problem.

Mittelschmerz: pain with ovulation, generally self-limited; manage with

NSAIDs

Gastrointestinal pathology: includes appendicitis; diverticulitis (pain

generally localizes to the left lower quadrant; usually seen at older ages);

irritable bowel syndrome (pain is usually intermittent, cramp-like, and

more common in the left lower quadrant; exacerbated by certain foods);

inflammatory bowel disease; infectious enterocolitis (pain cramping, diarrhea); obstruction (colicky pain, distension, vomiting, obstipation).

Opportunistic infections, including Cryptosporidia, CMV and M. avium

may be causes of chronic diarrhea in patients with AIDS and clinical fea- tures usually include abdominal pain.

Urinary tract pathology: renal/ureteral stones, cystitis, and pyelonephritis

Medication-related: indinavir (renal stones); ddl (pancreatitis)

VII. PELVIC MASS

A. HISTORY

Presence and duration of associated symptoms: pain, abnormal vaginal bleeding or discharge, urinary symptoms (e.g., frequency, urinary retention), gastrointestinal symptoms (e.g., nausea, vomiting, constipation, diarrhea), or

constitutional symptoms (e.g., fever, chills, weight loss or gain).

B. PHYSICAL EXAM

A complete abdominal and pelvic examination should be performed, with particular attention given to the size, location, mobility, and characteristics of the mass (if palpable) as well as to signs of ascites; lymph node survey. With functional ovarian cysts, a normal ovary may be up to 5—6 cm in size for a woman

in the reproductive age range. A palpable ovary in a postmenopausal woman is abnormal and requires further evaluation.

C. EVALUATION

Pregnancy test: if premenopausal

Laboratory tests: CBC with differential; chemistry panel; tumor markers, if indicated (e.g., CEA, Ca-125; frequent false positives and false negatives,

should only be used in conjunction with other diagnostic procedures)

Radiologic studies: pelvic ultrasound (transabdominal/transvaginal), CT, and

MRI, as indicated. Ultrasound is generally the first diagnostic modality

employed in evaluating pelvic anatomy; concerning characteristics include

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Gynecologic Problems

complex or solid mass, presence of ascites. CT/MRI are better at imaging

(il tract, retroperitoneal lymphadenopathy, liver

Additional evaluation involving procedures such as laparoscopy,

colonoscopy, etc. require referral to appropriate specialists.

D. DIFFERENTIAL DIAGNOSIS

Ectopic pregnancy: the primary consideration in the setting of an adnexal mass and a positive pregnancy test.

Ovarian functional cyst: Functional cysts are the most common ovarian masses found among women of reproductive age; resolution occurs spontaneously in one to three months.

Uterine leiomyomas (fibroids): often asymptomatic, but may be associated with heavy and/or prolonged menses, urinary frequency.

Endometrioma: consider in women with a documented or suspected history of endometriosis.

Hydrosalpinx/Pyosalpinx and tuboovarian abscess: consider with

history suggestive of PID; initial management with broad-spectrum

antibiotics.

Benign or malignant ovarian neoplasm: Surgical intervention is required.

No evidence of increased prevalence in HIV-positive women; anecdotal

reports suggest ovarian cancer may present at more advanced stage, with

poorer response to cytoreductive surgery and chemotherapy. (Rojansky,

1996) Non-Hodgkins lymphoma of ovary described in an HIV-positive

woman. (Neary, 1996)

Retroperitoneal lymphadenopathy: may present as pelvic mass; possible cause include tuberculosis, lymphoma

Gastrointestinal masses: includes diverticular abscess, bowel malignancy

In general, the presence of a pelvic or abdominal mass requires expert consultation and referral to an appropriate specialist.

VIII. URINARY SYMPTOMS

A. HISTORY

Duration and severity of urinary symptoms; specific symptoms: dysuria, fre- quency, urgency, hematuria, nocturia, incontinence; associated symptoms,

including pain (suprapubic or flank), fever, chills, and weight loss; other medical conditions (e.g., diabetes, sickle cell disease); surgical history; medications;

CD4 count and HIV-RNA level

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Civnccologic Problems

B. PHYSICAL EXAM

Vital signs;document presence of suprapubic tenderness or flank or costovertebral angle tenderness

C EVALUATION

Microscopic exam of urine

Urine culture and sensitivity

GC/chlamydia testing, if indicated

Cj^ology: consider in woman over the age of fifty who presents with irritative symptoms or hematuria and negative culture

Urine for AFB culture, PPD; if indicated, urinary TB suspected

Intravenous Pyelogram (IVP): if indicated; consider if stones, urinary tract anomalies, or urinary TB suspected

Other tests: cystoscopy, urodynamics-refer to appropriate specialist

D. DIEEERENTIAL DIAGNOSISAND MANAGEMENT

Bacterial urinary tract infection: lower tract (cystitis) or upper tract (pyelonephritis); may be asymptomatic and clinical signs and symptoms can- not reliable distinguish between upper and lower tract infection. Classically

cystitis characterixed by the presence of duU, suprapubic pain; typical associated symptoms include dysuria, and urinary frequency and urgency, and

occasionally hematuria. Pyelonephritis associated with flank or costovertebral pain and tenderness to percussion, as well as systemic signs/ symptoms,

including fever, chills,nausea, vomiting, tachycardia. Treat with appropriate

antibiotics; severe pyelonephritis requires hospitalization for IV antibiotics

and hydration.

Urethral syndrome: dysuria, frequency with negative urine culture; rule out

urethritis due to gonorrheal or chlamydial infection

Renal/ureteral stones: severe, coheky pain; usually associated with urinary

stasis or chronic infection, although may be related to metabolic abnormalities, such as gout or problems with calcium homeostasis; a significant side

effect associated with indinavir therapy.

Interstitial cystitis: symptoms include severe urinary frequency and

urgency, (urinating as often as every 1 5 minutes daytime and nighttime) as well as suprapubic or perineal discomfort before, during, and after urination; refer for definitive evaluation

Urinary tuberculosis: one of the most common sites of extrapulmonary

TB; gross or microscopic hematuria and pyuria with negative bacterial culture should lead to consideration; manage with expert consultation

U.S. Department of He.\lth and Human Services, HFj\i.th Resources and Services Administr/VDON, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Gynecologic Problems

Tumors: most common presenting complaint is gross or microscopic

hematuria; hematuria without identifiable etiology (e.g., infection) requires

referral to urologist

Urinary incontinence: can be caused by many factors, including anatomic

displacements related to aging and childbearing; bladder muscle (detrusor)

instability; neurologic disease; infection; fistulas secondary to surgical injury,

radiation, or cancer; and some medications. Rule out infection with culture

and “overflow” incontinence (secondary to overdistended bladder) with

post-void catheterization for residual urine determination. Further evaluation requires referral to urogynecologist or urologist..

Urinary retention: may be caused by obstruction, neurologic disorders, or

certain medications (e.g., antihistamines, antidepressants, antipsychotics, opiates, antispasmodics, terbutaline, over-the-counter cold remedies).

IX. GENITAL WARTS

(ienital warts are a common manifestation of HPV infection . HPV types 6

and 11 are usually the cause of visible genital warts. Oncogenic types (i.e., 16,

18, 31, 33, and 35) are occasionally found in visible warts and have been associated with squamous intraepithelial neoplasia of the external genitalia (see

section on Abnormal Pap smear above).

A. HISTORY

Location of warts, duration, and the presence of associated symptoms (itching, irritation, pain, bleeding); history of prior occurrences of similar lesions

and their treatment; history of abnormal Pap smear results

B. PHYSICAL EXAM

Complete examination of the external genitalia as well as of the cervix, vagina,

and perianal region should be performed; location and size of warts should be

documented. Genital warts can present as cauliflower-shaped growths (condyloma acuminata), smooth, dome-shaped, skin-colored papules, keratotic warts

with a thick horny layer, or flat or sHghtiy raised flat-topped papules.

C RELATION TO HIV

HIV-infected women are more likely to have HPV coinfection and both

prevalence and incidence of genital warts are increased as compared to HIVnegative women. (Chirgwin, 1995) Both prevalence and clinical expression of

HPV increases with progressive cUnical disease and immunologic decline.

Immunosuppressed women may not respond as well to treatment and have

more frequent recurrences after therapy. Squamous cell carcinomas that arise

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in or resemble genital warts may occur more commonly in the setting of

immunosuppression, making confirmation of diagnosis with biopsy more

frequently necessary.

D. EVALUATION

Biopsy: Typical condyloma accuminata are diagnosed by inspection and do

not require biopsy. A biopsy of the lesion and histopathologic confirmation

of the diagnosis are indicated in the following situations: • diagnosis is uncertain

#. warts do not respond to therapy • lesions worsen during therapy • warts are pigmented, indurated, fixed, or ulcerated

Colposcopy: Colposcopy and directed biopsies of the entire lower genital

tract should be considered in HIV-positive women with evidence of HPV

infection. Colposcopy should be performed to rule out the presence of

high-grade squamous intraepithelial lesions prior to initiating treatment of

cervical warts.

Treatment:The primary goal of treatment is the removal of symptomatic

lesions. When left untreated, visible warts may resolve spontaneously, may

remain unchanged, or may increase in number or si2e. There is no evidence

that currently available therapies eradicate HPV, have an effect on the natural

history of infection, or affect the subsequent development of cervical cancer. Infectivity may or may not be decreased by the removal of visible warts. The treatment modality depends on the number, size, and location of the

warts. When there are a small number of lesions and they are fairly small, a

Table 6-10: Recommended Management for Genital Warts

Prov/der-appued Patient-applied

80%-90% trichloroacetic acid (weekly if necessary);

cryotherapy with liquid nitrogen or cryoprobe-repeat every 1-2 weeks;

surgical removal

Podofilox 0.5% solution or gel applied

twice a day for 3 days followed by 4

days of no therapy;

may repeat application for up to 4

cycles; application should be limited

to 0.5 ml per day and < 10 cm^ area

of warts

10%-25% podophyllin resin weekly if necessary;

application should be limited to < 0.5 ml

of podophyllin or < 10 cm^ of warts

per session and preparation should be

thoroughly washed off 1-4 hours after application to reduce local irritation; because of concern about potential

systemic absorption and toxicity, avoid use on mucosal surfaces

Imiquimod 5% cream applied three

times per week for as long as 16

weeks;

the treated area should be washed with

mild soap and water 6-10 hours after application

Note: Avoid use of podophyllin, podofilox, and imiquimod during pregnancy

us. Department of Health and Human Services, Health Resources and Services Administr.\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Gynecologic Problems

topical agent may be employed. Table 6-10 displays provider-appHed and

patient-administered regimens recommended by the CDC (CDC,1998):

Most treatment modalities are associated with mild to moderate discomfort and local irritation. Intralesional interferon is an additional alternative

treatment but is expensive and associated with a high frequency of systemic

side effects. Treatment method should be changed if there is not substantial

improvement after three provider-administered treatments or if there is not

complete clearance after 6 treatments. Combining modalities does not

appear to increase efficacy but may increase complications. Recurrence rates are significant with aU modalities; frequent follow-up will allow re-treatment

when new warts are small and few in number. When the number of warts is large or the lesions are very extensive, referral for possible laser surgery

should be considered. In one study relapse rates of treated genital warts in

1 llV-positive patients was lower in those on combination antiretroviral therapy and was correlated with HIV-RNA levels (Giovanna, 1998)

X. GENITAL MASSES/NODULES

A. HISTORY

Duration; changes in size or appearance; associated symptoms (e.g., pain/ ten- derness, itching, edema); prior history of similar nodules and their treatment;

sexual history (including presence of similar lesions on genitals of partner);

medications; CD4 count and HIV-RNA level

B. PHYSICAL EXAM

Document anatomic location, number, and size of the nodules; presence of

associated edema, erythema, induration, fluctuance, tenderness, discharge, or bleeding

C EVALUATION

Biopsy indicated if etiology is unclear; culture of abscess contents

D. DIEEERENTIAL DIAGNOSISAND MANAGEMENT

BarthoUn’s abscess: Bartholin’s glands are normally non-palpable and

located deep in the perineum at the 5 and 7 o’clock positions of the entrance

to the vagina. Obstruction of a Bartholin’s duct by nonspecific inflammation,

infection (e.g, GC or chlamydia) or trauma can lead to the formation of an

abscess; exquisitely tender. Treatment consists of incision and drainage.

MoUuscum contagiosum: an asymptomatic viral disease that primarily

affects skin of the vulva, although it can present as a generalized skin dis- ease in immunosuppressed individuals; spread by close contact, both sexual

and nonsexual. CHnical features: small nodules or domed papules, usually

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Civnccologic Problems

1—5 mm in diameter; the more mature nodules appear to have an umbilicated center. This disease tends to be self-limited; however, treatment may

be complicated by repeat infection and autoinoculation of the virus. Treatment consists of serial applications of liquid nitrogen or of removal of the

nodules with a dermal curet and chemical cauterization of base with 85%

TCA or ferric subsulfate. MoUuscum contagiosum affects 5—10% of HIVpositive patients; extensive, severe lesions that show poor response to therapy are common; such unresponsive lesions, however, have been found to regress with HAART. (Calista, 1999)

Tumors, other masses: biopsy required; expert consultation indicated.

XI. GENITAL ITCHING/IRRITATION

A. HISTORY

Duration, location, and severity of pruritis/irritation; associated symptoms

(erythema, edema, vulvar burning, dysuria, dyspareunia); prior episodes of

similar symptoms and treatment; exposure to particular agents (e.g., soaps,

sprays, vaginal contraceptives, douches, colored toilet tissue, etc.) coincident

with the beginning of symptoms; presence of similar symptoms in close contacts; medications, including antibiotics; CD4 counts and HIV-RNA level

B. PHYSICAL EXAM

Physical appearance and distribution of the irritated area (e.g, diffuse rash,

papular or vesicular lesions, skin burrows, etc.); associated findings, including

erythema, edema, and tenderness, vaginal discharge; if a more generalized

process is suspected (e.g., allergic reaction to detergent, scabies, etc.) a more

thorough inspection of the skin throughout the body may be indicated.

C EVALUATION

Fungal culture/KOH prep: indicated if a fungal infection is suspected.

HSV culture: herpes may appear atypicaUy and should be ruled out in the

presence of vesicular lesions, unexplained abrasions or fissuring, or if warranted by history .

Skin scrapings: scraping of skin papule is with a needle, and the crust is placed under a drop of mineral oil on a slide; eggs, parasites, or fecal pellets

microscopically visualized by this technique are diagnostic of scabies or pubic lice.

D. DIFEERENTIAL DIAGNOSISAND MANAGEMENT

Fungal infection: although the primary symptom associated with fungal

infections is itching, women also complain of vulvar burning, dysuria, and

us. DRMRTMENT of .AND HUAUN SERVICES, He.\LTH RESOURCES .AND SERA'ICES AdMINISTR.ATION, HIWAIDS BliRIUAU
A Guide to the Clinic.\l Care of Women with HIV

Gynecologic Problems

clysparcunia, particularly with involvement of vulvar skin. Examination

often reveals edema, erythema, and excoriation; pustular lesions may be

found to extend beyond the line of erythema when extensive skin involvement is present. Diagnosis is established by means of a KOH prep or fungal culture. Treatment is topical application of an antifungal preparation.

(See vulvtjvaginal candidiasis in the Vaginal Discharge section above.)

AJlergic/irritative reaction: Contact dermatitis frequently affects the vul- var skin, particularly the intertriginous areas; etiologic agents include urine or feces, latex, semen, cosmetic or therapeutic agents (including vaginal contraceptives, lubricants, sprays, perfumes, douches, fabric dyes, fabric softeners, synthetic fibers, bleaches, soaps, chlorine, dyes in toilet tissues, and local

anesthetic creams); severe cases of dermatitis may be due to poison ivy or poison oak. Tjqjical symptoms are itching, vulvar burning, and tenderness.

F.xamination of the skin reveals erythema, edema, and inflammation; the

skin may be weeping and eczematoid. Secondary infection may occur.

Treatment involves removing the offending agent. Severe lesions may be

treated with wet compresses of Burow’s solution diluted 1:20 for 30 minutes

several times a day. If possible, the vulva should be dried with cool air from

a hair dryer following the compresses. Lubricating agents such as Eucerin cream or petroleum jelly can help reduce the itching. Nonmedicated baby

powders can be used to facilitate vulvar dryness. Symptomatic relief can be

achieved with hydrocortisone (0.5% to 1%) or fluorinated corticosteroid

(Valisone 0.1% or Synalar 0.01%) lotions or creams into the skin 2 to 3 times

a day for a few days. Dermatitis due to poison ivy or poison oak nay require

treatment with systemic corticosteroids. The use of white cotton undergarments is advisable, and tight-fitting clothing should be avoided.

Scabies/lice • Scabies is a parasitic infection produced by the itch mite, Sarcoptes scabiei. The main symptom reported is severe, intermittent itching that

tends to be more intense at night. Lesions can present as vesicles,

papules, or burrows; any area of skin may be affected: the hands,

wrists, breasts, vulva, and buttocks are most often infected. HIVinfected and other immunosuppressed patients are at increased risk for

Norwegian scabies, a disseminated dermatologic infection; this can

appear classically as hyperkeratotic, nonpruritic lesions or as crusting

with pruritis, a pruritic, papular dermatitis, or lesions resembling psoriasis. (Schlesinger, 1994)

CDC-recommended treatment for scabies (CDC,1998):

Permethrin cream (5%) applied to all areas of the body from

the neck down and washed off after 8 to 14 hours.

Alternative regimens:

Lindane (1%) one ounce of lotion or 30 grams of cream

applied to all areas of the body from the neck down and

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A Gl IDE TO THE CUN1C\L C\RE C^F WOMEN WITH HI\'

G\Tiecologic Problems

washed ott thoroughly after 8 hours OR Sulfur (6%) precipitated in ointment appUed thinly to all areas nighdv for 3

nights; pre^ious applications should be washed off before

new applications are applied. Thoroughly wash off 24 hours

after last application.

Lindane should not be used bv pregnant or lactating women;

or after a bath.

Itching may persist for days fonox^ing treatment; antihistamine therapy

should be considered for symptomatic relief. Norw egian scabies should

be managed in consultation with an expert.

• Pediculosis pubis is due to infestation by the crab louse, Phthiruspubis or pubic louse. Transmission is by close contact, but the louse can also

be acquired from bedding or towels. This infection is usually confined

to the hairy areas of the vulva (eyelids are occasionally infested). The

presenting symptom is constant itching in the pubic area. Eggs, adult

Hce, and fecal material can be seen upon close examination (without

magnification). The diagnosis can be definitively established by microscopic yisualizatioru as described above.

The CDC-recommended treatment (CDC,1998) is permethrin 1%

cream rinse applied to affected areas and washed off after 10 minutes. Alternativelv, lindane 1% shampoo (applied for 4 minutes

and thoroughlv washed off; lindane not recommended for pregnant or lactating women) OR pyrethrins \^'ith piperonyl butoxide

(applied to the atfected area and washed off after 10 minutes). If

symptoms do not resolve, patients should be re-examined in one

week; if lice or eggs are seen at the hair-skin junction, the patient

should be retreated. All clothing and bedding need to be decontaminated. Close household contacts and sexual contacts (vithin

the previous month) should be treated.

XII. BREAST LUMP

A. HISTORY

If palpable by the patient, duration of the lump; any associated symptoms

e.g., tenderness, nipple discharge, cyclic pain); changes in the characteristics of

the lump (e.g., increase in size); history of previous breast lumps; family history of breast disease or cancer.

B. PHYSICAL EXAM

Symmetry, contour, and appearance of the skin; presence of edema, erythema,

skin dimpling, or nipple retraction; presence and size of dominant masses,

nodularity, tenderness; nipple discharge ^eluding color); and lymphadenopathy (axillary and supraclavicular).

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A Guide to the Clinical Care of Women with HIV

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C EVALUATION

Mammogram: should be performed with any persistent palpable mass or

other suspicious changes in the breast (e.g., bloody nipple discharge, skin

retraction). A negative mammogram alone is not sufficient to rule out

malignant pathology in a patient with a palpable breast mass; further evaluation and possible biopsy are indicated.

Ldtrasound; most helpful to distinguish cystic and solid masses; useful initial

test in younger women when simple cyst suspected.

Needle aspiration: for cystic lesion; fluid can be discarded if clear and if mass disappears; otherwise biopsy may be needed.

Biopsy: biopsy is indicated in cases of dominant mass (even with normal

mammographic findings) or suspicious nonpalpable mammographic findings.

D. DIFFERENTIAL DIAGNOSISAND MANAGEMENT

Fibrocystic change: Typically found among women who are 30 to 50 years

old. I'ibrocystic changes usually present as breast nodularity associated with

cyclic bilateral pain or tenderness, which is worse premenstrually. Breast

engorgement, increased density, and cyst formation are common and vary

with menstrual cycle phase. The pain/discomfort associated with this

condition can be relieved wearing a brassiere that gives adequate support.

Analgesics can aid in symptomatic relief; some women have reported

improvement of symptoms with vitamin E (400 lU a day) and decrease in

caffeine consumption. Oral contraceptives are known to decrease benign

breast disease. The appearance of a persistent dominant mass requires biopsy.

Benign breast tumor: most frequently diagnosed benign tumors of the

breast are fibroadenomas, usually found in women aged 20 to 35. Typically,

most masses are about 2 to 3 cm in diameter, although they can become

much larger. Examination reveals a firm, smooth, rubbery mass that is freely mobile. Inflammation, skin dimpling, and nipple retraction are absent.

On mammographic examination, the mass appears smooth with welldefined margins. Definitive diagnosis is established by means of biopsy. A

fibroadenoma may simply be observed; however, a large, growing, or otherwise suspicious mass should be surgically excised.

Breast cancer: incidence of breast cancer increases with age; risk factors

include positive family history, early menarche, late menopause, and nulliparity or late child-bearing. If a palpable mass is present, it is usually firm

and nontender wtith irregular margins; it may be fixed to skin or underlying

tissue. Definitive diagnosis is established by means of biopsy and referral to

a surgeon is indicated. Although only a few cases of breast cancer have

been reported among HIV-positive women, the unusual clinical presentations that have been noted, together with the rapid progression of disease

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Ciynccologic Problems

that has been observed, have been suggestive of a “more virulent” course

in the setting of HIV infection. (Guth, 1999)

XIII. MENOPAUSE

As HIV-positive women Live longer and more women nearing menopause or postmenopausal become infected, menopausal issues become more important

to consider and address. At the current time, there has been no documented

association between HIV disease and premature ovarian failure.

Menopause is defined as the permanent cessation of menstruation caused

by the loss of ovarian function. The mean age at which women undergo

menopause is genetically predetermined and in the United States averages

between 51 and 52 years of age. Certain medical conditions, such as osteoporosis and cardiovascular disease, have been linked to estrogen deficiency;

associations have also been proposed between menopause and AHheimer’s

disease and colon cancer. (Hurd, 1996; Mishell, 1997)

A. HISTORY

Last menstrual period and recent menstrual pattern (cycle length, duration and

amount of flow); any irregular or intermenstrual bleeding or spotting; hot

flashes; genitourinary dryness /atrophy; decreased libido; anxiety, irritability,

sleep disturbances, and depression; difficulty with memory; urinary symptoms

B. PHYSICAL EXAM

Vagina appears smoother in contour, “drier”; may be more easily traumatixed

and more vulnerable to infection.

C EVALUATION

If indicated, confirmation of menopause can be provided by an elevated

serum follicle- stimulating hormone (FSH) level and a low estradiol level.

D. MANAGEMENT

Hormone Replacement Therapy (HRT)

The benefits and risks associated with HRT have been extensively studied

among women who are HIV-negative. HRT is known to ameliorate symptoms of vasomotor instability (e.g., hot flashes, sleep disturbances, irritability,

etc.) and urogenital atrophy (e.g., vaginal dryness, dyspareunia, etc.). More

importantly, HRT is protective against cardiovascular disease and osteoporosis. Additional beneficial effects have been suggested with regards to prevention of Alxheimer’s disease and colon cancer. One recent report found a trend towards increased survival among HIV-positive women on HRT and

us. Department of Health and Human Services, He.\lth Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Gynecologic Problems

recommended that “HRT should be considered in the management of postmenopausal HIV-infected women who do not have an established contraindication as part of standard of care because of the documented known

benefits among non-HIV-infected women.” (Clark, 1997)

In addition to HRT, adequate calcium intake (1200 mg/day for

menopausal women taking HRT; 1500 mg/day for women not on HRT)

and the regular performance of weight-bearing exercise are important for

bone protection.

Oral HRT can be administered in a continuous or cyclic fashion. The

most commonly prescribed regimens are: • (k>ntinuous therapy: Conjugated estrogens 0.625 mg po and medroxyprogesterone 2.5 to 5 mg po once daily (available in combined

formulations). • Cyclic therapy: Conjugated estrogens 0.625 mg po once daily and

medroxyprogesterone 5—10 mg po once daily for 12—14 days per

month.

Commonly used estrogen and progestin preparations are shown in Table

6-11. (ACOG, 1998)

Table 6- 11 : Commonly Used Estrogen and Progestin Preparations

Estrogen Preparations* Progestin Preparations**

Oral conjugated estrogen 0.625 mg Medroxyprogesterone acetate 10 mg

Oral micronized estradiol 1 mg Norethindrone 0.35 mg

Transdermal estradiol 0.05 mg/day Micronized progesterone 200 mg

Oral esterified estrogen 0.625 mg Progesterone vaginal suspension 90 mg

Estradiol vaginal ring

* doses listed (with exception of vaginal ring) are approximately equivalent in terms of relative potency

** doses listed are approximately equivalent in terms of relative potency, with exception of noethindrone (approximately 0.5 relative potency)

The most common side effects associated with hormone replacement

regimens are irregular vaginal bleeding and breast tenderness. There is an

increased risk of endometrial cancer in women treated with estrogen-only

hormone replacement. The addition of progestin to the regimen either

cycUcaUy or continuously (in women with a uterus) protects the

endometrium and prevents the development of hyperplasia and cancer. There is a small increase in the risk of venous thromboembolism in women

on HRT. The issue of the effects that HRT may have on the development

of breast cancer remains controversial; although some studies have demonstrated an increase in risk that may be related to the duration of hormone

replacement, other studies have found no increase in risk. Ckintraindications

to HRT include: undiagnosed genital bleeding, active liver disease, recent

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Ciynecologic Problems

myocardial infarction, active or prior history of thromboembolic disease,

and breast or endometrial cancer.

Alternatives to HRT

• Progestin-only regimens (medrox}’progesterone acetate 1 0-30 mg or norethindrone 1—5 mg daily) may help relieve hot flashes in women

who cannot or do not want to take estrogen-containing regimens. • Non-hormonal lubricants or and moisturizers or Estring (vaginal ring

with estradiol reservoir that is changed every 90 days — minimal sys- temic absorption) for the management of urogenital atrophy. • Bisphosphonates (e.g., fosamax) for the prevention or treatment of

osteoporosis. • SelectiA^e Estrogen Receptor Modulators (SERMs) (Evista 60 mg po a day) offer bone and cardiovascular benefit without ewdence of breast or endometrial stimulation; no effect on hot flashes, small increase in

risk of venous thromboembolism.

XIV. HEALTH MAINTENANCE ISSUES (Hilliard, 1996)

Gynecologic evaluation: annually and as indicated by presence of symptoms, follow-up of ongoing problems, exposure to STDs, development

of abnormal pap smear, or other need for referral based on primary

care evaluation

Pap smears; twice within the first year of diagnosis and then annually;

more frequent screening indicated with history of abnormal pap, HPV

infection, after treatment for cer\ical dysplasia, and with symptomatic

HIV disease

STD screening: • annual s^’phiUs screening or with development of neurologic

signs/ symptoms

• GC/chlamydia screening:offer annually at time of routine gynecologic

visit; perform as indicated by the presence of relevant symptoms or

findings on exam, Avith recent change in sexual partners, history of

STD in sexual parmer, periodically as indicated by sexual practices

(commercial sex workers, multiple partners, inconsistent use of con- doms), or with patient request

Mammography: baseline at 35M-0 years; then every 1—2 years until age 50,

then annually; women at increased risk (first degree family member(s) with

breast cancer) should have annual screening after 40. Mammograph should

be performed with presence of persistent palpable mass or other suspicious

findings on exam

us. Dep.\rtment of He.\lth .\.nd Hl'm.\n Sermces, HE.ALTH Resources .\kd Serwces ADMiNismmoN, HIA7-AIDS Burf.\u
A Guide to the Clinic\l Care of Women with HIV

Gynecologic Problems

Sif^moidoscopy/colonoscopy: sigmoidoscopy every 3—5 years after age 50;

colonoscopy in women at increased risk (first-degree family member with

colorectal cancer) every 3-5 years after age 40 or earlier with certain conditions (ulcerative colitis, familial pol}^osis, personal history of colon cancer)

XV. GUIDELINES FOR GYNECOLOGIC REFERRAL

In general referral to a gynecologic specialist should be considered under the

following circumstances:

Uncertain diagnosis with gynecologic condition part of differential diagnosis

Inadequate response to standard treatment regimens for gynecologic

conditions

Possible need for surgical intervention

A premalignant or malignant condition is suspected

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,

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us. Department of Health and Human Services, Health RiisouRCiis and Services Administration, HIV/AIDS Bure.w
COLOR PLATES

Plate 1. Tricholmonads in a saline wet mount (high power). (Monif, 1982;

Fig. 22-2)

US, Department of Health and Human Services, Health Resources and Si'rvicks Adminis'i-r,\tion, II1\7AIDS Hi'ri ai' 195

COLOR PLATES
A Gumi' TO TiiF, Ci.iNicAL Cari; of Women with HIV

Color Plates

power). (Monif, 1982; Fig. 22-3)

us. Department of Health and Hunun Services, Health Resources and Services Administr/\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 3. Candida in a saline wet mount (high power). (Monif, 1982;

Fig. 22-4B)

us. Department of Health and Hum/\n Services, Health Resources and Services Adminis"TM vhon, I II\7.\IDS HrRi- 197

COLOR PLATES
A CJuioi'. I'o riii; (j.inicai. Cari', oI' Womicn wrni HIV

Color Plates

Color Plate 4. Vaginal candidiasis: thrush patches on the vaginal wall of a patient with candidiasis. (J, Anderson, MD, ed.)

us. Department of He.\lth and Hum,\n Services, Health Resources and Services Administr.\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 5. Severe vulvar intraepithelial neoplasia (VIN3). (Wilkinson

and Stone, 1995; Fig 6.27)

us. Dep-\rtment of Health ,wd Hunwn Services, Health Resources anp Services ADMiKisiu vnoN, lll\7AII)s Hi m 199

COLOR PLATES
A (iUlDE TO THE CUNICAI, CARE OE WoME:N WITH HIV

Color Plates

Color Plate 6. Nontender chancres (Kissing lesions) in a woman with

primary syphilis. (Wilkinson and Stone, 1995; Fig 8.46)

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 7. Extensive vulvar condylomata accuminata (HPV). (Wilkin- son and Stone, 1995; Fig 9.3)

U.S. Department of Health and Human Services, Health Resources and Services Adminis-i-raiion, I IIV/AIDS Hi ri ,\u 201

COLOR PLATES
A Cil'lDK I'O mi'. (^UNICAl. C\KI'. ()!' WOMKN WI TH 1 IIV

(^olor l^latcs

Color Plate 8. Cervical intraepithelial neoplasia (CIN3) demonstrating

coarse mosaicism and punctuation on posterior lip. (Burghardt, 1991;

Fig. 11.37)

us. Dep.\rtment of Health and Human Services, Health Resources and Services AoMiNisncvnoN, HIV/AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 9. Mucopurulent cervicitis caused by C trachomatis. (Holmes,

1999; Plate 16)

us. Department of Health and Human Services, Health Rilsources and Si-rvicils ADMiNiyiRuins, I ll\ / \ll)s It 203

COLOR PLATES
A CU'IOK I'O Till'. Cl. INK' \l, (;.\RI'; OK WoMI'N Wl'l'll HIV

(]()lor l^latcs

Color Plate 10. Profuse purulent frothy vaginal discharge due to tri- chomonas. (Holmes, 1999; Plate 21)

Color Plate 11. PID, proven chlamydial pyosalpinx. Right tube is swollen

and tortuous (arrow). (Holmes, 1999; Plate 17)

us. Department of Health and Hunun Services, Health Resources and Services Administr,\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 12. Chancroid. (Holmes, 1999; Plate 32)

us. Demrtment of Health and Hunlan Services, Health Rksourci-s and Si:r\ i(,i s .\dmim.<jr vhon, I II\ A\II l. Iti . 205

COLOR PLATES
A CJuini': I'o tiiI', (Ii.inicai. (].\r|' or' Womi'n with HIV

('olor Plates

Color Plate 13. Condyloma latum in secondary syphilis. (Holmes, 1999;

Plate 47)

us, Dep.\rtment of Health and Human Services, Health Resources and Services AoMiNisTiumoN, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 14. Lesion of herpes simplex. (J, Anderson, MD, ed.)

us. Department of Health and Human Services, Health Resources and Servici-s ADMiNis-niA-noN, I IIW.MDS Hi'ri.m 207

COLOR PLATES
A (Juini; TO tiiI'. (j.inicai. CvRii oi' WomI'.n with HIV

('olor Plates

Color Plate 15. Herpes simplex (HSV) in woman with AIDS, CD4<50.

(}, Anderson, MD, ed.)

us. Department of Health and Human Services, HE/\lth Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Color Plates

Color Plate 16. Apthous genital ulceration. (J, Anderson, MD, ed.)

Color Plate 17. Apthous oral ulceration. (J, Anderson, MD, ed.)

US. Department of Health and Human Services, Health Resourciss and Services Adminisiti vi ion, I IIV/AIDS Hi rim 209

COLOR PLATES
A CAudi; to rnii Clinical Carl ol' Womkn wrni HIV

Color Plates

REFERENCES

Burghardt, Erich. Colposcopy — Cervical Pathology — Textbook and Atlas, 2nd Revised and

Enlarged Edition. NY: Thieme Medical Publishers Inc, 1991.

Holmes, King K, Sparling, P Frederick, Mardh, per-Anders, et al. Sexually Transmitted

Diseases, 3rd Edition. NY: McGraw Hill, 1999.

Monif, Gilles RG. Infectious Diseases in Obstetrics and Gynecology. Philadelphia: Harper

and Row Publishers, 1982.

Wilkinson, Edward J and Stone, I Keith. Atlas of Vulvar Disease. Baltimore: WtHams &

Wilkins, 1995.

U.S. Department of Health and Human Services, Health Resources and Services Administr-viion, HI\'/AIDS Bureau
VII: HIV AND Reproduction

Jean Anderson, MD

I. INTRODUCTION

The ability to become pregnant and to bear children is uniquely female. With

increasing numbers of HIV-infected women, 80% of whom are of childbearing age, and concerns about perinatal transmission of HIV, pregnane}^ in the

setdng of HIV infection has been a focus of much interest, research, and

often discrimination. From 1989—1994 it was estimated that 1.5 to 1.7/1000

U.S. childbearing women were HIV-positive (Da\tis, 1998); however, this number may grow as more women become infected through sexual exposure,

often unaware of their risk, and as more women who know they are infected

choose to become pregnant because of therapeutic advances in care and prevention of vertical transmission.

This chapter will re\iew issues related to contraception and pregnancy and

will discuss guidelines for care during pregnancy to optimize the health of

both the mother and and the fetus and infant.

II. COUNSELING

For w’omen known to be HIV-infected, education and counseling about pregnancy and HIV should be done early in the course of HFV^ care, not delayed

until the woman is pregnant, so that decisions about contraception and if or when to get pregnant can be most informed and carefully considered. Over

one-half of pregnancies in US women are unplanned and many of the risk

factors for unintended pregnancy also place women at increased risk for HIV.

These include:

substance abuse (patient or partner)

mental illness

domestic violence

Women with advanced HFV disease and HIV dementia may be at increased

risk for unintended pregnanev^ if they are dependent on a contraceptive method

(such as condom use or oral contraceptives) which requires negotiation with a sexual partner or other ongoing patient action (i.e., remembering to take pills).

Issues to discuss when counseling about reproductive issues are listed in

Table 7-1.

U.S. DeP.\RTMENT of HE.U.TH .WD HUNL\N SERVICES, He.\LTH RESOURCES .\ND SERMCES .\D.MISI.s-rR.An()N. UIWAIDS Bl Rl 'I 211
A Guide to the Clinical Care of Women wi th HIV

HIV and Reproduction

Table 7-1 : HIV and Pregnancy Counseling Issues

Impact of HIV on pregnancy course/outcome

Impact of pregnancy on HIV progression

Other reproductive issues based on maternal factors • coexisting drug/alcohol • advanced maternal age • hypertension, diabetes, etc. Long term health of mother and care for children (guardianship issues)

Perinatal transmission

Use of antiretrovirals and other medications in pregnancy

Safe conception if partner HIV negative

III. CONTRACEPTION

The majority of HIV-infected US women use some form of contraception,

most commonly condoms. (Wilson, 1996; Watts, 1999) Women using no form

of contraception do not necessarily intend to become pregnant but may lack

significant power in their sexual relationship, be under pressure from partner or family to have children, be unaware of their options concerning contraception or beUeve they cannot become pregnant, have a disorganized lifestyle that

precludes consistent use of contraception, or simply have decided to take their

chances. Unplanned also does not necessarily mean unwanted; several studies

show low rates of elective pregnancy termination in HIV-positive women

(Smits, 1999; Greco, 1999) and no significant difference in repeat pregnancy

rates in HIV-positive compared to HIV-negative women from an inner-city

population. (Lindsay, 1995) Table 7-2 outlines currently available methods of

contraception, their effectiveness, side effects and contraindications, and noncontraceptive benefits.

Hormonal methods of contraception, particularly oral contraceptives, can have significant drug interactions, resulting in either decreased contraceptive

effectiveness or increased or decreased concentrations of the co-administered

drug. Use of nelfinavir, ritonavir, amprenavir, and efavirenz may be associated

with decrease in effectiveness of oral contraceptives (and possible increase in

break-through bleeding); an alternative or additional method should be used.

(CDC, 1998) Other medications which are known to interact with oral contraceptives (and in some cases with progestin-only contraceptives) include tetra- cyclines, penicillin, oral hypoglycemic agents, rifampin, tricyclic

antidepressants, oral anticoagulants, beta-blockers, methyldopa, vitamin C,

benzodiazepines, and seizure medications. Clinicians treating women who are

at risk for drug interactions should review the need for possible use of alter- native methods of contraception or dose adjustment for the interacting agent.

Concerns have been raised about possible increased risk of HIV transmission or acquisition in hormonal contraceptive users. There is evidence that

both combined oral contraceptives and progestin-only contraceptives may

increase genital tract HIV shedding; furthermore, oral contraceptives have

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Buri;au
A Guide to the Cunic\l Care of Women with HIV

HIV and Reproduction

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us. Department of Health and Human Services, Health Resources and Services ADMiNisncvnoN, HIV/ AIDS BuRiLUi 215
A CiUlDI' TO THE ( j.INICAL CARE OH WOMEN WI TH HIV

HIV and Reproduction

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\ C'lUioF. TO i'l II- Ci.iNiCAi. Cari; oi'' WoMi'N wrni I IIV HIV and Reproduction

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U.C0

US. Department of Health and Human Services, Health Resources and Servicf.s ADMiNi.sTR,\noN, HIV/AIDS Hurim 219
A CJuiDi; TO rill': (j.inical Cari-; oh Womkn with HIV

HIV and Reproduction

US. Department of Health and Hum,\n Services, Health Resources and Services ADMiNis'niAnoN, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

been associated with increased cervical ectopy, which has also been Linked with

genital tract HIV shedding. Similarly, ectopy or other epithelial changes sec- ondary to hormonal contraception or associated effects on immune response

may increase susceptibility to HIV and animal studies have suggested a link

between progesterone implants and vulnerability to simian immunodeficiency

virus (SIV). (Plummer, 1998; Mostad, 1998) Data from epidemiologic studies

are conflicting and inconclusive regarding the relationship of these methods of

contraception and HIV transmission. (Martin, 1998; Stephenson, 1998) At the

current time, given their effectiveness, overall safety, and ease of use, hormonal methods of contraception remain an appropriate option for HIVinfected or at-risk women. These women should be advised that these

contraceptives do not protect against HIV transmission and consistent con- dom use should be emphasi2ed.

Use of the lUD has been linked to increased susceptibility for HIV trans- mission (Gervasoni, 1992) and is associated with increased menstrual flow

and duration, possibly contributing to transmission risk and anemia in HIVpositive women; furthermore, risk of pelvic inflammatory disease (PID) is increased in lUD users who are at increased risk for acquiring other STDs.

For these reasons, the lUD should generally be avoided in the setting of

HIV infection.

Spermicides have in vitro activity against HIV and significant activity

against gonorrhea and chlamydia; however, a recent study of a standard spermicidal dose of nonoxynol-9 (N-9) daily for one week found an increase in

irritation, colposcopic and histologic evidence of inflammation, and decreased

numbers of vaginal lactobacilli in N-9 users, as compared to placebo recipients

(Stafford, 1998); these findings raise concerns that regular use of spermicides

may not only negate any protective effect, but may potentially increase risk of

HIV transmission. A recent randomized, double-blind, placebo-controlled

smdy of vaginal film containing N-9 in over 1200 HIV uninfected sex workers

in Africa found no difference in rates of HIV infection between the two

groups. (Roddy, 1998)

Condoms —used consistently — provide the best known protection

against sexual transmission of HIV and should be emphasized for all HIVinfected and at-risk.women to decrease risk of HIV transmission/acquisition,

as well as transmission/acquisition of other STDs. Other barrier contraceptive

methods provide limited STD protection and have not been shown to offer

significant protection against HIV transmission.

Since male and female condoms are used for both prevention of infection

and prevention of pregnancy, these two separate issues should be distinguished when counseling patients. Condom use should be reinforced for HIVpositive or at-risk women when prevention of pregnancy is not a concern:

postmenopausal women; during pregnancy; infertility; and with the use of

other methods of contraception.

us. Department of Health and Human Services, Health RiisouRCPa and Skrvice.s Adminis-iradon. HIV/AIDS Hi ri-.m 221
A Guide to the Clinic.\l Care of Women with HR"

HR" and Reproduction

V. PREGNANCY TESTING

Indications for pregnancy testing in currently or recently sexually active

women:

missed menses (unless on Norplant or DepoProvera)

irregular bleeding (unless on Norplant or DepoProvera)

new onset of irregular bleeding after prolonged amenorrhea on

Norplant/DepoProvera

new onset pehtic pain

enlarged uterus or adnexal mass on exam

consider prior to institution of new therapies

Pregnancj- tests are performed on blood or urine and may be qualitative

(positive/negative) or quantitative. Quantitative tests are useful in early pregnancy when ectopic pregnancy or abnormal intrauterine pregnancy (e.g.,

missed abortion) are suspected. Several qualitative urine pregnancy tests are

available over the counter. Most pregnancy tests in current use are positive

before the first missed menses with normal intrauterine pregnancy. Table 7-3

lists R"pes of available pregnancy tests and sensitiAUty.

Table 7-3: Pregnancy Tests

Sensitivity Comments

Radioimmunossay

blood

positive within 7 days of

fertilization quantitative or qualitative

used to follow women with

possible ectopic

pregnancy

Enzyme immunoassay

(EIA)

blood

urine

positive approximately

10 days after fertilization

available for home urine

testing — positive results require confirmation

Antibody agglutination

inhibition

urine

positive approximately

18-21 days after

fertilization

false positives with

hypothyroidism, renal

failure, immunologic

disorders, increased

lutenizing hormone (LH)

VI. HIV AND FERTILITY

Recent studies in Africa, as well as in developed countries, have suggested that

HIV may have an adverse effect on fertility in both symptomatic and asymptomatic women. (Desgrees, 1999; Lee, 1998; Zaba, 1998) A cross-sectional study

from Uganda found likelihood of pregnancy lower in HIV-positive women as compared to HIV-negative women and lowest in women who were symptomatic from HIV or were coinfected with sjqjhilis. A prospective study in the

same population found that pregnancy rates were lower and pregnancy loss was more common in HIV-infected women. (Gray, 1998)

us. DEP.ymtENT of He.u.th and Human Sermces, Health Resoitrces .\nd Sermces Ad.ministr.\tion, HUV-MDS Bure.au
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EFFECTS OF PREGNANCY ON HIV INFECTION

A. CD4 COUNTAND HIV-RNA LEVELS LN PREGNANCY

In both Hl\'-posidve and HI\ -negative women there is a decline in absolute

(d)4 cell counts in pregnancy, which is thought secondary to hemoddution; on

the other hand, percentage of CD4 cells remains relatively stable. Therefore,

percentage, rather than absolute number, may be a more accurate measure of

immune function for HI\ -infected pregnant women. (Miotti, 1992; Bretde,

1995; European Collaborative Smdy and the S’utiss HT\" Pregnancy Cohort,

199”^) When comparing changes in CD4 count/percentage over time, there is no difference between HR -positive pregnant and nonpregnant women (O’Sullivan, 1995), suggesting that pregnancy does not accelerate decline in CD4

cells. HR’-RN'A levels (viral load) remain relatively stable throughout pregnancy in the absence of treatment (Burns, 1998).

B. CLINICAL COURSE OE HLVIN PREGNANCY

Most studies to date examining the impact of pregnane}' on HR" disease have

been small but have not shown significant differences in HR" progression or surHval between pregnant women and nonpregnant women \^ith HR" infection. A recent meta-analysis of seven prospective cohort smdies found no

overall significant differences in death, HR" disease progression, progression

to an AIDS-defining illness, or fall in CD4 count to below 200/mm^ between

cases and controls. (French, 1998) A subsequendy reported prospective smdy

of 331 women with known dates of seroconversion were followed for a median of 5.5 years; during this time 69 women were pregnant. There were no

differences in progression between those who were and were not pregnant

during follow-up. (.AUiegro, 1997)

VIE EFFECT OF HIV ON PREGNANCY COURSE AND

OUTCOME

Adverse pregnancy outcomes may occur secondary to underlying disease

processes (or their treatment), as well as for unknown reasons. Approximately

10% of US pregnancies end premamrely and preterm birth is the leading cause of perinatal morbidity and mortaHtv. Data has accumulated that HR",

especially when more advanced, may result in increases in certain pregnanev

complications. Furthermore, concerns have been raised that antiretro\'iral

treatment itself may increase some adverse outcomes in pregnanev. Table ~-4

summarizes the relationship between common pregnanev related complications and HR". (Brocklehurst, 1998)

Both HR" and pregnanct' may affect the natural history, presentation, treat- ment, or sigmficance of certain infections, and these, in turn, mav be associated with pregnancy complications or perinatal infection.

U.S. Dervrtment of He.vi.th .vnd Hl-m.\n Services, He.\lth Resocrces .\sd Services .\i»ONL<rR.vno\, HD" AIDS Bv v 223
A Gl'idI' to the Ci.iNiCAi. Care oI' VC'omen wi th

Hl\' and Reproduction

Table 7-4: Adverse Pregnancy Outcomes and Relationship to HIV

Infection

Adverse Pregnancy Outcome Relationship to HIV Infection

Spontaneous Abortion Limited data, but evidence of possible increased risk

Stillbirth No association noted in developed countries; evidence

of increased risk in developing countries

Perinatal mortality No association noted in developed countries, but data

limited; evidence of increased risk in developing

countries

Infant mortality Limited data in developed countries; evidence of

increased risk in developing countries

lUGR Evidence of possible increased risk LBW (< 2500g) Evidence of possible increased risk Preterm delivery Evidence of possible increased risk, especially with more advanced disease

Pre-eclampsia No data

Gestational diabetes No data

Chorioamnionitis Limited data; more recent studies do not suggest an

increased risk; some earlier studies found increased

histologic placental inflammation, particularly in those

with preterm deliveries

Oligohydramnios Minimal data

Fetal malformation No evidence risk of increased risk

A. VULVOVAGINAL CANDIDIASIS

Pregnancy is associated with both increased rates of coloni2ation and increase

in symptomatic infections with species of Candida. HIV infection is also associated with increase in coloni2ation and possible increased infection rates,

especially with declining immune function. (Cu-Uvin, 1999; Schuman,1998;

Duerr, 1997; SpiniUo, 1994; Burns, 1997) Therefore, pregnant women with

HIV infection may be particularly susceptible to yeast infections. Only topical

a2ole agents should be used during pregnancy and should be given for at least

7 days. Prophylactic topical therapy should be considered during courses of

systemic, especially broad spectrum, antibiotics are given.

B. BACTERIAL VAGINOSIS (BV)

Bacterial vaginosis has been associated with several adverse pregnancy outcomes, including preterm labor and birth, premature rupture of membranes,

low birth weight infants, chorioamnionitis and amniotic fluid infection, postpartum and postabortal endometritis, and perinatal HIV transmission. If BV is diagnosed during pregnancy, preferred therapies are metronida2ole 250 mg po

tid X 7 days or clindamycin 300 mg po bid x 7 days, since only oral agents have

been shown to reduce preterm births in women with BV. (Morales, 1 994;

McGregor, 1995; Hauth, 1995) Since the majority of BV episodes are asymptomatic, screening for BV should be performed at intervals during pregnancy

and infection treated if identified. A recent meta-analysis (Caro-Paton, 1997)

found no relationship between metronida2ole exposure during the first trimester of pregnancy and birth defects.

us. Dep.\rtment of He.\lth and Hum.\n Services, He.vi.th Resources .and Services Adshnistration, HI\7AIDS Bureau
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HIV and Reproduction

C GENITAL HERPES SIMPLEX (HSV)

Primary I ISV infection during pregnancy has been associated with sponta- neous abortion and prematurity. Congenital or intrauterine infection is uncommon but maternal HSV shedding at delivery is associated with neonatal HSV

infection, which is almost always symptomatic (including skin, eye, central nervous system involvement, or disseminated infection involving multiple

organ systems) and frequently lethal. The risk of neonatal herpes is greatest

with primary HSV, especially when acquired close to delivery (approximately

50%), whereas only 0—3% of neonates become infected with recurrent maternal disease at delivery; however, since recurrent HSV is more common than

primary disease, the majority of neonatal infections are associated with recurrent HSV. Two-thirds or more of mothers with infected infants are asymptomatic during pregnancy; only one-third have a prior history of HSV in

themselves or their sexual partner. Since most neonatal infection occurs during

vaginal delivery, if genital lesions or prodromal symptoms are present at the

time of labor or membrane rupture. Cesarean section should be performed.

Cesarean section is not indicated for recurrent HSV distant from the genital

tract (e.g., thigh, buttocks). (ACOG, 1999)

HIV infection, particularly with evolving immunecompromise, is associated

with increased viral shedding and more frequent, severe, and prolonged

episodes of genital or perianal herpes. (Augenbraun, 1995) Higher doses

and/or longer courses of antiviral agents may be required and suppressive

therapy is often beneficial in nonpregnant individuals. Infection with HSV-2 is common among pregnant HIV-infected women and reactivation of herpes in

labor occurs more frequently in the setting of HIV infection. (Hitti, 1 997)

During pregnancy a first clinical episode of genital herpes, especially in late

pregnancy, may be treated with antiviral therapy. The use of oral acyclovir prophylacticaUy in late pregnancy has been shown to significantly reduce symptomatic recurrences and decreased need for Cesarean section, though not with

statistical significance. (Brocklehurst, 1998) Suppressive therapy may be indicated in women with frequent, severe recurrences; antiviral therapy may also

be considered at 36 weeks and beyond in women at risk for recurrent HSV.

There is no current evidence of increased risk for major birth defects or

other adverse pregnancy outcomes with exposure to acyclovir. Glaxo-Wellcome, Inc., in cooperation with CDC, maintains a registry to assess effects of

acyclovir and valacyclovir use during pregnancy. Women who receive either of

these drugs in pregnancy should be reported to this registry (telephone (888)

825-5249, ext. 39441).

Prevention of neonatal herpes should also emphasize prevention of acquisition of herpes in susceptible women in pregnancy. If her sexual partner has

a history of oral or genital HSV infection, serologic evidence of HSV infection, or infection status is unknown, the pregnant woman should be counseled

to avoid unprotected genital and oral sexual contact during pregnancy.

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HIV and Reproduction

D. HUMANPAPILLOMA VIRUS (HPV)

Genital warts often enlarge and become friable during pregnancy and in some

cases may mechanically obstruct the vaginal canal in labor; perinatal exposure

can result in laryngeal papillomatosis in infants and children, although a recent

prospective study suggests that the risk of perinatal transmission of HPV is low. (Watts, 1998) Both HPV infection in general and genital warts are more

common in HIV-infected individuals, correlated with level of immunesuppression. Imiquimod, podophyllin, and podofilox should not be used in pregnancy.

In women with large volume or bulk of genital warts treatment in late pregnancy with laser, excision, or cavitronic ultrasonic aspiration (CDSA) may be

considered. Cesarean section is not currently recommended to prevent neonatal exposure to HPV, although in rare instances C-section may be indicated

when extensive lesions obstruct the vagina.

E. SYPHILIS

Syphilis is more prevalent in HIV-infected populations and HIV may affect

clinical manifestations, serologic response, or response to treatment for syphilis.

Pregnancy does not alter the clinical manifestations of syphilis but untreated

primary or secondary syphilis during pregnancy affects essentially all fetuses,

with 50% rate of prematurity, stillbirth, or neonatal death. (Radolf, 1 999) Even

with later stages of syphilis, there is a significant increase in adverse pregnancy

outcomes, although the frequency and severity of fetal disease decreases with

longer duration of untreated maternal infection. Manifestations of congenital

syphilis in the newborn include mucocutaneous lesions, hepatosplenomegaly,

osteochondritis/periostitis, jaundice, petechiae/purpura, and meningitis.

Congenital syphilis can generally be prevented by identification and appropriate treatment of syphihs during pregnancy. All pregnant women should

have serologic testing for syphilis at the beginning of prenatal care and testing

should be repeated at 28 weeks gestation and at delivery, particularly in women

who remain at risk for infection. Any woman with stillbirth after 20 weeks

gestation should be tested for syphilis. Development of neurologic symptoms

mandates evaluation for possible neurosyphihs. Treatment of syphilis during

pregnancy should be the penicillin regimen appropriate for the stage of

syphilis, although some experts recommend additional weekly doses in women

with primary, secondary or early latent syphilis who are HIV-infected or pregnant. HIV-positive women with late latent syphilis or syphilis of unknown

duration should have CSF examination before treatment. (CDC, 1998)

Ultrasound evidence of hydrops or hepatosplenomegaly suggesting fetal syphilis increases risk for treatment failure and should be managed with expert

consultation. Treatment in the second half of pregnancy is associated with the

Jarisch-Herxhelmer reaction in up to 40% of cases, with resulting premature

labor and/or fetal distress (Myles, 1998); they should be advised to seek immediate attention after treatment if contractions or decrease in fetal movements

occur. Pregnant women with a history of penicillin allergy should be skin

us. Dep.\rtment of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

tested and, if necessary, desensitized and treated with penicillin, as there are no proven effective alternatives to penicillin for treatment and prevention of

congenital syphilis. Even with appropriate treatment of the pregnant woman

with syphilis, fetal infection may still occur and neonates should be carefully

evaluated for evidence of congenital infection.

(dinical and serologic follow-up should be performed at 3,6,9,12, and 24

months after treatment. Treatment failure should be managed with CSF examination and re-treatment.

E CYTOMEGALOVIRUS (CMV)

('ytomegalovirus is the most common cause of congenital viral infection in

the U.S. with 0.2—2.2% of liveborn infants acquiring this infection perinatally.

(A(X)G, 1993) Most maternal CMV infections are asymptomatic but may

cause a mononucleosis-like illness. Transmission can occur sexually or with

injection drug use, since CMV has been recovered from virtually aU body fluids. Perinatal transmission can occur with both primary and recurrent infection, but frequency of transmission and severity of infection in the infant are greater with primary infection. Ninety percent of infected infants are asymptomatic at birth, but symptomatic infection is more likely with maternal infection

acc|uired early in pregnancy. Even if asymptomatic, many infected infants subsequently develop deafness, mental retardation, or delayed psychomotor development. More severe clinical manifestations include symmetric growth

restriction, hepatosplenomegaly, chorioretinitis, microphthalmia, hydrocephaly,

microcephaly, and cerebral calcifications.

In the setting of HIV infection, mothers seropositive for CMV do not

appear to be more likely to transmit CMV perinatally than HIV-negative mothers. Furthermore, the frequency of CMV infection at birth is similar between

HIV-infected and —uninfected infants born to HIV seropositive mothers.

There have been some reports that co-transmission of HIV and CMV may be

related to more rapid HIV progression. (Kovacs, 1999; Mussi-Pinhata, 1998)

There is no effective therapy to prevent or treat perinatal CMV infection.

Testing for antibody to CMV should be considered in pregnancy, especially if the CD4 count is < 100/mm^; however, seropositivity is common and does not

preclude viral shedding during pregnancy and perinatal transmission. Methods

to reduce risk of exposure to CMV include safer sexual practices; careful handwashing; and transmission of only CMV antibody-negative blood products. Primary prophylaxis is not routinely recommended; however, after CMV disease,

chronic suppression is indicated in pregnancy and should be continued with

expert consultation concerning choice of agents, (see below OI Prophylaxis).

G. TOXOPLASMOSIS

Approximately one-third of U.S. women have toxoplasma antibodies, reflecting prior infection. Primary infection occurs in approximately 0.1—0.5% of

U.S. Department of He,\lth and Hum^kn Services, He.\lth Resources and Services /VoMiNi.sTR.vnoN, HI\7.\IDS Bi ri.m 227
A Guide to thi; Q.inicai, Care of Women with HIV

HIV and Reproduction

pregnancies and places the fetus at risk for congenital toxoplasmosis. Congenital infection is more common when infection in the mother occurs during the

third trimester (59% in third trimester vs 9% in first trimester) but is generally

more severe when occurring in the first trimester. Although the majority of

infected infants are asymptomatic at birth, most will develop some sequelae of

congenital toxoplasmosis; two-thirds of infants infected after maternal first trimester infection have severe manifestations and 5% are stillborn or die in

the perinatal period. (ACOG, 1993)

Congenital toxoplasmosis may affect all systems, but the most common

findings are chorioretinitis, microcephaly, hydrocephaly, and cerebral

calcifications.

Transmission of toxoplasmosis from a mother with antibody evidence of

prior infection can occur in the setting of HIV infection, but does not seem

to be common, although there is limited data in more immunosuppressed

mothers. (Minkoff, 1997; European Collaborative Study and Research Network in Congenital Toxoplasmosis, 1996)

Testing for IgG antibodies to toxoplasma is recommended for all HIVinfected individuals soon after the diagnosis of HIV is made and should be

considered as part of prenatal testing in HIV-positive pregnant women. Primary prophylaxis and prophylaxis against recurrent disease in pregnancy are discussed below. Pregnant women with symptoms including fever, chills,

malaise, lymphadenopathy, myalgias, headache should be evaluated serologically for possible primary toxoplasmic infection. Evidence of primary infection or active toxoplasmosis should be evaluated and managed with expert

consultation. Infants born to women infected with HIV and seropositive for

toxoplasma should be evaluated for evidence of congenital toxoplasmosis.

To prevent exposure to toxoplasmosis, pregnant women should be counseled to avoid raw or undercooked meat; wash hands after contact with raw meat or with soil; and wash fruits and vegetables well before eating them raw. Cats should preferably be kept inside and fed only canned or dried commercial

food; litter boxes should be changed daily, preferable by someone who is not

HIV-positive or pregnant.

H. HEPATITIS B (HBV)

Approximately 300,000 new cases of hepatitis B occur each year and more

than one million Americans are chronic carriers. Most patients who become

infected have complete resolution of infection and develop protective levels of

antibody (anti-HBs). Chronic HBV infection develops in 1—6% of persons

who are infected as adults; they are chronically HbsAg+ and are at risk of

chronic liver disease, including cirrhosis and hepatocellular carcinoma. (CDC,

1991) The presence of HbeAg indicates active viral replication and increased

infectivity. HBV is transmitted parenteraUy, sexually, perinatally, and through

household or institutional contact. Approximately one-quarter of regular sexU.S. Department of He/U,th and Human Service^ Health Resources and Services Administration, HI\VAIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

ual contacts of infected individuals will become seropositive and sexual trans- mission accounts for 30-60% of new infections. Perinatal transmission, usually with intrapartum contact with maternal blood and genital secretions, occurs in 10-20% of women who are HbsAg+, but increases to approximately 90% if the mother is also HbeAg+. Chronic HBV infection develops

in about 90% of infected newborns, who are at high risk of chronic liver disease. (ACOG, 1998)

All pregnant women should be screened for HbsAg. Infants born to

women who are HbsAg+ should receive hepatitis B immune globuLine

(11 BIG) and initiate HBV vaccination within 12 hours after birth. HBV vaccine can be safely administered during pregnancy and should be considered in

women who are high risk (injection drug use, STDs, multiple sexual partners,

household or sexual contact of HBV carrier) and are anti-HBs or anti-HBc

negative, indicating susceptibility. Some experts argue for more liberal use of

vaccination in HIVinfected individuals, since HBV infection in the setting of

HIV infection increases risk for chronic HBV infection. HIV can impair

response to HBV vaccine, and, therefore, testing for hepatitis B surface antibody is recommended 1—2 months after the third vaccine dose. Full revaccination should be considered for those who are nonresponders. (ACOG, 1998;

Bartlett, 1999)

I. HEPATITIS C (HCV)

Hepatitis C infection is primarily transmitted by injection drug use, but may

also be transmitted sexually. Approximately 50% of tliose with acute HCV

infection develop biochemical evidence of chronic liver disease, and 20% or more ultimately have chronic active hepatitis or cirrhosis and are at risk for

hepatocellular carcinoma. (CDC, 1998) Women newly diagnosed with HIV in

pregnancy should have testing for antibody to HCV by enzyme immunoassay;

positive results should be confirmed with recombinant immunoblot assay

(RIBA) or HCV PCR and Hver function abnormalities should be documented.

Women coinfected with HIV and HCV should avoid alcohol, both during and

after pregnancy, since alcohol use increases risk of cirrhosis. Vaccination

against hepatitis A, if the woman is anti-HAV negative, is recommended

because the risk for fulminant hepatitis associated with hepatitis A is increased

in HCV-infected individuals; this vaccination may be safely given during pregnancy. (ACOG, 1998; Bartlett, 1999)

Perinatal transmission of HCV has been documented and may be more

likely in HIV coinfected women or in HIV-infected infants born to dually

infected mothers. (Thomas, 1998; Papaevangelou, 1998) Furthermore,

maternal coinfection with HIV and HCV may also increase risk for perinatal HIV transmission. (Hershow, 1997) Risk of vertical HCV transmission

is proportional to amount of HCV RNA present in maternal blood.

(Thomas, 1998)

US. Department of Health and Human Services, Health Resource-s and Services ADMiNi.s-i-R.vnoN, HIN'/AIDS Brm ,\i' 229
A CAuof. to THU Cmnical CarI': of Women with HIV

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VIII. PERINATAL TRANSMISSION

The baseline rate of perinatal HIV transmission without prophylactic therapy

is approximately 25%. The timing of transmission is a critical factor impacting

on development of preventive interventions. There is evidence that transmission can occur during the course of pregnancy, around the time of labor and

delivery, or postpartum through breastfeeding; however, V3 to V-* of transmission appears to occur during or close to the intrapartum period, particularly in

non-breastfeeding populations. (Mofenson, 1997)

A. POTENTIAL VARIABLES IN TRANSMISSION

HIV-related Factors

HIV-RNA level (Garcia, 1999; Mofenson, 1999; Shaffer, 1999): HIV-RNA

levels correlate with risk of transmission in both antiretroviral-treated and

untreated women. The risk of perinatal transmission appears to be

extremely low in women with undetectable plasma viral loads, but transmission has been reported at aU levels of maternal HIV-RNA. There is no

upper limit of HIV-RNA above which perinatal transmission always occurs.

Strain variation (genotype): Each HIV-infected individual’s viral pool is comprised of a variety of HIV quasispecies. One recent study found that in

utero transmission was associated with transmission of major maternal viral

variants, whereas intrapartum transmission was associate with transmission

of minor maternal viral variants, suggesting that different selective pressures

may be involved in determining the pattern of viral strain transmission

depending on timing of transmission. (Dickover, 2000) HIV in vaginal

secretions can be derived from local expression and may have significant

genotypic differences from plasma virus, with possible implications for perinatal transmission. (Subbarao, 1998)

Biologic growth characteristics (phenotype): Fetal blood mononuclear

cells may be more susceptible to macrophage-tropic, non-syncytium-inducing HIV phenotypes and this may influence mother-to-infant HIV transmission. (Reinhardt, 1995; Palasanthiran P, 1994)

Plasma vs genital tract viral load: There is general correlation between

plasma and genital tract viral load but discordance has been reported and

may help explain some cases of transmission with undetectable plasma

HIV-RNA. In the Thai short-course ZDV clinical trial, both plasma and

cervicovaginal HIV-RNA levels were suppressed by ZDV treatment and

both were independently correlated with transmission. (Chuachoowong,

2000) The female genital tract can also be a reservoir for virus with a different drug resistance pattern than that observed in plasma. (Fang, 1 998) Further studies are needed to assess suppression of genital tract virus with

other antiretroviral agents and with HAART therapy, and the association of

this suppression with perinatal transmission.

us. Department of Health and Hunwn Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

Genotypic resistance: Use of antiretroviral regimens (particularly single

agents) for the purpose of perinatal prophylaxis has raised concerns about

the induction of resistance mutations, possibly increasing the risk for vertical transmission or progression in infected infants. Studies to date of resist- ance mutations in the setting of ZDV monotherapy during pregnancy have

shown increasing prevalence of these mutations over time and an association with length of drug exposure. (Palumbo, 1999; Eastman, 1998; KuUy,

1999; Hscus, 1999) Perinatal transmission of virus with known ZDV resist- ance mutations has been described (Colgrove, 1998) and one recent study

found that maternal ZDV use was associated with rapid disease progression

in infants who acquired HIV despite maternal ZDV use. (Pitt, 2000) Most

concerning, a recent study from the Women and Infants Transmission

Study (WITS) of women who received ZDV during pregnancy, found that

25% of 142 maternal isolates had at least one ZDV-associated resistance

mutations; a lower CD4 % and higher plasma HIV-RNA level were associated with ZDV resistance mutations at delivery and, with multivariate analysis, the presence of resistance mutations was independently associated with

vertical transmission. (WeUes, 2000)

Eschleman et al found that a subset of Ugandan women developed a K103N nevirapine resistance mutation after receiving a single dose of nevirapine at the onset of labor for prevention of perinatal transmission; the

implications of this finding for perinatal prophylaxis with nevirapine and

the relevance to HIV subt)q3es more prevalent in other areas of the world

are unknown. (Becker-Pergola, 2000)

CD4 cell count: Lower CD4 count or decreased CD4:CD8 ratio have been

consistently associated with increased risk of transmission.

Maternal immune response: Studies have been inconsistent when evaluating the role of maternal antibodies, including anti-gpl20, anti-gp41, and

autologous neutralizing antibody titers. Beta-chemokine and cytokine

responses may affect risk of transmission. (Rich, 1998)

B. MATERNAL/OBSTETRICAL EACTORS

Clinical stage: Maternal symptomatic disease or AIDS-defining illness are consistently associated with higher risk for transmission. Women with primary HIV infection in pregnancy, at which time plasma viremia is high, are

also at increased risk for transmission. (Nesheim, 1996)

STDs/other coinfections: STDs have been shown to increase genital tract HIV shedding and also increase plasma viremia (Plummer, 1998), both of

which may increase risk for perinatal transmission. STDs (Mandelbrot,

1996), syphilis (Lee, 1998), bacterial vaginosis (Taha, 1998), and placental

malaria have been associated with increased risk for vertical transmission, as have increased levels of genital tract inflammatory cells. (Panther, 2000)

us. Department OF Health and Human Services, Health Resources and Service.s ADMiNismvnoN, HIV/ AIDS Huri \u 231
A C'jUIDi; to tiii; Clinical Carl: ol Woml;n wrni HIV

HIV and Reproduction

Vitamin A deficiency: Vitamin A deficiency has been associated with

increased risk of perinatal HIV transmission and increased genital tract HIV shedding. (Nimmagadda, 1998) However, a recent randomized trial of

vitamin A supplementation in South Africa found no overall reduction in

mother-to-child transmission of HIV, although vitamin A recipients were

less likely to have a preterm delivery and in deliveries which were preterm,

those infants assigned to the vitamin A group were less likely to be infected.

(Coutsoudis, 1999)

Substance abuse: Illicit drug use during pregnancy has been associated

with increased risk for perinatal transmission. (Landesman, 1996; Rodriguez,

1996; Lyman, 1993)

Cigarette smoking: Cigarette smoking has been associated with an

increased risk of perinatal transmission. (Burns, 1994; Turner, 1997)

Antiretroviral agents: ZDV (antepartum/intrapartum/neonatal),

ZDV/3TC (intrapartum/neonatal), and nevirapine (intrapartum/neonatal)

have all demonstrated effectiveness in reducing periantal HIV transmission

in randomized clinical trials. In the PACTG 076 study, reduction in viral

load accounted for only 17% of ZDV’s effectiveness, suggesting pre-and/or

post-exposure prophylaxis as other possible mechanisms of action. (SperUng, 1 996) Although there are no clinical trials completed with HAART

regimens, these regimens result in optimal reductions in viral load, which

would be expected to lead to reductions in transmission. Very few perinatal

HIV infections have been reported in infants exposed to HAART.

Sexual behavior: Unprotected sex with multiple partners has been associated with increased risk for perinatal transmission. (Bultreys, 1 997)

Gestational age: Preterm delivery has been associated with increased risk

for perinatal transmission. (Kuhn, 1999; Kuhn, 1997)

Duration of membrane rupture: A recent meta-analysis from 1 5 prospective cohort studies, including over 7500 deliveries, examined the role of

duration of ruptured membranes in perinatal transmission. (Read, 2000)

The likelihood of transmission increased linearly with increasing duration of

ruptured membranes, with a 2% increase in risk for each hour increment.

Women with clinical AIDS had the most pronounced increase in risk, with

a 31% probability of vertical transmission after 24 hours of ruptured membranes.

Placental disruption-abruption, chorioamnionitis: Clinical and histologic chorioamnionitis (Goldenberg, 1998) has been associated with

increased risk of transmission. Placental abruption causing disruption of

fetal-placental barrier and possible increased exposure of the fetus to

maternal blood, has also been suggested as a risk factor for transmission.

Invasive fetal monitoring: Use of fetal scalp electrodes or fetal scalp sampling increases exposure of the fetus to maternal blood and genital secreUS. Department of Health and Human Services, Health Resources and Services Administr,\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

dons and may increase risk of vertical transmission. Amnioscopy and amniocentesis increased risk in the French Perinatal Cohort (Mandelbrot, 1996)

Episiotomy, forceps: Use of episiotomy or vacuum extraction or forceps

may potentially increase risk of transmission by increasing exposure to

maternal blood/genital secretions with trauma to maternal or neonatal tissue. On the other hand, judicious use of these techniques to shorten duration of labor or ruptured membranes with vaginal delivery may decrease

likelihood of transmission.

Vaginal versus cesarean delivery: Several recent studies indicate that cesarean delivery performed prior to the onset of labor and rupture of

membranes significantly reduces the risk of perinatal HIV transmission.

(Mandelbrot, 1998; Kind, 1998; European Mode of Delivery Collaboration,

1999; The International Perinatal HIV Group, 1999) Rates of transmission were reduced to approximately 2% with scheduled C-section and receipt of

ZDV (similar risk of 2% or less is seen among women with HIV-RNA levels less than lOOOc/ml, in the absence of systematic use of cesarean section). Whether cesarean delivery offers any benefit when the mother is on

HAART and/or if she has low or undetectable viral load is unknown.

C FETAL/NEONATAL FACTORS

Fetal/ neonatal factors, including an immature immune system (particularly in

the premature infant) and genetic susceptibility, as expressed by HLA genotype (Just, 1992) or CCR-5 receptor (a co-receptor for macrophage-tropic

strains of HIV; a homozygous deletion in this gene confers a high degree of

natural resistance to HIV sexual transmission) mutations may play a role in

perinatal transmission. (Weiser, 1998; Mangano, 2000; Kostrikis, 1999) A

recent study from South Africa (Kuhn, 2000) found that early acquired cellular

immune responses to HIV, presumably from in utero exposure, were present

in over one-third of 86 uninfected infants born to HIV-infected mothers.

These detectable immune responses appeared to provide complete protection

against subsequent HIV transmission at delivery and through breastfeeding.

D. BREASTFEEDING

Breastfeeding plays a more significant role in perinatal HIV transmission than

was once thought and was estimated to have accounted for up to 50% of

newly infected children globally in 1998. (Fowler, 1999) Breastfeeding in the

setting of established maternal infection has an estimated additional risk of

14% transmission, while the risk is 29% in the setting of acute maternal infection or recent seroconverson. (Dunn, 1992) HIV-DNA can be detected in over 50% of breast milk samples and is correlated with CD4 depletion and

vitamin A deficiency. Risk of transmission is highest in the earliest months of

breastfeeding but increased duration of breastfeeding increases risk. (Kreiss,

1997; Leroy, 1998) Other potential variables include the presence of cracked

nipples or breast abscess, infant oral candidosis, and the use of exclusive

us. Department OF Health and Human Services, Health Resourcils and Services Adminis-i r vik in, III\'/ ,\II).s Bum m 233
A C'lUini- TO ruH Cunicai, C\rf. oi' WoMiiN wiiii HIV

HIV and Reproduction

breastfeeding vs mixed feeding. A recent randomized clinical trial of breastfeeding vs formula in Kenya (Nduati, 2000) found that formula feeding

prevented 44% of infant infections and was associated with a significantly

improved HIV-free survival.

Strategies for Prevention of Perinatal Transmission:

Based on the potential factors impacting on perinatal HIV transmission discussed above, several basic approaches to prevention have been suggested.

These include decreasing viral load, decreasing viral exposure, identification

and treatment of modifiable risk factors, and ultimately, stimulation of the

immune system, such as with passive or active immunization.

IX. GUIDELINES FOR CARE

A. ANTEPARTUM

History/physical examination

(See Chapter IV on Primary Medical Care.)

HIV history: date of diagnosis; history of HIV-related symptoms or

opportunistic infections or malignancies; lowest CD4 cell count; complete

antiretroviral history, including specific drugs, side effects or toxicity, length

of treatment, adherence and response to treatment

Pregnancy history; previous pregnancies and outcomes; complications;

mode of delivery; use of antiretroviral prophylaxis; and HIV status of other

children

Signs or symptoms of HIV/AIDS: The initial and follow-up evaluations

of HIV-positive women during pregnancy should assess signs or symptoms

suggestive of symptomatic HIV infection or AIDS(e.g., generalized lymphadenopathy, thrush, constitutional symptoms such as fever (38.5 degrees

C) or diarrhea > 1 month, herpes zoster involving two episodes or > 1 dermatome, peripheral neuropathy, wasting, dysphagia, shortness of breath,

persistent mucocutaneous herpetic ulcerations, cognitive dysfunction, etc).

Signs or symptoms of pregnancy-related complications: elevated

blood pressure, significant edema, severe headache, vaginal bleeding or

leakage of fluid, intractable nausea and vomiting, dysuria, abnormal vaginal

discharge, persistent abdominal or back pain or cramping, decrease in fetal movement, etc.

Certain symptoms of HIV disease and normal or abnormal pregnancy

may overlap, resulting in possible delay in appropriate diagnosis and management.

Relevant family history of possible heritable diseases.

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

Laboratory Examination By Trimester

(See Table 7-5)

Table 7-5: Laboratory Evaluation in the HIV-Infected Pregnant

Woman

Test Comment

Entry into Prenatal Care

HIV serology unconfirmed HIV infection; -I test with other

techniques

CD4 cell count/%

HIV-RNA

repeat every 3-4 mo; at milestones for therapeutic

decisions, re: ARV therapy/01 prophylaxis

CBC repeat every 3-6 mo; more frequent testing if low or

receiving marrow-toxic drugs (e.g. ZDV)

Serum chemistry panel repeat as indicated with abnormal results or use of

hepatotoxic/nephrotoxic drugs

Syphilis serology

Hepatitis serology

HbsAg, anti-HCV

order anti-HBs or anti-HBc to screen for vaccine

candidates

Rubella

Blood type and Rh

Antibody screen

Urine culture

GC/chlamydia testing

Pap smear PPD -F skin test= > 5mm induration; anergy testing not

indicated

Hemoglobin

electrophoresis, red

blood cell indices

perform in women at increased risk for

hemoglobinopathies

G6PD optional — may consider screening black women or those receiving oxidant drugs (e.g. dapsone,

sulfonamides)

CMV IgG consider especially with CD4 <100 mm^ or in patients

at low risk for CMV

Toxoplasmosis IgG screen all patients with initial HIV diagnosis; repeat

with CD4 < 100/mm^ and not on TMP-SMZ, or with

symptoms suggestive of toxoplasmic encephalitis

Urine toxicology screen as indicated

Serum screening for

Tay Sachs disease

consider screening both partners if at increased risk (Ashkenazi Jews, French-Canadian or Cajun descent)

16-20 WEEKS

Ultrasound gestational dating, anomaly screen

Maternal serum alpha

fetoprotein*

screening test for neural tube and abdominal wall

defects voluntary; requires counseling; abnormal result (usually > 2.5 multiple of the median) requires further

evaluation

Triple screen

(heg, unconjugated estriol,

alpha-fetoprotein)**

voluntary; requires counseling; noninvasive test to determine risk of neural tube & abdominal wall defects,

Down syndrome and trisomy 18

* accurate gestational age is essential for interpretation of both tests ** OligohydramniosrMinimal data; Fetal malformation: No evidence risk of increased risk

Table continues . . .

us. Department of Health and Human Services, Health Resources and Services ADMiNi.s-iR.vnoN, HIWAIDS IJi’Ri.Mi 235
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HIV and Reproduction

Table 7-5: Laboratory Evaluation in the HIV-Infected Pregnant

Woman (continued)

Test Comment

24-28 WEEKS

CBC

Syphilis serology

Antibody screen

Diabetes screen glucose 1 hour after 50 gm glucola — 3 hr oral GTT if abnormal; may need additional glucose monitoring in women on protease inhibitors

Bacterial vaginosis

screening

women at high risk for preterm labor

32-36 WEEKS

GC/chlamydia testing

Group Bstrep culture

(35-37 wks)

optional; offer intra-partum chemoprophylaxis with

IV PCN G (2.5 million units q 4 hr) if positive.

Alternative is prophylaxis strategy based on presence

of intrapartum risk factors (CDC, 1996)

CD4, HIV-RNA results may influence decisions about mode of delivery

Syphilis serology consider in high risk patients or populations

ARV- antiretroviral

01- opportunistic infections

Antepartum Fetal Surveillance/Testing (ACOG, 1999)

The general purpose of antepartum fetal testing and surveillance is to identify

fetal abnormalities or compromise so that appropriate interventions can be

undertaken to optimi2e fetal health and prevent fetal damage or death; or, in

some instances, to aid in decisions regarding continuation of pregnancy.

Fetal surveillance: Indications include: • maternal conditions in which risk of fetal death is increased. This

includes (but is not limited to) hemoglobinopathies, chronic renal dis- ease, systemic lupus erythematosus, hypertension, and diabetes.

• pregnancy-related conditions in which risk of fetal death is increased.

This includes pregnancy-induced hypertension, decreased fetal movement, oligohydramnios, polyhydramnios, intrauterine growth retardation, post-term pregnancy, mild to moderate isoimmunization,

previous fetal demise, and multiple gestation.

There are no data specifically on the need for and use of fetal sur- veillance techniques in the HIV-infected woman during pregnancy, and

HIV per se is not an indication for fetal testing. However, HIV-infected

women who have co-existing medical conditions placing the fetus at increased risk should have fetal surveillance; furthermore, HIV infection, especially when more advanced or associated with substance abuse,

may be associated with increased risk for poor fetal growth, which

us. Department of Health and Human Services, Health Resources and Services ADMiNisncmoN, HFV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

places the fetus at increased risk. Need for fetal surveillance in the HIVpositive pregnancy should be determined on an individual basis.

betal surveillance techniques include:

fetal movement assessment: perception of 10 distinct movements in a period of up to 2 hours is reassuring

nonstress test (NST): reactive or reassuring test is defined as two or more fetal heart rate accelerations (at least 15 beats per

minute above baseline and lasting at least 1 5 seconds from baseline to baseline on fetal monitor) within a 20 minute period.

contraction stress test (CST): negative or reassuring test is absence of late or significant variable fetal heart rate decelerations with at least three contractions (lasting at least 40 seconds)

within 10 minutes

biophysical profile: consists of a NST combined with observations of fetal breathing, fetal movements, fetal tone, and amniotic fluid volume by real-time ultrasonography. Each

component is given a score of 2(normal or present) or 0

(abnormal or absent); a composite score of 8 or 10 is normal.

Modified biophysical profile: combines NST and amniotic fluid

index (API), which is the sum of measurements of the deepest

amniotic fluid pocket in each abdominal quadrant; normal API

is > 5 cm. This test combines a short-term indicator of fetal acid-base status (NST) and an indicator of long-term placental

function (API); placental dysfunction often leads to poor fetal growth and oligohydramnios.

Umbilical artery doppler velocimetry: evaluation of flow velocity

wave forms in the umbilical artery; in the normally growing fetus,

characterized by high velocity diastolic flow; of benefit only in

pregnancies complicated by intrauterine growth restriction.

Although data from randomized clinical trials are missing, antepartum fetal surveillance has been consistently associated with lower rates of fetal death than in untested pregnancies from the same institution or than historic controls with similar complicating factors. Testing

should be initiated at 32—34 weeks gestation, but may be started as

early as 26—28 weeks in pregnancies at very high risk. When the condition prompting testing persists, testing should be repeated periodically

(weekly or, in some cases, biweekly) until delivery. Petal reevaluation

should also be repeated with significant deterioration in maternal medical condition or acute decrease in fetal movement, regardless of the

time elapsed since the previous test. NST, CST, biophysical profile and modified biophysical profile are the most commonly used forms of testing and have a negative predictive value > 99%. However, they are not predictive of acute events,

such as placental abruption or umbilical cord accidents. On the other

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A CJuiDE ro THE Clinical Cari; oe Women with HIV

HIV and Reproduction

hand, the positive predictive value of an abnormal test can be quite

low and the response to an abnormal result should be dictated by the

individual clinical situation. Any abnormal test result requires further

evaluation or action. Maternal perception of decreased fetal movements should be evaluated by NST, CST, biophysical profile or modified biophysical profile. If normal the mother can be reassured that the

fetus is in no immediate danger. A nonreactive NST or abnormal modified biophysical profile is usually followed by additional testing with a CST or full biophysical profile. Management will be based on results of

these tests, gestational age, degree of oligohydramnios (if assessed),

and maternal condition. OUgohydramnios should prompt evaluation

for membrane rupture. Depending on the degree of oligohydramnios,

the gestational age, and the maternal medical condition, oligohydramnios warrants either delivery or close maternal/ fetal surveillance.

Ultrasound. Indications for obstetrical ultrasound are many. Some of the

more common include (ACOG, 1993): • pregnancy dating • evaluation of fetal growth • evaluation of vaginal bleeding during pregnancy • determination of fetal presentation • suspected multiple gestation • significant uterine size/ cUnical dates discrepancy • pelvic mass • suspected ectopic pregnancy • document fetal viability/rule out fetal death • biophysical profile for antepartum fetal surveillance • suspected polyhydramnios /oligohydramnios • placental localization • abnormal serum alpha- fetoprotein or triple screen • evaluation for fetal anomalies • evaluation of fetal condition in late registrants for prenatal care

With transvaginal ultrasound, an intrauterine gestational sac can be seen by five weeks after the last menstrual period and fetal heart activity can be

detected by 6 weeks. First—trimester bleeding is the most common indication for early ultrasound, when the major differential diagnoses are threatened abortion (miscarriage) and ectopic pregnancy. Accurate pregnancy

dating is best accomplished in the late first and second trimesters.

In the setting of HIV infection, an ultrasound should be considered in

the second trimester for accurate dating, which is important later in gestation if scheduled cesarean section is planned to avoid premature delivery

(see below). This will also allow survey of fetal anatomy and screening for

us. Department of He/U,th and Human Services, Health Resources and Services Administoation, HIV/AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

anomalies. Depending on the individual situation, including stage of illness,

therapeutic regimen, and presence of other maternal/pregnacy-related factors, ultrasonography may be useful in monitoring fetal growth.

Amniocentesis /Chorionic villous sampling (CVS)/Percutaneous

umbilical blood sampling (PUBS). Because of concerns about increasing

risk of perinatal transmission with these invasive techniques, they should

generally be avoided in pregnancies complicated by HIV infection.

Antiretroviral Treatment

(See Table 7-6 on the following page) Although there are special considerations in using antiretroviral drugs during pregnancy, the basic principle is that

therapies of known or possible benefit to the woman should not be withheld

during pregnancy unless there are known adverse effects for mother, fetus or

infant which outweigh the potential benefits. (Minkoff, 1997) Pregnant women

meeting the criteria outlined for other adults and adolescents should be

offered standard combination antiretroviral therapy, usually including two

nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor

(1^1). (See Chapter IV on Primary Medical Care)

Nevertheless, there are additional issues to consider with treatment in

pregnancy;

Pharmacokinetics: There are potential changes in dosing secondary to

the physiologic changes during pregnancy; at the current time, pharmacokinetic information on existing antiretroviral agents during pregnancy is limited, but has not suggested need for dose adjustment.

Perinatal transmission: The effect of different drugs and drug combinations on vertical transmission. Current information on the use of antiretroviral agents during the antepartum period and perinatal transmission

are summarized below: • PACTG 076: ZDV given antepartum, intrapartum, and to the

neonate for 6 weeks of life reduced risk of vertical transmission by

66%, from 22.6% in placebo recipients to 7.6% in ZDV recipients.

(Sperling, 1 996) AU women participating in this trial had CD4 counts

> 200/mm^ and were antiretroviral naive. Subsequent studies, including women with more advanced disease and with prior ZDV exposure, confirm the effectiveness of this regimen with transmission

rates as low as 3-4%. • short-course ZDV; ZDV 300 mg twice daily beginning at 36 weeks

gestation and 300 mg every 3 hours orally in labor reduced transmission by approximately 50% (19% placebo vs 9% ZDV) compared to placebo in a nonbreastfeeding population in Thailand. (Shaffer, 1999) • ZDV/3TC: (PETRA trial) ZDV/3TC twice daily beginning at 36

weeks gestation and orally in labor (ZDV 600 mg and 3TC 1 50 mg

orally at onset of labor, then ZDV 300 mg orally every 3 hours and

U.S. Department of Health and Human Services, Health Resources and Services ADMiNi.sTRAnoN, Hl\'/ \IDs Hi'ri ' 239
A Guidf, to thf: Clinical Carr or Womrn with HIV

and Reproduction

240 us. Dep.artment of He.\lth .\nd Human Services, Health Resources and Services Administr-voon, Hr\^/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

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U.S. Departnent of He^clth and Human Servtces, Health Resources and Services Adminis-i-rahon, HI\7AIDS Buri ai 241
A Guide to the Ceinicai. Care of Wome:n with HIV

HIV and Reproduction

3TC 150 mg orally every 12 hours) and for one week postpartum to

the infant and mother reduced transmission by approximately 50%

(17% placebo vs 9% ZDV/3TC) compared to placebo at 6 weeks.

The majority of infants in this study were breastfed. (Saba, 1999)

Fetal/infant adverse effects: Potential teratogenicity, carcinogenicity,

mutagenicity, or fetal/ neonatal side effects/ toxicity from transplacentally

transferred drugs. The potential for adverse effects may be related to several factors: the drug itself, dose, gestational age at exposure, duration of

exposure, interactions with other drugs or agents to which the fetus is exposed, and the genetic make-up of mother and fetus. Information about the safety of drugs in pregnancy comes from animal toxicity studies, anecdotal experience, registry data, and cUnical trials. PrecHnical data do not necessarily correlate with adverse effects in

humans. There are approximately 1200 known animal teratogens, but

only about 30 are known human teratogens. Of currently available drugs,

zidovudine (ZDV) is the agent for which there is the most information,

and information about the other antiretrovirals is limited. Some specific concerns have been raised and are addressed below; for more in depth

discussion of each drug, see Chapter XIV on Pharmacology and the U.S.

Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant Women Infected with HIV-1 for Maternal

Health and for Reducing Perinatal HIV-1 Transmission in the United

States, which is updated regularly on-line at http:/ /www.hivatis.org. • safety of ZDV exposure: In the PACTG 076 study the only side

effect significantly different between ZDV and placebo recipients

was the presence of anemia in ZDV-exposed infants; however, the

anemia was mild and resolved spontaneously without need for trans- fusion. (Connor, 1994) There has been no evidence of increase in

congenital abnormalities in infant exposed to ZDV in utero, compared with the general population. Uninfected children who were

participants in the PACTG 076 study have now been followed for over 4 years with no evidence of impact of ZDV on growth, neu- rodevelopment, or immunologic status. (Culnane, 1999)

ZDV carcinogenicity: Two transplacental carcinogenicity studies

in mice showed different results: in one study (OUvero, 1 997) two

very high doses (approximately 25x and 50x daily human therapeutic

exposure) were associated with an increase in lung, Uver, and female

genital tract tumors; in the second study (Ayers, 1997), a much lower

dose (approximately 3x human therapeutic exposure) was not associated with an increase in tumors. A consensus conference reviewed all available information and concluded that the known benefits of

zidovudine far outweighed the theoretical risks, but recommended

long-term foUow-up of infants exposed in utero to zidovudine or

other antiretrovirals. In a foUow-up of over 700 infants with in utero

us. Department of Heai;TM and Human Services, Health Resources and Services Administration, HIWAIDS Bureau
A Guide to the Clinical C.are of Women with HIV

HIV and Reproduction

exposure to ZDV, no malignancies were observed in up to 6 years of

age. (Hanson, 1999) • Efavirenz: In primate studies efavirenz was associated with anencepahaly, anopthalmia, microphthalmia, and cleft palate at doses

comparable to human exposure, suggesting that this drug should be

avoided during pregnancy, particularly early pregnancy, and in

women at risk for pregnancy (trying to get pregnant or unsafe sexual

practices). Pregnant women who have conceived while on efavirenz

should be counseled about possible fetal risks. It is important to

acknowledge that animal studies in primates have not been performed with any of the other antiretroviral agents. • Hydroxyurea: Although hydroxyurea is not a true antiretroviral

drug, it has been used in many antiretroviral regimens, particularly in

ddl-containing regimens. There is limited human information on the use of hydroxyurea in pregnancy and there are reports of exposure

during pregnancy without apparent adverse outcome; however,

hydroxyurea has been referred to as a “universal teratogen” with evidence of teragenicity in every animal species studied and defects

involving multiple organ systems. This agent should be avoided during pregnancy and in women at risk for pregnancy; pregnant women

who have conceived while on a hydroxyurea-containing regimen

should be counseled about possible fetal risks. • Indinavir: Indinavir has been associated with indirect hyperbilirubinemia and increased risk for renal stones. Because of theoretical concerns about risk for renal stones in neonates who cannot voluntarily hydrate themselves adequately and possible complications associated with exacerbation of physiologic hyperbilirubinemia

(especially in premature infants, who are at greater risk for neonatal

jaundice and kernicterus), this drug should be avoided in late pregnancy. Because of its short half-life, these concerns may not apply to use of indinavir earlier in pregnancy. • Amprenavir: Amprenavir oral solution contains high levels of

propylene glycol (the capsule form does not contain propylene glycol). Pregnant women and infants and children under the age of 4

are unable to adequately metabolize and eliminate propylene glycol,

leading to accumulation and potential serious adverse events, including hyperosmolarity, lactic acidosis, seizures, and respiratory depression. Amprenavir oral solution is contraindicated in pregnancy and

in children under the age of 4 years. • Preterm delivery: concerns about possible increased risk for

preterm delivery were raised by a small retrospective series of pregnant women on combination antiretroviral therapy (I.orenzi, 1998);

however, some studies have found increased preterm birth rates in women who were not on ARV therapy, especially with more

us. Department of Health and Hum/\n Services, Health Resources and Services Adminis-ulviion. IIU'/AIDS Hi ri-.ai' 243
A Guide to the Clinicae Care of Women with HIV

HIV and Reproduction

advanced disease. (Martin, 1997; Leroy, 1998; Brocklehurst, 1998)

Furthermore, other factors, such as substance abuse, nutritional

status, smoking, and cocaine use, may also increase risk and be con- founding variables. Preliminary analyses of multiple PACTG clinical

trials do not show an increased rate of preterm birth in women on

ARV therapy, with or without protease inhibitors. (Shapiro, 2000) • Mitochondrial toxicity: a small series of uninfected infants

exposed in utero to nucleoside analogue agents was reported with

laboratory or clinical evidence of mitochondrial dysfunction; two

developed severe neurologic disease and died. (Blanche, 1999) Subsequent studies have been reassuring. A review of 353 deaths in over

20,000 children (with and without ARV exposure) born to HlV-positive mothers followed prospectively in the U.S. found no evidence of

mitochondrial toxicity as a contributing factor in the deaths. (Smith,

1999) Neurologic adverse events were reviewed in 1,798 infants

exposed to ZDV/3TC or placebo in the PETRA study, an African

perinatal prophylaxis trial; no increased risk of adverse neurologic

events was observed in infants exposed to ZDV/3TC as compared

to placebo. (Lange, 1999) Although these studies do not rule out the

possibility of an association between mitochondrial dysfunction and

ARV exposures in utero, the likelihood of severe or fatal manifestations appears to be extremely small.

Given the limited and relatively short-term experience with all antiretroviral agents in pregnancy, long-term follow-up of infants exposed to

these medications in utero is important.

Interaction of drugs with pregnancy-related side effects /physiologic changes: • Drugs which cause GI upset may not be well tolerated in early pregnancy when morning sickness is common and may increase risk for

nonadherence or inadequate blood levels from vomiting • Protease inhibitors and hyperglycemia: protease inhibitors have been

associated with the development or worsening of existing hyperglycemia or diabetes and pregnancy also increases risk for glucose

intolerance. It is unknown whether the use of Pis in pregnancy will

exacerbate risk for development of gestational diabetes. Women

receiving protease inhibitors in pregnancy should have their glucose

levels monitored closely.

General Principles for Antiretroviral Treatment in Pregnancy (CDC, 2000)

Decisions regarding initiation or alteration of antiretroviral therapy should

be the same in pregnant and nonpregnant women, with the additional considerations oudined above.

Monitor CD4 count/viral load according to guidelines for nonpregnant

adults: in pregnancy, this should be done approximately each trimester, but

us. Dep.artment of He.u,th and Human Services, He.\i,th Resources .u-jd Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women uaTH HIV

HIV and Reproduction

may be needed more frequendy with failing or altered therapy. CD4 percentage may be a more accurate reflection of immune status during

pregnancy than absolute CD4 cell count, because of possible variation in

absolute CD4 count secondary to dilutional effects associated with hemodynamic changes in pregnancy

The three-part ZDV chemoprophylaxis regimen (Table 7-7) should be rec- ommended for all HIV-infected pregnant women to reduce the risk of perinatal HIV transmission. Current clinical trial and epidemiologic data

confirm the effectiveness of this regimen; furthermore, no other regimen

studied to date in randomized clinical trials has shown superior results.

Table 7-7: Zidovudine Perinatal Transmission Prophylaxis Regimen

ANTEPARTUM Initiation at 14-34 weeks gestation and continued throughout

pregnancy

A. PACTG 076 REGIMEN: ZDV 100 mg 5 times daily

B. ACCEPTABLE ALTERNATIVE REGIMEN:

ZDV 200 mg 3 times daily orZDV 300 mg 2 times daily

INTRAPARTUM During labor, ZDV 2 mg/kg intravenously over 1 hour, followed by

a continuous infusion of 1 mg/kg intravenously until delivery.

POSTPARTUM Oral administration of ZDV to the newborn (ZDV syrup, 2 mg/kg

every 6 hours) for the first 6 weeks of life, beginning at 8 - 12

hours after birth.

In women already receiving antiretroviral therapy when they become

pregnant and this regimen does not include zidovudine, ZDV should be

added or substituted for another nucleoside analogue agent after 14 weeks’

gestation. There is evidence that duration of prior ZDV therapy in women

with more advanced disease may not reduce effectiveness of ZDV in

decreasing perinatal transmission. (Stiehm, 1999) However, ZDV should

not be substituted for another antiretroviral agent when this is likely to

reduce the efficacy of this regimen in treatment of maternal disease,

i.e., with previous clinical failure of ZDV or history of documented

ZDV resistance.

In some circumstances ZDV cannot be used during the antepartum

period (e.g., intolerance to ZDV). d4T and ZDV appear to be pharmacologically antagonistic and should not be used together; therefore, women on

d4T-containing regimens with prior ZDV failure should be continued on

the most effective regimen for their disease and ZDV should be excluded if d4T is maintained. ZDV administration is recommended during the intrapartum period and for the newborn regardless of the antepartum antiretroviral regimen.

Women who present in labor with no prior antepartum antiretroviral

therapy may be treated with one of several effective regimens, described

below (Intrapartum Management) and in Table 7-8.

us. Department of Health and Human Services, Health Resourcf.s ,\nd Services ADMiNi.sTRAnoN, HIN'/.MDS Ui ri.m 245
A Guide to the Ci.inicae Care: of Women voth HR’

HR' and Reproduction

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A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

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US. Dep.\rtment OF He.\lth AND HimuN Services, Health Resources and Services ADMiNiSTR.vnoN, HIV/AIOS Bi ki.m 247
A Guidk to the Ci.iNiCAi. Care of Womf:n with HIV

HIV and Reproduction

Women with high CD4 counts and low or undetectable HIV-RNA

levels, for whom initiation of antiretroviral therapy for the treatment

of maternal infection would be considered optional, should be counseled

about the potential benefits and risks of standard combination therapy

and offered this therapy, along with the three-part ZDV perinatal prophylaxis regimen.

Using ZDV alone is an option in this situation. This has the advantage of

limiting exposure to other drugs during pregnancy but there are theoretical concerns about the selection of ZDV-resistant viral variants and Limitation

of future maternal therapeutic options, as well as increasing the risk for

transmission. A recent study in women with moderately advanced HIV,

many of whom had been treated with ZDV before pregnancy, found that

maternal ZDV resistance was predictive of transmission. (Welles, 2000)

However, the development of resistance should be minimized by the relatively short duration of therapy and the more limited viral replication present in individuals with low HIV-RNA level and high CD4 count. Follow-up

of women enrolled in the PACTG 076 study has shown no significant differences in immunologic status or progression of disease (median follow-up

4.2 years) in women who received ZDV compared to placebo recipients.

(Bardeguez, 1999)

In antiretroviral naive patients clinicians may consider delaying initiation of

ARV therapy until after 10—12 weeks of gestation, based on considerations

of the woman’s health status, the potential risk of delaying therapy for several weeks, and the potential benefits of avoiding first trimester drug exposure for the fetus.

In antiretroviral-experienced patients, who become pregnant or are referred

into prenatal care while on ARV therapy, therapy should be continued or

modified, subject to the considerations outlined above. If pregnancy is rec- ognized in the first trimester, some women and their clinicians may consider

temporary discontinuation of therapy until after completion of the first trimester because of concerns about potential teratogenicity, or because of

significant nausea and vomiting in early pregnancy leading to concerns about inadequate absorption of medications.

Current data are insufficient to either support or refute fetal risk with

early exposure to antiretroviral agents. Discontinuation of therapy may lead

to viral rebound, which could theoretically increase risk of intrauterine HIV

transmission or have an adverse effect on maternal disease. The woman’s

clinical, immunologic, and virologic status should also be considered in

decisions regarding continuation of therapy in the first trimester.

If the decision is made to stop therapy temporarily, all agents should be

stopped simulataneously and restarted simultaneously in the second

trimester to avoid development of drug resistance.

us. Dep.artoent of Health .and Human Services, Health Resources and Services Administration, HIV/AIDS Bure.au
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

Decisions regarding use of ARV therapy during pregnancy should be made

by the woman after detailed discussion of benefits and potential risks of

therapy. This includes discussion of: • Treatment recommendations for health of the HIV-infected woman

• Current information regarding effectiveness of antiretroviral therapy

in reducing perinatal transmission • Known or potential effects of antiretroviral drug exposure on the

fetus/ newborn • The importance of adherence to any prescribed antiretroviral regimen

There continue to be missed opportunities in prevention of transmission

of HIV from mother to child. HIV has to first be identified in the woman; sit- uations where counseling and testing have not been available or not utilized

because of lack of perception of risk on the part of the woman or her health

care provider have been associated with perinatal transmission in some cases. Women who become infected or seroconvert during pregnancy may be missed

unless HIV testing is repeated later in pregnancy. Lack of prenatal care and

active substance abuse, which frequently co-exist, have also been linked to

potentially avoidable increased risk for transmission. (Bardeguez, 2000)

Antiretroviral Pregnancy Registry

The Antiretroviral Registry is a collaborative effort between pharmaceutical

companies, the Centers for Disease Control and Prevention, the National

Institutes of Health, and obstetrical and pediatric practitioners to collect

observational information on antiretroviral exposure during pregnancy in

order to assess potential fetal/infant anomalies after exposure to these agents.

Patient names are not used and information is confidential. Health care proHders who are treating HIV-infected pregnant women are strongly encour- aged to report cases of prenatal exposure to antiretroviral drugs to the Registry: 1410 Commonwealth Drive, Wilmington, NC 28403; telephone (800)

258-4263; fax (800) 800-1052.

Opportunistic Infection Prophylaxis

Indications and recommendations for primary prophylaxis of opportunistic

infections in pregnancy are noted in Table 7-9. Once an individual has had the

following infections, prophylaxis to prevent recurrence is recommended as standard of care for the life of the individual (see Chapter IV on Primary

Medical Care). First-choice regimens are outlined:

Pneumocystis carinii pneumonia: same regimen as for primary prophylaxis

Toxoplasmic encephalitis: sulfadiazine 500—1000 mg po q.i.d. plus

pyrimethamine 25—75 mg po q.d. plus leucovorin 10—25 mg po q.d.; counsel regarding concerns about potential teratogenicity of pyrimethamine and

benefits of Hfe-long therapy

us. Department of Health and HuM/\n Services, He,\lth Resources and Services ADMiNisT-R.vnoN, HIWAIDS Bi rilm' 249
A Guide to the Clinicai, Care of Women with HIV

HIV and Reproduction

250 us. Department of He.\lth and Hunun SER\ncES, H&\lth Resources and Services Administr.\tion, HI\'/AIDS Bureau
A Guide to the Clinic.\l C.\re of Women with HW

and Reproduction

US. Dep.\rtment of He.\lth and HimuN Services, He.\lth Resources and Ser\icrs Administr,\tion, HU'/.MDS Bi rkai 251
A CJuioii TO riiT. Ci.iNicAi. (^Aiu; oi' Womicn wmi 1 UV

m\' and Reproduction

Disseminated MAC: azithromycin 500 mg po q.d. plus ethambutol

15 mg/kg po q.d.

CMV: choice of agents should be individualized in pregnancy after consultation with experts; discontinuation of maintenance therapy with history of

CMV retinitis may be considered with sustained (> 3—6 months) elevation

of CD4 count above 100—150/mm^ and durable suppression of plasma

HIV-RNA levels. Opthalmologic consultation is recommended if discontinuation of secondary prophylaxis is considered.

Histoplasmosis: amphotericin B 1.0 mg/kg iv q.w- may be preferred,

particularly during the first trimester, because of occurrence of craniofacial

and skeletal abnormalities in infants after prolonged in utero exposure

to fluconazole.

Crytococcosis: amphotericin B 0.6—1.0 mg/kg iv q.w.-t.i.w- may be preferred, particularly during the first trimester, because of occurrence of

craniofacial and skeletal abnormalities in infants after prolonged in utero

exposure to fluconazole

Coccidiomycosis: same as for histoplasmosis

Immunizations (CDC, 1993; cdc, 1999; acog, 1991)

Immunization should be considered in pregnancy when the risk for exposure is high, risk of infection for mother or fetus is high, and the vaccine is thought

unlikely to cause harm. HIV-infected individuals should avoid live virus or live bacteria vaccines. HIV-positive persons who are symptomatic or have low CD4

cell counts may have suboptimal responses to vaccination. Some, but not all, studies have shown a transient (< 4 weeks) increase in Hral load after immunization. This is of some theoretical concern, given the association between

viral load and perinatal transmission. This increase in viremia may be prevented

with appropriate antiretroviral therapy. (Bartlett, 1999) For this reason, clini- cians may consider deferring routine vaccination until after the patient is on an

effective antiretro\dral regimen and avoiding administration late in pregnancy,

close to delivery, when most transmission is thought to occur.

Current immunization recommendations for HIV-positive pregnant

women are: pneumococcal vaccine — “generally recommended”

influenza vaccine — “generally recommended”; administer before flu season tetanus-diphtheria (Td) vaccine — booster dose every ten years after

completion of primary series

hepatitis B vaccine — “generally recommended” for all susceptible

(anti-HBc-negative) patients; three doses at 0,1,6 months

hepatitis A vaccine — “generally recommended” for all susceptible

(anti-HAV-negative) patients with chronic hepatitis C ; also indicated

us. Department of Health and Human Services, Health Resourcp.s and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

prior to travel to endemic areas, in injection drug users, and with community outbreaks; two doses at 0,6 months

enhanced potency inactivated polio vaccine — use if not previously

immunized and traveling to areas where risk for exposure is high; oral

polio vaccine is a live virus vaccine and is contraindicated in HIVpositive persons

immune globulins • immune globulin recommended for measles exposure in symptomatic HIV-positive persons and hepatitis A with exposure to HAV

in close contact/ sex partner or travel to underdeveloped country

(especially in patient with advanced HIV, who have have poor antibody response to vaccine) • hyperimmune globuUns recommended:

varicella-zoster immune globuHn (VZIG)-susceptible adult

(undetectable antibodies to VZV) after significant contact

(household, hospital room, close indoor contact > 1 hour, prolonged face-to-face contact) to chickenpox or zoster; give within

96 hours of exposure

hepatitis B immune globulin (HBIG)-needlestick or sexual contact with HbsAg+ person in susceptible individual (anti-HBcnegative); HBIG and HBV vaccine series should be started

within 14 days of last exposure

Reduction of Secondary Risk Factors

Treatment of STDs or other co-infections; encouragement of safer sexual

practices during pregnancy; discouragement of smoking and drug use; and

substance abuse treatment should be employed as measures which may

decrease risk of perinatal transmission.

Frequency of Visits

Determined on an individual basis, based on gestational age, health of the

mother, presence of pregnancy-related complications, antiretroviral regimen

and response, and psychosocial needs. In uncomplicated pregnancies visits

generally are scheduled monthly in early pregnancy and every 1—2 weeks from

28—30 weeks of gestation until delivery.

Counseling and Support

Support systems: At the initial visit the health care provider should assess the patient’s support system —who knows her HIV status, problems

encountered with disclosure, family and/or friends to whom she turns for

ongoing support, barriers to disclosure to sexual or needle-sharing partners.

These issues should be readdressed at intervals throughout pregnancy as needed. The use of peer counselors may be especially helpful.

us. Department of Health and Human Services, Health Resources and Services ADMiNis'ni.vnoN, III\’/.\IDS Hi 'ri ai 253
A CJuioi': TO riii; (j.inicai, (^ari; oi' WoMiiN with HIV

Hl\' and Reproduction

Contraception use postpartum: Discussion about postpartum contraceptive plans should be initiated in early to mid-pregnancy to allow comprehensive education and counseling about available options and adequate dme for

informed decision making.

Condom use during pregnancy: Sexual activity should be reviewed at each visit and condom use reinforced.

Drug use/treatment: History of and/or ongoing substance abuse, including tobacco and alcohol, as well as illicit drugs, should be assessed at the initial visit and at intervals during prenatal care, if indicated. Type of

substance(s), amount of use, route of administration, and prior drug or alcohol treatment should be documented. The patient should be counseled

about specific risks associated with substance abuse in pregnancy (See

Chapter X on Substance Abuse) and drug or alcohol treatment during pregnancy should be encouraged and facilitated for active problems.

Adherence: Each patient should be educated and counseled about the

importance of adherence to prescribed medications, particularly antiretroviral drugs, before they are initiated and medication adherence should be

assessed and reinforced at each visit, (see Chapter V on Adherence)

Clinical trials: Pregnant HIV-positive women should be informed about

the availability of and offered participation in clinical trials to which they

are eligible.

Advance directives: The issue of advance directives for care in the event

of sudden deterioration in the woman’s health, as well as guardianship plans

for children in the event of the mother’s incapacitation or death should be

discussed; legal assistance should be facilitated, if needed.

X. INTRAPARTUM

A. UNIVERSAL PRECAUTIONS

Gowns, gloves, and eye protection should be used in aU deliveries and in

examinations or procedures likely to generate splashing of blood or amniotic

fluid. (See Chapter XIII on Occupational Exposure)

B. EETAL/MATERNAL MONITORING

External fetal monitoring should be employed but avoid use of fetal scalp electrodes or fetal scalp sampling. Avoid artificial rupture of membranes if possible.

C MODE OE DELIVERY

Based on data showing a reduction in perinatal HIV transmission (in addition

to that seen with ZDV prophylaxis alone) with scheduled C-section (see

above), all HIV-infected pregnant women should be counseled about the posU.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS BurRtIU
A Guide to the Clinic.\l C.\re of Women \xtth

HR'^ and Reproduction

siblc benefit versus risk of scheduled C-section and the limitations of current

studies. Infants born to mothers with high plasma \tiral loads benefit most

from planned Cesarean delivery. Data are insufficient to demonstrate benefit

in women with very low or undetectable \tiral loads and/or women on

1 lAART therapy. There is no evidence that performing C-section after onset

of labor or rupmred membranes reduces transmission rate; this needs further

study given the recent data about duration of ruptured membranes and

increasing risk of transmission. Women should be informed that there is no

therapy or combination of therapies which can guarantee an uninfected infant.

Ultimate decisions about the route of delivery must be indi\tidualized and

the woman’s autonomy must be respected. If scheduled C-section is planned,

best clinical estimates of gestational age should be used and scheduling is rec- ommended at 38 completed weeks of gestation to niinirnize the likelihood of

labor and membrane rupture. (ACOG, 1999)

D. INTRAPARTUMARVPROPHYLAXIS

VCbmen who have been on an appropriate antiretroviral regimen during the course of pregnancy should receive ZDV in labor: 2mg/kg ZDV in a one- hour IV loading dose, followed by 1 mg/kg/hr by IV infusion. If scheduled

cesarean section is planned, ZDV infusion should be begun 3 hours preoperatively to achieve adequate blood levels.

For women who present in labor with no prior antiretro\tiral therapy,

there are several effective regimens available. (Guay, 1999; Saba, 1999; Wade,

1998; Perinatal HIV Guidelines Working Group, 2000) These are outlined

in Table 7-8.

Women of unknown HIV status who present in labor with no prenatal

care may be offered rapid HIV testing, after careful counseling and with

informed consent. Positive results should be confirmed by standard serologic

testing but enable the initiation of an appropriate antiretroviral regimen to reduce the risk of perinatal transmission.

E. ANTIBIOTIC PROPHYLAXIS:

Data are limited on the relationship between HIV infection and incidence of

peripartum (e.g., chorioamnionitis, postpartum endometritis) infections.

Results of histologic placental studies are conflicting but more recent studies

do not suggest an increased risk of chorioamnionitis in HIV-positive pregnancies. (Hofman, 1998; Ladner, 1998) Several earlier studies (Gichangi, 1993)

found an increase in histologic chorioamnionitis in HIV-positive pregnancies,

particularly in those with preterm deliveries. (Gichangi, 1993; Kumar, 1995)

Maternal HIV infection has been associated with an increased risk of postparmm endometritis, particularly in more immunosuppressed women (Ternmerman, 1994); furthermore, some studies have shown an increase in

post-Cesarean section infectious morbidity in HIV-positive women, correlated

us. DEMRTMENT of HE.U.TH .\ND HUNL\N SeR\1CES, HE.\LTH RESOL’KO-.S ,\ND SERVICES .XOMINISIR VIION. HIV/.\IDS Hi RI.M 255
A Cuioi' i() rill' ('i.iNiCAi. CakI', oi' Womi<:n wrm 1 IIV HIV and Reproduction

with lower CD4 counts, (Maiques-Montesinos, 1999; Semprini, 1995) as compared to HIV-negative controls. A recent analysis of complications

according to mode of delivery among HIV-positive women with CD4

< 500/ mm^ found peripartum infectious complications were common and

were seen more frequendy in women delivered by C-section compared to vaginal delivery; however, rates of complications were not significantly different

from those found in similar HIV-uninfected women; in this study peripartum

antibiotic prophylaxis was given in approximately three-quarters of patients

undergoing C-section and in approximately one-third of those with vaginal

delivery. (Watts, 1999) Increased rates of infectious complications may be

related to confounding factors, such as poor nutritional status, substance

abuse, or prevalence of genital tract infections, rather than to the presence of

HIV infection. (Hanna, 1997)

There are currently no data on the role of prophylactic peripartum antibiotics in reducing risk of infectious morbidity for HIV-positive women. However, because of the concerns about possible increased risk of post-Cesarean

infections in HIV-positive patients, prophylactic antibiotics are recommended

at the time of scheduled C-section.

E VAGINAL CLEANSING

A promising potential intervention to reduce transmission at the time of vaginal delivery is vaginal cleansing to decrease neonatal exposure to maternal

blood and genital secretions. A clinical trial of 0.25% chlorhexidine manual

vaginal cleansing on admission and every 4 hours until delivery had no significant impact on HIV transmission, except when membranes had been ruptured

for more than 4 hours before delivery. (Biggar, 1996) Further study is needed.

XL POSTPARTUM

A. INEANTEEEDING

When safe alternatives are available, breastfeeding is discouraged because of

documented risk for transmission from mother to infant.

B. ASSESS HEALING

Assess healing of wound sites, uterine involution, and appropriate cessation of

postpartum bleeding

C. CARE EOR MOTHERAND INEANT

HIV-infected mothers may neglect their own care while trying to provide

appropriate care for their infant and other children or family members. It is essential that she be linked with comprehensive medical and supportive care

services, including HIV specialty care; primary medical and gynecologic care;

us. Dep.\rtment of He.u,th and Hum-AN Services, Health Resources and Services Administration, HIV/AIDS Bure.au
A Guide to the Clinical C.\re of Women with HIV

HIV and Reproduction

mental health or substance abuse treatment services; and assistance with food,

housing, transportation and legal/advocacy services, if needed.

\Xbmen who have received ZDV monotherapy during pregnancy should be

re-evaluated in the postpartum period with clinical assessment, CD4 count and

HIV-RNA level to determine need for ongoing antiretroviral therapy. It is

essential that access to and continuity of antiretroviral treatment as needed for

maternal health be ensured.

Similarly, the HIV-exposed infant should be linked into ongoing pediatric

care, with HIV diagnostic tests as described below and appropriate HIV specialty care if HIV-infected.

D. CONTRACEPTION/CONDOM USE

Discussions about contraception and condom use should be continuous

throughout pregnancy and reviewed and reinforced at the time of the postpartum visit.

E. LONG-TERM EOLLOW-UP OPMOTHERAND INFANT

All HIV-positive mothers and infants exposed to ZDV and/or other antiretroviral drugs or combinations during pregnancy should have long-term foUowup to assess possible late effects of these therapies on HIV progression in the

mother or neoplasia or organ-system toxicity in exposed children.

XII. CARE OF THE HIV-EXPOSED INFANT (CDC, 2000)

A. DIAGNOSIS OF HIV

The standard for diagnosis of HIV infection in exposed infants is the use of

\tiral assays (HIV-DNA PCR (preferred), HIV-RNA PCR, or viral culture)

obtained within 48 hours of birth, at 1—2 months, and 3—6 months. HIV can be excluded with two or more negative tests, two of which are performed at age > or = 1 month, and one performed at age > or = 4 months. HIV IgG

antibody tests will generally be positive in exposed infants up to 18 months of

age because of transplacental passage; two negative tests performed at > or =

6 months and at least 1 month apart will also exclude infection in infants without clinical evidence of infection. P 24 antigen testing is less sensitive than

other virologic tests and has a high frequency of false positive results in

infants < 1 month of age. HIV-DNA PCR is the preferred virologic assay for diagnosis with 93%

(90% CI=76%—97%) sensitivity by age 14 days. Data on use of HIV-RNA

PCR is more limited. HIV culture is sensitive for early diagnosis but is more

complex, expensive, and has a longer turnaround time for results. Using these

tests approximately 40% of infected infants can be identified by age 48 hours

and are considered to have early or intrauterine infection; infants with initial

us. Demrtment of He.\lth .\nd Human Services, He.\lth Resources and Skrviceis ADMiNi.s-ravnoN, HIW.MDS Hi ri m 257
A C'lUlOK TO THK Cl.lNICAl. (^\1U•, Ol- WOMI'.N WITH HIV

Hl\' and Reproduction

negative testing during the first week of life and subsequent positive tests are considered to have intrapartum infection. Almost all infected infants can now

be diagnosed by the age of 6 months. ZDV monotherapy for perinatal prophylaxis has not been shown to delay detection of HIV or decrease sensitivity or predictive value of virologic assays (Connor, 1994; Kovacs, 1995), although

performance of these tests when the mother has received more intensive combination antiretroviral therapies has not been studied.

B. ARV TREATMENT

All HIV-exposed infants should receive ZDV prophylaxis (2 mg/kg/dose every

6 hours) for the first six weeks of Hfe as part of the three-part 2idovudine regimen to prevent perinatal HIV transmission. If the mother has received no

antepartum or intrapartum ZDV, the newborn regimen should be started as soon as possible after delivery, preferably with 12—24 hours of birth. Initiation

of ZDV prophylaxis for the neonate within 48 hours of birth resulted in an

approximately 50% decrease in infection compared to no therapy. (Wade, 1998)

When the mother has received no therapy, it is unknown whether combining

newborn ZDV with administration of a single dose of nevirapine (2 mg/kg) to the infant as soon as possible after birth, or the use of nevirapine alone (particularly when there are concerns about the infant care provider’s ability or willingness to administer ZDV for 6 weeks) wiU be as effective or more effective

than zidovudine only. This approach has some theoretical attractiveness, since

nevirapine can decrease plasma HIV-1 -RNA concentration by over 1 log by 7

days after a single dose, is active immediately against both intracellular and

extracellular virus, and has prolonged elimination in infants. Another theoretical benefit with combining ZDV and nevirapine includes potential efficacy in

the presence of virus that is resistant to either drug.

Once infection is documented, more intensive combination antiretroviral

therapy is recommended with clinical symptoms of HIV infection or evidence

of immunesuppression (immune categories 2 or 3 — Table 7-10) regardless of

age or viral load. Some experts recommend initiating potent ART as soon as the diagnosis is confirmed, regardless of clinical or immunologic status or

viral load since HIV-infected infants under the age of 12 months are considered to be at high risk for disease progression and the prognostic value of

standard virologic or immunologic parameters is less than that for older children. Once HIV infection is confirmed, decisions about antiretroviral therapy

should be made in consultation with a specialist in the treatment of pediatric

HIV infection.

C PCP PROPHYLAXIS

All HIV-exposed infants should receive PCP prophylaxis with trimethoprimsulfamethoxazole (150/750 mg/m^/d in two divided doses po t.i.w. on consecutive days) beginning at 4—6 weeks and extending for the first year of life or

until HIV infection is excluded. Dapsone or atovaquone are alternatives.

us. Department of Health and Human Services, Health Resources .and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

HIV and Reproduction

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A CiuiDii TO ini' (j.iNic.Ai. Cari; oI' Womi:n wriii HIV

Hl\' and Reproduction

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us, Dep;\rtment of Health and Hunlvn Services, Health Resources and Services Administration, HtV/AIDS Bure;\u
VIII: Psychosocial and Cultural

Considerations

Barbara Aranda-Naranjo PhD, RNand Rachel Davis RN

I. INTRODUCTION

Minority women are disproportionately affected by the HIV/AIDS epidemic.

The incidence of HIV is 19 times higher for African-American women and

seven times higher for Latina/ Hispanic women, as compared to the incidence

in Caucasian women. Among women of color age 25 and older, 73% of

those with AIDS and 90% of those with HIV infection are African American. (CDC, 1998) Furthermore, the majority^ of the women diagnosed with

HIV infection are women of childbearing age between the ages of 16-^4

years. These women must make a series of complex decisions concerning

contraception, pregnancy, and abortion. Although little is known about how

women living with HIV/AIDS make such decisions, the decision to have a baby is likely influenced by the interrelationship of intrapersonal factors,

family influences and social pressures. (Sowell, 1993; Moneyham, 1997;

Aranda-Naranjo, 1999)

Growing rates of HIV infection among minority women have created a burden on often already impoverished families. Numerous psychosocial and

economic obstacles may prevent these women from seeking health care. (Metcalfe, 1998) When women in HIV clinics in a mid-south city were given an

opportunity to identify their concerns they listed 349 needs: 32% psychosocial,

14% physical, 13% service and maintenance, and 11% financial and legal.

(Bunting, 1999)

This chapter will identify the psychosocial issues for women living

with HIV infection: economic concerns, human relationship issues,

psychological issues, and cultural considerations. Interventions will be

introduced to address the challenges of working with women and their

families and to maintain cultural sensitivity. These interventions will

facilitate the treatment and care of Latina/Hispanic and African-American

women living with HIV. Providers may find it helpful to establish a broad

sociocultural program that can assess and address the women’s lifestyle

issues. The inclusion of the socio-cultural aspects of a woman’s life will

allow a program to be more hoHstic in the provision of care for the woman

and her family.

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II. ECONOMIC ISSUES

A. DISCUSSION

The majority of women living with HIV infection Uve in poverty and struggle

with complex economic issues as a result of homelessness, substance abuse,

immigration status, mental health disorders, and violent relationships. They

often lack health insurance. Those women who do have health insurance usually obtain it during their pregnancy and lose it after the baby is born. Most of

their energy is spent meeting basic needs such as food, housing, and employment for themselves and their families, which take priority over any health

problems, including HIV infection. Furthermore, because of past experiences,

many minority women tend not to trust the medical system or the entire health

and human service infrastructure. These factors combine to make health care

less accessible and less of a priority in the lives of many HIV-infected women.

Strategies that utilize a linkage approach within the community have been

effective in addressing basic economic needs. (Anderson, 1999) A number of

resources are funded specifically for HIV infected individuals and there are community-based organizations that provide assistance with food, housing,

and other basic needs. An important aspect of linkage development is to

assign a case coordinator or case manager for the woman and her family. This

individual can facilitate the development of a care plan and advocate for the

family. Because the woman is usually the primary caregiver in the family, she

will often be overwhelmed, especially in the first few months after learning of

her diagnosis, with all the medical and social service appointments she will be

asked to keep. The case coordinator or case manager can decrease anxiety for

the woman by facilitating the appointments and serving as the broker in Unking her to needed services.

B. INTERVENTIONS

Assign a case manager/case coordinator to Unk the woman to social services which can meet her basic needs

Teach the woman about the structure of the health and human serwces sys- tem in her community

EstabUsh peer interventions so that women are able to talk with other

women about negotiating Ufe with HIV disease

III. HUMAN RELATIONSHIP ISSUES

A. DISCUSSION

Women with HIV have many significant relationships-with their family, particularly their children, their partner/ significant other, friends, members of the

health care team, and with themselves. Each of these relationships may affect

us. Department of Health and Hum/\n Services, Health Resources and Services Administration, HIV/AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

Psychosocial and Cultural Considerations

tin- others and each can have a profound impact on how the woman deals

with her HIV infection and other comorbidities.

I IIV infection in women is clearly a family issue, imposing social, psychological, and economic burdens on women who care for family members while

they are ill. Many women see themselves as they relate to their children and

significant others and to the roles they take in their family structure. When multiple family members are also infected with HIV, a systems

approach, which looks at the whole in order to understand the parts, is needed

to assist the woman in managing her own care and that of her entire family.

I’he well-being and the return of normalcy for a family depend on the care- seeking ability of the woman and the sensitivity of health care providers in

facilitating the process of seeking care. Women often defer their needs to

those of their children and significant others. In a recent study of inner-city

1 llV-positive women and their infants, the large majority of women smdied

were likely to secure medical care for their infants, while only 46% reported

ever seeking HIV-related health care for themselves. (Butz, 1993)

Many women have low self-esteem and have trouble negotiating safe sexual

practices with their partners. The implementation of an empowerment program for Latina immigrant women demonstrated that targeting broader sociocultural issues may increase the skills necessary for these women to avoid

transmission of HIV infection by their sexual parmers. (Gomez, 1999) The

women in this smdy showed significant increases in comfort with sexual communication, were less likely to maintain traditional sexual gender norms, and

reported changes in decision-making power (N=74).

Because many women with HIV live with other conditions, such as substance abuse and/or mental illness, in addition to poverty and domestic violence as a part of their Uves, they have had to rely on the government public

health and social service system for help and health care. Many have experienced difficult moments in asking for help and have suffered humiliation on

behalf of their families in trying to get what they need. Because of issues of

stigma and poverty, women are vulnerable to a decreased ability to meet their

needs such as housing, food, and work as well as decreased access to health

care services, and/or delayed health-care seeking for themselves. (Amaro,

1990; Mays, 1987) Women with dependent children and those who are pregnant may be even more reluctant to seek care, due partly to a fear of having

their children taken from them. Issues of substance abuse or prostitution may

make the decision to seek health care more complex. (Pivnicka, 1991)

A case manager or coordinator can help establish trust by participating in the initial overall assessment (if possible, in the home), giving straightforward

explanations, and having a working knowledge of the structure and roles the

woman plays within her defined family. Medical providers should also make

extra time for the initial visit in order to begin the process of developing trust with the patient.

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Psychosocial and (Cultural Considerations

Within the African-American population, one can find various arrangements that constitute a family. Some women may have “play sisters” or “play

moms” who are not biological family members but who provide great support

for the women in times of crisis. (Asante, 1995) Many Hispanic women have

madrinas (godmothers) and comadres (friends related by marriage or baptism)

who are great sources of support for them during times of crisis. Understanding the family dynamics is important for providers to facilitate trust and

understanding. Before giving the initial HIV test results and discussing disclo- sure issues, it is essential to have an understanding of the communication

dynamics in the family, especially with the “significant other” of the woman.

B. INTERVENTIONS

Don’t rush the first visit; trust takes time

Initial assessment by the case manager in the home may give additional

insights into the family structure and the roles the woman plays within her

family

Give simple straightforward explanations

Family dynamics needs to be understood before recommending disclosure

actions

Develop or link with empowerment programs targeting sexual communication, negotiation and self-esteem

Understand each woman’s priorities and develop strategies to meet those

needs she considers most important

IV. PSYCHOLOGICAL ISSUES

A. DISCUSSION

Women face an array of psychological issues, not only related to possible

coexisting substance abuse, mental illness, domestic violence, and poverty, but

also related to the stresses of living with HIV disease and being the primary

care provider for the family. Most HIV/AIDS-infected minority women are stigmatized even before HIV, infected by drug use, race and poverty. (Wofsy,

1987) The majority of these women are single heads of households with

young dependent children, and, in general, lack a community of support such

as that seen among gay men. (Weiner, 1991) This situation affects the actual

and perceived availability of supportive resources to respond to varied manifestations of HIV disease. Limited financial and emotional resources affect

HIV-infected women’s access to both psychological and medical services. Low

self-esteem is the rule rather than the exception and plays a major role in ability to access and adhere to care.

U.S. Department of Health and Hum,an Services, Health Resources and Services Administr.ation, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HW

Psychosocial and Cultural Considerations

Many women experience a variety of emotions related to infecting their

child and/or the mode of transmission for themselves. They may feel anger at a partner who infected them sexually or guilt with a parmer to whom they have

been unable to disclose. Some of the emotional issues can be categori2ed by

the time of the encounter with the woman. At the initial visit with the medical

provider the women is most vulnerable to a number of emotions such as shock, disbelief, guilt, anger, sadness and even suicidal ideation. At intermediate

visits, which may be with various members of the multidisciplinary team (social

worker, nurse, psychologist, counselor, nurse practitioner or physician), many of

the same emotions are still present, although some may be more attenuated

while others may have greater prominence. The importance of intermediate

visits is to continue emotional assessments in order to provide effective interventions and help establish trust. Regular visits are those visits established for

routine follow-up and for optimal health maintenance. Typically, women maintain the regular visit schedule for all members of the family. Therefore, it is important to take time to address the emotional needs of the women at these

regular \isits. The most difficult visits are those occurring for crisis reasons.

(Tisis visits often occur frequently until the woman and her family stabili2e

their lives and the medical conditions of all family members. Reasons for crisis range from HIV issues to domestic violence to medical deterioration of one or more family members. It is not unusual for a women to be hospitaH2ed at the

same time as her child. These scenarios call for all team members to work

together and provide anticipatory guidance — that is, devise a plan or procedure

that will address the issues and problems that may arise. A debriefing session by

the care coordinator/ social worker with the woman after the crisis has been

resolved is important to prevent potential future crises.

Despite this complex picture and against aU odds, many of these women

have strong coping abilities and profound survival instincts. Some studies have

suggest that interventions to support attempts to use active coping strategies

as physical symptoms increase may be effective in promoting positive adaptation to HIV disease. (Moneyham, 1998)

B. INTERVENTIONS

The initial visit is often filled with shock, disbelief, guilt, anger, sadness, or even suicidal ideation. Take time to deal with these reactions, assess possible

suicidal thoughts, and give information in “small bites” over several closely

spaced visits

During intermediate visits, work on the establishment of trust between the

woman and her provider/health care team

During regular visits, inquire about the health status of all members of the

family, especially the children; continue to assess the emotional status of the

woman

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Psychosocial and Cultural Considerations

At times of crisis address the situation at hand, consider the possible value

of peer counselors; after resolution, revisit it and develop plans to prevent reoccurrence of similar situations when possible

V. CULTURAL ISSUES

A. DISCUSSION

Since the majority of women living with HIV infection come from two primary groups, African and Hispanic Americans, this section will focus on the

cultural beliefs of these two groups. Culture functions as a guiding framework

that assists individuals, families and communities to interpret and respond to

internal and external stimuli. “Culture describes learned behavior affected by

home, religion, ethnic group, language, neighborhood, school and age-group.”

(Cruickshank, 1989)

B. HISPANIC CULTURE

Discussion

In Hispanic populations, one complex facet of cultural sensitivity and competency lies in the diversity of the subgroups that make up this population in the

United States. The subgroups and their representation are: Mexican American,

62 percent; Puerto Rican, 13 percent; Cuban, 5 percent; Central and South

American, 12 percent; other Hispanic (Spanish/Mexican/Native American

population in the Southwest), 8 percent. (U.S. Bureau of Census, 1990) Each

of these subgroups has their distinct culture, as well as various levels of assimilation into the general population.

Providers need to address these distinctions in developing intervention and

prevention programs for HIV/AIDS and other health issues. Amidst the

diversity among Hispanic Americans, social scientists have identified cultural

values that are shared by most Hispanics regardless of country of origin. The

identified core values are (Marin, 1989):

Familismo — the importance of the family to the individual

Colectivismo — the importance of friends and extended family members such as godmothers (madrinas) and godfathers (padrinos)

Simpatia — the act of being polite; respectful not confrontational

Personalismo — the preference to be with other persons of the same

ethnic group

Respeto — the act of upholding one’s own integrity without damaging

another person

For Hispanics, HIV/AIDS is not an individual issue, but one that affects

the family structure and the unity within the community. In many Hispanic

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with

Psychosocial and Cultural Considerations

families the husband makes the decisions for all members of the family,

including his wife. The extended family in the Hispanic culture may also play a major role in the making of decisions. Clinicians need to assess the role of the

woman within her culture and her adherence to strict cultural beliefs.

Interventions

Identify the woman’s ethnic subgroup of origin

Provide a bilingual provider on the health care team (do not use the children or the custodian to translate; this demonstrates a lack of respect)

Diagram the family structure and discuss the role of each member

Review the role of women in her family

Link the woman to appropriate social service providers

Case Study: Hispanic

Name: DE

Age: 35 years

Ethnicity: Mexican American

DE came into our program on 1 1/4/93 - her first visit with the physician was the

day she learned of her HIV status. She was 27 weeks pregnant with her second

child. She had a 14 month-old daughter who was followed by a specialist because

of urological problems. Her risk factors included two heterosexual partners and

history of a blood transfusion after her first pregnancy in 1992 secondary to hemorrhage. She stated she was tested because of the blood transfusion.

We performed HIV testing on her daughter, and explained the risk to her

unborn child because of her HIV status; the plan of care for the child after birth was reviewed.

At the time of diagnosis DE received a classification of AIDS due to a CD4

count of 178. Despite these obstacles, she maintained her health during her

pregnancy, continued to care for her daughter, and began getting care for her own

HIV disease. DE tested in the lower ranges for verbal intelligence and conceptual

processing with psychological evaluation.

DE's support system included her mother (who initially did not know DE's

status), and her common-law husband, who was not the father of her oldest child,

but was the father of the child she was carrying. The HIV test results for her

daughter and husband were negative. DE experienced an variety of emotions,

including fear, anxiety, and depression, and needed much support from the entire

staff to assist her in understanding more fully not only what HIV was or how it affected her and her family, but also in obtaining financial support.

As with most new clients, DE was distrustful of staff initially, but with care, concern and perseverance, our entire team (physicians, nurses, social workers,

psychologist, foster granny volunteers, etc.) developed a trusting relationship with

her. DE was empowered to take control of her own life and that of her children.

Her second child was a boy, and within

1-2 months of life it was obvious he was infected and he had a very low CD4

count. She never missed a clinical appointment for him, and in fact, was always

there even before clinic began. DE provided excellent care to her son, learned to give him his medications, and had good relationships with the medical staff, so

that she would call with any problems he was having.

By 1996 her own health had deteriorated significantly and her care was

transferred to another physician, but she continued to bring her son to our program for care. She was linked with hospice services and almost died several

Case Study continues . . .

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A CiUlDF. TO Till' Cl.INICAI. CARI-: OI' WOMICN WITH HIV

Psychosocial and Cultural Considerations

Case Study: Hispanic (continued)

times, but each time improved to the point where she was ultimately taken off the

hospice list. Her determination to personally care for her son was a strong

motivating factor in her ability to not only stay alive, but to actually improve her

health status. DE was able to make the choice as to how and where her son would spend his

last days, and was at his bedside when his short life ended. She let balloons loose

into the sky at his burial to signify that her son had gone to heaven.

DE continues to live, and both she and her husband have dropped in to the

clinic occasionally to visit and to show us photos of the family trip to Disneyworld,

pictures of her son in his last hours, etc. DE has also become involved with the

Pediatric AIDS quilt project, started by one of our program nurses. C AFRICAN-AMERICAN CULTURE

Discussion

As in other minorities, African Americans experience high rates of unemployment and overall poverty. Any discussion of core values must be evaluated in

the context of these sociodemographics characteristics. According to Gibbs, even though family conflict is reported in aU races and socioeconomic groups,

minorities have a higher rate because they are more vulnerable to detection

and arrest by the poUce and referral to pubUc agencies. (Gibbs, 1990) These

problems may be more appropriately viewed as community problems rather

than problems of the black family. Amidst the complexity of life for AfricanAmerican individuals and their families they are sustained by their core values

which have historical roots in Africa.

The core values that most African Americans embrace have been described

by Sudarkasa. (Sudarkasa, 1996) They are the seven “R’s”: respect, responsibility, reciprocity, restraint, reverence, reason and reconciliation. The core values

defined are; Respect — the respect of others from parents and relatives to elders or

leaders in the community

Responsibility — being accountable for self and for those less fortunate in one’s own extended family and even one’s community

Reciprocity —giving back to family and community in return for what

has been given to one (mutual assistance)

Restraint —giving due consideration to the family or community/group

when making decisions

Reverence — deep awe and respect firstly toward God, the ancestors as well as for many things in nature

Reason — taking a reasoned approach to the settling of disputes within

the family or the community

us. Department of Health and Human Services, HE/VLTh Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Psychosocial and Cultural Considerations

Reconciliation — the art of settling differences; that is, putting a matter

to rest between two parties

Two of these values, respect and responsibility, were major guiding principles for behaviors within families from Africa which have been carried over to

African-American families today. “Restraint” is related to the notion of “sacrifice.” Parents exercise restraint over their own destinies in order to provide for

their children, who in turn repay the “sacrifice” by putting their parent’s needs

before their own in many instances. (Sudarkasa, 1988)

Spirituality is a strong cultural value among both African- and HispanicAmerican women. Historically, the church in the African-American community

has been the single most important organization advocating for public policies

to influence improvements in health, education and financial quality of life. (Poole, 1996) From this perspective there is a continuum between rehgion and

one’s quality of life. “As the center for the extended family, reinforcing the sense of self and self-esteem within the culture, the church offers opportunities for the whole family’s development.” (Butler, 1992) Churches in the

African-American community have created and mobilized leaders and

increased hope. (Neeleman, 1998; DHHS,1998) In order to provide comprehensive health care to these populations, programs should include the spiritual

dimension and beliefs in all aspects of care. Many African Americans share a distrust of the health care system related

to historical experiences such as the Tuskegee experiment. Airhihenbuwa,

(1990) suggests that African Americans operate in a society where rules and

social systems appear to be adversarial. “The degree to which they perceive the

odds against them as manageable or overwhelming wiU depend to a significant

degree on the transactional competency and success of their parents, the competence of the role models in their primary community, and the availability

and accessibility of resources and support to help them in their coping

efforts.” (Meyers, 1983)

Interventions

Trust is a continuous, dynamic process requiring open and ongoing communication between women and their health care providers / team

Educate team members about the values of African Americans

Show respect for spiritual beliefs and how they affect advanced directives

and other decisions the woman may make

Recognize extended family members as key supports for the patient

An essential role for the case manager/coordinator is to help the woman

negotiate multiple parts of the health care/ social services system and to serve as a broker and advocate for her specific needs

us. Department OF Health and Human Services, He,\lth Resourcf.s and Services AoMiNisTR-vnoN, MIN'/AIDS Hi hi.m 277
A CJiuDi' TO nil', ('linic.m. ('.mu; oi' Womi;n wrni }1IV

Psychosocial and (Cultural (Considerations

Case Study: African American

Name: BA

Age: 43

Ethnicity: African American

BA was referred to the program after delivering a baby boy IVi weeks

prematurely; he was born withdrawing from drugs and was found to be HIV

infected. After the referral was made at 5 p.m. on a Friday, two nurse-case managers went to the hospital to meet with BA and to initiate the process of caring

for her child. While there, local law enforcement officers came into the patient's room and informed her that they were removing her newborn son from her

custody because of her drug use during pregnancy.

BA was 43 years old and had a history of injectable drug use since the age of

15 when she ran away from home. She was homeless at the time of delivery and was attempting to reunite with her family.

On initial assessment she was happy but nervous and apprehensive about the

possibility that her child could be infected with HIV. She did not get prenatal care because doctors had told her that her uterus was so badly scarred from sexually

transmitted diseases that she was unlikely to get pregnant. This pregnancy was a pleasant surprise for her and she saw this baby as a gift, a miracle from God.

She was admitted to an outpatient drug rehabilitation program and her baby was placed in foster care. With the help of her caseworker she reunited with her

mother and sisters after revealing her HIV status. She also met with her spiritual

counselor on a regular basis to discuss life and death issues.

She completed her 6-month drug rehabilitation program successfully and was

able to petition the courts and get her son back. She was in the hospital when her son became very ill and was also hospitalized. She was able to talk with her

pediatrician and sign advanced directives for her child. He died during their

simultaneous hospitalization in his mother's arms. When the nurses and

caseworker came to be with her at the hospital she shared the following story:

"I have done a lot of things wrong in my life and I didn't think I had a chance to get in the pearly gates. But you know I have loved my son and he knew that. I tried to be the best mother I could be for the short time I had him. So when I die and I go up and see St. Peter at the pearly gates he is just going to nod his head "no" . As I am just about to leave I hear someone running and I turn around to hear a

little boy screaming: "St. Peter, that's my mom and she loved me and I love her. You have to let her in!" BA remained clean for the entire year that her infant was alive, but relapsed

back into drug addiction upon his death. This was the way she had always coped

before. BA was distrustful of the system (all the team members), had been

estranged from her family, and had an array of health problems. Early in her

assessment she said, "I have come home to die." She did live two years, during

which time she was back and forth between drug rehabilitation programs and

hospitalizations for her HIV infection. A key factor in her care was the assignment

of a case manager and the coordination with her drug rehabilitation team. She had

constant contact with her spiritual counselor, with whom she had had a longlasting relationship since her childhood. She was referred late in the stages of HIV

infection. She was given medical information about herself and child in a straightforward manner, which she appreciated, commenting "tell it to me

straight." She had a very close relationship with her child's pediatrician. She

tended not to keep her own medical appointments and deferred most of her

energy to her child's care. BA died one month after her son's death surrounded by

her family, the staff and her spiritual counselor.

D. COMMUNITY

Discussion

In addition to the major core values of a culture, other considerations are the

“vital signs” of the community in which the woman Lives. Community “vital

U.S. DeparTMent of HE;\lth and Human Services, Health Resources and Services AdministR/\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Psychosocial and Cultural Considerations

signs” include, but are not limited to: prevailing cultural beliefs, pressing issues

for the community, employment rate, the level of poverty, the definition of

health espoused by most people in the community, access to health care, characteristics of the community leaders and their followers, support structures,

and the level of trust in the health care system.

These factors can be described as a community’s ecological system. (Meyer,

1988) Health care practitioners should be encouraged to view the people of

the community in the context of their environment. The interrelatedness of

individuals to their environment leads one to view people not as solitary subjects, but as integral parts of a whole community.

With both Hispanics and African Americans the community is vital to a good and healthy life. However, both of these populations experience a disproportionate level of displacement due to the requirements for economic

survival. Health and human service providers who want to serve these populations with sensitivity and quality must understand the complexity of living

with HIV disease in poverty. According to Mindy FuUilove (1996), psychological well-being depends on strong, nurturing places.

Interventions

Identify and have a working knowledge of the core values of the community you are serving

Develop an alliance with key community based organizations

Teach staff about the effect of community on the woman’s decision making

and belief system

Identify women who have to leave their community for long periods of

time for employment (e.g, migrant workers), and assist them in making

connections for health care while away and in ensuring access to needed

medications

VI. SUMMARY

Women living with HIV infection are living with a multitude of medical and

social problems. They live not in isolation but as integral members of their

communities and primary caregivers for their families. Although HIV infection

is often not their primary concern, this does not mean they do not want help.

To understand and assist women living with HIV, it is important to take a sys- tems approach, to look at the whole in order to understand the parts, to think

in loops rather than in straight Unes. (O’Connor, 1997) High quality care for

women living with HIV disease is best given by addressing not only her med

ical needs, but also her economic needs, her relationships, her emotional

responses, and her culture and her community-all of the faces of a multifaceted life.

us. Department OF Health AND Human Services, Health Resources and Services AD.\iiNisTRAno\, IIIW.AIDS Uuri.m 279
A CJUIDF. TO TUP. Cl.lNIC.M. CARP OI* WOMl'N WITH HIV

Psychosocial and (Cultural Consideradons

REFERENCES

Airhihenbuwa, C. Health Promotion Disease Prevention Strategies for African Americans: A Conceptual Model. In R. Braithwaite & S. Taylor (Eds.), Health Issues In The Black Community, (pp. 267—280). San Francisco: Jossey-Bass Publishers, 1990.

Amaro, H. Love, sex, and power: Considering women’s realities in HIV prevention.

American Psychobgist, 50 (6), 437-447, 1995.

Anderson, M.D.., Smereck, G.A., Hockman, E.M., Ross, D.J., & Ground, K.J. Nurses

decrease barriers to health care by “Hyperlinking” multiple diagnosed women liv- ing with HIV/AIDS into care. Journal ofthe Association ofNurses in AIDS Care

10(2): 55-65, 1999.

Asante, M.K. African-American History: A Journey ofLiberation. Maywood, NJ: Peoples

Publishing Group, 1995.

Bunting, S.M., Bevier, D.J., Baker, S.K. Poor women living with HIV: Self-Identified

needs. Journal ofCommunity Health Nursing, 16, 41—52, 1999.

Butler, J.P. Of kindred minds: The ties that bind. In Orlandi, M.A. (ed). Cultural competence for evaluation: A guidefor alcohol and other drug abuse prevention practitioners

working with ethnic/racial communities. Rockville, Maryland: US. Department of

Health and Human Services, 1992.

Butz, A.M., Hutton, N., Joyner,M.,Vogelhut, J.,.Greenberg-Friedman, D, Schreibeis, D,

& Anderson, J.R. HIV-infected women and infants: Social and health factors impeding utilization of Health C^xe. Journal ofNurse-Midwifery. 38 (2), 103—109,

1993.

Centers for Disease Control and Prevention. HIV/AIDS Weekly Surveilbnce Report, 1998.

Cruickshank, J.K. & Beevers, DG. Ethnic Factors in Health and Disease. Wright Butter- worth & Co., 1989.

FuMove, M.T. Psychiatric implications of displacement: Contributions from the psy- chology of place. American Journal ofPsychiatry, 153, 1516—1523, 1996.

Gibbs, J.T. “Developing Intervention Models For Black Families: Linking Theory and

Research.” In Harold E. Cheatham & James B. Stewart (Ed.), Bbck Families. Inter- disciplinary Perspectives. New Jersey: Transaction Publishers, 1990.

Gomez, C.A., Hernandez, M. & Faigeles, B. Sex in the New World: AN empowerment

model for HIV prevention in Latina immigrant women. Health Education &

Behavior, 26, 200-212, 1999.

Marin, G. AIDS prevention among Hispanic needs, risk behaviors and culmral values. Public Health Reports, 104, 411^15, 1989

Mays, V.M., & Cochran, S.D. Acquired immnodeficiency syndrome and Black-Americans: Special psychological issues. Public Health Reports, 102, 224-231, 1987.

Metcalf, K.A., Langstaff, J.E., Evans, S.J., Paterson, H.M.& Reid, J.L. Meeting the needs

of women living with HIV. Public Health Nursing, 15, 30—34, 1998.

Meyer, C.H. “The eco-system perspective.” In R. A. Dorfman (Ed.), Paradigms ofClinical Social Work. New York: Brunner Mazel, 1988.

Moneyham, L., Hennessy, M., Sowell, R., Demi, A., Seals, B. & Mizuno, Y. The effective- ness of coping strategies used by HIV-seropositive women. Research in Nursing &

Health, 21, 351-362, 1997.

Myers, H.E, & King, L. M. “Mental Health Issues in the Development of the Black

American Child.” In E.G. Powel (Ed.), The Psychosocial Development ofMinority

Group Children. New York: Bruner/Mazel, 1983.

us. Departoent of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Psychosocial and Cultural Considerations

Ncclcman, J.,Wesscly, S., & Lewis, G. Suicide acceptability in African and white Americans: The role of religion. Journal ofNervous and Mental Disease, 186, 12—16, 1998.

O’Cionnor, )., & McDermott, I. The Art ofSystems Thinking:: Essential Skills for Creativity

and Problem Solving.. San Francisco: Harper CoUins Pub., 1997.

Pivnicka. Reproductive decisions among HIV-positive drug using women: The importance of mother/child co-residence. International Conference on AIDS, 7 (2), 352,

1991.

Poole, Thomas G., Black Families and the Black Church: A Sociohistorical Perspective.

In H.F. Cheatham & James B. Stewart (Ed.), Black Families. Interdisciplinary Perspectives. New jersey: Transaction Publishers, 1990.

Sowell, R., Moneyham, L. & Aranda-Naranjo, B. The care of women with AIDS: Special

Needs and Considerations. Nursing Clinics ofNorth America 34(1): 179—99, 1999.

Sudarkasa, N., African and Afro-American family structure. In Cole, J.B. (ed.). Anthropology for the Nineties. CoUier Macmillan, Inc.: New York, 1988.

Sudarkasa, N. The Strength ofOur Mothers. African &African American Women & Families: Essays and Speeches. New Jersey: Africa World Press, Inc., 1996.

U.S. Bureau of Census. Department ofStatistical Information, Washington, D.C., 1990.

U.S. Department of Health and Human Services. Cultural Competence working with

African-American communities: Theory and Practice. CSAP Cultural Competence

5m>t7, 1998.

Weiner, DC. Health Issues at the U.S. Mexican Border. Journal ofthe American Medical

Association, 265 (2), 242—247, 1991.

Wofsy, C.B. Human Immunodeficiency Virus infection in women. Journal ofthe American Medical Association, 257 (15), 2074—2076, 1987.

us. Department OF He.alth and Hum,\n Services, Health Relsources .vnd Skrvicfis ADMiNis-i-RA-nos. HIV/AIDS Him 281
This Guide is a

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IX: Psychiatric Issues

Joyce Kobayashi, MD

I. OVERVIEW

The experience of being a woman who is HIV-positive must be examined from

several perspectives: A) from the perspective of the individual seropositive

woman as she makes the journey through the common emotional milestones of

HIV; B) from the perspective of women as a group, because women, in contrast to men, tend to cope with HIV within the context of the relationships

which are most important to their self-definition; and C) from the perspective

of the contemporary context of most HIV-positive women who are, on average, African-American and Hispanic women living and needing to survive in

poverty, in the midst of drugs and commonly with personal experiences of

childhood sexual abuse or adult victimization through sexual or physical assault.

The experience of the woman living with HIV may be affected by the

emotional dynamics described by any or aU of these three perspectives. The

healthcare provider who is mindful of aU three may be able to provide care with deeper understanding and more precise appreciation of her daily struggles with this disease.

Even the asymptomatic phase of being seropositive should be managed

and understood in these psychological dimensions. In fact, the experience of

the asymptomatic phase of HIV is entirely emotional and psychological, rather

than a disease characterized by physical symptoms. It can be an intense experi- ence ranging from individual fears of stigma and suffering, to common concerns about rejection and abandonment by a partner, to a deep feeling about

HIV as further victimization in the context of daily concerns about survival.

Interventions by the healthcare provider during normal adjustment phases

and common emotional transitions include skilled emotional support, education and empathy, while maintaining awareness of the provider’s own reactions

to the HIV-positive woman, her experiences and her ways of coping .

Accurate assessment might also indicate the need for referral to a substance

treatment program or psychiatric evaluation, in addition to referral to programs of social support, housing, case management and concrete services,

depending on the needs of the individual. Care providers who focus on medication adherence without a comprehensive treatment plan addressing harm

reduction and treatment for illicit drug use, psychiatric treatment for comorbitl

us. Department of Health and Human Services, Health Resources and Skrvicis ADMiNisTR,vnos. HI\7AIDS Bi ri ,m 283
C'lUlDE TO Cl.lNICAI. MaNAGI'MI'NT OF WOMFN WITH HIV

Psychiatric Issues

psychiatric conditions, and a full range of support services are likely to fail, leaving the HIV-positive woman with the feeling that her real sources of pain

and suffering have been left unrecognized.

When normal adjustment issues give way to formal psychiatric disorders,

accurate diagnosis is essential as well as knowledge of appropriate treatment

and awareness of potential drug-drug interactions, complemented by thorough

assessment of suicide risk.

This chapter will address this range of psychiatric issues relating to HIV

disease in women and will make specific recommendations for provider and

program response, evaluation and management.

II. THREE PERSPECTIVES ON THE EXPERIENCE OF

BEING A WOMAN WITH HIV

A. EMOTIONAL MILESTONES: THE EXPERIENCE OE THE

INDIVIDUAL HIV-POSITIVE WOMAN

Emotional adjustment to the experience of learning that one is HIV-positive,

coping with the demands of being HIV-positive in daily function, and becoming a patient for HIV care commonly follow a natural course of progression

through stages. The milestones which mark the transition from one stage to

another are often powerful emotional experiences and should be understood

as important opportunities for clinical intervention. (See Table 9-1) Knowledge of these milestones will enable the healthcare provider to provide appropriate emotional support, education and empathy.

Reproductive decisionmaking has not been included in Table 9-1, as discussion of this complex decision must be individually tailored to the current cir- cumstances, both social and clinical, of the particular woman considering the

variety of options now available. The decision to get pregnant is an important

and emotional one and the healthcare provider should be ready to explore a variety of feelings with the patient within the emotionally intensified circumstances of seropositivity without a sense of pressure, before launching into

current percentage rates of vertical transmission. (See Chapter VII: HIV and

Reproduction)

B. COPING WITH HIV: THE EXPERIENCE OE HIV-POSITIVE

WOMENIN THE CONTEXT OE THEIR RELATIONSHIPS

Contemporary psychiatric research about the developmental psychology of

women suggests fundamental differences in the way women and men think

about themselves (GilUgan, 1990), with significant implications for clinical

practice. While it may be speculative as to whether these differences are more

evolutionary and transcultural or locally socialized and economic, an understanding of this perspective is likely to amplify sensitivity in working with HIV

us. Department of Heai.th and Human Services, Health Resources and Services Administrapion, HIV/AIDS Bure.\u
Guide to Clinic.\l M.\NAGENffiNT of Women with HIV

Psychiatric Issues

us. Department of He.\lth and Human Services, He.m.th Resources and Services Administr-viion. MI\7,MDS Hi ri ai 285
CiuiDE I'o Ci.iNiCAL Manac;emf,nt of Womf-n wi th HIV

Psychiatric Issues

seropositive women,

whatever the ethnicity or racial background.

While acknowledging that any generali2ation about gender

is often wrong in the

individual case, two

overarching propositions derived from

this research may help

health care providers

understand the ways

HIV-positive women

often differ from men

in their adjustment to

being seropositive or having AIDS. First,

women more fre- quently define themselves in the context

of their relationships

to others. Second,

while men may fear

intimacy, women

more often fear separation. (Surrey, 1982)

For example, it is not uncommon to

hear HIV-positive

men express fears

about becoming

dependent on others

in the course of their

illness, while HIVpositive women often

tend to worry more

about those who are dependent on them as their illness progresses. Of course,

everyone fears being

abandoned and left alone when they are dying. While these

U.S. Department of Health and Hum/\n Services, Health Resources and Services Administration, HIV/AIDS Bureau
Guide to Clinical Management of Women with HIV

Psychiatric Issues

differences may sound simple or obvious, in clinical practice the differences

are striking.

Men often lose self-esteem if they are not able to continue working, or feel anger and may wish to distance themselves from others whom they feel obligated to support, while women more frequently lose self-esteem if they are unable to continue taking care of others. Many HIV-positive women are single

mothers and feel deep shame if they are unable to take care of their children or jirovide for them as they feel they should.

Women may also accept being the target of anger or even abuse, or suppress their own anger, in order to avoid finding themselves alone. They may

be more likely to end up in an abusive relationship if they have been abused in

their childhood. (See Section C)

There are subtleties in these differences which can guide the care provider

in recognizing the adaptive and maladaptive aspects of these concerns for

their female patients, and should inform their clinical approaches to seropositive women as they struggle with emotional adjustment to the vicissitudes of

HIV-related illness. On the positive side, women who are coping with HIV/AIDS may be

motivated to take care of others to the extent that they can undertake major

changes in their own behavior, such as giving up longstanding drug dependencies during pregnancy, or engaging in discussions about permanency planning

which frighten them or that they would rather avoid. Other HIV-positive

women may take on the responsibility of bringing their children or partners

into medical care despite great distance or significant barriers (including their

own fatigue or iU health). They may also demonstrate remarkable resourceful- ness in seeking out additional avenues of support for others.

The clinician who understands that the strength of this motivation often

derives from a deeper level of self-definition and not simply a conventional

wish to “do good” will realize the importance of pausing to show respect for

the degree of caring the woman demonstrates in making this effort. These are

clinical opportunities to build trust and strengthen an aUiance around common

concerns. The maladaptive side of similar situations for an HIV-positive woman may

include starting or continuing to use drugs simply out of fear of losing a substance using partner; staying in a dysfunctional or even abusive relationship

because of anxiety about the loss of the relationship; feeling guilty about taking time away from responsibilities for others to address her own needs; or simply not being able to self-motivate and establish good self-care independently when “no one” will benefit from these efforts except herself

Women who have lived in poverty or have in multiple additional ways experienced powerlessness about their lives are even less convinced about self effi- cacy; or at a deeper level, that they are “worth it.”

us. Department of Health and Human Services, Health Resources and Services Ai^MiNisncvnoN. HI\7A1DS Hi'ki m 287
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Psychiatric Issues

Astute care proviciers understand that affirming or even “giving permission” for the seropositive woman to attend to her own needs may over time

be more important than instructions about what specific health behaviors to

follow. In certain circumstances, such as in negotiating safe sex with an unreceptive partner, the provider may even be more directive, without implying

criticism about past behaviors, and encourage a woman to develop the necessary skills to become more assertive about her own health concerns. The practitioner who is able to establish a trusting relationship with the

patient should also learn to feel comfortable with the fact that the strength of

their relationship may help motivate the HIV-positive woman as much as lec- tures about viral load. Another proHder may convey frustration or disappointment about a patient’s nonadherence to medication or some other medical

recommendation, only to find that the patient does not return because she has

personalized this as a rejection within the context of their relationship.

The woman with AIDS who may feel guilty about taking any time for herself win feel much more supported by a healthcare provider who first acknowledges the importance of her concerns for taking care of others and

then builds on that concern by gently reminding her she will not be able to

continue unless she takes care of her own health first. This is most effectively

done within the context of a relationship where the seropositive woman has

felt her values have been respected, and where sufficient trust has been established that maladaptive behavior may be confronted by the provider, and yet

be experienced as caring and supportive, rather than as rejection or criticism

by the patient.

C: SURVIVING WITH HIV: CONTEMPORARYHIV-POSITIVE

WOMENIN THEIR CONTEXT OE POVERTY, SEXUAL

ABUSEAND DRUGS

Poverty

“The majority of women with AIDS in the United States are unemployed, and

83% Hve in households with incomes less than $10,000 per year. Only 14% are currently married, compared to 50% of all women in the United States, aged

1 5—44 years. Twenty-three (23%) of HIV-infected women live alone, 2% live

in various facilities, and 1% are homeless. Approximately 50% have at least

one child less than the age of 15 years. Similar to other population groups

with AIDS in the United States, the majority of women with AIDS are from

minority racial and ethnic groups, with African Americans comprising 57% of

women with AIDS in the US., Latinas comprising 20% and Caucasians comprising 23%.” (CDC, 1997; Barkan 1998)

The clinician should be as mindful of the devastating impact of poverty

and intermittent homelessness on the person and personality, as the physical

sequelae of HIV. For many women who are working the streets, are constantly

us. Dep.artment of He.alth and Human Services, He/\lth Resources and Services Administration, HIV/AIDS Bureau
Guide to Clinical 1VL\nagement of Women with HR''

Psychiatric Issues

on the move in transient residences, or are feeling overwhelmed by the needs

of their children, illicit drugs are sometimes the most available antidote. It is hard to make the medical treatment needs for HIV relevant unless the woman

feels her provider recognizes and has some understanding of her daily struggles for survival. There are many concrete services such as transportation,

childcare, food programs and housing that can increase the ability of these

HI\^-positive women to participate in their healthcare, amplified by the knowledge that their treatment team wants to address aU issues which are fundamental to her survival and longevity.

In the book. Women, Poverty andAIDS (Farmer, 1996), which contains a comprehenswe discussion of these issues, Shayne and Kaplan state that “safe sex is an economic compromise for many poor women who rely on sex as a source of employment, as a means to establish ownership or proprietary rights

in relationships, or as a means of getting tanghble supports, generally short in

supply.” (Shayne, 1991)

Most women with AIDS in the United States are unemployed minority

women living in poverty, often as single mothers, and frequently without easy

access to medical care. Poverty and the related experiences of racism, sexism

and stigmatization are the predominant themes in their lives. This may leave

these women with the feeling that their medical teams are simply adding to

their burdens by admonishing them to adhere to complicated medical recommendations such as antiretroviral medications. In one study investigating ways

to improve healthcare utilization by inquiring about needs for services, a sample of two groups of HIV-positive women, from a Needle Exchange Program

and a correctional facility, all indicated that “shelter and food/clothing ranked

first among unmet needs for services.” (Thompson, 1995)

While a source of income is not traditionally conceptualized as within the

realm of medical treatment, it certainly becomes a major factor in medical ill- ness and cannot be ignored. Many women who have substance abuse disorders with psychiatric comorbidity may qualify for entitlement programs which

Table 9-2: A Demographic Comparison of HIV-positive Women and

Men

Women Men

Level of

Significance

African American 54% 27% <.001

Unemployed 76% 59% NA

Incomes < $5,000/year 30% 17% <.001

Without medical insurance 85% 63% <.001 < 35 years old 44% 31% <.001

Analysis based on 1996 figures of men versus women living with HIV/AIDS;

Women were 26% of 231,4000 reported cases Source: Bozzette, 1998.

us. Dep.\rtment of He.\lth and Human Services, Hf.alth Resources and SF,Rvia-s ADMiNi.sTRAnoN, HIN'/AIDS Hi riai- 289
CJuiDF. TO Clinical Managf.mfnt ol' Womi;n wrni HIV

Psychiatric Issues

they have not explored. Vocational rehabilitation programs often entail medical or psychiatric referrals. While housing is not traditionally considered part

of medical care, it is also a major factor in medical illness and should be considered. For example, residential programs which require substance abuse

treatment contracts should be made available when feasible. Treatment teams

should consider this dimension of care in making a comprehensive plan to encourage antiretroviral medication adherence.

Childhood Sexual Abuse and Adult Victimization

Sexual abuse, sexual assault and domestic violence are experienced within the

lifetimes of a significant portion of American women regardless of their eco- nomic status or ethnicity. When childhood sexual abuse is defined as physical

contact of a sexual nature to children under 14 years of age, estimates range

from 28% to 36%. (Wyatt, 1986) Childhood abuse research is limited by the

methodology of self-report, sampling and definitional issues, but shows

remarkably consistent high lifetime prevalence rates for women who are HIV-positive or at risk for HIV, for both childhood sexual abuse and adult

sexual assault. In turn, these are associated with multiple HIV transmission

and risk behaviors.

In a study of 186 HIV-positive or at risk individuals, 28% of the women

(and 15% of the men) had been sexually abused during childhood. The female

survivors of sexual abuse were significantly more likely to work as prostitutes,

become pregnant during teenage years, abuse alcohol or tranquilizers, and

were less likely to finish high school. (Zierler, 1991)

A recent study of 1645 subjects enrolled in the Women’s Interagency HIV

Study (Cohen, 2000) found that among both HIV-positive and seronegative-atrisk women 2 out of every 3 women (67%, 66%) had experienced domestic

violence during their lifetimes, and almost one out of three (31% and 27%)

had been sexually abused as children. There was no significant difference in

prevalence associated with race, ethnicity, education level or marital status,

although domestic violence was more frequently reported among older,

unmarried, unemployed women.

Early sexual abuse was strongly associated with increased HIV risk behaviors:

using drugs

having more than 10 male sexual partners

having male partners at risk for HIV infection

exchanging sex for drugs, money or shelter

Sexual assault for adult women has been estimated to be two to four times

as likely in women who were survivors of childhood sexual abuse. In a study

of 327 women with or at risk for HIV, Zierler (1996) found that35%of

women with HIV were sexually assaulted as adults. Forty-five percent of

women who reported rape as adults had been sexually abused during childUS. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
Guide to Clinical M.\nagement of Women with HIV

Psychiatric Issues

hootl or as teenagers. Among women with HIV, adult rape experiences were

associated with:

more sexual partners

unprotected sex involving drugs

earlier age of injection drug use

teen pregnancy

sexually transmitted diseases

gj necologic surgery

Similar results were found in a study of street-recruited women from three

different major urban sites, with demographics similar to a large portion of

the female HIV-positive population: 114/918 women (12%) reported they had

been sexually assaulted in the previous 12 months. In comparison to those

who were not sexually assaulted, this study (Wong, 1 993) found that rape was

associated with:

higher rates of sex for drug exchanges (79% vs 37%)

reporting more than 100 lifetime sex partners (55% vs 18%)

smoking crack (86% vs 55%)

twice the likelihood of being infected with HIV and syphQis

In another study, of 40 HIV-positive women seeking medical care in one

survey, a trauma history was reported by 95%: 63% reported sexual abuse and

70% reported physical abuse. (Nelson, 1996)

In addition, multiple studies have estabhshed a relationship between childhood sexual abuse in women and adult-onset depression. (Weiss, 1999) Of

interest is that HIV-positive and HIV-at risk women both have higher rates of

depression than the general population, although depression increases with

physical symptoms. There is also evidence that a range of psychiatric disorders

are more prevalent in women and are associated with childhood sexual abuse:

Bulimia nervosa

Panic disorder with agoraphobia

Generalized anxiety disorder

Borderline personality disorder

Adult-onset depression

There are major implications from these findings for medical care, psychiatric and substance treatment as well as for HIV prevention efforts. A significant segment of the HIV-positive and at risk female population have

experienced childhood sexual abuse and/or sexual assault as an adult and their

feelings about their disease, their likelihood of continuing high risk transmission behaviors, their methods of coping, such as the use of substances, and

their relationship to the healthcare system are seen through the prism of those

experiences.

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Medical care and treatment targetting women should be conceptualized

with attention to the important impact of violence and trauma in the lives of

these women. When individuals whom these women were supposed to be able

to trust have victimized them, it is not surprising that healthcare providers will

have to very consciously earn their trust. Lack of trust, low self-esteem and

feelings of powerlessness are frequently experienced by these women and supportive measures such as: having a female healthcare provider, participation in

women’s support groups, getting supportive therapy or treatment with psychiatric medications, providing social resources or vocational rehabilitation can

increase trust, self-esteem and ultimately etnpower them. Education about prevention should also be a part of medical treatment when there is high risk for

continuing transmission behaviors.

It is also important to be aware that women with a history of childhood

sexual abuse may be susceptible to a variety of misperceptions. A directive

style of recommending medical treatment, for example, may be perceived as coercive by women sensitized through past experiences. A treatment with

major side effects or a surgical procedure may be experienced as abusive intrusions in their lives or bodies. A friendly relationship with a healthcare provider

may take on unwarranted sexual overtones. Efforts at health education may

not be heard when the individual is suddenly lost in thought or actually dissociating because of suddenly being overwhelmed by memories of abuse. Pain

may be amplified because of experiences of physical abuse and might be dismissed as drug-seeking.

Clinicians, in turn, may have particular responses to these women and

should understand their vulnerability to unproductive “countertransferential”

reactions such as either being provoked into being the anticipated abusive fig- ure, or feeling compelled to rescue the individual. Responses of the clinician are more specifically addressed later in this chapter.

Finally, it must be noted, that the clinician must ask in order to know. A

simple and direct question may be used, such as, “Would you mind if I ask if you have ever been the victim of physical or sexual abuse?” or “Has anyone

ever hurt you physically or abused you sexually?” This should routinely be

asked as a pertinent part of the medical history. If there is a positive response,

the details need not be explored. If there is a negative response, the possibility

of an abuse history should nevertheless be kept in mind. With regard to the

possibility of domestic violence, the clinician can ask, “Is there anyone in your

life right now who makes you feel unsafe?” If there is a positive response, the

details should be explored.

Illicit Drug Use

Women with HIV who are impoverished and struggling with sequelae of

childhood abuse and adult victimization are also frequently struggling under

the burden of significant substance use which is often further complicated by

psychiatric comorbidity. Whether or not they are etiologically related, each

us. Department of Heai,th and Human Services, He.vlth Resources and Services AoMiNiSTTumoN, HIV/AIDS Bureau
Guide to Clinic.\l Management of Women with HIV

Psychiatric Issues

factor can exacerbate the other and relapses, in turn, are often associated with

increased medical morbidity. Medical providers who consider a substance

using 1 IlV-posidve woman an inappropriate candidate for multiple drug antiretroviral medication should consider clinical efforts to assure that she is enrolled in substance abuse treatment as a specific part of the treatment plan.

W'hile it is beyond the scope of this chapter to explore the range of studies

addressing substance use among HIV-positive women, a few have been

selected for discussion. (Also see Chapter X on Substance Abuse)

There is a high rate of psychiatric comorbidity among HIV-positive

women who use substances:

In a study of a population of HIV-positive individuals on methadone,

79% were found to have a current DSM-III-R Axis I psychiatric disorder

and nearly two thirds had two or more concurrent disorders. (Batki, 1996)

If psychiatric and substance use treatment are not offered at the same time,

a relapse in one condition can often destabilize the other, such as with crack

use and bipolar disorder, or with intravenous drug use and post-traumatic

stress disorder. Investigators using a National Survey of Veterans found

that the combination of substance abuse and PTSD increased the rate of

HIV infection by almost 12 times, as compared those without either disorder. (Hoff, 1997) Psychiatric evaluation and treatment should accompany

substance treatment when there is comorbidity, and has been shown to be

effective. (Lyketsos, 1997)

As many as one-third of HIV-infected women exposed to HIV

through heterosexual contact use noninjection drugs and engage in

high risk behaviors:

Analysis of data from 2270 questionnaires administered to HIV-infected

women from 12 state or local health departments over five years focussed

on the 488 (21%) who used noninjection drugs only. • 36% of crack users, 11% of primarily marijuana users and 7% of primarily cocaine users had received money for sex in the past five years; • 66% of crack users, 37% of marijuana only and cocaine primarily

users had had an STD. (Kacanek, 1 996)

Crack cocaine use results in increased HIV exposure and HIV-positive status in multiple ways:

Comparing a national sample of 796 high-frequency (daily during the previous month) and 855 low-frequency (1—10 days during the previous

month) crack using women, high fequency users were more likely to be

infected with HIV (14.2% vs 5.8%), had six times the number of sex part- ners (13 vs 2.4), were more than three-fold as likely to have sex while high, were nine times more likely to trade sex for drugs or money, and were

about 50% more likely to have had unprotected oral sex, as compared to low-frequency users. (Klein, 1997)

us. DeP.WTMENT of HE.U.TH AND HUMLAN SERVICES, HEALTH RESOURCES AND SERVICJiS .ADMINKSTRAnON, HIWAIDS Bi RI.M 293
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It is likely that one of the most important interventions for preventing

further HIV transmission in the seropositive woman who continues to use

crack is substance abuse treatment and needed psychiatric and other concrete services.

Women IDUs frequently borrow injection works or follow as a second

user with shared needles, increasing the risk of HIV transmission: • New York neighborhood with high HIV seroprevalence: Among 286

women IDUs who had been injecting drugs an average of 14 years

and on an average had injected 55 times/month during the past 12

months, 48% reported having borrowed used injection works. Being

African American and having more than one injecting male sex partner

in an average month during the past year was significantly (p< .05)

associated with borrowing used needles. (Abdul-Quader, 1993) • San Francisco Needle Exchange Programs: Among 150 female IDUs,

younger women (< 30 years) were more likely to be Caucasian, have an IDU parent, start injecting at an early age and more likely to share needles and inject second when sharing with a main parmer (74% vs 38%). (Lum, 1998) Needle exchange programs have been found to be

effective in preventing HIV exposure and reducing transmission of

HIV among injection drug users.

HIV-positive women with substance abuse problems have high utiUzation of emergency services, low utihzation of health services, and

HIV-positive women in general tend to have lower rates of utilization

of antiretrovirals and OI prophylaxis.

Seropositive individuals who use drugs are more likely to be without a primary care provider and use emergency medical services than people with

AIDS who do not use drugs. (Mauskopf, 1994) Injection drug users either

tend to delay initiation of treatment (Broers, 1994), or have less access to

antiretroviral medications as a group. (Shapiro, 1 999) In women with < 200

CD4/mm^, at a baseline visit, utilization of antiretroviral medication was

only 49%, and prophylaxis for opportunistic infections, 58%. (Solomon,

1996) People who use injection drugs are often not diagnosed as HIVpositive until they are symptomatic. (Hu, 1 994)

III. NEED FOR MULTISERVICE CLINICAL PROGRAMS

As the above discussions indicate, many HIV-positive women have multiple

diagnoses, and require a variety of services to be adequately supported

through this illness. Many HIV-positive women are living in poverty or as sex workers, often while still addicted to drugs. A large percentage of seropositive

women are also struggling with the multiple sequelae of childhood sexual

abuse and may have formal psychiatric disorders.

us. Dervrtment of Health and Hunlan Services, He.alth Resources and Servtces Administr,ation, HR7AIDS Bure.au
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The varied needs of these HIV-positive women will generally require specific multiservice program components and care provider training as Listed

below for good comprehensive care. Common cHnical issues for these diverse

subpopulations of HIV-positive women with complex histories and comorbidities can be managed best through such programs, which are responsive to

both their clinical and concrete needs. Some of these services may be available

through community-based AIDS service organizations and require close coordination with medical care.

( )ptimally, treatment for formal psychiatric and substance use disorders,

which will be discussed below, would be available on site (Kobayashi, in press)

and be integrated with primary medical care. Savings from emergency room

visits and hospitalizations prevented help offset the labor intensive costs of

these muldservice programs; if a broad array of services is not provided for

these populations with such a complex layering of needs, routine medical care

will generally be complicated by intermittent foUow-up, medication non-adherence or frequent presentations in crisis in emergency room settings.

Table 9-3: Multiservice Clinical Program Components

Common Clinical Issues FOR HIV-positive Women Clinical Program Response

lack of trust; fears of

abandonment

continuity of care; non judgmental attitude;

patience; female providers

chronic low self-esteem respect, acceptance, listening, time

complex personal situations multiservice coordination: housing; transportation;

vocational rehabilitation and education; linkage to entitlement programs

responsibility for children and

others in household

childcare, respite programs; integrated

pediatric and women's care; permanency planning

and advance directives assistance

stigmatization awareness of care provider reactions; social

support groups

continuing high risk behaviors prevention education via the primary healthcare

provider

feelings of powerlessness;

lack of assertiveness and skills case management; outreach support; patient

education; new skills training

domestic violence;

exploitive relationships

women's shelters; domestic violence counseling;

legal aid; psychotherapy

substance use and psychiatric

comorbidities

psychiatric and substance tx programs integrated

with medical care

IV. PSYCHIATRIC DISORDERS

There are a number of formal psychiatric disorders among women with HIV

infection which require diagnosis and treatment. Women with HIV as well as women at risk for HIV have higher lifetime prevalence of major depressive

disorder, PTSD and borderline personality disorder than the general population. If women with these disorders do not receive appropriate treatment.

us. Department of Health and Human Services, Health Resources and Services Administr,\tion, I IIX’/AIDS Hi iki > 295
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their participation in medical follow-up or their ability to adhere to complicated medication regimes can be compromised.

Seropositive women with untreated psychiatric disorders which are associated with impulsive or self-destructive tendencies may also engage in high risk

transmission behaviors, potentially infecting others or being exposed to other

STDs themselves. Abuse histories frequently leave them susceptible to feelings

of learned helplessness or powerlessness in sexual situations which may result

in high risk behaviors, inability to negotiate safe sex, or engaging in sex for

drug exchanges. (FuUilove, 1992)

Women across cultures and around the world have lifetime incident rates of

major depressive disorders twice that of men. In the United States, the incidence of major depression in the general population is approximately

10—15%. (DSM-IV, 1994) Among a sample of 234 African-American men

who have sex with men (159 HIV-positive and 75 HIV-) and African-Ameri- can women (100 HIV-positive and 35 HIV-), there was a high prevalence of

anxiety spectrum disorders (38%) and mood disorders (23%) in both samples,

and signifcant rates of PTSD (50%) among the women. (Myers, 1999)

Major depressive disorders may be missed as care providers project their

own feelings and think “Td be depressed too, under those circumstances.”

Once diagnosed, these disorders are often undermedicated with doses of

antidepressant medication which are too low to insure a clinical response.

Substance disorders are sometimes missed as contributors to the depression,

and bipolar disorder is often not recognized when depression is the

presenting symptom.

There are a number of specific psychiatric issues for the clinician who is treating HIV-positive to consider. Women who are incarcerated have a higher

prevalence of psychiatric disorders and substance use disorders than women

in the general population or even men who are incarcerated . The chronically

mentally ill have higher rates of HIV than the general population in high sero- prevalence areas. (Cournos, 1991) Psychotic symptoms also need to be differentiated from delirium in any HIV-positive individual. Central nervous system

causes of change in mood and mental status should be ruled out. (The differential diagnoses of minor cognitive motor disorder, HIV-associated dementia,

and other CNS diseases such as cryptococcus, syphiUs, herpes, CNS lymphoma, progressive multifocal leukoencephalopathy, toxoplasmosis and other

conditions are beyond the scope of this chapter.) Although initial rates of suicide were much higher than in the general population in the early days of the

epidemic, it is likely that these rates are decreasing. (Marzuk, 1997) Suicidal

ideation may be used defensively, as a reminder that the individual stiU retains

ultimate control over their illness; these cases should be differentiated from

those individuals who are actively suicidal.

Some of the clinical misperceptions which get in the way of evaluating

these disorders are listed below, along with reminders for the complete assessUS. Department of Health and Human Services, HealTM Resources and Services Administration, HLV/AIDS Bure.\u
Guide to Clinical Management of Women with

Psychiatric Issues

merit. For the complete diagnostic criteria of each disorder, see the DSM-W

of the American Psychiatric Association. (DSM-IV, 1994)

Table 9-4: Common Clinical Misperceptions Regarding Psychiatric

Issues

Psychiatric Issue/

Disorder CuNiCAL Misperceptions Remember to Ask About

Major

Depression

"Anyone would be

depressed or grieving,"

forgetting biologic

depression

Vegetative symptoms (early AM

awakening, diurnal mood variation,

appetite disturbance); anhedonia more than sadness

Bipolar Mood

Disorder

"Depressed mood must

mean depression,"

forgetting bipolar sx

Hypomanic/Manic sx (hx of racing

thoughts, hyperactivity, no need

for sleep,grandiose plans, irritability)

Psychosis "The patient seems

normal," forgetting

hallucinations and

paranoia

Psychotic sx: "Do you ever hear

your name called, turn around and

no one is there? or a phone ringing?"

"Ever feel like people are talking

about you walking down the street?"

Delirium "The patient is clearly

schizophrenic or psychotic" forgetting

acute medical etiologies

Distractibility, Disorientation,

Dysarthric speech; Inability to sustain, focus attention;

misperceptions; mumbling or muttering

Sexual Abuse/

Assault Hx

"Too personal; may

embarrass or offend"

"Were you ever sexually, physically

abused in childhood? Assaulted as an adult?" Do not ask details.

Anxiety, Panic,

Agoraphobia

"Must be drug-seeking";

"Anyone would be

anxious"

Panic sx,sense of Doom, Tachycardia

repeated episodes, impairment of

function; avoids crowded places

Domestic

Violence

"Seems like a nice

person"

"Is there anyone in your life now or

in the past who makes you feel unsafe?"

Suicidal

Ideation

"May plant the thought

in their mind, provoke it" "Have you ever felt like hurting orkilling yourself? Have a plan?" Have

the means?

V. DIAGNOSIS OF MAJOR DEPRESSIVE DISORDER

The diagnosis of a major depressive disorder should focus on “anhedonia,” or

the loss of pleasure in all activities, rather than sadness alone. The sadness of

grief, for example, can be as profound, but is often accompanied by moments

of pleasure or even laughter as the most acute grief subsides. Sadness from

other sources, such as major disappointments, is also responsive to environmental change such as an enjoyable activity, and the mood would be quickly

reversed if the source of the disappointment were to change. This is not the case in a major depressive episode, where the world has no joy regardless of

the actiAUty or turn of events, where the oudook is gloom and doom regardless of the Likelihood of positive events, and where there can be obsessive

rumination on past wrongs or regrets which are impossible to balance w’ith

any feelings of accomplishment or hope. The mood is often worst in the

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I^sychiatric Issues

morning, whereas the sadness of adjusting to difficult or stressful events tends

to worsen over the course of the day and the new day is often filled with more

hope. Hopelessness indicates severe depression and is the most consistent

predictor of completed suicides; suicidal ideation is associated with both

depressive and bipolar mood disorders.

In addition to depressed mood and anhedpnia, often with a sense of hopelessness, there are a variety of vegetative or biologic symptoms which should

be explored: low energy and psychomotor retardation; sleep disturbance

(hypersomnia or insomnia), frequently with early morning awakening around

2:00 AM to 4:00 AM; appetite disturbance (hyperphagia or hypophagia) usually

accompanied by loss of appetite and enjoyment of food regardless of the

amount actually consumed; constipation may occur. Finally, there may be cognitive changes such as decreased attention and concentration (see Table 9-5);

social withdrawal and tendency toward isolative behavior; preoccupation with

guilt or regrets; obsessive rumination; diminished range of affect; uncharacteristic irritability; and increased use of substances of abuse. A family history of

mood disorders is often present. In the most severe cases, psychotic symptoms such as delusions and hallucinations can be present. The fact that there

Table 9- 5 : Differential Diagnosis of Major Depressive Disorder

(MDD)

Disorder Differentiated from MDD by:

Bipolar

Disorder

Racing thoughts, increased energy, decreased need for sleep

irritability, hypersexuality (these may coexist with depressed mood

in a mixed Bipolar state)

Grief Onset associated with the loss; responsive to changes in the

environment with less sadness or enjoyment; decreasing severity

overtime; preoccupation with deceased; "psychotic" symptoms

related to deceased such as seeing, being visited by the deceased;

rare suicidal intent although reunion fantasies may exist

Adjustment

Disorder

with

Depressed

Mood

Sadness is rarely as profound; little anhedonia; no vegetative

symptoms; identifiable precipitant; responsive to environmental

change; suicidal ideation and intent may still occur

Organic

Mood

Disorder

Identifiable agent linked by time; less anhedonia or hopelessness;

test for specific medical conditions such as TSH, B12, VDRL CNS

evaluation; no family history

Dementia Less concern re: cognitive decline; more gradual changes; may

respond with laughter; worse at night; specific neurological deficits; CT scan often abnormal

Delirium Fluctuating mental status with altered level of consciousness;

distractibility; inability to focus or sustain attention; dysarthric

speech; agitation; medical etiology

MedicationInduced

SubstanceInduced

Mood

Disorders

Onset with use of: steroids, anticholinergics, sedative-hypnotics,

anticonvulsants, antiparkinsonians. Beta-blockers, anti-TB meds;

sympathomimetics; Azidothymidine, Stavudine; all illicit drugs;

urine tox screen; medication history

us. DeparTMent of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
Guide to Clinical M,\nagement of Women with HIV

Psychiatric Issues

is a constellation of depressive symptoms which develop together over a course of weeks or months helps differentiate major depressive disorders

from similar disturbances related to medical illnesses.

VI. PSYCHOPHARMACOLOGY FOR THE HIV-POSITIVE

WOMAN: GENERAL GUIDELINES

There have been numerous studies indicating that psychotropic medications

are safe for HIV-positive individuals, and do not adversely affect the immune

system. While specific medications and dosing will be discussed later, the fol- lowing general guidelines should be kept in mind when approaching psychotropic medications with the seropositive woman:

“Start Low, Go Slow”: Low dosing, slow upward titration as with geriatric

patients.

“Always expect the unexpected”: HIV-positive patients often experience

unusual side effects; or common side effects at low doses; or complicated

drug-drug interactions.

“Dynamic Monitoring”: Changes in weight, metabolism, other medications, or medical iUness episodes require frequent updating and reevaluating

dosing ranges.

“Interdisciplinary Coordination”: Psychiatrists should be in regular communication with primary healthcare providers, and vice versa, about clinical

updates, dosing changes, major medical events.

“Suspect Substances”: Depression may be complicated by alcohol, anxiety by withdrawal syndromes, mania by psychostimulants; patients often

forget that, when their consumption has decreased, their CNS sensitivitiy to

the effects of these substances increases over time.

Amplify psychotropic medication adherence with medication boxes,

simple regimes, written instructions, coordination with antiretroviral therapies and patient education.

The primary Cytochrome P450 systems at issue for psychiatric medications are Cyp2D6 and Cyp3A4. The major Cytochrome P450 drugdrug interactions to keep in mind are: ritonavir may increase levels of

benzodiazepines, desipramine and selective serotonin reuptake inhibitors

(2D6), or nefazadone (3A4); venlafaxine (and St. John’s Wort) may decrease

indinavir concentration; nevirapine may decrease methadone levels; methadone increases zidovudine levels; valproate increases the level of zido\oidine.

(See Chapter Chapter XIV on Pharmacologic Considerations in HIVinfected Pregnant Patients for more information re: drug-drug interactions)

While a complete discussion of psychotropic medications (including complete side effect profiles) is beyond the scope of this chapter, the following

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medications are useful for the practitioner wishing to initiate psychotropic

medications, with dosage ranges for common indications. (Modifed from

Schat2berg, 1998)

Common potential side effects of all of the antidepressant medications

include agitation, irritability, sedation, sexual dysfunction, weight gain,

headache, gastrointestinal distress, dry mouth and potentiation of mania. Side

effects of antipsychotics include cognitive slowing, the extrapyramidal symptoms of dystonia and akathisia with long-term risk of dyskinesia; with the newer “atypical” antipsychotics, hyperprolactinemia may occur and with olanzapine in particular, significant weight gain. There are discontinuation synTable 9-6: Common Psychiatric Medications

Disorder Medication(s)

Major Depressive

Disorder

(with or without anxiety)

Sertraline (Zoloft) 25-200mg (SSRI)

Fluoxetine (Prozac) 10-80mg (SSRI)

Paroxetine (Paxil) 10-50mg (SSRI)\

Citalopram (Celexa) 10-40mg (SSRI)

Venlafaxine (Effexor-XR) 37.5-225mg

Buproprion (Wellbutrin-SR) 50-300mg ; in divided

doses

HIV-related Depression/

fatigue (with or without

Minor Cognitive Motor

Disorder)

Methylphenidate 10-80mg in divided doses

Bipolar Mood Disorder Valproate/Valproic Acid (Depakote) 500-2000mg,

titrated by blood levels (50-100 micrograms/ml)

Lithium Carbonate 600-1 800mg titrated by blood

levels (0.6-1 .OmEq/L)

Psychotic Symptom

(also severe PTSD)

Olanzapine (Zyprexa) 2.5-20mg

Risperidone (Risperdal) 0.5-6mg

Quetiapine (Seroquel) 50-600mg

Anxiety Disorders

(also PTSD)

Buspirone (Buspar) 15-30mg in divided doses

Lorazepam (Ativan) 1-6mg in divided doses

Alprazolam (Xanax) 1-4mg in divided doses

Clonazepam (Klonopin) 1-4mg in divided doses

Panic Attacks Paroxetine (Paxil) 10-40mg

Sertraline (Zoloft) 25-200mg

Imipramine (Tofranil) 25-200mg

Alprazolam (Xanax) 1.5-4mg in divided doses

Lorazepam (Ativan) 3-6mg in divided doses

Insomnia Lorazepam/Clonazepam at night dose

Temazepam (Restoril) 15-60mg

Zolpidem (Ambien) 5-1 Omg

Trazadone (Desyrel) 25-1 OOmg

Alcohol Dependence Disulfiram (Antabuse) 250-500mg

Alcohol Withdrawal Tranxene 15-30mg q2-6hrs

Opiate Dependence Methadone 60-1 20mg

Opiate Withdrawal Methadone 5-20mg in divided doses, tapered by

5 mg/day

Clonidine 0.3mg in three divided doses; increase

to 2mg/day in divided doses

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure.\u
Guide to Clinical Management of Women with HIV

Psychiatric Issues

dromes with paroxetine and venlafaxine; these drugs should be tapered. Sedation and cognitive effects; tolerance, dependence and withdrawal syndromes,

including rebound anxiety, occur with the benzodiazepines (BZDZ), especially

with alprazolam.

Patients who require multiple medications, have severe side effects, have

multiple diagnoses, or are not responding routinely or at routine doses should

be referred for psychiatric evaluation.

VII. EVALUATION OF SUICIDE RISK

Women are significantly more likely to attempt suicide than men, while men

are significandy more likely to complete the suicide by a male:female ratio of

at least 4:1. Caucasians commit suicide at twice the rate of African Americans

and Hispanics. It is estimated that 90% of individuals have a psychiatric disorder at the time of suicide, 45-79% of whom have major depression. Fifteen

percent of individuals with a mood disorder commit suicide. (Buzan, 1999)

Women more commonly attempt suicide by overdose, while men use more

violent means such as firearms or hanging. Women who have few social supports, have been widowed or divorced, or who have a history of sexual abuse

are at increased risk for suicide. Women with children attempt suicide less fre- quendy. Any risk factor is increased by the presence of alcohol, psychosis or an organic mental syndrome.

As mentioned, it is likely that suicide rates are decreasing among HIV-positive individuals. This may be due to antiretroviral therapies which can improve

organic mood disorders and cognitive function (Ferrando, 1998), as well as increase longevity and hope.

Table 9-7 : Risk Factors and Considerations in the Evaluation of

SUICIDALITY

Significant Suicidal Ideation*

Specific Intent or Plan*; available means

Hopelessness*

Previous Suicide Attempts*

Depressed Mood, Mood Disorders*

Family History of suicide or Mood Disorders*

Schizophrenia, Psychosis (not necessarily command hallucinations)*

Organic Mental Syndromes*

Intoxication with Alcohol*, other Substances

Recent Major Loss, particularly through suicide

Preoccupation with death

Fantasies of Reunion through death

Homocidal Rage

Caucasian Race*

* These factors have been documented as risk factors for suicidality.

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In order to assess suicide risk, the clinician must inquire about it. This does

not increase the likelihood an individual will attempt suicide. The clinician

should practice a standard way of asking, such as “Have you ever had

thoughts of hurting yourself?” or “. . . of ending your Ufe?” or “Do you ever

feel that life is not worth living?”

VIII. CARE PROVIDER ISSUES

One of the most important relationships the seropositive woman has is the

relationship with her healthcare provider. The dynamics of this relationship can have significant impact on the experience of the individual HIV-positive

woman, and the woman will be affected not only by what the cUnician communicates about HIV disease and treatment, but by the way the information is communicated, and the manner in which the provider relates to the HIV-positive woman herself

Whether or not it is conscious, healthcare providers may experience different reactions to HIV-positive women than with seropositive men. As previously discussed, it has been estimated that one out of every three women in

the United States has experienced a sexual assault, from childhood sexual

abuse to rape. This is even more common among women in poverty where

the HIV epidemic increasingly resides.

Women who have been victims of abuse or assault may provoke a variety

of reactions in care providers, the most common of which is frustration and

disapproval of the substance use which many women use to distance themselves from their trauma. Male or female care providers may find it particularly

difficult not to be angry or put off with the substance using woman who is pregnant or who has children.

Providers may also coUude with the seropositive woman’s feelings of powerlessness and try to take control over things she can actually handle with sufficient support; protective concerns and anger at an abusing partner may

tempt the caring provider to cross professional boundaries and try to rescue

the patient.

The provider may feel anger when the woman’s sense of powerlessness,

particularly in sexual situations, results in submitting repeatedly to unsafe sex. They may unknowingly continue the trail of abuse by not allowing her concerns to be heard or with inadequate pain control, often in response to

provocative and insistent behavior on the part of the patient, which provokes

the clinician to try to assert control. It is important to stop to consider the

powerful drive for self preservation that leads women with few options to try

to neutralize or forget painful memories with drugs or alcohol. Pregnancy and

motherhood do not automatically erase these feelings.

As with other medical populations, nonadherence with medications or medical follow-up can be personalized by providers as lack of commitment.

us. Department of Health and Hlhvlkn Services, Health Resources and Services ADMiNiSTR,vrioN, HIV/AIDS Bureau
Guide to Clinical Management of Women with HIV

Psychiatric Issues

clinical failure or an affront to their good intentions, rather than adherence to

tlifferent priorities. Appointments missed to take care of children or because

of problems with transportation may be misinterpreted as not caring about

medical follow-up.

b'rank disregard or avoidance of medical treatment, on the other hand,

may be mistakenly excused without exploring the real meaning of the behaviors. (Areproviders often assume that a woman is missing visits because

she is overwhelmed with the care of her children, when she is actually angry

at a particular provider, or so frightened about the iUness that she avoids

treatment in order not to be confronted with it. Initiating multiple medications may be the point at which she is forced to break through the denial

and confront her illness.

For the woman health care provider, the experience of taking care of HIVpositive women can be both more rewarding and more depleting than general

medical or HIV care. Personal identification with the patient may work positively to increase empathy, or negatively to increase projection of one’s own

values and expectations on the individual. Female providers may also experi- ence amplified grief, through personal identification, concern for orphaned

children, or because of the death of a patient with whom they developed a genuine connection. Providers who are either prone to experience patient

deaths as their own clinical failures, or who have deep compassion for the suffering of their patients, may be vulnerable to experiencing professional burn

out, particularly if subjected to multiple, sequential losses.

REFERENCES

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borrowing injection equipment in female injecting drug users in New York City. Int Conf AIDS (2):822, 1993.

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4th Edition. Washington, DC, American Psychiatric Association, 1 994.

Barkan SE, Melnick SL, Preston-Marrin S, et al. The Women’s Interagency HIV Study.

The WIHS Collaborative Study Group. Epidemiology 9:117—125, 1998.

Batki SL, Eerrando SJ, Manfredi LB, et al. Psychiatric disorders, drug use, and medical

status in injection drug users with HIV disease. Am JAddictions 5:249-258, 1996.

Boland RJ, Moore J, Schuman P. The Longitudinal Course of Depression in HIVInfected Women. Psychosomatics 40(2): 160, 1999.

Boland RJ, Moore J, Solomon L, et al. Depression and HIV in Women: Prevalence and

Associations in a National Cohort. Psychosomatics 37(2):198, 1999.

Bozzette SA, Berry SH, Duan N, et al. The Care of HIV infected adults in the United

States. New EnglandJournal ofMedicine 339:1897—1904, 1998.

Broers RP, Morabia A, Hirschel B. A cohort study of drug users’ compliance with

zidovudine treatment. Arch Intern Med 154:1121—1127, 1994.

Brown GR, RundeU JR, McManis SE, et al. Prevalence of Psychiatric Disorders in l iarly

Stages of HIV Infection. Psychosomatic Medicine 54:588—601, 1992.

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Buzan R. Assessment and management of the suicidal patient. In Jacobson JL, Jacobson

AM.. Psychiatric Secrets. Philadelphia: Hanley & Belfus, Inc., 1996.

Centers for Disease Control. Estimated incidence of AIDS and deaths of persons with

AIDS, adjusted for delays in reporting, by quarter year of diagnosis/death. United

States, January 1985 through June 1987. HIV/AIDS Surveillance Report

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AIDS, adjusted for delays in reporting, by quarter year of diagnosis /death. United

States,January 1985 through June 1987. HIV/AIDS Surveillance Report

1997.

Cohen M, Deamant C, Barkan S, et al. Domestic violence and childhood sexual abuse in HIV-infected women and women at risk for HIV. AmJ Public Health

90(4):560-565, 2000.

Farmer P, Connors M, Simmons J, eds. Women, Poverty and AIDS. Monroe, Maine:

Common Courage Press, 1996.

Ferrando S, van Gorp W, McElhiney M, et al. Highly active antiretroviral treatment in HIV infection: benefits for neuropsychological function. y^l/D^ 12:F65—F70, 1998.

GiUigan, C. In a Different Voice. Cambridge: Harvard University Press, 1982.

Hoff RA, Beam-Goulet J, Rosenheck RA. Mental disorder as a risk factor for human

immunodeficiency virus infection in a sample of veterans. J Nerv Ment Dis

185(9):556-560, 1997.

Hu DJ, Byers R Jr, Fleming PL, et al. Characteristics of persons with late AIDS diagnosis in the United States. Am J Prev Med 11:114—119, 1995.

Kacanek D, Diaz T, Ward |W. Noninjection drug use and sexual risk behaviors of

women with HIV and AIDS — United States. Int Conf AIDS 11(1):252, 1996.

Klein H, Rodriguez-Crane SM, Hoffman JA, et al. HIV risk behavior involvement

among low-frequency and high-frequency crack-using women. Natl Conf Women

HIV 120, 1997.

Kobayashi and Standridge, in press. Lyketsos CG, Fishman M, Hutton H, et al. The Effectiveness of Psychiatric Treatment

for HIV-Infected Patients. Psychosomatics 1997.

Lum PJ, Guydish JR, Brown E, AUen R. Younger female injection drug users report

higher riskd for HIV and drug-related harm in San Francisco. Int Conf AIDS

12:382 (abst 23202), 1998.

Markowitz JC, Kocsis JH, Fishman B, et al. Treatment of Depressive Symptoms in Human Immunodeficiency Virus-Positive Patients. Arch Gen Psych 55:452—457,

1998.

Marzuk P, Tardiff K, Leon A, et al. HIV seroprevalence among suicide victims in New

York City, 1991—1993. J Psychiatry 154: 1720—1725, 1997.

Mauskopf J, Turner BJ, Markson LE, et al. Patterns of ambulatory care for AIDS

patients and association with emergency room use. Health Serv Res 29: 489—510,

1994.

Myers HF, Durvasula RS. Psychiatric disorders in African-American men and women

living with HIV/AIDS. Cultural Diversity and Ethnic Minority Psychology

5(3):249-262, 1999.

Nelson WL, Ferrando SJ, Stanislawski DM, et al. Childhood trauma, substance abuse,

and distress in HIV-infected women. Inti Conf AIDS U(2):429, 1996.

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Psychiatric Issues

Paonc 1), (Ailoir S, Shi Q, et al. Sex, drugs, and syringe exchange in New York City:

women’s experiences. 50(3—4): 109—114, 1995.

Shapiro Mh’, Morton SC, McCaffrey DF et al. Variation sin the care of HIVinfected

adults in the United States: results from the HIV Cost and Services Utilization

Siudy. JAMA 281:2305-2315, 1999.

Schatzberg AF, Nemeroff CB. Textbook ofPsychopharmacology. Washington DC: American Psychiatric Press, 1998.

Shayne VT, Kaplan BJ. Double Victims: Poor Women with AIDS. Women and Health

17(l):21-37, 1991.

Solomon U, Stein M, Flynn CP, et al. Service Utilization by HIV-1 infected women from

four United States urban centers: the HERS study. Int Conf AIDS 11(2):20, 1996.

Surrey )F. The ‘Self-in-Relation’: A Theory of Women’s Development. Work in Progress

Series, The Stone Center, Wellesley College, 1982.

Thompson AS, Blankenship KM, Winfrey J, et al. Improving health care utiliz ation and

access for drug-using women with or at risk for HIV infection in a correctional

facility and at needle exchange sites. HIV Infect Women Conf S19, 1995.

Weiss EL, Longhurst JG, Mazure CM. Childhood Sexual Abuse as a Risk Factor for

Depression in Women: Psychosocial and Neurobiological Correlates. Am J Psychiatry 156 (6): 816-828, 1999.

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syphilis infection among the rape victims in 3 US cities. The Multicenter Crack

Cocaine and HIV Study Team. Inti Conf AIDS 9(2):649, 1993.

Wyatt GE, Peters SD. Issues in the definition of child sexual abuse in prevalence

research. Child Abuse and Neglect \Q-.2?>\—2AQ, 1986.

Zierler S, Ftiingold L, Laufer D, et al. Adult Survivors of Childhood Sexual Abuse and

Subsequent Risk of HIV Infection. Am J Public Health 81:572—575, 1991.

us. Department of Health and Human Services, Health Resources and Services ADMiNis-mAnoN, HIV/AIDS Bureau 305
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X: Substance Abuse

Henry L Francis, MD and Victoria A Cargill, MD, MSCE

I. SUBSTANCE ABUSE

Substance use is more prevalent in the United States than most persons realize. Statistics described in the 1998 National Household Survey on Drug

Abuse (NHSDA) give the following picture on drug use in American men and

women. (NHSDA, 1998) Approximately 53% of the American population will use an illegal drug in their lifetime. It is estimated from the NHSDA data that

in the general population, 8.1% of males and 4.5% of women have used ille- gal drugs in the last month. Over the past year, 23.1 million persons Americans wiU have used an illegal drug. Only a fraction of drug using persons are

truly drug addicted (also called drug dependent). It is estimated that at there

are 4.1 million people who meet the definition of drug addiction, defined as compulsively continuing drug seeking and drug using behavior even in the face

of negative health consequences.

The general rates of legal drug addiction dwarf the amount of illegal drug

addiction. In 1998, 113 million persons reported consuming alcohol in the last 30 days and 64 million persons consumed cigarettes. At least 43 million of the

alcohol consumers are dependant on alcohol through binge or very heavj'

drinking. The alcohol dependant indi\tiduals are more than twice as numerous

as the number of illegal drug users combined. In contrast to illegal drug use

rates where twice as many men use illegal drugs than women, alcohol con- sumption rates are nearly equal for men (59%) and women (45%) in the general population. However, women were much less likely to be binge drinkers.

Regular use of cigarettes, nicotine dependence, was nearly equal for men and

women, 29.7% vs. 25.7 % respectively.

Unfortunately, the majority of substance dependant women and men, who

could benefit from substance abuse, and substance abuse related emotion/psychological and health treatment never receive any form of therapeutic intervention. In 1998, 846,000 substance dependent women needed clinical health

care, 1.6 million women needed emotional/psychological treatment and more

thanl.7 million women needed substance abuse care. Yet only 390,000 of all three groups of women combined received any care at all.

This chapter will focus on addiction as a disease, discuss associations with a variety of comorbid conditions, review the epidemiology of substance abuse

us. Der\rtment of Health and Human Services, He.\lth Resources .knd Servicils .^dminis'j'r.vtk >n. HUV.Mn.s Hi ri ai' 307
A Glide to the Cunicll Cvre of Women voth H1\’

Substance Abuse

in the United States, and outline ways to identih' and treat substance abuse

in women.

II. EPIDEMIOLOGY OF SUBSTANCE ABUSE

The frequency and danger of drugs and beha\*iors of drug use are gready

underestimated by the American public and health care professionals. The two

commonly used legal drugs, alcohol and tobacco, are more frequently con- sumed than all the illegal drugs combined (Table 10-1). Marijuana, and cocaine

(including crack cocaine) are the most frequently used illegal drugs. Inhalants

are used predominately by

adolescents. A more recent

trend in adolescents is to use

club drugs like gamma-hydroxybutyrate (GHB), Ecstasy

(MD^L\), Roh}-pnoL, Ketamine, methamphetamine and

LSD at all night parties called

“raves” or “trances”. Surprisingly, heroin, which is viewed

as a highly prevalent drug is actually one of the least

favored drugs of preference in

the U.S. population.

The rates of illicit drugs used vary by slightly by ethnicity and in a major

way bv gender. Estimates for the gender specific drug use indicate that women

are at least 50% less likely to use illicit drugs compared to males. The male to

female illicit drug use rate relationship is consistent thorough out aU ethnic

groups (Table 10-2).

However, x\frican

American males and

females have higher

rates of illicit drug

use than X'Hiite

Americans and Hispanic Americans.

Ethnic comparisons

of drug used demonstrated that the highest rated of drug use

occurs in the adolescents, aged 18—25.

The males in all 3

ethnic groups are comparable though

Table 10- 2 : Illicit Drug Use Estimates by Age,

Gender, and Ethnicity in the U.S.

Age

Percent U.S. Population

White Hispanic

African

American

12-17 10.3 9.9 9.9

18-25 13.6 11.1 17.1

26-34 7.1 5.4 9.4 > 35 3.2 3.5 4.8

Male 7.7 7.7 12.0

Female 4.5 4.5 5.2 Source: Adapted from Summary from the 1998 National Household Survey on Drug Abuse, DHHS, SAMSHA.

Table 10- 1 : Prevalence of Drug Use

Drug Current Users Estimate

Alcohol 113,000, 000

Tobacco 64,000,000

Marijuana 11,000,000

Cocaine 2,187,000

Hallucinogens 1,500,000

Inhalants 713,000

Stimulants 633,000

Opiates 180,000

Source: Adapted from Summary from the 1998

National Household Survey on Drug Abuse,

DHHS, SAMSHA.

C. S. Dep.\kivent of He-U-th ,\nd Hlvas Services, He-Mth Resocrces .\nd Sermces ,\dministr.\tion, HT\VAIDS Bltie.\u
A Guide to the Clinic.\l C.\re of Women 'ktth HW

Substance Abuse

African Americans

are to be more likely to use drugs past the

age ol 26.

White American

men and women

have higher rates of

alcohol use than

African Americans or Hispanic Americans

(Table 10-3). For all alcohol using groups,

alcohol consumption

is highest in adolescents. White Americans have a notably higher rate of

chronic alcohol consumption after the age of 26 than Hispanic or African

Americans.

Table 10-3: Alcohol Use Estimates by Age,

Gender, and Ethnicity in the U.S.

Age

Percent U.S. Population

White Hispanic

African

American

12-17 20.9 18.9 13.1 18-25 65.0 50.8 50.3

26-34 65.2 53.1 54.8 > 35 56.2 47.7 38.3

Male 61.2 56.8 49.0

Female 49.2 33.6 32.3

III. CO-MORBIDITY RELATED TO SUBSTANCE ABUSE

Substance abuse is associated with a number of medical consequences, as well

as co-morbid conditions. Some of these are listed in Table 10-4, and include

the hepatitis’s (A, B, C, D and G), sexually transmitted diseases (STD’s), tuberculosis and trauma. These represent conditions associated directly and indirectly with substance use. Not only does the abuse of psychoactive substances

cause a significant number of accidents, but excessive alcohol intake places

users at risk for cirrhosis, malignant disease, neurological disorder, neuropathy

and psychiatric disorders. Intravenous

drug use is a major

factor in transmission of certain infectious diseases.

Smoking of drugs is the most common

cause of bronchial

carcinoma, other

malignancies and air- way diseases.

Underl}ing medical conditions, such as depression or other mental disorders may influence initiation or continuation of substance use (“self medicating” depression). The prolonged use of drugs in this setting can exacerbate,

rather than improve these problems. Female drug users, as a group are more

likely to suffer from depression and anxiety disorder than the general population, or other medical groups. The strong association between drug use and

Table 10-4: Medical Conditions and Sequelae

Associated with Substance Use

HIV Cellulitis STDs Thrombophlebitis

Tuberculosis Poor nutrition

Hepatitis (A, B, C, D, Pneumonia

and G) Cutaneous abscesses

Endocarditis Cognitive Dysfunction

Alcoholism

Liver Disease

Septic Embolic

us. Dep.\rtment of He.\lth .\nd HU^L^ Services, He.\lth Resources ,\nd Services Admimstraiion. HIWAIDS Hi ri m 309
A (JuiDi; TO Tin; (j.inicai. Cari; oi-' Womi;n wrni HIV

Suhsrance Abuse

mental health disorders is evident in environmental and genetic predisposition

to acidictive, impulsive and compulsive behaviors and personality disorders. A

conservative estimate is that 53% of drug abusers have one or more mental

health diagnoses. Successful treatment of the drug addiction is unlikely until

their mental illness is treated.

The cognitive effects of drug use may result in unrecognized disease exposure. These cognitive effects include impaired decision-making or a reduced

ability to understand or evaluate one’s actions. Drug effects, such as disinhibition, are known to decrease compliance with safer sex precautions or drug

paraphernalia hygiene. Crack use is associated with high-risk sexual behavior,

other drug use, and the exchange of sex for money and/or drugs. Although

IDU-related HIV transmissions is most closely associated with the sharing of

injection equipment, a significant portion is related to sexual risk. Sex and

drug related HIV risk behaviors are strongly associated in women. Women

acquire HIV, Hepatitis B and STDs through sexual partnerships with injection

drug users. Prevention intervention strategies for women at risk must include

both contextual relevance (e.g. dealing with an IDU sexual partner) and real

world appropriate planning like condom use strategies in the setting of

drug/alcohol intoxication. Also important are treatment and prevention of co- morbid conditions Hke STDs and Hepatitis C, which facilitate sexual and perinatal HIV transmission.

Signs and symptoms of drug addiction, HIV and other infectious or medical diseases often overlap, complicating surveillance and early identification

efforts, as well as care. Cognitive dysfunction, neuropathy, liver disease, and

various infections may be caused by drug use or co-morbid conditions, complicating appropriate and timely diagnosis and management. Among IDUs,

important presenting symptoms include thrombophlebitis, endocarditis, pericarditis, septic emboh, cellulitis and pneumonia.

Although women have lower rates of drug use than men, they are more

likely to become infected with HIV and other infections by their own drug use

habits and sexual contact with their partners. About sixty percent of AIDS

cases in women are drug-related. Although minority groups constitute about

26% of the U.S. population, about half of drug-related female AIDS cases are among black women, for whom AIDS has been the leading cause of death

since 1993. (Krieger, 1997) Co-morbid diseases among HIV infected drugusing women are likely to occur more often and progress more rapidly, complicating treatment. Drug use and related co-morbid conditions influence a number of other health outcomes in HIV+ women, including mortality and

maternal fetal HIV transmission.

In both substance abuse treatment programs and primary care cUnics,

strategies are needed to identify and manage HIV and other co-morbid problems like tuberculosis, sexually transmitted diseases (STD), Hepatitis B and C,

as well as mental health and social/economic problems.

us. Department of Health and Hunun Services, He.alth Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical C.\re of Women with

Substance Abuse

l^rimary care providers are uniquely positioned to identify early indications

of drug-use related HIV risks and signs of other comorbidities and to engage

drug users in treatment at earlier stages of drug dependence. New and younger

initiates to injection drug use engage in particularly high-risk behaviors for

acquisition and transmission of infectious diseases and HIV. (Carneiro, 1999) In

primary care settings, interventions can be put in place to prevent further trans- mission (Anderson, 1996) of HIV or other infections. Misconceptions about

the legal, social and health implications of testing positive for HIV reduce early

detection efforts, are particularly among patients at high risk. (Harvey)

IV. SUBSTANCE ABUSE IN WOMEN

Women have different risk factors for initiating drug use, require different

diagnostic approaches to detect drug use and should have treatment plans and

care sites which address their personal, social and familial needs. Historically

however, most treatment and diagnostic paradigms for addiction treatment were based on experience in treating male users. Stigma, family circumstances,

community emtironment and social status affect the treatment of substance

abuse, especially for women. Very few facilities accommodate women who are pregnant or have small children. It is now clear that care sites should be able

to address medical, drug use and H\ting circumstance problems simultaneously.

The relationship of drug use to the spread of infectious diseases such as HIV, can be challenging to assess, particularly when, as in many cases, no specific risk factor for exposure is reported. (Warner, 1995) It is possible that

pressures of stigma and fear associated with drug abuse may cause some indi-

\iduals, particularly women, to be reluctant in identi£}ting injection drug use as

a risk factor. For this reason, many women are not identified as having health or drug use problems until very late in the natural history of these diseases.

V. IMPACT OF SOCIETAE PERCEPTIONS AND BELIEFS

There are numerous social, moral, personal and situational beliefs adversely

affecting a drug using woman’s health. Historically, the U.S. society’s response

to drug addiction is punitive, stigmati2ing and prejudiced against drug users and their families. The negative public sentiment surrounding illicit and injection drug use is especially evident in criminal justice sentencing practices.

Health pro\tiders often share these views of drug users as unreliable and noncompliant. Value-laden judgments may impact provider willingness to treat this

population and influence the care provided and therapeutic regimens prescribed. Providers may be also being reluctant to raise the subject of substance

abuse or treatment with patients because of misconceptions about the effectiveness of treatment.

Women with substance abuse are more likely to experience poor health and

are less likely to access services, receive treatment or seek health care, partially

us. Department of Health and Hurun Services, Hevlth Resources -and Services .\DMiNisTRAnos, HU’/AIDS Hi ri 311
A ('jUIOk ro THU (j.iNiCAL Carf, of Womhn wi th HIV

Substance Abuse

because of the stigma of drug use. Suspicion, fear and distrust of the health

care system result in reluctance among drug users to disclose medically necessary information. Negative sanctions, such as mandatory HIV testing during

pregnancy and incarceration of drug using pregnant women for child abuse,

have intensified fears about contact with the health system. For economically

disadvantaged women with HIV and drug abuse problems, the fear of discrimination, retribution, loss of housing or loss of children may become more

important than seeking or engaging in health services (Sly, 1997) and may keep

them from receiving personally tailored prevention messages.

Individuals who are drug dependent, even though they may exhibit dysfunctional behavior, retain the right to be evaluated as individuals and to be

treated with respect and equality, regardless of conflicts in values or beliefs

between patient and physician.

VI. IDENTIFICATION OF SUBSTANCE USE

A. DIAGNOSIS BYHISTORY

Identification of substance use can be a challenge, given the myriad of illnesses

it can mimic. However, the biggest barrier to identification is denial. Given the

stigma associated with substance use, as well as the stereotypes associated with

substance use, health care providers must entertain the diagnosis in all patients.

Substance use must be a diagnosis to be excluded in the differential diagnoses

of many medical conditions. Table 10-5 lists clues to a possible substance use

diagnosis. These clues include erratic behavior, agitation, disorientation, doctor

‘hopping’, child custody loss and frequent unexplained accidents.

Table 10- 5 : Clues to Substance Use

Medical History Behavioral Clues Social History Clues

HIV infection infection

Endocarditis

Hepatitis B or C infection

Septic Embolic

Septic thrombophlebitis

Agitation

Somnolence

. Disorientation

Erratic behavior

Doctor "hopping"

Frequent unexplained

accidents

Inability to retain

employment

Child custody loss

Seemingly unexplainable

financial difficulties

The diagnosis of drug addiction is made by taking a careful history of drug

use, as well as a directed medical and psychosocial history; performing a complete physical evaluation; and laboratory testing for the presence of drugs or

the complications of drug use. Providers must also be aware of the variable

duration of time drug metabolites are present in blood and/or urine. Hence, if the index of suspicion is high, a single negative lab result should not exclude

the diagnosis.

us. Department of Health and Human Services, He.m,th Resources and Services Administr.\tion, HIV/AIDS Bureau
A Guide to the Clinical C.\re of Women with HR’

Substance Abuse

The most commonly used instruments to detect and assess drug and alcohol use are the CAGE survey, the Diagnostic and Statistical Manual ofMental

disorders. Fourth Edition (DSM IV) substance abuse diagnostic criteria, and the

Addicdon Severity Index (ASI).

I f the provider cannot get a sense of the patients drug use from unstructured questions, the CAGE survey offers a non-threatening alternative

approach. The CAGE survey is a four-question format intended to be used in

primary care and other non-substance abuse-related health care facilities.

1. Have you felt that you ought to Cut down on your drinking or drug

use?

2. Have people Annoyed you by criticizing your drinking or drug use?

3. Have you ever felt bad or Guilty about your drinking or drug use?

4. Have you ever had a drink or used drugs first thing in the morning

(Eye opener) to steady your nerves, get rid of a hangover, or to get

the day started?

This Rq3e of screening test though simplistic is very useful for getting substance addicted patients into a trajectory for drug use care. Otherwise, they

may be seen in different parts of the health care system for other problems,

while the substance abuse is not addressed.

Finally, some patients will come to medical attention due to substance

intoxication or withdrawal. As with substance abuse, entertaining the diagnosis, as well as recognition of the constellation of signs and symptoms is critical to recognition of intoxication and withdrawal syndromes. Alcohol intoxication

maybe characterized by inebriation, sedation, ataxia and slurred speech. However, this extreme of beha\tior is witnessed in a subset of patients of the 113

million Americans age 12 and older who reported alcohol use, 33 million

reported binge drinking (meaning they drank 5 or more drinks on one occasion 5 or more days during the past 30 days). (SAAIHSA, 1999) Alcohol withdrawal can vary from agitation, to the more florid syndromes associated with

the delirium tremens. This includes labile blood pressure, autonomic instability,

Gsual hallucinations and death. It should be noted that delirium tremens is associated with a 10—15% fatality risk.

Opiate intoxication is associated with sedation, including somnolence or

‘nodding.’ There has been a resurgence in heroin popularity, with and esti- mated 81,000 new heroin users in 1997. (SAMHSA, 1999) Opiate withdrawal

is characterized by the loss of CNS depression. These signs include piloerection, vomiting, diarrhea, agitation, irritability^ and sweating. Cocaine, and its alkaline cheaper form, crack, are highly addictive. Intoxication with cocaine is associated with euphoria, as well as profound h}q)ertension (secondary to the

vasoconstrictive effects). Increased pulse rate and dilated pupils are also associated with cocaine intoxication. Cocaine/crack withdrawal is associated with

irritability, agitation, and mood liability.

us. DEP.\RTMENT of HE.ALTH .\ND HUMAN SERMCES, He.\LTH RESOURCES AND SERNHCES ADMINISTRATION. HIV’/AIDS B( 'Rl-AI 313
A C'lUiDi-; I'o rill' Ci.inicai. Cari; of Women wi ih HIV

Substance Abuse

The DSM IV criteria for drug addiction are developed for the 1 1 classes of

abused drugs and include 7 major criteria (Table 10-6). DSM IV criteria determine addiction by finding evidence of physical or psychological dependence on

a drug or tolerance to it, disruption of social life patterns, and disregard of the

negative medical consequences of using drugs. A person is considered to be

drug addicted if they fulfill 3 of the 7 criteria within the previous 12 months.

Table 10-6: DSM IV Drug Addiction Criteria

Presence of drug use withdrawal

Escalation of drug doses

Persistent inability to reduce or control drug use

Increased time obtaining the drug

Personal and business activities are reduced by drug use Development of drug tolerance

Knowledge of drug use's negative health and personal effects, yet continuing to use drugs

Source: Adapted from DSM IV, 4th edition, 1994.

The Addiction Severity Index (ASI) (Assessing Client Needs Using the ASI,

1995) is most commonly used to help health caregivers assess the severity of

the drug addiction in persons who are already determined to have a drug use problem and for whom a treatment plan must be developed. The ASI is a

detailed one hour assessment of environmental, historical, physiologic and drug

related factors contributing to that individual’s drug use. The specific areas of

evaluation include: drug and alcohol use, psychiatric problems, legal problems,

family/social issues, and employment/support concerns. Physical and psychological signs of drug use, and changes in medical and mental health status are

also assessed. The data accumulated by ASI information is useful for developing treatment plans that include lifestyle change goals. The ASI is also a useful

instrument for assessing progress at different follow-up points because it is time-based and yields quantitative composite scores for each problem area.

B. DIAGNOSIS BYLABORATORYAND CLINICAL

EXAMLNATLON

Substance abuse disorders are erratically diagnosed on physical examination

because of caregivers’ lack of interest or awareness of drug use symptoms or because the symptoms may be subtie. The majority of drug addicted persons

have jobs and lead a “normal” life, without the stereotypic dysfunction of

severe injection- and non- injection users. Cocaine snorting can be suspected

by seeing a damaged nasal mucosa; hypodermic marks or “tracks” suggest

injection drug abuse, although the absence of visible marks does not rule this out. The single most useful examination is of the eyes. Nystagmus is often seen in abusers of sedatives /hypnotics or cannabis. Mydriasis is often seen in

persons under the influence of stimulants or hallucinogens or in withdrawal

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Substance Abuse

from opiates. Miosis is a classic hallmark of opioid effect. Evidence of multiple

minor (or past major) injuries can also be a clue to possible substance abuse.

Drugs may be detected in almost any fluid or tissue in the body. The most

commonly samples for drug tests are urine, blood, saliva, hair, sweat and

breath samples. (Wolff, 1999) Urine testing is the most available and useful

testing format. There are test kits which may be used in offices and at home

and require simple collection of a urine sample. Urine test limitations however

are numerous. These limitations include the ability to detect only recent drug

use as seen in Table 10-7. Furthermore, the samples can be adulterated, drug

detection changed by the

acidity of the urine and it

is unable to quantitatively

analyze drug use. Blood

testing is available to many

caregivers but is more

expensive and more cumbersome than urine analysis. Blood testing is more

accurate at quantitative

detection of drugs in the

user. Saliva may also be

useful and correlates well

with drug levels in the

blood. However, to use

the saliva assay, complex

test standardization assays and calculations are needed to verify that saliva and

blood drug levels are comparable. Hair analysis is a more recent technology

which may be a future tool for drug detection. It has the advantage of detecting drug use over a 1 to 3 month period of time depending on a person’s hair

growth rate. The reasons that the test is not used widely are that cosmetic hair

treatments, i.e. hair bleaching, may change drug level results as well as other

factors such as hair pigmentation and hair growth rate. Sweat testing is another non- invasive test which is more useful for monitoring drug relapse during

drug treatment. It is designed to continuously monitor a person’s drug use over a period of time by placing a special absorbant pad on the skin. The pad

continuously collects microscopic amounts of sweat produced by the body

over time and is analyzed later for presence of drugs. Breath testing is commonly used to estimate the concentration of blood in a alcohol user and is a

reliable reflection of blood alcohol. In research settings, marijuana may also be

detected using breath testing. (Manolis, 1983)

Overall, The urine tests are the most reliable tests for clinicians to use. However, test results may be difficult to interpret for the inexperienced care

giver because the results may be confounded by secondary drug exposures,

chemical characteristics of the drugs to be detected, drug level variations in

Table 10-7: Duration of Drug Detection

Drug Duration of Detection

Alcohol 48 hours

Amphetamines 12 hours

Barbiturates 1 0-30 days

Valium 4-5 days

Cocaine 24-72 hours

Heroin 24 hours

Marijuana 3-30 days

Methaqualone 4-24 days

Phencyclidine (PCP) 3-10 days

Methadone 3 days

Sex, Food, Gambling N/A

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different body tissues and fluids and test method variations. Drug testing

properly used, is a useful adjunct to clinical and behavioral drug use assess- ment and a useful but limited drug use screening tool. Drug tests should not

be used as the sole criteria for detecting substance abuse but properly used is helpful during drug use, therapy and follow up.

VII. TREATMENT READINESS/HARM REDUCTION

Readiness for treatment involves a desire for drug abstinence. The motivating

factors for treatment readiness in women are most commonly associated with

difficulty in raising their children or in response to interventions by social

services departments. (Brady, 1999) Unlike men, women are more likely to

express their treatment readiness in non-substance use settings, especially in

mental health care sites. (Lex, 1991) For that reason, drug use readiness should

be evaluated in all health care settings for any drug.

For persons who are not ready for addiction treatment, caregivers can provide harm reduction interventions, aimed at reducing the damaging effects or harm resulting from risk behaviors and practices such as the sharing of

syringes and other drug injection equipment and/or unsafe sex practices

resulting from the use of drugs. (Des Jarlais. 1995) Comprehensive strategies

that can effectively target high risk populations consist of a hierarchy of risk

reduction approaches that, depending on the composition and needs of the

populations being served, may include needle exchange programs or community outlets providing condoms. (Sumartojo, 1996) Sexually transmitted disease

prevention programs, education programs, social and work skills building programs, health and drug use treatment health access programs should be provided through community resources. Programs targeting drug use populations

and sub populations are all useful in preventing diseases such as HIV, STDs,

Hepatitis and Tuberculosis and should eventually lead to encouraging the drug

user to seek help in stopping drug use. (Needle, 1997)

A patient’s history and behavior may be more predictive of treatment readi- ness and potential for engaging in care and adhering to therapeutic regimens

than provider judgments based on gender, racial or ethnic background. There

is a direct relationship between patient adherence with substance abuse treat- ment and the quality of the patient-physician relationship; however, the lack of

physician training in the care of injection- and other drug abusers and the negative attitudes about drug use pose significant barriers. (Laine, 1998)

VIII. TREATMENT OF SUBSTANCE ABUSE

A. TREATMENTPROGRAMS

The most effective treatment programs are comprehensive and multi-dimensional and can be effectively delivered in outpatient, inpatient, and residential

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A Guide to the Clinical Care of Women with HIV

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Table 10- 8 : Components of Drug Use Treatment

Personal Needs Treatment Needs

Family services

Housing and transport

Financial services

Legal services

AIDS/HIV services

Educational services

Medical services

Vocational services

Child care services

Behavioral therapy

Clinical and case management

Intake and processing

Treatment plans

Pharmacotherapy

Continuing care Substance use monitoring

Self-help/peer support groups

settings. In addition to behavioral (counseling, cognitive therapy or psychotherapy) and/or pharmacological therapies, the patient may need other medical

services, family therapy, family planning, violence prevention, parenting

instruction, vocational rehabilitation, and social and legal services (Table 10-8).

Treatment programs should also provide repeated assessments for HIV,

AIDS, hepatitis B and C, mberculosis, and other infectious diseases, as well as non-infectious diseases like diabetes and hypertension, and counseling and

referral for relevant mental health treatment.

The most successful treatment occurs when the environmental, social,

behavtioral, medical and addiction problems are found early and treated over

a long period of time (more than a year). Though it would be desirable to

detect and treat drug use early after onset, when patterns of drug use are more easily treated or modified (Coates, 1998), most drug treatment modalities

target more advanced stages of dependence, when medical or legal interventions are needed. Women’s drug use problems tend to occur at an older age

of onset and develop more rapidly than men. Women also learn of their

HIV infection and other co-morbid conditions much later than men. The

late diagnosis of drug use and other diseases often results in shorter survival.

The confluence of factors which complicate health care for female drug users underscores the importance of early engagement and retention of women

in care.

Effective treatment of drug dependence produces reductions in drug use by 40—60%, and significant decreases in crirninal activity during and after treat- ment, and increases full-time employment. Establishment of accessible care in

primary care settings offer countless opportunities to initiate prevention and

treatment interventions targeted to adults, adolescents and other population

groups at risk for drug abuse and associated problems. Easy health access for

women is particularly important since their motivation for drug use is most

often to cope with negative mood or anxiety. (McCaul, 1999) Providers should

be accessible and should monitor individual triggers for stress and levels of

stress sufficient to produce drug use complications or relapse.

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B. PHARMACOLOGICAL INTERVENTIONS

Today even the most severe physical withdrawal symptoms can be managed

with appropriate pharmacological treatments, reducing the emphasis on

physiologic dependency as the focus of treatment of drug addiction. Drugs

for alcoholics and sedative-hypnotic addicts are important for controlling and

preventing serious medical consequences of drug withdrawal while other

medications like methadone can help stabilize a patient and facilitate a return

to productive functioning. Other important pharmacological interventions

include the treatment of comorbid conditions common in drug using populations. Use of anti depressants in mentally ill drug users are as important as therapies directed to the effects of the drugs of abuse.

The pharmacological treatments for drug use are well known but not well

understood by many health care givers. There are several classes of medications which maybe used to treat, modulate or prevent drug use.

Opiate Addiction

opiate agonist drugs Like methadone, 1-alpha-acetyl-methadol (LAAM) and

buprenorphine are used as opiate substitutes for opiate-dependent addicts.

These 3 drugs, used to treat addiction, block the ability of the illicit drugs to

attach to opiate receptors therefore decreasing a person’s craving for the drug

without causing euphoria. This is the most misunderstood medical approach

to addiction treatment. Although methadone, LAAM and buprenorphine are

addictive, they are successful helping the addict stop their negative and harmful drug use associated behaviors and begin to concentrate on developing the

skills to discontinue drug use entirely. It is the drug craving which is associated

with drug use relapse and criminal behavior and it is its prevention that makes

substitution medications work successfully as part of a drug use treatment

program. Methadone suppresses withdrawal for 24 hours (four to six times the

duration of the effects of heroin) and decreases or eliminates drug craving; it

is not sedating and can be dosed once a day. Furthermore, it is medically safe even when used continuously for 1 0

years or more. LAAM is a newer synthetic opiate resembling methadone. LAAM can block

the effects of heroin for up to 72 hours with rninimal side effects when taken

orally. Its long duration of action permits dosing just three times per week,

thereby eliminating the need for daily dosing and take-home doses for weekends.

These substitution medications are not a cure for addiction but important

adjunct to care. It has been shown that while an opiate user is on methadone,

she is much less likely to commit a crime and more likely to succeed in completing a drug use program.. However, when combined with behavioral therapies or counseling and other supportive services, these pharmacologic

approaches are highly effective for treating heroin addiction, particularly in

those with long-term addiction.

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Substance Abuse

Antagonist medications like Naloxone and naltrexone block the effects of

morphine, heroin and other opiates. As antagonists, they are especially useful

as antidotes. Naltrexone, with a duration of action ranging from 1 to 3 days

depending on the dose, blocks the pleasurable effects of heroin and is useful

in treating some highly motivated indi\iduals, such as professionals who do

not want to lose their jobs. It is also successful in preventing relapse by former

opiate addicts released from prison on probation.

Alcohol Addiction

Antabuse (disulfiram) is used in alcohol abusers by causing negative side

effects when the patient tries to consume alcohol. The drug interferes with

alcohol metabolism, causing the production of acetaldehyde, a noxious chemical which causes severe flushing, nausea, and vomiting. The effectiveness of

therapy is dependent on patient adherence to a daily medication dose. Acamprosate (Putzke, 1 996) is a newer drug currently used in Europe W'^hich also

decreases the desire to drink alcohol by affecting gamma aminobutyric acid

and glutamate brain receptors causing decreased alcohol cra\ing.

Cocaine Addiction

There are no effective medications for treating cocaine addiction but in some

cases treating comorbid mental health problems may improve a cocaine or

crack addict’s chances of stopping cocaine use. Pharmacologic therapies have

been specifically targeted at decreasing the dysphoric effects of cocaine withdraw’al. Unfortunately, studies exarnining anti depressant medications targeting

numerous neuron targets and multiple generations of antidepressant medications such as fluoxetine, sertraline, maprotilene, phenelizine, trazodone and

lithium have not been proven successful in assisting a person in permanently

stopping cocaine or crack use. (McCance, 1997) Dopaminergic agents such as bromocriptine, amantadine, haloperidol, bupropion and others have also not

been proven to be effective. However, in a studies using desipramine, carbamazine and bupropion , the drugs’ effects on the mental health of the affected

patient were cHnicaUy helpful for a patient’s successful drug cessation in drug

use treatment program. (Kranzler, 1999)

Detoxification

Addiction detoxification is used to either prevent serious medical or psychologic complications of drug withdrawal from alcohol or sedative hj-pnotics or

is used to ease the symptoms of withdrawal from the other drugs which do

not have withdrawal syndromes with any significant morbidity or mortality (all other drugs of abuse). (Prater, 1999) In either case, detoxification protocols

are not treatments for drug use but are part of a drug use treatment strategy.

Detoxification of alcoholics and sedative ht'pnotic users will prevent severe and sometimes fatal complications of drug withdrawal. For alcoholics, chlordiazepoxide (Librium) sedation is an important part of patient therapy. In most

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cases, the treatment should be done in hospital settings and if a woman is pregnant, Librium shoulci not be used. Alternative medicadons especially for per- sons widi severe liver disease are lorazepam (Ativan), oxazepam (Serax) and

phenobarbital. In conjunction with the sedatives, thiamine to prevent WernickeKorsakoff syndrome and clonidine or beta blockers may be helpful to control

noradrenergic symptoms in individuals. Withdrawal from sedative hypnotics is characterized by severe, chronic anxiety which may need one year of controlled,

tapering doses of sedatives. Carbamazine (Tegretol) and valproic acid have also

be used to control anxiety in sedative-hypnotic patients. (Eickelberg, 1998)

Detoxification for other types of drug abuse are useful for diminishing the

symptoms of drug withdrawal but do not have any long lasting beneficial

effect on the drug user. For example, clonidine (Gold, 1979) and Lofexidine

(Bearn, 1996) are used in this way because they decrease the adrenergic symptoms of opiate withdrawals. These measures are short term and do not

address the true underlying problems of drug use. Even though the effects of

detoxification are only short term, it is one of the few drug use interventions

which is reimbursable in most health systems. (O’Brien, 1997)

New Pharmacologic Approaches

The combined use of antagonist-agonist medications has been evaluated for

drug treatment, with the biological objective of preventing activation of opiate

receptors with two medications blocking the activation of opiate and other drug

use- related cell receptors. Recent research has found that treating nicotine

addicted persons with mecamylamine prevents smoking relapse. (Rose, 1994)

This may be a useful adjunct therapy for persons in tobacco cessation programs.

Anticraving medications are used to prevent a person from wanting to take

the drug. The biology and psychology of craving and its prevention is not well

understood but it has been proven to be effective in treating addiction to nicotine. Buproprion (Wellbutrin), a anti depressant medication, has been successfully used to treat cigarette craving. (Ferry, 1999)

Vaccines against addictive drugs are intended to block the binding of illicit drugs to their cellular receptors. Though no vaccines are currently available for

human use, there is evidence that a vaccine against cocaine may be possible to

develop. Much future research is planned in this area. C COGNITIVE/BEHAVIORAL INTERVENTIONS

Behavioral and cognitive interventions are not as weU known as the pharmacologic approaches, but are a vital part of drug addiction treatment and prevention. Cognitive-behavioral therapies are based on the assumption that learning

processes play an important role in the development of drug use and dependence and therefore is important for efforts to reduce use and dependence.

Behavioral methods are employed to identify high-risk relapse situations, create an aversion to drug use, develop self-monitoring of use behavior, and

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A Guide to the Clinical Care of Women with HIV

Substance Abuse

establish competing coping responses. By learning to recognize situations conducive to drug use, patients can develop individual coping strategies to avoid

circumstances that place them at risk for relapse. Perhaps the single most

important factor for short- and long-term relapse prevention is the learning

and applicadon of individual coping skills. Avoidance of other drug users and

drug use environments are key tools for maintaining abstinence.

There are at least 11 research-validated therapies (Table 10-9) using a variety of behavioral, social, and incentive based systems to treat drug use. (Principles of Drug Addiction Treatment, 1999) The objectives of the different

programs include removing patients from stressful environments to get care

(short and long term residential homes); providing alternatives to pharmacologic treatment (outpatient drug free programs); and providing community

specific interventions (community based programs for drug users and recentiy

released criminals). There are several psychotherapy programs, based on the

patient’s willingness to recognize drug use as a problem and to stay off drugs,

with or without incentives.

Table 10-9: Non-pharmologic Drug Addiction Treatments

Supportive — Expressive Psychotherapy

Individualized Drug Counseling

Motivational Enhancement

Behavioral therapy for adolescents

Multi-systemic Therapy

Combined Behaviroal and Nicotine Replacement Therapy

Community Reinforcement Approach

Voucher-based Reinforcement Therapy (Methadone Maintenance)

Day Treatment with Abstinence Contingencies and Vouchers

Matrix Model

Source: Adapted from Principles of Drug Addiction, NIH publication No. 990-4180, 1999.

The 12 step self help drug use problems are important non medical,

behavioral drug use intervention and prevention programs which are used by

10 to 15 million Americans in 500,000 or more groups. (Goldsmith, 1989)

These programs emphasize fellowship and provide support for maintaining

drug abstinence from alcohol, other drugs or addictive behaviors like overeating. These programs are not intended to replace medical and behavioral drug

use treatments but are meant to add to their effectiveness. The largest 12 step

groups are AlcohoHcs Anonymous, Narcotics Anonymous, for all drug users including alcoholics, A1 Anon, to support family and friends of alcoholics and

drug users and Overeaters Anonymous. (Chappel, 1999) In 1976, Women for

Sobriety was established as a 12 step program to help women when it was rec- ognized that Alcoholics Anonymous did not address adequately the specific

needs of alcoholic women. (Katkulas, 1996)

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IX. PREDICTORS OF DRUG TREATMENT RETENTION

AND THE DURABILITY OF TREATMENT GAINS

Predictors of treatment retention include high motivation, legal pressure,

receiving psychological counseling while in treatment, no prior violations of

the law, and an absence of other psychological problems. (NIDA, 1998) Specific characteristics such as: IV drug use, age, race, socioeconomic stams, level

of education and occupation are actually poor predictors of adherence to drug

treatment programs. The most accurate predictors of drug program retention

and medication adherence are health care beliefs, health care access, familiarity

of the treatment setting, availability of social support, perceived support from

the cUnical staff, and simplicity of the treatment.

Provider and patient recognition of the chronic nature of drug addiction

and the need for treatment is essential to successful and durable addiction

care. It has also been recently shown that lasting reductions in drug use are greater for patients who remain in treatment for 3 months or longer (Drug

Abuse Treatment Outcome Study, 1997) and are treated with a combination of

medical, behavioral and cognitive treatments.

/ Available treatment options continue to expand, providing therapeutic

combinations that, when appropriately matched to patients’ specific treatment

problems, can increase the patient’s chances of staying drug free. (McClellan,

1997) Treatments taking care of a patient’s specific social and personal needs,

increases an individual’s chances of successfully completing the treatment program, and have improved post-treatment outcomes. Treatment for women that

is woman-focused and targets the unique needs of women, including their

children, interpersonal, cultural and contextual issues, and employment and

housing considerations are also known to increase effectiveness. (Metsch,

1995) Participation in these programs provides women with children to develop stronger Hfe and social skills to insure stable independent living practices. (Hughes, 1995)

X. RELAPSE

Drug addiction is a chronic disease characteri2ed by periodic drug use relapses.

Although many treated addicts relapse, it is wrong to conclude that treatment

has failed or that the addict is hopeless. Dke diabetes or hypertension, the individual with a substance abuse problem will need frequent and long-term fol- low-up to maintain a drug free state. Not surprisingly, simultaneous treatment

for co-occurring medical, mental health and drug use problems offers significantly higher rates of success. The interventions that successfully address co- morbidity maximize linkages between school, community, clinic and other

health service delivery systems. Woman- focused HIV prevention interventions

include overcoming gender, cultural and power barriers that increase risks, such

as learning negotiation strategies for gaining parmer acceptance for condom

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Substance Abuse

use, dealing with parenting responsibilities and interpersonal conflicts. The relati\-e success and durability of approaches that have multiple and mutually

reinforcing outcomes depends on coordination among professional and material resources in a rational, systematic, and cost-effective manner.

Treatment should be judged by the same criteria used for other chronic dis- ease interventions: Will it help lengthen the time between relapses, ensure the

individual can function in society, and minimize long-term physical damage?

XI. SUBSTANCE ABUSE IN PREGNANCY

It is difficult to determine the true prevalence of substance abuse by pregnant

women. Stigma, criminal laws regarding child endangerment and denial aU

contribute to the epidemiological conundrum. Cross sectional studies at large

urban center, given the high risk populations served, may overestimate community drug use health problems. In 1990, a Centers for Disease Control and

Prevention smdy in Rhode Island revealed a statewide prevalence of 6.5%. A

cross-sectional study the same year in Pinelen County in Florida revealed that

15% of unselected women had evidence of recent drug use. (Chasnoff, 1990)

Despite 1975 data demonstrating the improvement in women’s health and

pregnancy outcomes, punitive approaches td the problem of substance abuse

during pregnancy risk threatening privacy rights. This treat further serves as a deterrent to health seeking behavior, and may further threaten the health of

women and children.

The sequelae of substance use in pregnancy is beyond the scope of this

chapter, however, a few specific drugs will be highlighted.

Alcohol use in pregnancy is associated with fetal alcohol syndrome (FAS).

This congenital syndrome is characterized by 3 findings: growth retardation,

facial abnormalities, and central nervous system dysfunctions. Skeletal abnormalities strucmral cardiac defects are also seen in the FAS, but it is the performance deficits that are most obvious. Decreased IQ, fine motor

dysfunction and hyperactivity are aU common findings. (ACOG, 1994)

Cocaine use in pregnancy poses maternal as well as fetal hazards. Some of

these stem from the intense vasoconstriction associated with cocaine (malignant hypertension, cardiac arrthymias and cerebral infarction). Cocaine has

been associated with premature rupture of membranes, pre-term labor and

delivery, growth retardation, cognitive development delays and placental

abruption. There are also documented cases of in-utero fetal cerebral infarction. (MacGregor, 1987)

Opiate addiction during pregnancy also poses serious risk to the mother, as well as the fetus. Newborn infants of narcotic addicted mothers are at risk for

several complications, including the potentially fatal narcotic withdrawal syndrome. Withdrawal syndromes may appear 24 hours after birth, but may be

delayed as long as 10 days after birth. (Levy, 1993)

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XII. ANTIRETROVIRAL THERAPY IN SUBSTANCE

ABUSERS

There is often a lack of compassion toward people who have contracted HIV

through stigmatized behavior, such as drug use. (Hajela, 1998) Such sentiments

are compounded by perceptions about adherence among drug users and the

threat to public health associated with non-adherence leading to multi-drug

resistant strains of HIV or other infectious diseases. (Gourevitch, 1996) These

assumptions may lead to blanket denial of appropriate antiretroviral therapy to individuals with a past or current history of substance abuse.

Although active substance abuse (including alcohol, cocaine, or heroin) are associated with non-adherence, patient readiness for antiretroviral therapy must

be carefully assessed on an individual basis, and those who have been treated

for drug dependence may even be more adherent than the general population

or other medical groups. However, drug users are less likely to receive care, with IDUs being among the least likely to receive antiretroviral therapies even when these treatments are available and free. (Shapiro, 1999) In fact, active

IDUs may be up to 3 times less likely to receive HAART. (Carrieri, 1999)

XIII. CRIMINAL JUSTICE SETTINGS

Women are the fastest growing segment of the prison population, and their

drug-related crimes are increasingly more serious. (FBI, 1997) Criminal justice

reports show that substance use is implicated in the incarceration of 80% of

men and women in state, federal and local prisons. Persons either violated

drug laws, stole property to buy drugs, or have a history of substance abuse or

addiction, or engaged in some combination of the above. (Maruschak, 1997)

The more prior convictions an individual has, the more Ukely s(he) is to be

drug dependent.

The most serious offense for 40% of women in state and federal prisons is the violation of drug laws. The enactment of mandatory sentencing policies

has been associated with a ten-fold increase in the number of women incarcerated for drug crimes between 1986 and 1996.

Statistics show alcohol present in 31% of crimes, a combination of alcohol

and other drugs in 16%, and other drugs alone 8.8%. A recent study confirms

what many criminologists have long known: alcohol is associated with more

violent crime than any illegal drug, including crack, cocaine, and heroin.

Twenty-one percent of violent felons in state prisons committed their crimes

while on alcohol alone. Only 3% were high on crack or cocaine alone, and

only 1% were using heroin alone.

State officials have estimated that 70% to 85% of inmates need some level

of substance abuse treatment; however only about 13% actually receive treat- ment. (Harlow, 1997) Those individuals with substance abuse histories also

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A Guide to the Clinical Care of Women with HIV

Substance Abuse

liave an increased likelihood of a history of physical and sexual abuse.

(National Minority AIDS Council, 1997) Criminal Justice reports attribute the

overwhelming majority of AIDS cases among inmates to injection drug use, with an incidence of new AIDS cases among inmates 17 times higher than

that in the general population.

Inmates who have received appropriate treatment in prison are 50 to 60

percent less likely to be arrested again during the first 18 months after release.

I 'or each offender who successfully completes treatment and returns to the

community as a sober citizen with a job, it is estimated that reduced crime,

arrest prosecution and incarceration costs, health care savings and potential

earnings accrue in the first year after release. (CaHfano, 1998) One smdy found

that total savings can exceed costs by a ratio of 12 to 1, another that for every

$1 invested in drug treatment, there is a return of up to |7. Levels of criminal

activity have also been shown to decline by two-thirds from the period before

treatment to a comparable period after treatment.

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Gourevitch MN, Wasserman W, Panero MS, Selwyn PA. Successful adherence to observed prophylaxis and treatment of tuberculosis among drug users in a methadone maintenance ptogrxm. Journal ofAddictive Diseases. 1996 15:93—104.

Hajela R. The stigma facing drug abusers impedes treatment. CMAJ. 1998 May

19;158(10):1265-6.

Harlow CW HIV in U.S. prisons and jails, special report (NCJ-143292). Washington,

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Harvey D and Wyatt G. Study Tracks HIV-Positive Women’s Psychosocial Issues: Women and Family Project.UCLA and Drew University medical centers. Hughes, PH, Coletti, SD, Neri, RL et al. Retaining cocaine-abusing women in a thera- peutic community: The effect of a child hve-in program. American Journal ofPublic Health 1995 85(8):1 149-1 152. Katkulas LA. Pathways to Self Help among Women for Sobriety. Am J Drug Alcohol

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us. Department of Health and Human Services, Health Resources and Services ADMiNis-re-vnoN, HIWAIDS Bi ki-.ai- 327
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XI: Adolescents^

Donna Futtermany MD

Adolescence is a time of significant cognitive, emotional and physical development and is often characterized by exploration and experimentation. As adolescents explore intimacy, sexuality and develop autonomy, it is also a time of

heightened vulnerability, including risk for HIV infection. This chapter focuses

on young women as it reviews the epidemiology of HIV/AIDS in adolescents

and provides guidelines for HIV counseling and testing, medical and psychosocial care and strategies for Unking HIV-infected and at-risk youth to care.

I. EPIDEMIOLOGY

Adolescents are at high risk for HIV infection. Worldwide, one out of every

two new cases of HIV — half of 5.8 milMon new infections during the past

year — occurred in youth ages 1 5—24. In developing countries, women are becoming infected at significantly younger ages than men, with more young

women in their teens and early twenties becoming infected than women in

any other age groups. In the U.S., (CDC, 1999) more than half (53%) of

adolescents newly infected with HIV are female, and 25% of all new infections, or some 10,000 new cases per year, are estimated to occur in youth

ages 13 to 21. In addition, 19% of U.S. AIDS cases are reported in young

adults in their 20s. Given a ten-year period, on average, from initial infection

to cUnical manifestations of AIDS, most of these young people were Ukely

infected during their teens. Compared with adults, female adolescents represent a much higher proportion of HIV/AIDS cases. In 1998, adolescent girls ages 13—19 years

accounted for 51% of incident adolescent AIDS cases while female adults

comprised 23% of incident adult AIDS cases. Between 1988 and 1993, esti- mated HIV prevalence increased 36% among young women aged 1 8 to 22,

while dropping 27% among young men in the same age group. At highest risk are African-American youth, who comprised 58% of incident teen cases in

1997, while representing only 15% of the U.S. adolescent population.

' This article was adapted with permission from a 2 part series that appeared in the AIDS Clinical Care February and March 1999 issues: Chabon, B and Futterman, D. Adolescents and HIV. AIDS

Clinical Care 11(2):9—16; Hoffman ND, Futterman D, Myerson A. Treatment Issues for HIV+

Adolescents. AIDS Clinical Care 11 (3): 17—24.

us. Department of Health and Human Services, Health Resources and Servicils Administra-hon, HIWAIDS Hi iri-.m 329
A Guide to the Cunicu. Cari-: of Women voth HI\'

Adolescents

A. SEXUAL RISK

The majorin' of adolescent females (52%) with AIDS were infected through

heterosexual intercourse. Moreover, an additional 15—20%, who are classified as haAng “no identified risk” because they were unable to identifi’ their partners’ risk, are also assumed to have been infected through heterosexual

encounters. This is consistent with widespread lack of awareness of their

potential risk for HIV infection among sexually active adolescents and adult

women. For example, of adolescents known to be HIV positive, 75% of

young w'omen are unable to identifi’ their parmers’ risk factors. (Futterman,

1993) A much smaller proportion of female youth (13% of 13—19 year olds

and 27% of 20—24 year olds) were infected through injection drug use, compared with 44% of adult w'omen with AIDS. Adolescents w’ho were infected

perinatally account for a small but growing number of adolescents with

HR’^/AIDS, and some are not diagnosed until adolescence.

Clinicians w'orking with adolescents have noted additional risk factors for

youth. A significant proportion of adolescents with HI\^^ have experienced

childhood sexual abuse; of adolescents screened at the Adolescent AIDS Program (AAP) at Montefiore Medical Center, 25-40% report ha\'ing been sexually abused. (Futterman, 1993) Childhood sexual abuse has been associated

with subsequent feelings of powerlessness in sexual situations and increased

risk for unsafe sexual activity.

Moreover, 20% of sexually infected HIA'^T youth seen in an Adolescent

Program reported having a parent who is also HFV^-infected. (Chabon, 1997)

Further research is needed to assess parental influence on their children’s HFV

stams. Nevertheless, children of parents with HI\^ generally live in the same

high prevalence neighborhoods as their parents and may also face increased

risk as a sequela of parental illness, or substance abuse. Clinicians should

ascertain a histor}' of sexual abuse or forced sex as w'ell as parental HFV history w'hen taking a histon’ with adolescents.

B. SEXUALLY TRANSMITTED DISEASES AND PREGNANCY

Sexually active teens are also at risk for pregnancy and other STDs. According

to the 1997 Youth Risk BehaHor Suiw'ey, nearly half of all U.S. female high

school students are sexually active (including 62% of 12 graders), and 9%

report haA’ing been pregnant. (CDC, 1998) Approximately one million teens

become pregnant each year, 74-85% of them unintentionally Both STDs and

pregnancy are markers for unsafe sexual actiAiU' and, in addition, STDs (both

ulceratiA'e and inflammaton') increase susceptibilit}' for HIV infection. Twothirds of the 12 million cases of STDs reported in the U.S. each year occur in

youth under age 25, and 1 out of 4 are reported in adolescents. Younger teens,

particularly females, are least hkely to be considered at risk or to be screened,

particularly if they are asymptomatic, w'hich is the case with the majority of

STDs in women. For example, chlamydia is asymptomatic in three-fourths of

infected w'omen, w^hile approximately half of gonorrhea infections in w'omen

U.S. DEP.\KrMENT OF HE.U.TH .\ND HniL\N SERMCES, He.\LTH RESOURCES .VST) SERVICES ,\D.VfINISTR.VTIOS, HW/.UDS BCRE.VC
A Guide to the Clinical C\re of Women with PiR"

Adolescents

have n<i symptoms. This is especially salient since adolescent women have the

highest age-specific incidence rates for both gonorrhea and chlamydia; 79% of

reported cases of chlamydia occur in young women (46% in 15—19 year olds

and 33% in 20—24 year olds).

C HEIGHTENED VULNERABILITYEOR INFECTION

Adolescents are at risk for HIV and STDs as a result of the interplay betw^een

behaHoral, biological and socioeconomic factors. (lOM, 1997)

Behavioral Risk

During adolescence, sexual actiwty is often initiated, risk taking and experimentation are normative, and many sexually active adolescents fail to take appropriate prevention precautions, despite basic knowledge of HIV transmission and

prev'ention. During their last sexual encounter, nearly half of 9—12 grade girls

did not use condoms, while one 1 in 7 (14%) reported having more than 3 sexual partners. Many teens follow a pattern of sexual “serial monogamy” and

may not consider themselves as having multiple partners. Nearly 1 in 5 (19%)

reported using alcohol and drugs which can impair judgment and increase

potential for high risk behaviors. Most high school seniors have used alcohol,

and 1 out of 3 students report having five or more drinks at least once during

the past 30 days. More than 25% smoke marijuana, 16% report using inhalants

and nearly 1 in 50 have injected illegal drugs. (CDC, 1998)

Specific populations of teens are at especially high risk, including adolescents who are lesbian, bisexual and transgender, homeless or runawa}’, injection drug users, mentally ill and youth who have been sexually or physically

abused, incarcerated or in foster care. These youth experience increased vnlnerability and multiple health and social problems as a result of abuse and

neglect and lack of services and care. Lesbian and bisexual }"outh may view*

themselves at lower risk but those who are sexually activ^e with gay male peers

are at risk for infection due to higher HIV prevalence among gay males.

Biological Risk

Sev'eral biological factors also contribute to heightened risk in adolescent

females. During puberty, the cervix undergoes physical maturation that makes

the cellular Hning less susceptible to infection as the single-layer columnar

epithelium of the cervix is replaced with thicker multilayered squamous cells. Until this occurs, the cervix is much more vnilnerable to STDs, particularly

chlamydia and gonococcus, which have an affinity for columnar cells and have

also been shown to facilitate STD transmission. At the same time, male to

female transmission of STDs is much more efficient than female-to-male

transmission giv^en the larger surface area of the lower female genital tract and

mechanics of sexual intercourse, which can result in mucosal trauma to

women. In addition, STDs in women are more likely to remain asymptomatic

and thus, unrecognized and untreated, for a longer period of time.

U.S. Department of He.uth .and Hualan Seratces, He.alth Resoltices .and Services .\dministr.ation. HIV/ AIDS Bi ri-.u 331
A Guidi; to tub Clinical Garb ol' Womb:n with HIV

Adolescents

Socioeconomic Risk

Adolescents are the most uninsured and underinsured group in the United

States and are the least likely to receive office-based medical care or to use primary care services. Twenty-five percent of youth ages 15—29 have no health

insurance and approximately 1 in 5 suffers from at least one serious health

problem. Poverty, poor access to care and lack of education and prevention

skills further increase vulnerability to HIV. Additional barriers include mistrust

of the health care system, fear of inappropriate disclosure and providers’ lack

of understanding of adolescent rights to confidentiality and care without

parental consent for sensitive health issues.

Moreover, many adolescents use emergency and walk-in facilities for acute

care needs. As a result, they lack a primary care provider who can ensure ongoing care and address prevention and health promotion needs. Because

adolescence is a time when help-seeking behaviors and attitudes about health

and self-care are formed, the experiences adolescents have with health care providers are especially important. They form the basis for future providercKent interaction, communication patterns and relationships.

II. HIV CARE FOR ADOLESCENTS

Cornerstones of adolescent care include consent policies, confidentiality,

accessibility, outreach and linkage to care and prevention. Even though youth

prefer health care settings that are geared to their needs, most teens will not

receive care in adolescent programs. Although most facilities are unable to offer the ideal “one stop shopping” for teens, quality care can be provided by

identifying a staff member and/or provider team who wants to work with

adolescents and by adapting adult and family programs to meet an adolescent’s

needs. This can be done by accommodating walk-ins since youth do not often

plan ahead, addressing payment barriers and providing flexible appointments

that win not conflict with school or work.

A. CONFIDENTIALITYAND LEGAL ISSUES

All states have laws that allow minors to consent to treatment without parental

consent for specific health services including emergency care, STDs or reproductive health and substance abuse treatment services. In many, but not all

states, this includes the right to consent for HIV counseling and testing. However, not aU providers are aware of these rights or understand their significance

for adolescents and these rights vary by state and the medical service provided.

Most importantiy, lack of confidentiality may cause adolescents to avoid or

delay needed care. Even though parental consent may not be needed to provide an HIV test or HIV-related care, providers should carefully assess an adolescent’s cognitive capacity to understand the implications of having HIV

disease and should encourage them to involve a supportive adult in their care.

us. Department of Health and Human Services, Health Resources and Services Administration, HFV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Adolescents

B. COUNSELING AND TESTING

Although most youth do not think they are at risk for HIV infection, they prefer providers to inidate discussion concerning HIV prevention and risk assess- ment. All adolescents should receive HIV prevention education, and sexually

active adolescents should routinely receive HIV counseling and be offered

I IIV testing with informed consent. This enables providers to identify positive

youth and provide ongoing medical care and support services, while relieving

anxiety and reinforcing preventive behaviors for youth who are HIV negative.

For adolescents who are not sexually active, counseling provides an opportunity to talk about sexual readiness, delaying intercourse and low risk ways to

explore intimacy.

New testing options such as those that test for antibodies in oral fluids or

urine are helpful with youth who are afraid of needles and allow providers to offer testing in a variety of settings including mobile vans, school-based clinics

and drug treatment programs. Same-day testing may also be useful by eUrrdnating the need for a return visit for results, but will require careful planning for

the delivery of HIV-positive results. Meeting adolescent needs for flexibility,

accessibility and low or no fee HIV testing is important in overcoming primary

barriers to accessing care and can serve as an entry point to care. Like other

underserved populations, adolescents are generally diagnosed with HIV/AIDS

late in the course of illness, relatively few receive care for HIV disease and most

do not know they are infected. Thus, ensuring access to HIV counseling and

testing is essential in enabling adolescents to receive ongoing treatment and care.

Although counseling and testing for adults has generally been based on one

initial pre-test counseling session with providers, a “one-shot” approach to

counseling is not effective with aU at-risk youth. Two short counseling sessions

prior to testing, using personalized risk reduction plans, can increase condom

use and prevent new HIV and other STD infections. Pre- and post-test counseling provide an opportunity to promote preventive health behaviors and to

assess substance use and family planning needs, while providing basic information on HIV, obtaining consent and conducting a comprehensive risk assess- ment. (Table 11-1, on the following page) More extensive guidelines are also

\available for adolescent HIV counseling and testing in aU health settings.

(Chabon, 1998) Because adolescents may have misconceptions about aspects

of HIV transmission and prevention, providers should assess their capacity to understand basic concepts of HIV disease and viral transmission. Effective

HIV counseling for adolescents should be culturally sensitive and tailored to an adolescent’s developmental needs. In addition, providers should take special

precautions to ensure confidentiality in institutional settings such as foster

care, residential treatment or detention.

Knowledge of appropriate condom use and widespread availability of

condoms are especially important in promoting risk reduction behaviors

among youth. All facilities that provide health care for adolescents should

make condoms available and providers should demonstrate condom use with

U.S. Department of Health and Human Services, Health Resources and Services Administrahon, HIV/AIDS Buri- \i 333
A (iuii)i; TO rui' (Iunicai. Cxui- of Womi;n wnii HIV

Adolescents

Table 11-1: Teen AIDER (Assess, Inquire, Discuss, Educate,

Readiness) Interview for HIV Counseling, Testing and

Risk Reduction

Assess and Inquire

Create a confidential atmosphere

Assure youth about confidentiality of visit and ability to consent for testing per

local laws

Assure youth that testing is their choice

Acknowledge that it can be embarrassing to discuss sexual behaviors

Help youth to identify supportive adult who is aware that youth is being tested

HIV/AIDS Knowledge

Allow adolescent to verbalize understanding of HIV, clarify misconceptions and

fill in gaps in knowledge

Assess feelings about testing and previous HIV testing experiences

Inquire if youth knows anyone with HIV/AIDS (e.g., sexual partner, family

member)

Sexual Risk Assessment

Assess sexual behaviors without making assumptions about sexual orientation, not all youth are heterosexual and not all youth who have engaged in same sex

behavior self-identify as lesbian or gay

Assess number of partners, age differential and partner's known risks Assess frequency of substance use in the context of sexual behavior

Assess consistency of condom use and obstacles to use such as unassertiveness, desire to become pregnant, fear of violence and religiosity

Assess for history of sexual abuse or rape

Substance Use and Other Risk Assessment

Assess level of drug and alcohol use and reasons and context in which use

occurs Review risk of impaired judgement that may result leading to unsafe sex Assess potential need for drug treatment

Assess violence and substance use in home and community

Table continues . . .

anatomical models. Adolescents have difficulty using condoms during inter- course for several reasons, including: 1) lack of knowledge about effective use;

2) lack of communication and social skills; 3) lack of availability of condoms

at the time of sexual activity; and 4) impulsive behavior exacerbated by drug

or alcohol use. Gender and power imbalances in relationships make condom

use especially difficult for adolescent women whose partners are older and

who are just beginning to develop communication and negotiation skills. Helping youth identify their personal values may increase self-esteem and help

them resist pressures to engage in sexual risk behaviors. (Table 11-2)

C PREVENTION

Promoting risk reduction among adolescents is especially challenging since

developmental characteristics encourage concrete, short term thinking and

experimentation and increased reliance on peers. Thus, successful primary and

secondary programs for adolescents are those that provide interventions to

us. Department of Health /\nd Human Services, He/MTH Resources and Services AdministR/\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Adolescents

Table 11-1: Teen AIDER (Assess, Inquire, Discuss, Educate,

Readiness) Interview for HIV Counseling, Testing and

Risk Reduction (continued)

Discuss and Educate

Discuss sexual activities that don't involve exchange of body fluids (outercourse)

Demonstrate proper male condom, female condom and dental dam use on

anatomical model and provide opportunity for practice

Rehearse effective ways to communicate risk reduction with sexual partner (s) Discuss harm reduction strategies for youth using drugs

Develop a personalized risk reduction plan

Discuss postponing sex for youth who are not sexually active

Determine referral needs (e.g.. Medical, Psychosocial, School /Vocational,

Substance Abuse, Reproductive Health, Legal, Housing, Psychiatric)

Readiness For HIV Testing and Referral

Adolescent should be informed about both anonymous and confidential testing

Provide education about Partner Notification programs and other options for

disclosure to partners

Assess understanding of meaning of a positive and negative test result Assess understanding of benefits of early intervention

Determine with youth if testing should occur at this time and obtain informed

consent

Strategies for coping (how to relieve stress and anxiety during the testing

process)

Arrange follow-up appointment and method for confidentially contacting youth,

if needed

Source: Reprinted with permission from: Chabon, B and Futterman, D. Adolescents and HW/.A/DS

Clinical Care. Vol. 11:2, pp. 9-16, February 1999.

Table 11-2: Factors Associated with Condom Use

Encourages Use Discourages Use

Knowledge about condoms

Belief in effectiveness

Discussion with health care provider

Self-esteem/self-efficacy

Communication/negotiation skills

Availability/accessibility

Drug/alcohol use

Relationship power imbalances

Peer pressure may discourage use

Lack of effective sex education

Lack of media/cultural support of

condom use

increase self-esteem and self efficacy, build social skills and provide basic

information geared to the adolescent’s developmental level, using a peer

support model. For high risk youth, the AIDS Risk Reduction Model (Catania,

1990) has been widely used to foster primary and secondary prevention, based

on the premise that behavior must first be acknowledged as risky before youth

wiU initiate change.

School-based programs that provide comprehensive health education in conjunction with school health clinics offer optimal opportunities to reinforce

us. Department OF Health and Hum,\n Services, Health RESOURCiii and Servicics Admini,si-k.\tion, IIIW.MDS Hi'ri.m- 3.35
A CJuini' TO I'lU': (j.inicai. (^\Rii oi' W()Mi:n with HIV

Adolescents

positive health behaviors and ensure routine screening for a range of health and

mental health concerns. But they are especially important in reducing risk and

identifying sexually active youth who are at risk for STDs and pregnancy. A

comprehensive review of school-based programs designed to reduce risky

behavior in teens found that adolescents who received AIDS education were

less likely to engage in sexual activity and more Ukely to practice safer sex than

peers who lacked AIDS education in school. (Kirby, 1 998) In particular, successful programs include skills building, reinforcement of values and norms to prevent unprotected sex that are based on age and experience levels, and discussion of social influence and pressure. School clinics also offer an important venue for access to condoms and appropriate instruction on condom use. Although not widely available, school clinics provide an important site for HIV

counseling and testing for in-school youth, given new rapid testing options. Ultimately, successful prevention must also involve society and the media — until

youth see condom use and safer sex discussions incorporated into sex scenes in

music videos and movies, they will not believe that this is a social norm.

D. LINKING YOUTH TO CARE

Linking at risk youth to care is essential in meeting their needs for risk reduction education and appropriate ongoing HIV medical and psychosocial care. Most HIV-infected youth do not know they are infected, and many providers

are not aware of available community service agencies that can help address

their multiple mental health and social service needs. Community outreach is a primary component in ensuring access to care for youth with HIV disease.

Peer-based outreach services are frequently employed, as adolescents are more

likely to Listen to their peers. Unlike adult women who have more opportunities to obtain HIV testing and to access care related to their reproductive

health needs, adolescents who are not pregnant require proactive outreach

efforts to promote HIV testing and engage them in care. This includes citywide campaigns to encourage testing and to make it more widely available,

with direct linkages to adolescent health care facilities. One such initiative — a

social marketing campaign spanning the continuum from HIV prevention

through testing to care — was developed by the Adolescent AIDS Program at Montefiore Medical Center in New York City ini 996. “HIV. Live with it. Get

Tested” was designed with marketing experts, health providers and most

importantly youth themselves, to combine media advertisements such as posters, radio and TV ads with community outreach in settings where at-risk

youth access information and are likely to congregate. Using teen language for

sexual activity (e.g., “Knockin’ Boots” or “Hittin’ the Skins”) to promote test- ing and care services through a coalition of adolescent HIV programs and

community based youth agencies, the initiative is intended to help adolescents

link having sex with HIV risk and the importance of HIV testing. Now in its third year, the initiative focuses annual activity around a “Get Tested! Week”

launched with a youth-led Town Hall meeting and peer outreach. The campaign’s success has also resulted in a national initiative that during 1999 took

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bure,\u
A Guide to the Clinical Care of Women with HIV

Adolescents

place in 5 additional cities — Baltimore, Los Angeles, Miami, Philadelphia and

W ashington, D.C. — within the NIH- and HRSA sponsored Adolescent Medicine 11 IV/AIDS Research Network (AMHARN) Network. In each city, new

coalitions were successfully built, increased numbers of youth were tested, and

HlV-posidve youth were identified and linked to care. (Futterman, 2000)

E. HIV CLINICAL AND PSYCHOSOCIAL CARE

Although the namral history of HIV infection in adolescence is still being

defined, the course of disease appears to foUow that of adults. A national

prospective smdy with sites in 13 cities —AMHARN — has been funded by

the Nadonal Insdtutes of Health and the Health Resources and Services

Administradon to idendfy the course of disease in adolescents, including its spectrum, manifestadons, effects of puberty, and developmental and psychosocial interacdons. (Rogers, 1998) Inidal findings suggest that adolescents

may have greater potendal for immune reconsdtudon than adults as a result of

residual thymic funcdon, which underscores the need for aggressive outreach

efforts and access to early effecdve treatment and has also idendfied a high

prevalence of sexually transmitted disease in this populadon.

Physical Exam, Laboratory Tests and Immunizations

Physical examinadons for adolescents should foUow guidelines for adults,

however, providers should use Tanner staging of puberty (characteri2ing

breasts, genitalia and pubic hair) to interpret blood values and prescribe medicadons. (Schneider, 1998) Because sexually acdve adolescents are at very high

risk for STDs, providers should roudnely screen with cervical cytology, and

for chlamydia, gonorrhea, syphilis, and hepadds B and C, as well as follow

Tuberculosis screening guidelines for adults with HIV infecdon. Pregnancy

tesdng should be performed when indicated by history or exam findings, but

should always be considered with missed menses, abnormal bleeding or development of pelvic pain. Adolescents require more immunizadons than adults.

(Table 11-3) Since immunizadons may briefly boost viral load, they should be

Table 11 - 3 : Immunizations for Adolescents

Measles, Mumps and Rubella (MMR) booster

Diphtheria-Tetanus toxoid (dT) booster

Hepatitis B Vaccine (3 in series)

Hepatitis A Vaccine (2 in series) (not routine; recommended for males who have

sex with males)

Influenza (yearly)

Pneumococcal vaccine

HIB (optional)

Varicella zoster vaccine for contacts (not currently approved for HIV-i persons)

Source: Reprinted with permission from: Hoffman ND, Futterman D, Myerson A. Treatment Issues

for HIV+ Adolescents. A/DS Clinical Care. Massachusetts Medical Society. Vol. 11:3, 17-24, March 1999.

us. DEPARTTVfENT OF HE.U.TH AND HUM.\N SERVICES, HEALTH RESOURCES AND SERVICES AD.MINISTR VnoN, HIV/AIDS III RI.AI 337
A CJuini-: ro riii'. (j.inicai. CakI' oi- WomI'N with } IIV

Adolescents

scheduled on the same day or after viral load measurements. At present, CD4

counts and viral load measurements are interpreted as for adults and used to

guide treatment.

HIV Treatment

Information from clinical trials is limited since few adolescents have participated

in existing clinical trials. Although adolescent trials are under development, HIV

and opportunistic infection treatment and prophylaxis recommendations for

post-pubertal adolescents currently follow clinical guidelines for adults. Because

pubertal changes may affect pharmacokinetics, dosage is based on Tanner staging, rather than age. For example, pediatric dosing should be used for adolescents who have entered/are in early puberty (Tanner stage I/II), while dosing

for adolescents in mid-puberty (Tanner III/IV) should be based on whether or not they have completed the growth spurt. Adolescents who have completed

puberty, (Tanner V) should receive adult dosages.

Treatment adherence, which is challenging for adults, can be especially challenging for adolescents who struggle with a range of developmental tasks that

require them to balance dependence with increasing autonomy. As with any

successful work with adolescents, the first step in promoting adherence is establishing a solid therapeutic alliance. Providers must develop a systematic

approach that facilitates adherence by addressing four areas of interaction,

including building trust, assessing and facilitating readiness, helping teens initi- ate and practice the new treatment regimen and providing ongoing support for

adherence. (Table 11-4) This approach addresses barriers to maintaining a complex medication schedule for adolescents, such as lack of privacy in

school, home or residential settings, the need to develop a reminder system,

and the incongruity of having a serious illness while exhibiting few visible

indicators of disease. For example, the most common reasons for missing

medication by youth in a Los Angeles adolescent HIV/AIDS program

include: forgetfulness, side effects, the inconvenience of having to take so many pHs, and the fact that taking the medication is a continual reminder of

being HIV infected. (Belzer, 1998)

AMHARN has designed a multi-level adherence initiative: Project TREAT

(Treatment Regimens Enhancing Adherence in Teens) to address medication

adherence in adolescents. A monograph describing the model has been developed for providers and is available from HRSA. (Schietinger, 1 999) Based on

Prochaska and DiClemente’s Transtheoretical Model of Change, Project

TREAT acknowledges the uniqueness of each adolescent’s readiness for treat- ment. The model has developed specific interventions and materials (video

and audio tapes and booklets) for each stage of readiness to facilitate successful adherence. (The Stages of Change are: Precontemplation, Contemplation,

Preparation, Action, Maintenance and Relapse.) Practice regimens with vitamins help youth rehearse their medication regimen, while enabling them to

problem-solve potential barriers without risking under-dosing. Medications

us. Dep.^rtnient of He,\lth ,\nd Human Services, He.ai.th Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Adolescents

Table 11-4: Adherence: Using your EARS

Engage

Establish therapeutic alliance and build trust; goal is active participation by

adolescent in all aspects of treatment

Address immediate needs (health, housing, insurance, family, and partners)

Educate about HIV infection: transmission, disease course and benefits of

medications

Assess

Stage HIV infection

Assess mental health and cognitive abilities Assess physical ability to take medicines

Assess support systems and disclosure issues: family and friends

Assess readiness to begin medications

Readiness

Decide with adolescent on regimen that integrates clinical needs with lifestyle —

show different pills/combinationss

Solidify support systems: family and/or treatment buddy

Pratice chosen regimen with surrogate vitamins; distribute medications into a weekly medication planner, program one-day pill timer with the adolescent

Address adherence barriers discovered in practice run Support

Provide ongoing support with frequent clinic visits and phone contact

Acknowledge and address side effects

Develop strategies to ensure tolerability and regularity

Facilitate interactions with other youth taking medications

Source: Reprinted with permission from: Hoffman ND, Futterman D, Myerson A. Treatment Issues

for HIV+ Adolescents. A/£)S Clinical Care. Vol. 11:3, 17-24, March 1999.

must be integrated into the adolescent’s daily routine. Ideally, adolescents

should be prescribed a daily or twice-daily medication regimen. Many

providers also initiate treatment without using protease inhibitors (PI); these

are incorporated into later regimens after the adolescent has demonstrated

effective adherence, to avoid risking potential cross-resistance to Pis.

Psychosocial Issues

The Adolescent AIDS Program has identified five key issues that adolescents

with HIV/AIDS must address in coping with their changing health status. These include; 1) receiving an HIV diagnosis; 2) disclosing an HIV status to parents, parmers and others; 2) coping with HIV disease; 4) becoming symptomatic; and 5) preparing for death. (Kunins, 1993)

1. Receiving an HIV Diagnosis: Providers should instill a sense of

hope and encouragement when giving adolescents an HIV diagnosis.

Asymptomatic youth must learn to balance healthy denial and preoccupation with HIV infection. Concrete thinking makes it difficult

for some youth to integrate the concept of disease latency and

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Adolescents

asymptomatic infection. Support is essential in helping youth integrate

this life changing information. Individual and peer group interventions

with psychologists and social workers can help facilitate adjustment.

Psychotropic medication may be needed to manage pre-existing psychiatric problems and for anxiety and depression that may accompany

the diagnosis.

2. Disclosure of HIV Status: After learning their diagnosis, adolescents

must decide who to inform and when to disclose their HIV status. Telling their parents is difficult for many adolescents who fear losing

their love and support. Fear of rejection and loss of confidentiality is also a concern in disclosing to sexual partners. Providers should offer

to help with disclosure and offer guidance in determining when it is safe and appropriate for the youth to disclose her HIV status. Role

playing and working through scenarios ahead of time can help the

adolescent manage potential fears and concerns.

3. Coping with HIV: Adolescents also need guidance in learning how

to interpret changes in their viral load and CD4 counts. Since fluctuation in results may cause some youth to panic, providers can help by

explaining that variation is common and significant changes will not

prevent them from leading satisfying and productive lives.

4. Becoming Symptomatic: The appearance of HIV-related symptoms

can be especially disturbing for adolescents who may have only superficially acknowledged their HIV status. For some youth, becoming

symptomatic may encourage them to fight HIV and may enhance

treatment adherence and self-care. Others, however, may feel over- whelmed and may lose their motivation to Hve. When symptoms

occur, providers should explore their meaning, correct misconceptions

about their significance and ensure that adequate services and support

are available.

5. Preparing for Death: Many adolescents have Limited experience with

death and have naive perceptions about what to expect. Introducing

the topic by talking about Living wiLls and health care proxies before

HIV becomes too advanced is a practical way to help youth begin to

deal with issues related to death. When clinically appropriate,

providers can help adolescents explore their feelings about dying by

discussing options for dying in the hospital or at home, talking about

funeral or memorial services, and exploring child custody or permanency planning with adolescent parents.

Mental Illness and Substance Use

Mental Tlness and substance abuse are important co-morbidities for HIV-positive adolescents. Accurate screening and diagnosis are essential in helping adolescents cope with their disease and successfully maintain their treatment

regimen. Case studies- of adolescents and young adults with HIV indicate a

us. Department of Health and Hum/\n Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Adolescents

high prevalence of depression, bipolar disorder and anxiety, often pre-dating

their 1 IIV diagnosis. Similarly, many adolescents with HIV report alcohol and

drug abuse. Of adolescents in the REACH study, 14% percent of females and

more than 25% of males report weekly use of alcohol during the past three

months. During the same period, 7% of females and 20% of males reported

using hard drugs. (Rogers, 1998) In addition, as already noted, a high proportion of H1V+ male and female youth report childhood sexual abuse. (See

(Chapter 1 on Epidemiology and Natural History) which has many psychological and behavioral sequelae, including depression, post traumatic stress disorder, substance abuse, suicidality and risk for HIV infection.

III. SUMMARY

The high risk of adolescent females for HIV infection makes the development

of realistic prevention programs a vital necessity. This includes wider availability of prevention skills building and the routine offering of HIV counseling

and testing to sexually active teens in all programs that provide adolescent

care. While most youth will not receive services in adolescent programs, services can be readily adapted to provide a “youth-centered” approach, by such

basic accommodations as offering flexible hours and low or no payment for

services and care as well as providers who are knowledgeable about adolescents. Relevant clinical trials should be made available to adolescents, and there

should be wide dissemination of information to health care providers about

providing adolescent-related HIV care, such as use of Tanner staging for

assessing test results and determining appropriate dosage. Youth at high risk

for HIV should be identified and engaged in primary care as soon as possible

and outreach programs are an important component for programs that seek to

link HIV-positive youth to care. Adolescents with HIV need intensive individual and group support to maintain health and reduce transmission to others.

Health care providers in aU settings that serve adolescents need to assist in

making services visible, flexible, affordable, confidential, culturally appropriate

and available for all adolescents.

REFERENCES

Belzer M, Slonimsky G, Tucker D. Antiretroviral adherence issues among HIV+ youth.

Presented at the Annual Meeting of the Society for Adolescent Medicine 1998,/

Adol Health 22:\m, 1998.

Catania JA, Kegeles SM, Coates TJ. Toward an understanding of risk behavior: An

AIDS risk reduction model. Health Education Quarterly 17: 53—72, 1990.

Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report 11 (No. 1): 1-42, 1999.

Centers for Disease Control and Prevention. Youth risk behavior surveillance — United

States 1997. MMW7? 47(SS-3), 1998.

us. Dep.\rtment of Health and Human Services, Health Resources and Services Adminis-i-R-viion, HIWAIDS Bi ri.vl 341
A Ciuini'. TO iniv ('i.inicai, (Iaki; oi' Womi:n wmi HIV

Adolescents

(diabon B, I'urterman D, jones Adolescent HIV counseling and testing protocol. In Ryan, C. and butterman, D. Lesbian and Gay Youth: Care and Counseling. New

York: (Columbia University Press, 1998, pp. 152-161.

Chabon B, Hoffman N, Hershey B, P’utterman D. High prevalence of HIV among par- ents of H1V+ youth. Presented at the Annual Research Meeting of the Society for Adolescent Medicine, San Francisco, CA, March 1997.

Futterman D, Rudy B, Peralta L, et al. Social Marketing to Promote HIV Counseling and

Testing to Youth: A Six City Initiative. Presented at the Annual Meeting of the

Society for Adolescent Medicine, 2000, Washington, DC.

Futterman D, Hein K, Reuben N, et al. Human immunodeficiency virus-infected adolescents: The first 50 patients in a New York City program. Pediatrics 91:730-35,

1993.

Institute of Medicine. The Hidden Epidemic: Confronting Sexually Transmitted Diseases. Washington, DC: National Academy Press, 1997.

Kirby D, Short L, Collins et al: School based programs to reduce sexual risk behaviors: a review of effectiveness. Public Health Reports 109:339—360, 1994.

Kunins H, Hein K, Futterman D. et al. A Guide to Adolescent HIV/AIDS Program

Development. JAdolesc Health, Special Suppl., 1—168, July 1993.

Rogers AS, Futterman DC, Moscicki AB, et al. The REACH project of the Adolescent

Medicine HIV/AIDS Research Network: Design, methods, and selected characteristics of p2LTtieip2ints. JAdol Health 22:300—311, 1998.

Ryan C and Futterman D. Lesbian and Gay Youth: Care and Counseling. Columbia University Press, New York, 1998.

Schietinger H, Satvyer M, Futterman D, et al. Helping Adolescents with HIVadhere to HAART. TREAT Monograph: Rockville, MD: HRSA/HAB, 1999.

Schneider M. Physical Examination. In Friedman S. et al. Comprehensive Adolescent

Health Care. St. Louis: Mosby-Year Book, 1998.

U.S. Department of Heai.th and Human Services, Health Resources and Services Administration, HtV/AIDS Bureau
XII: Palliative and End-of-life Care

Carla Alexander, MD

I. INTRODUCTION

This chapter is meant to provide ideas for coping with symptoms which

impact quality of life throughout HIV disease and to prepare for issues faced near the end of life. Aggressive paUiative care anticipates, prevents, and

relieves suffering on emotional and spiritual levels as well as the physical.

Because of gaps in traditional medical education related to end-of-life issues

(Weissman, 1998; Field, 1997), information in this chapter focuses on care near the end of life. (Hanson, 1997) The newer definitions of palliative care used in women with chronic illness does not only refer to “end-of-life” care. As a comparatively new field, paUiative medicine, which has been largely an

oral tradition continues to be in need of research and Uterature. The chaUenge

to readers is to share successes and faUures in order to expand the Uterature

especiaUy for those Uving in countries with fewer resources.

Hospice, an early form of paUiative care, developed in London during the

late 1960’s when Dame Cicely Saunders proposed using an z>2 rerdiscipUnary

team to focus on the “reUef of suffering” rather than simply on long-term

survival for persons Uving with advanced cancer. This care was ideaUy deUvered in the home and focused on relieving physical symptoms which might

impede successful psychosocial and spiritual Ufe closure prior to death. (Saunders, 1989) In 1980, the World Health Organixation defined paUiative care as: “The active total care of patients whose disease is not responsive

to curative treatment. [It] . . .affirms Ufe and regards dying as a nor- mal process, . . . neither hastens nor postpones death, . . . integrates

the psychological and the spiritual aspects of care, . . . offers a support system to help patients Uve as actively as possible until death, . .

. and offers a support system to help the famUy cope during the

patient’s iUness and in their own bereavement.” (Doyle, 1998)

There are many differences between patients with cancer, who eventually

learn that their disease is no longer being contained by treatment and persons

with HIV/AIDS who suffer from a more episodic iUness with very difficult to predict end-points. In HIV disease paUiative care is best woven into the general fabric of care from the time of diagnosis. A smaU group of HIV

providers, invited by the Health Resources and Services Administration

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A Guinis TO 11 ii; C'i.inicai. (^\ri; op' Womi:n with HIV

Palliarivc Care and End-of-life Care

(HRSA) of the Department of Health and Human Services which oversees

the Ryan White CARE Act, have attempted to define what this care should be

in HIV disease:

. . that care which is patient and family-centered and optimi2es quality of life by active anticipation, prevention, and treatment of

suffering through respectful and trusting relationships formed with an interdisciplinary team throughout the continuum of illness: addressing physical, intellectual, emotional, social, and spiritual needs

and facilitating patient autonomy, access to information, and choice.”

(HRSA staff, 1999)

As HIV disease becomes a chronic rather than terminal illness, management must be accomplished in the overall context of life. (Breitbart, 1996)

Good supportive care means “to be safe and not to be hurt, to be given

refuge or sanctuary, to be comforted and accepted, to belong, and to give and

receive love.” (Standards Comm, N.H.O., 1997) Adjusting goals may be challenging for health care workers who use only a “cheerleading” approach to

support. Involving the patient and her support system in decision-making

affords her a sense of control over her disease which ultimately extends to the

end-of-life. (Fogel, 1993; Newsham, 1998; Sanei, 1998) All staff must learn to

value the impact of symptoms on the woman’s daily life as much as they do

viral load and the CD4 cell count.

HIV disease has been associated with shame and a negative stigma (Abercrombie, 1996; Chung, 1992; Sowell, 1999) resulting in the isolation of many

who are infected but especially of women. Those who suffer from the disease

are frequently without social support or the financial means, including health

insurance, necessary for coping with their disease. (Cohen, 1998; Chung, 1992;

Nannis, 1997; Pergami, 1993; Sowell, 1997.) As the traditional care-giver, a woman may not have anyone else to provide her own care. She may have also

suffered many personal losses leaving her emotionally drained and unable to provide care for someone else. (Sarna, 1999) She must cope with knowing that

she will one day be dying herself and that she must make provisions for her

children and other dependents who will be left behind.

II. QUALITY OF LIFE

The overarching goal of palliative care is to relieve or reduce suffering and

promote quality of Ufe. With HIV disease, the unpredictable and episodic course of illness makes it difficult to estimate an individual’s prognosis. Use of

combination therapy has decreased mortality rates by 23—90% depending on

the population examined. (Pez2otti, 1999 ; Sendi, 1999) Quality of life (QoL)

alone has become an important outcome measure and providers now need to

pay more attention to pain, fatigue, anorexia and other symptoms which can be present even when the disease markers are improving. (Barrosa,1999; Van

us. Department of Health and Human Services, Health Re.sources and Servicf.s Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Palliative Care and End-of-life Care

Scr\’cllan, 1 998) Each provider must become adept at anticipating symptoms

related to therapies and offering the woman a mechanism for preventing or

controlling these side effects.

In spite of prolonged survival, physical and spirimal distress; psychological

pain; and grief remain a part of the illness. (O’Neill, 1997) There does come a point in illness when quality of Life becomes more important than quantity of

life. (I larris, 1985) The transition away from aggressive, curative care can be as

difficult for members of the health care team as it is for patients and families,

(hinucane, 1999)

Several studies have specifically considered QoL in women with HIV disease. (Sewell, 1997; Farsides, 1995; Rosenfeld, 1996) Sewell found that social,

and particularly psychological, symptoms have a major impact. Quality of life has been affected by “HIV treatment, physical symptoms, psychological wellbeing and [change in] role functioning.” (Hays, 1992) Sarna found that problems arise in four domains; physical, psychological, social, and sexual. Schag,

however, noted that financial concerns were the number one disrupter.. This is followed by “worry about family,” “distress at losing others,” and “worry

about progression of disease.”

Routinely measuring QoL throughout the disease (1) alerts health care providers to changes and stresses which may not always be obvious during a busy clinic visit. Completing questionnaires every 3-4 months or at the time

of a clinical change may help the woman communicate with her providers.

These answers can assist providers by monitoring problems and targeting

interventions more specifically. (Sarna, 1999) Quality of life scales have traditionally reflected functional status, for example, the Karnofsky Performance

Status assigns a global ranking which reflects activity during any given day. The

Medical Outcomes Study (Wu, 1997) is frequently used in the HIV population

and has been shortened for easier use in the clinical setting. However, many of

these scales, because they are function based, may not be as useful as the

woman becomes more debilitated and approaches end of life. (Pratheepawanit, 1999)

In advanced disease one’s focus is often directed to psychosocial and spiritual concerns which can be addressed even while bed-ridden. When we are

healthy, not being able to leave the bed might seem unbearable. Approaching

death, priorities shift; relationships and momentary pleasures become more

important. In fact, it is not unusual for people to feel that their quality of life

is better during this period because they are able to avoid mundane tasks and

to focus on personal goals. The Missoula-Vitas Quality of Life Instrument

(available through Vitas Healthcare Corporation, phone 305-350-6033) has

recently been developed specifically for those with deteriorating functionalitv.

With this form the patient notes the importance of each domain and scoring

reflects how the change in each characteristic, such as symptom control and

sense of well-being, affects the woman.. It is always useful simply to ask the

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woman how she would rank her own quality of life and what things are most

important to her at the present time.

III. SYMPTOMS THROUGHOUT DISEASE

Three symptom surveys of outpatients with HIV/AIDS (Ferris, 1995; Sims,

1992; Carr, 1994) are summarized in Table 12-1. As disease advances it may

not be possible to eliminate the cause of a symptom but the woman and her

family should be educated about symptom management, and thus be empowered to master these symptoms.

Table 12-1: Common Symptoms in HIV Disease

Symptom # 1 #2 #3

Anorexia/Weight Loss 91% 31% 61%

Fatigue/Weakness 77% 50%

Pain 63% 52% total 84%

Shortness of Breath 48% 22%

(respiratory

problem)

11%

(dyspnoea)

Nausea/GI upset 35% 28% 21%

Cough 34% 27% 19%

Anxiety /Depression 32% 24%

(Depression)

40%

(Anxiety)

20%

(Depression)

Skin Breakdown 24% 24%

(Skin Problem)

42%

(Skin Problem)

Diarrhea 24% 18%

Confusion/Dementia 43% 29%

Constipation 24% 18%

Fever 13% 27%

#1 Ferris F and Flannery J eds. A Comprehensive Guide for the Care of Persons with HIV Disease:

Module 4: Palliative Care. Mount Sinai Hospital/Casey Flospice Toronto, 1995. #2 Carr, DB, ed. Pain in HIV/AIDS, (La Douleur du SID/HIV), Robert G. Addison, publisher, 1994

#3 Sims R. and Moss VA. Palliative Care for People with AIDS, 2nd ed. Edward Arnold, London,

1995.

Fatigue, pain, and difficulty with sleep are three symptoms which occur throughout the course of HIV disease (van Servellan, 1998; Whalen, 1994)

and are often over-looked by providers. Patients believe they “must put up

with” these problems and may avoid acknowledging them to providers.

Women do not want to appear less^ courageous in coping with their disease or

to distract the provider. Women who have a history of past or current substance abuse may fear being labeled as “drug-seeking” or may fear relapse if given pain medication. On the other hand, providers often do not inquire

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A Guide to the Clinical Care of Women with HIV

Palliative Care and End-of-life Care

al)()Lit these symptoms because they may not know how to manage them or

feel inadequate to address them.

Dame (dcely Saunders, the founder of modern-day hospice at St. Christopher’s in London, introduced the term “total pain” (Saunders,! 966) which is a model for how to approach all symptoms. She recognized that each complaint

has a physical, emotional, and even spiritual component. If pain, or another

symptom, is difficult to relieve with usual measures it may be that the woman

has assigned special meaning to the symptom. She may be afraid her disease

is getdng worse or that “it is God’s punishment.” Both of these beliefs can

exacerbate any symptom. (Hankes, 1998) Particularly when a symptom seems

difficult to control, it is useful to ask the patient: “What does the pain (or nausea or shortness of breath) mean to you?” or “Why do you think you have

this symptom?”

A. IDENTIFYING AND DEFINING THE PROBLEM

Instead of a “review of systems,” it may be useful to think of a “review of

symptoms” moving from the head down to the feet. AU symptoms can be

approached similarly (MacDonald, 1 999) by asking about the character (what

does it feel like); the location (including radiation to other parts of the body);

what makes it worse, what makes it better; and are there any other symptoms

associated. It is also useful to ask how symptoms limit or affect daily activity.

Asking these questions lets the woman know that you are interested in the

particulars of how this effects her Ufe, that her perception of her daily comfort is as important to you as is her viral load.

In cancer patients with symptoms such as fatigue, it has been shown that

just the act of asking and being aware of the importance of this symptom to

the patient provides some relief from it. A problem often worsens when the

patient tries to deal with it alone and her fear of what is causing it grows. Routinely using a checklist of symptoms such as the Memorial Symptom Assessment Scale (Bookbinder, 1995) will alert the practitioner to issues facing the

patient. A review of symptoms will also alert the provider to the appearance

of new symptoms which might herald progression of disease.

B. QUANTITATING SYMPTOMS

Two simple methods can be used to quantify symptom severity: 1) on a scale

of zero to ten, where zero means the absence of any symptom and ten is the

very worst it can be, how would the patient score her pain or fatigue” 2) the

visual analog scale (VAS) is a straight, ten-centimeter line upon which the

patient can make a mark representing how severe the symptom feels with the

left end of the line representing “not at all” and the right being “the worst.”

Distance along the line can be measured in centimeters resulting in a numeric

figure to record in the medical record for comparison purposes. Actual numbers are unique to the individual reflecting her perception and should not be

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Palliative Care anti F-nd-of-life Care

used to compare her with other patients. Quantification is a mechanism for

judging effectiveness of therapy and may alert the provider to a change in

disease status.

Table 12-2 : Pain Intensity Scales

0-10 Numeric Pain Intensity Scale'

01 23456789 10

Moderate Worst

Pain Possible

Pain

Visual Analog Scale (VAS)^

No Pain As

Bad As It Could

Possilby

Be

' If used as a graphic rating scale, a 10cm baseline is recommended.

^ A 10cm baseline is recommended for VAS scales. Source: Adapted from Acute Pain Management Guideline Panel, 1992 (AHCPR, 1994).

No

Pain

C MANAGEMENT OF INDIVIDUAL SYMPTOMS

Effective symptom management is based on a thorough understanding of the

symptom and education of the patient and family, allowing them to anticipate

crisis episodes with appropriate planning. It requires a multidisciplinary

approach. The goal is to help the patient “move from a feeling of helplessness

to a feehng of supremacy over the symptom” and to develop and retain as much control over her life and illness as possible through the use of practical

advice and emotional support. (WH.O., 1998) Symptoms can be managed

with medications and/or non-pharmacologic interventions. In general, the oral

route for medications is preferred to the parenteral; treatment regimens are

tailored to the individual.

Fatigue

Scope of the Problem

This is the most frequent complaint of persons with HIV disease in a number

of different series. (Laschinger, 1999; von ServeUan, 1998) Seventeen to sixty

per cent of persons, even before they are diagnosed with AIDS, have this

complaint. (Breitbart, 1998; Groupman, 1998; Piper, 1993) “Chronic fatigue”

is present when symptoms of disproportionate tiredness, unrelated to activity

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Palliative Care and End-of-Ufe Care

or exertion last for one month or more. Patients complain of “lack of energy,

stamina, or endurance.” (Piper, 1993) Women with fatigue have complained of

decreased stamina at work, lowered quality of work, and frequent absenteeism

possibly putting their jobs at risk. (Semple, 1993)

Once the problem and its meaning to the woman are well-delineated it is important to rule out and treat correctable etiologies. Anemia, depression, fear

of the unknown, hypothyroidism, adrenal testosterone insufficiency (even in

women), occult infection (particularly abscess or MAC), end-stage renal, pulmonary, or cardiac disease, malnutrition, lack of exercise, and disease progression itself aU cause asthenia and fatigue. (O’Dell, 199 ; Groupman, 1998;

Piper, 1998) In HIV disease, it is often a combination of these factors.

Table 12- 3 : Treatable Causes of Fatigue

Adrenal/hormonal insufficiency Insomnia

Anemia Lack of exercise

Depression Malignancy

Disease progression Malnutrition

End-stage organ disease Medications

Fear of the unknown Metabolic (low K/Mg)

Hypothyroidism Occult infection (abscess/MAC)

In a study of 438 ambulatory patients in New York (52% of these had

intravenous drug use as an exposure factor), Breitbart showed a significant

correlation between fatigue and the presence of pain (p< 0.0001); higher psychological distress and poorer QoL (p< 0.0001); more depressive symptoms

on the Beck depression Inventory (BDI) (p< 0.0001 and greater hopelessness

on the Beck Hopelessness Scale (P< 0.0001). (Breitbart, 1998)

Approach to Management

It is important to work with the woman on ways to manage her fatigue even

while the work-up is being pursued:

1 . Showing interest in alleviating this symptom offers her emotional support which helps relieve the fatigue itself

2. Referring her for a physical therapy assessment and prescription of

simple strengthening exercises not only physically attacks the problem

but allows her to begin to rebuild her own self-esteem.

3. Keeping a diary of what helps minimize her fatigue and what she can accomplish in a day as well as a daily numeric score (see quantitating

symptoms) involve her in her own improvement and provide a better

picture of how this symptom affects her daily life.

4. As each possible etiology is addressed, remind the woman to have

realistic expectations in order to avoid becoming discouraged by

false hopes.

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5. Using a positive, encouraging tone and setting small goals are helpful.

6. Nurses are adept at helping women find ways to eliminate or modify

activities which are energy-consuming.

7. For many people, addressing spiritual issues or supportive counseling

at this time may also provide comfort and encouragement.

8. Making use of other health care practitioners not only helps the

woman to cope with this exhaustion but also releases the provider to concentrate more on those physical aspects of management which

need to be addressed.

Pharmacologic treatments include methylphenidate 2.5—5.0 mg in the

morning and repeated in early afternoon or high dose prednisone followed by

a rapid taper. These therapies are usually needed in very advanced disease

when the concern for further long-term immunosuppression is not the most

important aspect of management.

Pain

Scope of the Problem

Breitbart (1996) recendy reported that pain in women with HIV disease is “prevalent, often severe, and highly distressing.” Laschinger, (1999) in reporting a phenomenological study, states that the “pain experience embodies more

than physical pain” (not unlike the “total pain” of Saunders). For this reason,

understanding and controlling pain in women with HIV disease can be quite

difficult as the practitioner must tease out the myriad components in order to

optimally manage this symptom.

Surveys of ambulatory populations with HIV disease have documented

that the prevalence of pain is 40—60%. (Lebovits, 1989; Breitbart, 1996;

O’Neill, 1993; Singer,! 993) For those who have more advanced disease and

may be bedridden, these figures increase to as much as 83%. However, of

those who do have pain, only about 40% are actually treated (Holzemer) and

of those treated only about 40% (Holzemer) ever have adequate pain relief

and can still rate their pain as a “seven out of ten” in severity. (Anand, 1 994)

These findings are universal and not limited to those with a history of substance abuse.

In HIV disease, pain can be caused by the disease itself, by therapies used

to treat the disease, or by unrelated problems. The most frequent types of

pain are abdominal pain and peripheral neuropathy (Anand, 1994; Newsham,

1998) or those caused by infections such as oral, esophageal, or genital/perineal herpes or fungus. Medications for treatment are based on location and

type of pain.

As in cancer patients, up to 80% of persons with HIV disease having pain

will experience more than one pain simultaneously. (Singer,! 993) It is not

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A Guide to the Clinical Care of Women with HIV

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unusual tor a patient who has obtained relief from one pain to notice another

type of pain which has been masked by the now-relieved pain. It is important

to listen to and believe the patient. Carefully document all pain components

and their characteristics to avoid a picture of “pseudoaddiction” or a label of

“drug-seeking” in which an individual who is only partially treated continues

to ask for pain medication. (Weissman, 1989)

( )ne approach to pain management often neglected in the literature is the

“plienomenological” which means understanding the human experience of

pain from the perspective of the patient. Prior to the use of protease

inhibitors, Laschinger (1999) conducted a qualitative study of 22 Canadian

patients predominately gay men but with the one woman who had parallel

experiences. They identified four substantive themes as components of pain:

physical pain, painful losses, pain of not knowing, and social pain. The one

additional factor found in the woman was that she also had concerns related

to her children.

“Physical pain” included joint pain, headache, neuropathic and abdominal

pain, as well as skin and mouth lesions. “Losses” referred to loss of energy,

time, independence, and relationships. “Not knowing” meant the added anxiety of fearing that the pain might be life threatening. And “social pain”

reflected inability to continue to participate in usual activities. The woman’s

fears had to do with how the knowledge of her disease might impact her children’s schooling and how her death would impact their futures. This is a small

but important study because it records the actual feelings of patients as opposed to asking for a provider’s perception of what pain means to the

patient. Although only one woman was represented, the findings are in keeping with our clinical experience.

Barriers to Pain Relief

There are many reasons offered by providers throughout the world for not

prescribing adequate pain relief. (Am Pain Soc, 1999) Many societies fear

“addiction” or diversion of medications. Health care workers often approach

pain management with inadequate training in pain management skills. (Fields, 1998; Portenoy, 1994) Without appropriate knowledge of the pathophysiology either of pain or of its relief, providers may have the same fears

as the public, believing that treating pain can “cause” addiction or that they

must “save” powerful pain killers for a time when they might be “more

needed.” Also there may be the conviction that one should “bear the pain”

to show strength or religious faith. All of these notions, while widely believed,

have no basis in fact.

Principles of Pain Management

Pain, as with any symptom, should be described, quantitated, treated, and

promptly re-evaluated with appropriate dose modification of therapy. The

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Table 12-4: Barriers to Pain Management

Problems Related to Health Care Professionals

Inadequate knowledge of pain management.

Poor assessment of pain.

Concern about regulation of controlled substances.

Fear of patient addiction.

Concern about side effects of analgesics.

Concern about patients becoming tolerant to analgesics.

Problems Related to Patients

Reluctance to report pain • Concern about distracting physicians from treatment of underlying disease. • Fear that pain means disease is worse. • Concern about not being a "good" patient.

Reluctance to take pain medications. • Fear of addiction or of being thought of as an addict. • Worries about unmanageable side effects. • Concern about becoming tolerant to pain medications.

Problems Related to the Health Care System

Low priority given to cancer and AIDS pain treatment. Inadequate reimbursement. • The most appropriate treatment may not be reimbursed or may be too

costly for patients and families.

Restrictive regulation of controlled substances.

Problems of availability of treatment or access to it.

Source: Adapted from AHCPR Clinical Practice Guideline, Number 9, Management of Cancer

Pain, p.17, 1994.

AHCPR Guidelines for the Treatment ofCancer Pain recognize that pain

experienced by those with HIV disease is comparable to the chronic pain

experienced by persons with cancer which often requires management

with opioids. 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.

It is useful to start with the WH.O. ladder approach which uses nonopioids initially and progresses through combinations of therapies and

next to stronger opioids depending on the patient’s response. (See Table

12-5) However, in HIV pain, opioids are frequendy needed because of

the severity of the pain and there is growing literature that the use ofthe

“second step, or weak opioids” might best be eliminated in HIV-relatedpain.

This second step includes “combination” pain medications, those containing an opioid plus aspirin or acetaminophen, which may increase the risk of

hepatotoxicity or bleeding in women on HAART therapy. Becoming familiar

with one or two agents for pain relief makes pain management easier.

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Table 12-5: Pharmacologic Approaches to Pain Management:

W.H.O. Three-step Ladder

W.H.O. Three-step Ladder

Ste

i

p 3: Severe Pain

^ Morphine

Hydromorphone

Methadone

Levorphanol

Fentanyl

Oxycodone

±Nonopioid

analgesics

±Adjuvants

Step 2: Moderate Pain

j ^ APAP or ASA H- Codeine

Hydrocodone

Oxycodone

Dihydrocodeine

Tramadol (not available with ASA or APAP)

« ±Adjuvants

Step 1: Mild Pain

Aspirin (ASA)

Acetaminophen (APAP)

Nonsteroidal anti-inflammatory drugs (NSAIDS)

±Adjuvants

"Adjuvants" refers either to medications that are coadministered to manage an adverse effect of an opioid, or to so-called adjuvant analgesics that are added to enhance analgesia.

Source: Adapted from EPEC Project. Module 4: Pain Management, Part 1. American Medical

Assocation, 1999..

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 relief from pain for monitoring the effectiveness

of therapy.

2. Start with a dose that will acutely relieve the pain. This may be given

intravenously or sub-cutaneously to achieve a rapid response. Care

should be taken to observe for any signs of respiratory depression in

opiate-naive patients.

3. Next, begin a low dose every three to four hours (based on the halflife of the drug) “around-the-clock” and not on a PRN basis. The

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initial dose should be chosen based on the age, size, and renal/hepadc

function of the patient. (Suggestions are given in any standard painmanagement text such as Principles ofAnalgesic Use in the Treatment of

Acute and Cancer Pain, Fourth Edition available from the American

Pain Society at http://www.ampainsoc.org)

4. This dose given every four hours should include a supplemental, or “breakthrough,” dose of about 1 /6 of the total daily opioid dose to

be given every one—two hours between the scheduled doses should

the pain not be controlled. 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;

these 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 two and this number will be your dose every twelve

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 that the pain is not adequately controlled.

Table 12- 6 : Mnemonic for Assessment of Pain

A — Ask about pain regularly; Access 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

Source: Adapted from AHCPR Clinical Practice Guideline, Number 9, Management of Cancer Pain, 1994.

6.

Liquid formulations are useful for those with difficulty swallowing as well as rectal suppositories, “sprinkles” which can be mixed with soft

food, or patches which can be absorbed through the skin.

Side Effects

Opioids usually cause drowsiness in the first 24—36 hours and patients should

be advised that this will resolve. Use a low dose to initiate therapy but be prepared to increase the dose over the next 48 hours based on the patient’s pain

scores. Nausea is another common side effect in those first few days and can be treated with an anti-emetic such as prochlorperazine or lorazepam. AH opioids slow bowel motility and patients should be given a stool softener when

pain medication is prescribed.

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Many prescribers will use an anti-emetic or methylphenidate to counteract

these symptoms over a few days. Prolonged sleeping after the initial dosing

mav simply reflect the woman’s need for rest which has not been possible

because of the pain. If side effects are pronounced over a longer period, it is best to talk with the woman about what else is going on and it may be useful

to discuss with a pain specialist and involve other team members.

Although many providers fear respiratory depression, this is unusual unless an opiate- naive patient is given a large, parenteral dose initially. Most pain (85-

90%) can be controlled with oral medications. If the patient is having severe pain in a controlled situation such as a hospital or hospice, an initial subcuta- neous injection of morphine or hydromorphone may control the pain more

rapidly. Once a patient is on an appropriate dose, side effects (except for the

slowed bowel motility) generally resolve and patient’s return to their usual level

of functioning, or even improved activity, because the pain is relieved.

Table 12-7: Common Side Effects of Opioid Analgesics

Constipation Requires prescription of stool softener at the time of prescribing

opioid; tolerance does NOT develop

Drowsiness Resolves after 24-36 hours; extended sleeping can be from

exhaustion; may need psycho-stimulant e.g. methylphenadate

Nausea Prescribe anti-emetic with first prescription; resolves in several

days - may need around-the-clock dosing

Urinary Retention Uncommon side effect; change opioids or adjuvants

Itching/Twitching May indicate toxic levels due to decreased elimination; lengthen

interval; rotate opioids.

With very high doses, twitching or myoclonus may occur and in this case, it

is possible to alternate two different opioids (referred to as “rotating”) or to

change to another drug entirely. (Galer, 1992) If twitching develops, the

patient may have decreased renal or hepatic clearance. In this case the dosing

interval should be lengthened or different opioids can be used in an alternating fashion.

Opioid Conversions

There are many opioid preparations available. These drugs are not equivalent

on a rniUigram-to-rnilligram basis and it is possible to see what appears to be

“drug-seeking behavior” if the conversion dose chosen is too low. When

changing from one medication to another, use a conversion chart to find the

total dose in morphine-equivalent units and convert according to the table. There is “no ceiling effect” with opioids as there is with other medications

such as acetaminophen, aspirin or tricychcs; i.e., there is no toxic dose and the

patient should be given whatever dose relieves her pain. Just as pain scores are

individual, so are ultimate doses. It may be useful to seek the guidance of

someone knowledgeable in pain management if you as the provider are not

experienced with these medications.

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Table 12-8: Dose Equivalents For Opioid Analgesics in

Opioid-naive Adults and Children ^ 50kg Body Weight

Drug

Approximate Eouianalgesic

Dose

Usual Starting Dose for

Moderate to Severe Pain

Oral Parenteral Oral Parenteral

Opioid Agonist

Morphine 30 mg q 3-4 h

(repeat

around-theclock dosing)

60 mg q

3-4 h

(single dose

or intermit- tent dosing)

10 mg q 3-4 h 30 mg q

3-4 h 10 mg q3-4 h

Morphine,

controlled-release

(MS Contin,

Oramorph)

90-120 mg q

12 h

N/A 90-120 mg q

12 h

N/A

Hydromorphone

(Dilaudid)

7.5 mg q 3-4 h 1 .5 mg q 3-4 h 6 mg q

3-4 h 1.5 mg q

3-4 h

Levorphanol

(Levo-Dromoran)

4 mg q

6-8 h 2 mg q6-8 h 4 mg q6-8 h 2 mg q6-8 h

Meperidine

(Demerol)

300 mg q 2-3 h 100 mg q 3 h N/R 100 mg q 3 h

Methadone

(Dolophine, other)

20 mg q

6-8 h 10 mg q6-8 h 20 mg q 6-8 h 10 mg q6-8 h

Oxymorphone

(Numorphan) N/A 1 mg q

3-4 h N/A 1 mg q 3-4 h

Combination Opioid/NSA/D Preparations

Codeine (with

aspirin or acetaminophen)

180-200 mg q

3-4 h

130 mg q

3-4 h

60 mg q

3-4 h 60 mg q 2 h

(IM/SC)

Hydrocodone

(in Lorcet, Lortab,

Vicodin, others)

30 mg q

3-4 h N/A 10 mg q

3-4 h N/A

Oxycodone

(RoxicodonQ also

in Percocet,

Percodan, Tylox,

others)

30 mg q 3-4 h N/A 10 mg q 3-4 h N/A

Source: Adapted from AHCPR Clinical Practice Guideline, Number 9, Management of Cancer Pain,

p.52, 1994.

Pain Management with a History of Substance Abuse

Those who have used opioids in the past may have a higher tolerance and

thus require higher than usual doses. “Addiction” is a psychological craving

and the use of drugs “to get high” or despite personal harm and should not

be confused with tolerance. When treating someone who has previously (or is currendy) abused drugs, it its useful to discuss the full plan ahead of time. The

patient should understand that this is a two-way interaction, that she must be

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truthful about her pain and its severity/relief as the provider will endeavor to

control the pain. Most people with an addiction history who have legitimate

pain are thankful to have it dealt with in an adult manner and understand that

this is not a dme to engage in manipulative behavior. In fact, many are afraid

to take narcotics for fear of relapse.

Seeking a higher dose of drug does not necessarily mean that the patient is “drug-seeking.” “Losing” or forging prescriptions, stealing from or having

them “stolen” by others, visiting multiple providers for duplicate prescriptions

and injecting oral formulations (Portenoy, 1994) are signs that the patient may

not be using the medication appropriately. She must understand that she will

be given adequate drug to last for a clearly described interval; she cannot

obtain refills on weekends; and that there is only one provider who can write

her prescriptions. Situations involving tampering with prescriptions or selling

medication should be turned over to legal authorities and will sever the

patient-provider supply of medication. Written contracts are used in some

clinics but a well-documented discussion in the medical record is adequate.

Women with a history of substance abuse are often poorly emotionally

defended and may have inadequate coping skills for even minor frustrations.

Low self-esteem and Utde self-confidence can impact pain and make it worse.

Breitbart noted that pain in women is more intense and that those with a history of opportunistic infections or intravenous drug use are “more likely to

experience pain.?” (Breitbart 1995a)

Management of pain is not easy and requires a great degree of trust on

both sides. Being consistent, open, and fair are important attributes for the

pro\tider to model. Providing positive feedback, reducing harm through education, and attempting to understand individual circumstances are most helpful to

the patient. Clearly, as a patient approaches the end of Ufe, old habits and fears

often resurface and, at this time, the patient may need more support than usual.

Gender Differences

There is a growing literature suggesting that pain in women is under-treated.

Breitbart recently reported that women with HIV disease appear to have

“higher levels of pain intensity . .

. [and are] more likely than men with AIDS

to have their pain under-medicated.” (Breitbart 1995b)

Sleep Disturbance/Insomnia

Scope of the Problem

Insomnia and excessive daytime sleepiness are primary complaints in persons

with HIV disease regardless of stage. (Lashley, 1998) Cohen et al (1996)

reported that fuUy two thirds of patients with AIDS have difficulty falling

asleep without correlation with CD4 count. Insomnia includes difficulty falling

asleep, difficulty staying asleep, and early morning awakening.

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I’or women fatigue is not necessarily related to sleep patterns although it is important to document what the vsleeping pattern is. Using questions similar to those in the table, try to determine the pattern of sleep problems, the fre- quency, associated events, as well as other factors listed below. Treatment

should be tailored to the etiology. If you see patients in a busy setting, it is useful to have then fill out a card recalling specific characteristics of the symptom. A nurse can help the patient complete this card, leaving the provider to focus on therapy and documentation.

Assessment

Having the patient keep a sleep diary; bringing a family member to appointments to comment on sleep patterns; and clearly documenting bedtime, how

long it takes her to go to sleep, and how long she can stay asleep provide the

best picture of this problem. Include a full history of caffeine and alcohol

intake and describe the environment and other factors which might affect

sleep. (Lashley, 1998) Review current medications to eliminate these as a possible etiology which may cause insomnia particularly NNRTIs and selective

serotonin reuptake inhibitors (SSRIs) taken at bedtime. Remember that injections drug users may have night sweats and abdominal pains as signs of withdrawal. Simple sleep-wake reversal may herald liver damage. Sleep disorder,

classically early-morning wakening, may be a symptom of depression.

(Nokes, 1999)

Table 12-9: Sleep Problems (Sample questionnaire for office use)

Do you have trouble falling asleep? Or staying asleep?

Do you take naps during the day? Yes No How many hours ? Do any of the following wake you up?

headache fever/night sweats

bad or vivid dreams leg cramps

problems breathing fear

chest pain/heartburn another person in the house

abdominal pains other

need to pass urine

need to move bowels

What have you tried for sleep?

Drug store product Counting sheep

Sleeping pill from friend Warm bath

Hot milk other

Reading

Music

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Management of Insomnia

Treat the underlying problem whenever possible starting with simple environmental modifications e.g. fresh air; quiet (may need white noise emitter); avoiding exercise, heavy meals, large amounts of alcohol or arguing just before bed.

Plain acetaminophen or aspirin in low doses if not contraindicated may be

helpful, as well as short-acting hypnotics or sedating antidepressants e.g. traze- tlone 5(3 mg qhs. When underlying depression is identified, appropriate treat- ment with an SSRJ or a tricyclic antidepressant is indicated. (See Chapter IX

on Psychiatric Issues) Short-acting benzodiazepines are useful acutely but

should be avoided long-term or in patients with dementia since they may

increase confusion. (Ph i lli ps, 1999) Physical interventions such as massage,

relaxation exercises, and deep breathing are also beneficial.

Pruritus/Itching

Generalized pruritus without a rash may be secondary to dry skin, hepatic dysfunction, or an allergic reaction. The rash with scabies in an immunocompromised host may be diffuse and might require biopsy if symptoms do not

respond to empiric therapy.

Along with specific therapy for scabies, the patient should be given an antihistamine to break the cycle of itching. Low doses of an opioid are not

uncommmonly required to conquer this symptom. If the symptoms have been

present for weeks, it may be necessary to follow the night-time scabies treat- ment with 1% hydrocortisone lotion each morning..

If the itching is thought to be secondary to hepatic dysfunction, holding

hepatotoxic agents and using an H2 blocker such as around-the-clock cimetidine for several days is helpful. As the hepatic enzymes return to normal,

medications can be resumed at lower doses and/ or with longer dosing intervals. This is true if the underlying pathology is not related to the lactic acidosis

associated with some anti-retroviral therapies. In this case consult a liver specialist before re-introducing medications. These patients are partially relieved

with a 1% hydrocortisone lotion containing menthol.

Hiccups/Hiccoughs/Singultus

When intractable this symptom can lead to poor oral intake and weight loss as well as to depression because of an interruption of all normal activity. Simple

mechanical measures such as drinking out of the “wrong” side of the glass

and swallowing up-hiU against gravity may transiently interrupt these symptoms. The usual medical treatment is low-dose (12.5—25 mg) chlorpromazine

orally. Metachlopramide, baclofen, amantadine, benzodiazepines and haloperidol (Kaye, 1989; Woodruff, 1999) have also been described as useful although

there is little evidence base for these recommendations. One treatable cause

for this symptom is persistent and severe esophageal candidiasis which

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requires aggressive therapy of this infection for relief. Malignancy impinging

on the phrenic nerve can also cause hiccough and a chest x-ray is recom- mended to rule out a mass.

Xerostomia/Dry Mouth

This condition can be secondary to medications such as antidepressants, anticholinergics, or HIV medications such as ddl or ddC. It is generally reversible

if noticed soon enough and drug is stopped. However, if this condition persists without detection and treatment, it may become permanent. Direct invasion of the salivary gland with HIV can also cause dry mouth. Treatment

should be directed at the etiology.

Artificial saliva, drinking extra fluids with meals, and fluoride treatments

administered by a dentist may be necessary to reverse this symptom. If it is not noticed in a timely manner can lead to tooth decay and gingival disease

may occur, resulting in caries and “sore” teeth. Left untreated, the patient may

withdraw from society and become quite depressed because of the inability to

be comfortable during a meal with others. Pilocarpine drops taken orally four

times per day have been useful in this syndrome. (LeVeque, 1993) However,

the onus is on the provider to ask about the presence of this symptom on a regular basis in order to detect, treat, and reverse the problem.

Dyspnea/Shortness of Breath

In the original hospice studies in this country, dyspnea was one of the five

symptoms correlated with a shortened life expectance even when patients had

no demonstrable disease in the cardiovascular or pulmonary systems. Dyspnea

is an uncomfortable feeling of not being able to breathe although the oxygen

saturation may be normal. Treatment should be directed at the presumed etiology using bronchodilators, diuretics, and steroids as necessary. In the hospice

Literature morphine has been used anectdotally as an aerosol with significant

relief although this has not been formally proven to be useful; subcutaneous

morphine or oral can also be used (start with 5mg every 3^ hours). Clinical

trials are needed to compare aerosolized morphine with saline nebulizers,

which some authors have found equally useful.

Benzodiazepines are desirable to interrupt the cycle of dyspnea and panic

which set in when an individual is having difficulty breathing. A long-acting

drug such as lorazepam O.OSmg can be given around-the-clock every 6—8

hours to minimize the anxiety in this setting.

IV. PROGNOSIS

The use of combination, or highly active antiretroviral therapy (HAART), and

the ability to measure the existing human immunodeficiency viral burden have

significantly impacted the course of HIV disease. With improved antiretroviral

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therapy, use of prophylaxis for opportunistic infections, and treatment by

providers who are knowledgeable about HIV disease, patients can look forward to living longer and healthier lives. However, particularly in resource- poor nations, most will die of this disease. In order to set realistic goals, the

provider must have some sense of the individual’s expected survival time.

Being able to give the patient and family a realistic appraisal of Ufe expectancy, particularly near the end of life, is an important adjunct to disease management. h’or example, if the woman has several months to Hve, this may be

the best time to review and clarify who will help with decision making should

she become acutely or seriously ill. It is also a time to investigate and make

decisions about guardianship as well as to make a will and determine general

advance directives. Deciding which medications to discontinue and when

depend upon the providers projection of how long the patient has to Uve.

While overall prognosis may be difficult to estimate, there are general signs

which reflect advanced disease or failure of the immune system. (N.H.O.,

1 996) I'or example, repeated episodes of opportunistic infections, uncontrollable weight loss, or frequent hospitalizations all suggest that the woman is no

longer “doing well.” Once this decline begins and aU antiretrovirals have been

exhausted or the woman opts for no further aggressive therapy, it is reasonable to focus on issues related to life closure. As the woman becomes weaker,

certain therapies may be withdrawn and attention should be directed toward

psycho-social and spiritual tasks.

In 1996, prior to widespread use of combination therapies, the National

Hospice Organization published Medical Guidelines for Prognosis in Non-Cancer

Diseases, 2nd Edition (Standards Comm, N.H.O., 1996) which described indicators for a shortened life expectancy in several chronic diseases including

HIV/AIDS. When several of these indicators are present, one should consider

the prognosis to be limited unless the use of new or unapproved therapies is possible.

Wasting syndrome based on loss of lean body mass (Kotler, 1989) and ane- mia are both independent risk factors for decreased survival. (Moore, 1 999)

Median time to death can be related to the severity of each. Persistent oral

thrush is also an independent predictor of progression of AIDS. Concurrent

unresponsive malignancy or end-stage organ failure shortens the prognosis.

Worldwide, hepatitis C is rapidly becoming a leading cause of death.

Although it is not weU-documented, the woman’s personal goals may significantly affect life expectancy. The experience in hospice care is that people

must have completed psychosocial and spiritual goals before being able to peacefully “let go.” For women with children this may mean making reasonable

guardianship arrangements. For others it may mean resolving a relationship or coming to terms with her life events or accomplishments. Saying goodbye to loved ones and to care providers is a last necessary step before death.

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Table 12-10: Factors Associated with Shortened Life Expectancy

CD4 persistently low Advanced disease; < 50 cells/cc

Viral burden remains 100,000 copies/ml Despite combination therapy

Functional Status <50

(Karnofsky Performance Status)

Spending > 50% of day in bed

Failure of optimized therapy Multi-drug resistence or failure Desire to forego more therapy Often occurs after multiple

hospitalizations

Anemia (Hemoglobin < 12) Persistent oral thrush

Significant wasting Loss of > 30% lean body mass

Progressive hepatitis C Hepatic failure; drug intolerance

Progressive multi-focal

leukoencephalopathy (PML)

Progressive dependencies; dementia

Unresponsive Kaposi's sarcoma

involving an organ

Progression despite therapy

End-stage organ disease Renal, hepatic, or cardiac failure Persistent diarrhea > 1 mo. No response to treatment

Unresponsive lymphoma/ other

malignancy

Progression despite therapy

Desire of patient for death Acknowledgment by patient and family

of poor prognosis

Source: Adapted from Medical Guidelines for Prognosis in Non-cancer Diagnoses, 2nd Ed., 1997

Moore, AIDS, 1999.

V. TRUTH-TELLING AND BREAKING BAD NEWS

Communication skills are particularly important as the woman’s health begins

to decline. Being a good Listener is paramount and there are concrete skiUs

which can be learned. When discussing emotionally-laden issues or breaking

bad news, it is best to ask what the perceptions are of those present whether

you are addressing the woman alone or her friends and family. “Before I talk,

tell me how you think you are [she is] doing” “What are your concerns at this

time” Not only does this help the provider to know where to begin but it provides a vocabulary to use in this discussion.

Baile and Buckman discuss how to talk about difficult topics described in

Table 12-11. (Baile, 1998) They note the importance of paying attention to the

physical environment when having serious discussions with patients and famiTable 12-11: Mnemonic for Breaking Bad News

S — Setting and listening Skills P — Patient & family Perception of condition

/ — Invitation to patient to determine how much Information he/she wants to know

K — Knowledge; reviewing the facts £ — Explore Emotions & Empathize

S — Summary & Strategy

Source: Adapted from Pocket Guide to Communications Skills in Clinical Practice, 1998, (1-800-

757-4868).

US. DEPARTNmNT OF HEALTH AND HUMAN SERVICES, HEALTH RESOURCES AND SERVICES ADMINISTRATION, HIV/AIDS BUREAU
A Guide to the Clinical Care of Women with HIV

Palliative Care and End-of-life Care

lies. It is important to have privacy, quiet and lack of interruptions as much as

possible, d’he provider should sit down to talk with whatever “family” the

patient wishes to include. The use of touch may be comforting although it is important to gain permission first. Body language and eye contact are a part

of the setting.

Initially, it is useful to find out what the patient or family perceives to

be the current condition. “Before I talk, teU me how you think you are [or

she isj doing” Their answers will help the provider know where to begin.

W'ords used by them will suggest vocabulary as well as degree of comprehension. Avoiding jargon or strictly medical terms is helpful. In the case of bad

news, it is useful to provide a warning statement such as “I have some bad

news for you” or “This is a very difficult time and I want you to be prepared.”

( )nce the facts have been communicated, it is important to determine what

the reaction is to this news. Providing a period of silence may help those

involved to gather their thoughts before speaking. (Weissman, 1999)

Listening skills include asking open-ended questions and repeating the last comment made by patient or family member to clarify what has been said.

Acknowledge emotions by using empathic responses even if the feelings themselves are unimaginable to you. After a period of discussion, develop a strategic

plan with the patient or family by discussing expectations and goals. Use this

time to reassure that there will be future conversations. Summarize what has

been discussed and ask for any remaining questions.

Table 12-12: Making Plans Ahead of Time

1. Appointment of Power of Attorney

for health matters and for financial

matters

These are two different issues; the

healthcare POA does not last beyond

the death; therefore, all plans must be

made and executed ahead of time.

2. Appointment of guardian for children Be certain that children & guardian are both aware of these plans.

3. If there are children left behind Many people make a scrap book,

write a letter, or even make a video

to remind younger children who their

mother was.

4. Make a will if there is anything you

own that you would like to leave to a

particular person

This includes money, a home, dishes

from your grandmother, or jewelry that

has a special meaning to you.

5. Discuss with family or friends how

and where you would like to die

You can be involved in planning a funeral or memorial service; can pick out

your clothes and pallbearers.

6. Discuss desires regarding care before death: For nutrition and hydration

For cardiopulmonary resuscitation For being kept alive on machines

It may be helpful to think about what

you might want in different situations. For example, if you would be bedbound; if you were no longer able to care for yourself; if you would not be able to recognize people or carry on normal conversations.

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IV. REALISTIC GOAL SETTING AND ADVANCE CARE

PLANNING

We must all learn to think ahead to a time when we may not be healthy and

able to care for ourselves. Women, in particular, need to make provisions for

others they care for such as children or an elderly parent. Thinking ahead prevents confusion and also assures that no one person will be burdened with

matters near the time of death. Each woman needs to select someone who

will be able to accomplish her legal affairs and also someone to make medical

decisions for her should she not be able to do so. This may be two different

people but it is important for the woman to discuss her own wishes with that

person early in her illness. By doing it at a time when she feels well, she can remain in control and make her own choices.

A. IMPORTANCE OFMAINTAINING HOPE

To provide the most supportive and sensitive care throughout illness, the

provider must understand the overall goals of the patient. As the woman

moves through her disease it is necessary to intermittently discuss these preferably while the patient is feeling well and able to feel more in control of her dis- ease. Just as quality of life evolves, so do desired outcomes. Many medical

providers seem to fear that having these discussions might “take away hope.”

Hope is not false expectation. It can be re-defined in an acceptable way for

the individual. Whereas hope for a long life may no longer be possible, hope

for being able to leave good memories behind for children may be fulfilled by

making a scrapbook, audio tape, or even a video. One can simply hope for

days that are meaningful. (Bennett, 1 995) Multiple studies document that having a sense of spiritual (not necessarily religious) well-being has a positive

effect on health. (Colman, 1999)

Hope “. . . is the emotion upon which all the other emotions of elation are grounded. . . shaped by a glimpse of something not yet clearly within

sight. . . always looks toward creative changes. . . an expression of the will to

live. . . of an individual’s trust in Ufe. . . even terminally iU persons express the

feeling that things will somehow get better. . . that as long as we live, we live for a better future.” (Kast, 1 996) It is not a commodity that one person gives

to another but is within the individual and can be modified accordingly. Ernst

Bloch (19) in The Principle ofHope wrote

“What matters is learning to hope. Hope does not abandon its post. It

is in love with success rather than failure. Hope, superior to fear. . . reaches out; it broadens rather than narrows.”

He apparently “saw hope in daydreaming, fantasy, and imagination.” Albert

Schweitzer also believed that imagination was what allows the human to toler- ate the present.

us. Dhp.\rtment of Hixalth ,\nd Hu\l\n Services, HEAi.m Resources .\nd Services Administr-oton, HIV/AIDS Bure.au
A Guide to the Clinical Care of Women with HIV

PalUative Care and End-of-life Care

B. PERSONAL GOALS

In discussing goals, it is useful to ask the woman, “What aspects of your life

are most important to you? What have you accomplished in your life that

makes you feel proud?” This is also a time to determine which other persons

she cares about and who provides her support. Frequendy, it is a family

anniversary or event, such as the birth of a grandchild, that comprise the

woman’s true goals.

Each of us has dreams. It is up to the provider or other members of the

team to discover those and help the woman to see how they might be

achieved. With HIV disease the young woman may not have had time to realize her dreams. In this case, the team must help her value the life she has had

and to discover and acknowledge what it is that she wishes remembered about

her life. She can also be assisted in grieving the loss of future. Sharing a funny

story or memory of a special event helps the young woman know that she has

left her mark.

C. ADVANCE CAKE PLANNLNG

Once the provider understands what is important to the woman, it is much

easier to talk about the kind of care she would like to receive near the end of

life. Being able to hold her grand-daughter may be more important than living

another year. Once broad goals cans be identified, the team needs to shift

from a tactical approach to care to a more strategic one. (NEJM, 1996) Bennett (1995) refers to this as changing from a “cure-based approach to a psychosocial model.” It means to target an overall goal rather than to get bogged

down in correcting the electrolytes. Being at home may be more pertinent

than having the last potassium adjusted or receiving the final days of a course of intravenous antibiotics. Being free of pain and in a dry bed with loved ones

present may be the ultimate goal.

While the term “advance directive” makes sense to those in the health care environment, these words may be essentially meaningless to the woman and

those who make up her support system. In trying to determine what the

patient wants it is necessary to use concrete and explicit terms when discussing this topic. Clark (1989) stresses the importance of developing a “psychosocial success” register where psychosocial desires and resolutions can be

formally recognized; this might be done during a case conference with staff

VII. END OF LIFE ISSUES

A. PLLYSICAL COMFORTNEAR THE END OF LIFE

When the patient is bed-ridden, it is comforting to be surrounded by photos

or objects that remind her of events and people she would like to remember

or that make her happy. Being in a home-like environment is the desired

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resting place for many. (American Health Decisions, 1997) Attention to reducing noise, providing a fan or some means of air movement, serving small portions of food several times throughout the day rather than three large meals,

and playing music or reading stories may all provide comfort. If the patient

has a favorite pet or small children she might enjoy short visits with them.

Complementary therapies such as massage, guided imagery, or acupuncture

are widely used and can provide comfort to those for whom they are familiar.

Others may not appreciate being touched by strangers and it is always important to discuss these methods before introducing them. Likewise, incense or

Table 12- 13 : Physician's Card

Side One

Comfort Measures at UFES END

L — LIPS, mouth & eyes moistened; ice chips; artificial saliva /tears

/ — INCONTINENCE of bowel & bladder expected - use Foley/Texas; bed pad

F — FEVERS expected: around the clock antipyretics (po or supp)

E — ELIMINATE all but essential meds

S — SYMPTOM management - be aggressive

E — EATING less is expected; diet as desired

N — NURSING call orders-revise

D — DECUBITUS/skin care/turning q 2 hrs.

Side Two

Making the decision to write "Do Not Resuscitate" orders is often difficult but it does

not mean that there is "nothing else to be done." Once the order "No CPR" is written reverse your thinking and write orders for RPC:

R — REASSURANCE

you will continue to care for the patient and family

symptoms which interfere with good quality of life will be controlled

there are effective ways for coping with stresses and for grieving

patient and family concerns will direct how and where care is provided

P — PRESENCE

be there to hold conversations

visit on a regular basis

sit down and hold a hand

listen respectfully

C — CARING

provide comfort measures

honor the individual

share laughter and touch

Facilitate "life review" & these important conversations:

Thank you

Please forgive me

I forgive you

I love you

Goodbye

Source: © University of Maryland, Baltimore, 1999 Palliative Care Program, Permission to reproduce for educational purposes granted.

us. Department of He.alth and Human Services, Health Resources and Services Administration, HI\VAIDS BurE/\u
A Guide to the Clinical Care of Women with HIV

Palliative Care and End-of-life Care

peppermint oil may be used to mask unpleasant odors; activated charcoal on a gau/e pad or chlorophyll tablets can accomplish the same result.

(kiltural beliefs and rimals become very important at this time. Use the rest of your team to discover what practices must be respected as ignorance of

these might inhibit a peaceful transition as well as leave bad memories for

families and friends, hbr example, some cultures or religions require that the

patient receive fluids or that the healthcare workers give the appearance of

performing resuscitation attempts or efforts to prevent the actual death.

Knowing these beliefs ahead of time will allow the staff to prepare and conversations to be held which might preclude misunderstanding.

( )nce the patient and family have made the final decision for “No car- diopulmonary resuscitation (CPR),” many health care workers are at a loss for

exactly what to do. Although fluids and antibiotics may be withheld, there are

still many techniques which staff can employ to support the patient and family

as a unit. Dr. Linda Emmanual of the Ethics Institute of the American Medical Association has suggested that “Orders to Intervene” should be offered.

Alexander, Perrone, and Reiss have developed a mnemonic for remembering simple medical orders which might be implemented as an example of

these interventions. (See Table 12-13) The care provider should recognize that

despite the end of curative interventions, there is always something which can

be done to comfort both patient and family. By reversing “No CPR” and writing orders for “RPC” the team can continue to offer support. Reassurance of

continued involvement by the health care team, presence at the bedside on a predictable basis, and an attitude of caring which respects individual goals and

comfort are the least that can be done. The Oxford Textbook ofPalliative Medicine, 2nd Edition contains a wealth of knowledge for those who desire to give

good supportive care.

B. CLINICAL TREATMENT

Treatments which have been used throughout active disease may need to be

modified as the woman comes closer to dying. Using complex diagnostic procedures and prolonged courses of therapy may not be necessary at the end of

life and may be a significant burden to the patient. Short bursts of antibiotics

may be aU that is needed to arrest a symptom. Such judgements must be based

on realistic prognosis as discussed earlier in this chapter. For example, a woman resistant to oral antifungal agents may need a brief course of intra- venous therapy if this offers the quickest relief of her symptoms.

If there are high fevers and sweats presumed secondary to MAC she may

no longer tolerate the usual combination of drugs and single agent or short

burst doses may be adequate to control symptoms at a time when a reduced

pill count is the over-riding goal. One of the difficult aspects t)f managing the

end stages of iUness is knowing when it is appropriate to discontinue certain

therapies. Much of this decision making is based on the provider ability to

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provide realistic prognostic information to the patient and family, hbr example, prophylactic therapies might be discontinued in the last 3—4 weeks of life as they can easily be resumed should the woman become symptomatic.

C CONVERSATIONS FOR THE END-OF-LIFE

Families often fear that discussing death might “scare” the dying person.

However, most people know when they are dying and are relieved at being

able to discuss their fears or beliefs. Women in particular, often feel a need to “protect” those around them and may be more comfortable talking about

their impending death with someone who is not a family member. Although

most people feel awkward around someone who is very ill or dying because

they “don’t know what to say” there are a number of things to talk about.

Most people near the end of life want to know that their time on earth has

been worthwhile. They want to know that they have been loved, that they will

be remembered, and that they are forgiven for things they may have done

wrong. One simple method for achieving these goals is to “do life review”

which means to ask to hear stories of the person’s life: what she is most proud

of, what is the funniest thing that ever happened to her, what she is ashamed

of or wishes she hadn’t done. By asking these questions, the listener can reas- sure the person that those memories will stay alive. By talking about negative

events, they can be minimized or forgiven.

An anonymous hospice nurse once said that there are five important conversations for the dying person to have to assure a peaceful death. These are “Thank you,” “Forgive me,” “I forgive you,” “I love you,” and “Goodbye.” The

last of these is the most difficult both for the dying woman and for those who

will be left behind. But, this is the most important conversation because the

dying need to feel reassured that those left behind wiU be able to take care of

themselves. This is especially true of women regarding spouses and children; it

is accentuated when the woman is young and there are young children

involved. Those being left behind

must also say goodbye by giving the

dying woman “permission to go”

which represents their acceptance of

the finality of the death. This permission must also be verbally granted by

health care providers who may have

become like family members near the

end of a long illness.

Forgiveness and reconciliation are spiritual as well as personal issues. (HaU,

1998) Depending on the belief-system of the woman, it may be important to have a priest, a pastor, a rabbi, or other spiritual representative present

throughout the last month of life. In societies where large numbers of women

are dying, there may be insufficient care givers since this is a role often

Table 12-14: Five Important

Conversations to

Complete for a

"Peaceful" Death

Thank you.

/ forgive you.

Please forgive me.

/ iove you.

Goodbye.

us. Dep.\rtment of Heai.TM and Hunun Services, He.\lth Resources and Services Administration, HIV/AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

PaUiative Care and End-of-life Care

assumed by women. It is important to find someone to sit with the dying

woman to provide comfort and security in her last hours. Simple presence

without conversation represents real support and caring.

(ihristina Puchalski defines spirituality as “ whomever or whatever gives one a transcendent meaning in life.” She suggests doing a spiritual assessment

of the woman at the same time that other historical information is gathered,

'fhe mnemonic FICA is useful for remembering what questions to ask.

Table 12-15: Spiritual Assessment - FICA

F — Faith or beliefs Do you consider yourself spiritual or religious?

What things do you believe in that give meaning to your life?

/ — Importance and

Influence

What influence does it have on how you take care

of yourself?

What role do your beliefs play in re-gaining your health?

C — Community Is there a person or group who are really important to you?

Are you part of a religious community?

A — Address How would you like your health care providers to address

these issues?

D. TIME OF DEATH

At the time of death it is important to be familiar with the woman’s customs.

Friends and family present may want to hold hands or stand in a circle around

the bed. A prayer or song may be said or sung together. In many cultures, the

women, or men, depending upon the belief system will want to wash the

body, perhaps apply oils, and to wrap the body in appropriate garments. Staff

should be aware of these practices and allow the family as much time as is needed to complete these rituals. It may be necessary to wait for other friends or family members to arrive to say their own goodbyes. Children should not

be kept from participating and will understand the death within their own agerelated construct.

E. GRIEFAND BEREAVEMENT

Grief is the process and work of adjusting to the irrevocable loss of persons,

objects, relationships, and dreams. The grieving period often begins before

death (anticipatory grieving) but may appropriately extend for two years or more after death depending upon the nature of the relationship. Grief is a normal response to loss and includes such symptoms as sadness, crying, withdrawal from other friends and family, loss of drive or ability to concentrate,

and fears of “losing ones mind” or experiencing physical symptoms similar

those of the person who died. The grieving person requires significant support such as brief visits, phone calls, or invitations to simple social events. Many community hospice programs can provide this type of support.

One role of the palliative care team is to assure that care is given to those

left behind, the bereaved. Because of the concentration of activity near the

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time ot death, the bereaved may not feel the full impact of the death for at least two weeks after the actual event. Contact at this time is helpful as is remembering the person on important anniversaries such as one month after

the death, holidays, and days particular to the individual who died such as a birthday or wedding anniversary. The first and tenth year anniversaries of the

death are a often a difficult time for families and friends. Many cultures have

rituals related to the date of death which continue to comfort those surviving.

Coping strategies that have been useful throughout the disease can also be

applied after the death of a loved one.

Multiple Loss

Having to mourn a second or third person soon after the death of the first is generally more than any individual is able to cope with alone. Dean (1995)

found a direct relationship between the number of bereavement episodes suffered by one person and the development of “stress response” symptoms or

as Rando says “psychic numbing.” (Rando, 1993) Although the phenomenon

of “multiple loss” has been acknowledged in association with natural disasters

and concentrations camp survivors, there has been Htde published about how

to cope with and resolve the issues raised by multiple loss. Many survivors of multiple loss are afraid to openly grieve for fear of losing control of their emotions. Holding onto this grief produces a syndrome

similar to that seen with “burn-out.” (Bennett, 1998; Price, 1984) Emotional

numbing, withdrawal from others, mis-directed anger, a lack of pleasure in

anything, and resorting to use of drugs or alcohol are all common elements of

this syndrome. Kastenbaum (1969) called this series of consecutive losses

“bereavement overload.” More recently Nord has delineated four stages of

response to multiple AIDS-related loss. These are not mutually exclusive

stages and may occur at random rather than in a linear fashion. These stages

include: a) shock and denial; b) overload and confusion; c) facing reality; and

d) re-investment and recovery.

The traditional bereavement model is inadequate for grieving the multiple

losses experienced by survivors of AIDS-related loss. Care of persons with

AIDS is complicated by the fact that the care-giver may himself or herself be

infected and facing death. It is important to be able to refer the care-giver for

appropriate medical care and counseling. Depression is not unusual and, particularly in those who are also infected, should be treated appropriately and

aggressively, even at the time of death of the loved one. Not only members of the gay and hemophiliac communities (which have

been decimated by the epidemic), but mothers of inner city minority youth

who may have experienced the death of more than one child and are often

alone in trying to resolve their grief, are at risk for complicated mourning.

“When multiple deaths occur, the people to whom the mourner would ordinarily go for support are gone.” (Rando, 1 993) Therefore, new models for

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinic.^ Care of Women with HIV

Palliative Care and End-of-life Care

dealing with these losses need to be developed. Survivors of multiple loss

might be helped by a referral for professional counseling.

A time-honored hospice technique has been to attempt to make the sufferer aware of the many manifestations of grief by verbali2ing that thoughts

of “going crazy” are not unusual and by reassuring those grieving that they, as survivors, are and will be OK. According to Nord, “social support, community involvement, and fostering a sense of purpose are useful” toward achieving the goal of empowerment which helps reduce the role of victim.

Achieving a sense of balance in life and pursuing a “life outside of AIDS”

give survivors a necessary source of detachment. Physical exercise, meditation,

and trips away from the usual environment are acceptable methods used to

care for the care provider. An active sense of humor is also helpful.

“Bearing witness” means keeping the memory alive; the AIDS quilt is a good example. The quilt is also an example of the power and importance of

ritual. Making a quilt

panel is a shared experi- ence which provides support for the makers as for

the viewers. Memorial

services on a regular basis can be comforting and

assist the survivor in

bringing closure for an

individual death.

Guidelines for After the Death

Mallinson has outlined guidelines for addressing grief which might be useful

in working with those who are surviving loss from HIV disease. Simply

rehearsing words or phrases ahead of time make it easier for the health care team to interact with survivors during a time which many find awkward.

Acknowledge the death: “I understand that your [partner; spouse] died last week. How is this going for you?”

Validate the importance to the survivor: “You knew her for a long time, and

the two of you were very close. What was she like?”

Speak of the deceased when appropriate: “I remember when Tommy was

first born. This would have been his second birthday this week. How are you feeling?”

Note the existence of multiple losses: “Since you have been coming to

cUnic, you have lost your partner, your best friend, and now, your daughter.

I can’t imagine what it is Uke. How do you handle the grief?”

Learn about grief and loss: Take courses, attend workshops, read research

and acquire therapeutic communication skills.

Table 12- 16 : Methods for Coping with

Multiple Loss

Acknowledge the loss

Normalize feeling of "going crazy"

Physical exercise; adequate sleep

Community service; foster "sense of purpose"

Keep the memory alive

Perform rituals e.g. quilt panel; memorial service

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VIII. CARE OF THE CARE PROVIDER

Palliadve care is difficult work because it recjuires that team members suspend

personal needs or beliefs in deference to the desires of the patient and family.

It recjuires a degree of emotional maturity and insight regarding personal feel- ings/beliefs which might interfere with the work. One must develop coping

skills for both external and internal stressors. (Bennett, 1998) “Debriefing” is important and must be a recognized part of this care.

Although “support groups” often seem like a useful mechanism, they can be burdensome themselves and are not helpful for everyone. Staff must have a recognized way to “take a time-out” and be flexible enough to “cover” for a colleague who needs a bit of time to “re-group.” (Puckett, 1996) Many who

do hospice work have

learned to take breaks, or mini vacations; to develop

outside interests or to do

community service of

another type. Without

conscious support of all members of the team the

burn-out rate would

undoubtedly be high.

(Price, 1984)

Table 12-18: Mnemonic for LIFE'S END

L — LIPS, mouth & eyes moistened; ice chips; artificial saliva /tears

/ — INCONTINENCE of bowel & bladder expected - use Foley/Texas; bed pad

F — FEVERS expected: around the clock antipyretics (po or supp)

F — ELIMINATE all but essential meds

S — SYMPTOM management - be aggressive

E — EATING less is expected; diet as desired

N — NURSING call orders — revise

D — DECUBITUS/skin care/turning q 2 hrs.

Source: © University of Maryland, Baltimore, 1999 Palliative Care Program, Permission to reproduce for educational purposes granted.

Table 12-17: Facilitating the Grieving

Process

1 . Share your thoughts

2. Make time for enjoyable activities

3. Exercise regularly

4. Treat yourself to little extras

5. Work through your grief gradually

Source: Leash, M. Death notification: a practical guide to the process. Upper Access, Hinesberg, Vt. 1994.

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us. Department of Health and Human Services, Health Re.sources and Services Administration, HIV/AIDS_Bureau
A Guide to the Clinical Care of Women with HIV

Palliative Care and End-of-life Care

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us. Department of Heai.th and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
XIII: Occupational Exposure

Rani Lewis, MD

I. INTRODUCTION

The risk of HIV transmission to medical personnel has been recognized since

1 984, with the first reported case of HIV transmitted to a health care worker

(HCW) following needle stick injury. (Anon, 1984) Since that time, informadon regarding occupational exposure and outcomes has been collected. As of

October, 1998 , there have been 187 reported cases in the medical literature of

HIV transmission in the United States (CDC, 1998a) and 264 cases worldwide

(Ippolito, 1999), presumably related to occupational exposure. A HCW is defined as any person whose actiHties involve contact with patients or with

blood and/or body fluid from patients in a health care setting or laborator}-

setting. An exposure is defined as a percutaneous injury (needlestick or other

cut with a sharp object), mucous membrane or nonintact skin ( e.g., chapped

or abraded skin, dermatitis), or prolonged contact and/or contact invohting an

extensive area with blood, tissue, or certain other body fluids. Table 13-1 list t}pes of exposure that )leld a significant health care risk for HIV transmission. Table 1 3-2 lists body fluids with their relative relationship to risk to

exposure. Table 13-3 lists the occupations of people who have been suspected

of infection from occupational exposure. When possible, biomolecular assays, including nucleic acid sequencing, have been used to determine the similarity

in \lral strain between the infected HCW and the possible source. (Diaz, 1999)

Table 13- 1 : Types of Exposure Associated with Transmission’

Percutaneous Needle stick • Diameter of needle • Visible contamination of device • Placement of needle^ • Emergency situation

Sharp object

Skin Non-intact skin • Abraded

• Chapped

Mucous membrane

Intact skin®

Other®

' Not all these modes of exposure are associated with a significant transmission risk requiring PEP

^ Involving needles that had been placed in an artery or vein of the index patient

^There is a theoretical but undocumented risk to HCW from saliva, tears and amniotic fluid, and

with intact skin

us. Dep.^rtment of He-\lth .\nd Hu^LW Ser\ices, He.\lth Resolirces ,\nd Ser\ice.s .'Vdmini.str.mion, HI\7.\ir)S Hi ri-«’ 377
A Ciuini'. I’o •mi'. ( j.ink ;.\ i, (.iARi' oi* \Vomi:n wnii 1 UV

Occupational I'Aposurc

Table 13-2: Body Fluids and Risk of Exposure Requiring PEP

High Risk

OF Transmission

Poorly Defined Risk

OF Transmission Low Risk*

Blood, serum Semen

Sputum, phlegm

Vaginal Secretions

Amniotic Fluid

Cerebrospinal Fluid

Pleural Fluid

Peritoneal Fluid

Pericardial Fluid

Synovial Fluid

Cervical Mucous

Emesis

Feces

Saliva

Sweat

Tears

Urine

* Unless visibly contaminated with blood. Source: CDC. Public Health Service Guidelines for the Management of Health-Care Worker

Exposures to HIV and Recommendations for Postexposure Prophylaxis. MMWR 47{RR7): 2-3, 1998.

Table 13-3: U. S. Health Care Workers with Documented and

Possible Occupationally Acquired HIV Infection and

AIDS, Reported Through June 1998

Occupation Documented Possible

Dental Workers 6

Embalmer/Morgue Technician 1 2 Emergency Medical Technician/Paramedic 12

Health aide/attendant 1 14

Housekeeper/maintenance worker 1 12

Laboratory technician (clinical) 16 16

Laboratory technician (nonclinical) 3

Nurse 22 33

Physician (nonsurgical) 6 11

Physician (surgical) 6

Respiratory therapist 1 2

Technician (dialysis) 1 3

Technician (surgical) 2 2

Technician/therapist other than above 10

Other health care occupations 4

Total 54 133

Source: CDC-NCHSTP- Division of HIV/AIDS Prevention, Fact Sheet-Preventing Occupational HIV

Transmission to Health Care Workers

US. DeparTMent of Health and Human Servicfjs, Health Resources and Services Administr>\tion, HIV/AIDS Bure/\u
A Guide to the Clinic\l Care of Women with HIV

Occupational Exposure

In 1995, the Centers for Disease Control and Prevention (CDC) published

a report of known cases of occupational exposure in France, the United

Kingdom, and the United States. (CDC, 1995) This retrospective case-control

study ga\'e improved information regarding risk factors for transmission. An

important finding in this document was that post-exposure prophylaxis (PEP)

with zido\oidine (ZDV) was associated with an overall 79% reduction in trans- mission with the use of ZDV (OR=0.21, 95% Cl of 0.06—0.57) decrease in

the risk of seroconversion. This prompted the formation of a United States

Public Health Service interagency working group, comprised of members

from the CDC, the Food and Dmg Administration, the Health Resources and

Services Administration, the National Instimtes of Health and other expert

consultants, who developed guidelines for the use of PEP for HCWs after

occupational HIV exposure; these recommendations were updated in 1997.

(CDC, 1996; CDC, 1998b) (Table 13-4)

This chapter will review risk factors for transmission and the magnimde

of risk for HIV transmission from an occupational exposure, prevention

of exposures, and post-exposure management, including PEP with antiretroviral medications.

Table 13-4: Basic and Expanded Postexposure Prophylaxis

Regimens

Regimen

Category Application Drug Regimen

Basic Occupation HIV exposure

for which there is a recognized

transmission risk’

4 weeks (28 days) of both

zidovudine 600 mg every

day in divided doses (i.e., 300 mg twice a day,

200 mg three times a day, or

100 mg every 4 hours)

and lamivudine 150 mg

twice a day

Expanded Occupational HIV exposures

that pose an increased risk for

transmission (e.g. larger volum(

of blood and/or higher virus

titer in blood)’

Basic regimen plus either

indinavir 800 mg every 8 hours

j or

nelfinavir 750 mg three times

a day^

' See Figure 1 for further delineation of transmission risks

^ Indinavir should be taken on an empty stomach (i.e., without food or with a light meal) and with increased fluid consumption (i.e., drinking six 8 oz glasses of water throughout the day);

nelfinavir can be taken with or without meals. Source: CDC. Public Health Service Guidelines for the Management of Health-Care Worker

Exposures to HIV and Recommendations for Postexposure Prophylaxis. MMWR 47(RR7); 1-33, 1998

us. Department of Health and Human Services, Health Resources and Services ADMiNi.s'i'R.vnoN, H1\’/AIDS Hi ri m 379
A (Jiuoi', lo 'mi'. (j.iNicAi, (;ar|', oi' WoMiiN wmi I IIV

( )ccupational I '^xpt)surc

Figure 13-1: Determining the Need for HIV Postexposure

Prophylaxis (PEP) After an Occupational

Exposure’

Step One: Determine the Exposure Code (EC)

Is the source material blood, bloody fluid, other potentially infectious

material (OPIM),^ or an instrument contaminated with one of

these substances?

Yes No > No PEP needed

OPIM^ Blood or bloody fluid

What type of exposure has occurred?

Step Two: Determine the HIV Status Code (HIV SC)

us. Department of Health and Human Services, Health Rf.sources and Services Adminisitlation, HIV/AIDS Bureau
A Glide to the Clinicll Care of Wo.mex with HR"

Occupational Exposure

Figure 13-1: Determining the Need for HIV Postexposure

Prophylaxis (PEP) After an Occupational

Exposure (continued)

Step Three: Determine the PEP Recommendation

EC HIV SC PEP recommendation

1 1 pep may not be warranted. Exposure type does not pose a known risk for HIV transmission. Whether the risk for drug toxicity outweighs the

benefit of PEP should be decided by the exposed HCW and treating

clinician.

1 2 Consider basic regimen.’® Exposure type poses a negligible risk for

HIV transmission. A high HIV titer in the source may justify consideration of PEP. Whether the risk for drug toxicity outweighs the benefit of

PEP should be decided by the exposed HCVV and treating clinician. 2 1 Recommend basic regimen. Most HIV exposures are in this category; no increased risk for HIV transmission has been observed but use of

PEP is appropriate.

2 2 Recommend expanded regimen." Exposure type represents an

increased HIV transmission risk. 3 1 or2 Recommend expanded regimen. Exposure type represents an

increased HIV transmission risk. Unknown If the source or, in the case of an unknown source, the setting where

the exposure occurred suggests a possible risk for HIV exposure and

the EC is 2 or 3, consider PEP basic regimen.

' This algorithm is intended to guide initial decisions about PEP and should be used in conjunction

with other guidance provided in this report.

^ Semen or vaginal secretions; cerebrospinal, synovial, pleural, peritoneal, pericardial, or amniotic

fluids; or tissue.

^ Exposures to OPIM must be evaluated on a case-by-case basis. In general, these body

substances are considered a low risk for transmission in health-care settings. Any unprotected

contact to concentrated HIV in a research laboratory or production facility is considered an

occupational exposure that requires clinical evaluation to determine the need for PER

‘ Skin integrity is considered compromised if there is evidence of chapped skin, dermatitis,

abrasion, or open wound.

^ Contact with intact skin is not normally considered a risk fore HIV transmission. HOwever, if the exposure was to blood, and the circumstance suggests a higher volume exposure (e.g., and

extensive area of skin was exposed or there was prolonged contact with blood), the risk for HIV

transmission should be considered.

® The combination of these severity factors (e.g., large-bore hollow needle and deep puncture)

contribute to an elevated risk for transmission if the source person is HIV-positive.

’’ A source is considered negative for HIV infection if there is laboratory documentation of a negative HIV antibody, HIV polymerase chain reaction (PCR), or HIV p24 antigen test result from a specimen collected at or near the time of exposure and there is no clinical evidence of recent

retroviral-like illness.

® A source is considered infected with HIV (HIV-positive) is there has been a positive laboratory

result fore HIV antibody, HIV PCR, or HIV p24 antigen or physician-diagnosed AIDS.

® Examples are used as surrogates to estimate the HIV titer in an exposure source for purposes of considering PEP regimens and do not reflect all clinical situations that may be observed.

Although a high HIV titer (HIV SC 2) in an exposure source has been associated with an

increased risk for transmission, the possibility of transmission from a source with a low HIV titer also must be considered. TM Basic regimen is four weeks of zidovudine, 600 mg per day in two or three divided doses, and

lamivudine, 150 mg twice daily. " Expanded regimen is the basic regimen plus either indinavir, 800 mg every 8 hours, or netfinavir, 750 mg three times a day. Source: CDC. Public Health Service Guidelines for the Management of Health-Care Worker

Exposures to HIV and Recommendations for Postexposure Prophylaxis. MMWR 47(RR7):2-3, 1998.

US. DERunMENT OF He-Uth .\xd Hl"sl\n Sermces, He-U-TH Resoi-rces .\nd Services .\DvnNt.-mM’ HtV \IDS B. 381
A C'.u ini' TO ini'. CuNicAi, (L\kI'; oi' Wom1';n wrm HIV

( )ccupational Hxposurc

II. MAGNITUDE OF RISK

Correct estimation of the likelihood of transmission following occupational

exposure is limited by the relative infrequency with which HIV transmission to HCWs is reported. In addition, the retrospective nature of this reporting leads

to an increased potential for invalid analysis of the risks. There have been

prospective and retrospective reviews of all published cases that implicate

occupational exposure. The most complete prospective study performed on

data from the United States estimates that the risk of HIV transmission following occupational exposure via single needle stick injury is 0.03%. (BeU, 1997)

This is compared to a risk of approximately 30% for hepatitis B transmission

after percutaneous exposure to HbeAg-positive blood (Alter, 1976; Grady,

1978) and 1.8%—10% infection with hepatitis C after accidental percutaneous

exposure to an HCV-positive source. (Alter, 94; Puro, 1995; Mitsui, 1992)

Ippolito, et al, reviewed the world literature on occupational exposure from an HIV seropositive source, and determined risk to be approximately 0.09% fol- lowing a mucocutaneous exposure. (Ippolito, 1 993) As noted in Table 1 3-2, the

risk from skin exposure or exposure to body fluids/ tissues other than blood

has not been clearly defined. Risk of HIV transmission increases with multiple

exposures and with presence of risk factors listed below.

III. RISK FACTORS FOR OCCUPATIONAL HIV

TRANSMISSION

The likelihood of HIV infection following exposure is affected by the pres- ence of certain risk factors. Cardo, et al, performed a case-control study of

internationally gathered cases of percutaneous exposure of HCW in an

attempt to determine factors that increased or decreased the risk of transmission. (Cardo, 1997) (See Tables 11-5 and 11-6) Their data indicate that HCW’s

who took AZT after potential exposure had an 81% lower risk of becoming

infected (95% Cl 48—94 %) not take this medication.

In general risk factors include:

type of contact or exposure — Exposure has been classified into several risk categories (Table 13-1), including percutaneous, mucocutaneous,

and intact skin contact, with different risks of transmission.

quantity of blood — Exposure to larger quantities of blood from an HIV source, as indicated by a deep needlestick, exposure to needle placed

directly into a vessel, or visible blood on the injuring device is associated

with an increased risk of transmission. While the rates of transmission

have been best studied regarding the use of large bore needles (< 18

gauge), suture needles appear to have a comparable rate of transmission

(P=0.08). (Alter, 1976)

disease status of source patient — Exposure to blood from patients

with terminal illness increases risk. This Hkely reflects risk associated with

us. Department of Health and Human Services, Health Resources and Services Administradon, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Occupational Exposure

exposure to higher levels of virus in blood (higher viral loads). HIV-RNA

level has been shown to be a significant factor in the risk of perinatal

transmission. Individuals with acute HIV infection also have very high

I IIV-RNA levels and probably represent an increased risk of transmission

if occupational exposure occurs. HCW seroconversion has been reported

after exposure to an HIV-infected patient with undetectable viral load.

(CDC, 1998b) Other factors often present in late-stage disease, such as more virulent syncytia-inducing HIV strains, may also increased risk. host defenses — There is some limited evidence that the immune

response of the HCW may effect the risk of transmission. (Pinto, 1997)

Pinto, et al, demonstrated an HIV-specific cytotoxic T-Iymphocyte

(CTL) response among HIV exposed but uninfected HCWs, when the

peripheral blood mononuclear cells were stimulated in vitro by HIV

mitogens. Along with similar responses seen in other groups with

repeated exposure without infection, this suggests the possibility that the

host immune response may be able to prevent establishment of HIV

infection after exposure.

post-exposure prophylaxis —The data of Cardo, et al, confirm the

efficacy of PEP in limiting the risk of HIV transmission to HCW’s. Several cases reports of transmission in the setting of prompt initiation of

PEP, however, indicates that this therapy is not 100% effective. There are greater than 14 known cases of 2idovudine PEP failure following HCW

exposure around the world. (Jochimsen, 1997) HIV resistance to zidovudine or delay in initiation of medication has been hypothesized to play a

role in these (and other, non-HCW) prophylaxis failures.

Table 13- 5 : Logistic -Regression Analysis of Risk Factors for

HIV Transmission after Percutaneous Exposure to

HIV-Infected Blood

Risk Factor

U.S. Cases’ All Cases’

ADJUSTED Odds ratio (95% Cl)^

Deep injury 13.0 (4.4-42) 15.0 (6/0-41)

Visible blood on device 4.5 (1.4-16) 6.2 (2.2-21)

Procedure involving needle in artery or vein 3.6 (1.3-11) 4.3 (1.7-12)

Terminal illness in source patienf 8.5 (2.8-28) 5.6 (2.0-16)

Postexposure use of zidovudine 0.14(0.03-0.47) 0.19 (0.06-0.52)

' All risk factors were significant (P< 0.02)

^ All risk factors were significant (P< 0.01)

^ Cl denotes confidence interval. Odds ratios are for the odds of seroconversion after exposure in workers with the risk factor as compared with those without it.

" Terminal illness was defined as disease leading to death of the source patient from AIDS within two months after the health care worker's exposure. Source: Cardo DM, Culver DH, Ciesielski CA, et al. N Engl J Med 337:1485-90, 1997.

us. Department of Health and Human Services, Health RiisouRCHS and Serviqs Administr vik in, 1 1 I\’/ AIDS Hi ki ' 38.^
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384 us, Departkient of Hf.alth and Hunlxn Services, He.\lth Resources and Ser\ices Administration, HIV/AIDS Bureau
A Guide to the CLrNic\L C\re of \\ omex xxtth

Occupational Exposure

IV. PREVENTION OF OCCUPATIONAL EXPOSURE

Limiting the exposure that a health-care worker has to materials that are

potentially infectious is the key to reducing the risks of occupational exposure.

I'niversal precautions, as recommended by the Occupational Safety and

Health Act (OSHA), reflects the

concept that all blood and body

fluids are potentially infectious

and must be handled accordingl}’.

Personal protective equipment

(Table 1 3-7) should be used to

prevent blood and other potentially infectious material from

eyes, mouth, or mucous membranes. (CDC, 1987)

Handwashing should be done after touching blood, body fluids or secretions, or contaminated items, whether or not gloves are worn. Hands should

also be washed after remoHng gloves and between patient contacts. Gloves

should be worn when in contact with blood or body fluids (including blood

drawing), mucous membranes or nonintact skin, or items contaminated with

possibly infectious material; it is strongly recommended that gloves should be

w’orn when performing any invasive procedure. Clinicians performing surgery,

deliveries, or other invasive procedures likely to generate splashes of blood or

other body fluids should wear a mask and eye protection or face shield. The

use of double-glo\ing in surgical procedures has been showm to reduce the

risk of direct blood contact for operating room personnel. (Greco, 1995;

Konig, 1992) Needles and other sharp instruments should be handled with

great care and disposed of in approved sharps containers. As a rule, do not

recap, bend or break used needles. During surgery hand-to-hand passage of

sharp instruments (e.g. needles, scalpels) should be niinirnized-give consideration to passing these instruments first onto a surgical tray or pan.

Risk of occupational exposure and need for universal precautions applies

not only to physicians, nurses and laboratory workers, but also to medical,

nursing, or dental students, and to dentists. Since reports of patient-to-dentist

and dentist-to-patient HW transmission seen in the late 1980’s (CDC, 1991a),

both the CDC and the American Dental Association have included recommendations regarding the use of barrier precautions in dental settings and

sterile technique in the preparation of dental equipment. (American Dental

Association, 1988)

Another group at increased but less w’eU-defined risk are emergency medical techmcians, paramedics and law enforcement agents. These individuals are frequently in contact with patients of unknown or noncommunicated HIV

status, in emergency situations. NJCTtile 6 of the 133 w’ell documented cases

reaching a HCW^s clothing, skin.

Table 13- 7 : Personal Protective

Equipment

Gloves

Gowns

Laboratory coats

Face shields

Eye protection

Mouthpieces

Resuscitation bags

U.S. DEP.ySTNtENT OF HE-\LTH AND Hu^UN SERMCES, HE.ALTH RESOURCES AND SERVICES ADMINISTR \TK )N, HI\ / AIDS H' t 385
A CJl'idi; i() tiii; (j.inicai, (1\kI'; ()! Womi:n with HIV

( )ccuparional I'-xposurc

occurring in the United States, (.045%) of possible transmission were among

dental workers, twice that many transmissions have been reported among

emergency workers (12/133, 0.09%), placing this gfoup behind only laboratory technicians and nurses/phlebotomists in risk for occupational transmission. OSHA regialations requiring the availability of face masks, mouth shields

and ventilation masks are designed to reduce the risk to emergency technicians

and other public safety workers. Given the highly unpredictable nature of their

risk for exposure, general infection control measures are recommended, even when the risk appears low. (International Association of Fire Fighters, 1988)

Given the prevalence of HIV infection within prison populations, correctional

officers are also at increased risk for occupational exposure and should use

universal precautions. (Hammett, 1991) Intentional human bites and exposure

to saliva are more common in correctional facilities, and may present a risk of

infection transmission and should be evaluated appropriately. While Hepatitis

B has been transmitted via saliva in cases involving human bites (MacQuarrie,

1974; Cancio-BeUo, 1982); in the absence of visible blood in the saliva, exposure to saliva is not considered a risk for HIV transmission. (CDC, 1998b)

V. HIV INFECTION FOLLOWING OCCUPATIONAL

EXPOSURE

While limited, there is some information regarding the symptomatology seen

in HCW experiencing seroconversion from occupational exposure. Approximately four-fifths of cases were associated with symptoms consistent with primary HIV infection a median of 25 days after exposure . (CDC, 1998b) The

average time to seroconversion is 65 days and 95% of infected HCWs have

seroconverted within 6 months after exposure. (Busch, 1 997) There are rare reported cases of HCW who remain negative for HIV antibody at 6 months,

but seroconvert by 12 months after exposure. (Konig, 1992; Ciesielski, 1997)

Delayed seroconversion has been associated with simultaneous exposure to

hepatitis C in two cases, one of which resulted in fulminant and fatal HCV.(Ridzon, 1997) Further information regarding the effect of coinfection

with other viral illnesses remains to be determined.

HCW’s presenting for HIV exposure PEP need to be counseled regarding

risks of other viral illnesses to which they may have been exposed. Occupational exposure to both Hepatitis B and Hepatitis C virus has been reported.

While aU three of these viruses have similar routes and modes of exposure,

the risk of transmission differs due to the differing prevalence of infection.

The probability of a source patient from the general population being HBsAg

positive ranges from 5—1 5%; 6—30% on non-immunized HCW’s will become

infected following a needlestick injury. (CDC, 1989) HCW’s at risk for occupational exposure to hepatitis B should therefore assure appropriate vaccination

against this virus. PEP for HBV is available.

us. Demrtment of Health .and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Occupational Exposure

I Icpatitis C virus is the most common chronic blood borne infection in the

I'nited States. The Third National Health and Nutrition Examination Survey

(Nl lANES III) data estimates 3.9 milli on Americans have been infected with

1 ICV, with 36,000 new infections reported per year. (CDC, 1998c) The average

incidence of HCV seroconversion following a single needlestick exposure

from an HCV seropositive source is 1.8%. Exposure via mucous membranes,

while extremely rare, has been reported. (Sartori, 1993) Of note, there is no

vaccine or immunoglobulin available for HCV PEP.

VI. POST-EXPOSURE MANAGEMENT

1 lealth care organizations are required to have exposure-control plans, including postexposure management and follow-up for employees at risk. The

( Iccupational Safety and Health Administration mandates reporting of

exposure incidents.

A. MANAGEMENT OE THE SITE OE EXPOSURE

Wounds/puncture sites should be washed with soap and water; mucous membranes exposed should be flushed with water. The application of bleach to

skin or mucosal surfaces is not recommended.

B. EVALUATION OE THE EXPOSURE

The type of body fluid involved, type of exposure (e.g., percuaneous, mucosal,

intact skin, etc), and the severity of the exposure (quantity of blood, duration

of contact, etc) should be evaluated and will affect decisions about PEP. (See

Table 13-1)

C EVALUATION OE SOURCE PATIENT

The source individual of the exposure should be evaluated for possible HIV

infection and , if status is unknown, should be tested, after appropriate consent. Past medical information, such as past HIV test results, clinical signs,

symptoms, or diagnoses, and history of risk exposures (e.g., injection drug use,

etc) may be relevant in making initial decisions regarding PEP. The use of

rapid HIV testing , if available, may be particularly useful in the setting of

occupational exposure. Initiation of PEP, if indicate, should not be delayed

while awaiting test results. If the source is known to be HIV infected, information about clinical stage of infection, recent CD4 counts, viral load testing,

and antiretroviral treatment history are important in choosing an appropriate

PEP regimen; however, initiation of PEP should not be delayed if this information is not immediately available.

The source patient should also be tested for anti-HCV and HbsAg to

assess risk to the HCW for hepatitis B and C.

us. Department of Health and Human Services, Health RESouRCiiS and Services ADMiNis-re.vnoN, HIV/.MILS Huri-.m 387
A (Ji'ini: ro mi'. ('uNicAi, (;aki: ()! WoMi'N wirii IIIV

Occupational lixposurc

D. BASELINE AND EOLLOW-UP TESTING

Baseline testing for HIV antibody should be performed to establish serostatus

at the time of exposure and should be repeated at 6 weeks, 12 weeks, and 6

months postexposure, regardless of the use of PEP. An extended duration of

follow-up may be considered with simultaneous exposure to HCV or use of

HAART regimens for PEP because of theoretical concerns about delay in

HIV seroconversion in this situations. Pregnancy testing should be offered to HCWs of reproductive age if pregnancy status is unknown.

In addition to HIV, hepatitis B and C are significant concerns from occupational exposures. For the HCW exposed to an HCV-positive source, baseline

and follow-up testing (at 4—6 months) for anti-HCV and serum alanine aminotransferase is recommended. Confirmation by a supplemental assay (such as recombinant immunoblot assay) is recommended for all positive anti-HCV

results by enzyme immunoassay. (CDC, 1998b)

If the HCW has previously received HBV vaccine and anti-HBsAg level,

which reflects vaccine-induced protection, is unknown, this should be tested ; if inadequate, HBIG is recommended, as well as a booster dose of vaccine.

E. COUNSELING OE THE HCW

Decisions regarding appropriate post-exposure management should be individualized; the HCW should be counseled about their personal risk based

on considerations outlined above, and recommendations made re: initiation

of PEP

The HCW should be informed that knowledge about the effectiveness and

the toxicity of the antiretroviral drugs used for PEP is Limited; only ZDV

has been shown to reduce the risk of HIV transmission in occupational set- tings to date and failures of ZDV prophylaxis have been reported. (Jochimsen, 1997) The addition of other antiretroviral drugs to a PEP regimen is based on the superiority of combination antiretroviral regimens over monotherapy in the treatment of HIV-infected individuals and the theoretical considerations regarding possible resistance concerns and the utility of

using drugs having activity at different stages in the viral replication cycle.

The medical history of the HCW , including medications, presence or possibility of pregnancy, or other medical conditions should be obtained and

may influence decisions /recommendations about PEP, including choice of

regimen

A specific PEP regimen should be recommended, when indicated, and the

rationale for its selection should be discussed. (See Table 1 3-4) Information

should be given about how to take tlie medications; potential side effects

and measures to minimize these; possible drug-drug interactions with rec- ommended regimen and any medications that should not be taken while

taking PEP; clinical monitoring for toxicity; and symptoms that should

us. Dep.\rtment of Health .and Human Services, Health Resourcf.s and Services Adminisi-R/OTON, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Occupational Exposure

prompt immediate evaluation (such as back or abdominal pain or blood in

the urine, possibly suggesting renal stones in those on indinavir). The

importance of adherence should be emphasized.

may be declined by the HCW

The new should be urged to seek medical evaluation with the development of any acute illness during the follow-up period. The differential diagnosis in this situation must include acute HIV infection, drug reaction,

toxicity from the PEP regimen, or other medical illness.

Measures to reduce the risk of possible secondary transmission during fol- low-up (especially in the 6—12 weeks after exposure) should be discussed

and recommended. These include use of condoms or abstinence to prevent

sexual transmission and pregnancy; refrain from donation of blood, plasma,

tissue or organs ; and , in lactating mothers, consideration of discontinuation of breastfeeding.

There is no need to modify clinical responsibilities based on HIV exposure.

Each HCW should be given a contact name and/or number to caU with concerns or questions.

HBV prophylaxis: If the patient source of exposure is HbsAg positive and

the HCW has not been vaccinated, hepatitis B vaccination should be initi- ated and a single dose of hepatitis B immune globuUn (HBIG) should be

administered as soon as possible after exposure and within 24 hours if possible. If the source patient is HbsAg negative and the HCW has not been

vaccinated against HBV, vaccination should be initiated. (CDC, 1991b)

E POST-EXPOSURE PROPHYLAXIS

The decision regarding which and how many antiretroviral agents to use is largely empiric. Current recommendations are to use a two- or three-drug regimen based on level of HIV transmission risk and possibility of drug resist- ance (See Table 13-4) . PEP should be initiated as soon as possible following

exposure, and continued for 4 weeks. The HIV Postexposure Prophylaxis

(PEP) Registry demonstrated no specific adverse events associated with HIV

PEP in HCW’s; The registry was closed in December, 1998. Information

regarding this program can be obtained through the CDC’s Hospital Infections Program (404-639-6425) or on the internet. (URLaddress:

http:/ /www.cdc.gov/ncidod/hip/Blood/PEPRegistry)

Fifty to ninety percent of HCW receiving PEP (ZDV or combination of

agents) report subjective side effects and these have led to discontinuation of

therapy in 24—36% of cases. (CDC, 1998b) Common side effects in those on

ZDV include nausea, vomiting, fatigue, headache, and insomnia. Serious side

effects, including renal stones and pancytopenia have been reported with combination PEP regimens. For more details about side effects with different antiretroviral agents, see Chapter XTV on Pharmocology. Laboratory monitoring

us. Department of Health and Human Services, Health Resources and Services Administra i'ion, lll\7AID^ Hi ri .m- 389
A CSuioi; TO I'nr^ ('i.inicai, (L\r|' oI' Womi;n with HIV

Occupational l^xposurc

should include a complete blood count , renal and hepatic function tests at baseline and 2 weeks after initiation of PEP; more in-depth testing may be

indicated based on uncierlying medical conditions or specific toxicity associated

with drugs in PEP regimen (e.g., glucose testing if on a protease inhibitor).

VII. SPECIAL CONSIDERATIONS

A. ANTIRETROVIRAL RESISTANCE

It is unclear whether or how antiretroviral resistance influences risk of HIV

transmission. Transmission of drug-resistant strains has been reported, (Imrie,

1997) and therefore is a possible concern in PEP situations. If resistance of

the source patient’s virus to one or more of the drugs in the PEP regimen is known or suspected, drugs should be selected to include agents to which the

virus is likely to be sensitive. Clinical consultation with an expert in HIV treat- ment should be obtained for guidance in this situation. However, it is important to avoid delay in starting PEP because of resistance concerns; if resistance is known or suspected a third or fourth drug may be included in the

regimen until consultation is obtained.

B. PREGNANTHCW

In addition to the counseling issues noted above, the pregnant HCW should

be informed about what is known and not known about potential risks, benefits, and side effects for the fetus and herself related to the antiretroviral

agents used in PEP. (Issues relating to the use of antiretroviral drugs in pregnancy are discussed in Chapter VII on HIV and Reproduction, and in Chapter

XIV on Pharmacology.) PEP should not be denied on the basis of pregnancy

and pregnancy should not prevent the use of an optimal PEP regimen. For

breastfeeding HCWs, temporary discontinuation of breastfeeding should be

considered while on PEP to avoid infant exposure to these drugs.

VIII. THE HIV SEROPOSITIVE HCW

There has been great controversy about HCWs who are infected with HIV

and continue to work. The infection of several patients by an HIV seropositive dentist is well known although poorly understood. However, in four separate studies involving a total of 896 surgical and dental patients exposed to HIV infected providers, only one patient was found to be HIV seropositive

and this individual had other risk factors for HIV. (CDC, 1991c) Health care workers with HIV may also themselves be at risk for contracting a communicable disease; appropriate precautions should be taken and appropriate immunizations given.

All clinicians with exudative or transudative skin lesions should refrain

from direct patient care until these lesions have healed. It is believed that

us. Department of Health and Human Services, Health Resources and Services Administr^ition, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Occupational Exposure

I llV-positive nCWs who follow universal precautions and do not perform

im-asive procedures pose no risk to their patients. Furthermore, there are no

current data suggesting that HIV-positive HCWs performing non-exposureprone invasive procedures should have their practice restricted, assuming they

use universal precautions, appropriate technique, and adequate sterilization and

disinfection of instruments.

“lixposLire-prone” procedures require more consideration. Exposure-prone

characteristics include digital palpation of a needle point in a body cavity or

the simultaneous presence of the HCWs fingers and a needle or sharp instrument in a poorly visualized or highly confined anatomic space. These procedures are associated with increased risk for percutaneous injury to the HCW

and potential increased risk to the patient. It is recommended that all HCWs

who perform these procedures know their HIV status. HIV-positive HCWs

performing exposure-prone procedures should seek counsel from an expert

review panel on a case-by-case basis. Mandatory testing of HCWs in not rec- ommended. The ethics of patient notification of exposure to an HIV-infected

HCW continues to be argued. (Blatchford, 2000; Donnelly, 1999)

It is imperative that institutions have a standard policy on the management

of HIV-infected HCWs, as well as policies on the management of a HCW

potentially infected by a patient. (CDC, 1991c)

REFERENCES

Alter MJ. Occupational exposure to hepatitis C virus: a dilemma. Infect Control Hosp Epidemiol 15:742-4, 1994

Alter HJ, Seef LB, Kaplan PM et al. Type B hepatitis: the infectivity of blood positive

for re antigen and DNA polymerase after accidental needlestick exposure. NEJM

295: 909-913, 1976

American Dental Association. Infection control recommendations for the dental office

and the dental laboratory. JAm Dent Assoc 116:241—8, 1988

Anonymous. Needlestick transmission of HTLV-III from a patient infected in Africa.

Lancet 1984

BeU DM. Occupational risk of human immunodeficiency virus infection in healthcare

workers: an overview. Am J Med 102(suppl 5B):9—15, 1997

Blatchford O, O’Brien SJ, Blatchford M, Taylor A. Infectious health care workers:

should patients be told? J Med Ethics. 26(1):27—33, 2000

Busch MP, Satten GA. Time course of viremia and antibody seroconversion following

human immunodeficiency virus exposure. Am J Med 102(suppl 5B):117—124, 1997

Cancio-Bello TP, de Medina M, Shorey J, Valledor MD, Schiff ER. An instimtional out- break of hepatits B related to a human biting czintt. J Infect Dis 146:652-6, 1982

Cardo DM, Culver DH, Ciesielski CA Srivastava PU, Marcus R, Abiteboul D, lleptonstaU J, Ippohto G, Lot F, McKibber PS, Bell DM, and the Centers for Disease

Control and Prevention Needlestick Surveillance Group. NEnglJ Med

337:1485-90, 1997

U.S. Department of Health and Hum/\n Services, Health Resources and Services Adminis'ihation, HIX'/AIDS Hi'ri-.ai' 391
A CJuiDF, TO 'mi; Clinical Cari: oi' WoMKN wnii HIV

Occupati(jnal F-xposurc

Cicsiclski (]A, Metier RP. Duration of time between exposure and seroconversion in healthcare workers with occupationally acquired infection with human immunodeficiency virus. Am J Med 102(suppl 5B): 115-6, 1997

CDC. Recommendations for Prevention of HIV Transmission in Health-Care Settings.

MMWR 36(suppl 2S):1-16, Aug 21, 1987

CDC. Guidlines for Prevention of Transmission of Human Immunodeficiency Virus

and Hepatitis B Virus to Health-Care and Public Safety Workers. MMWR 38(suppl

6):l-37,June 23, 1989

CDC. Epidemiologic Notes and Reports Update: Transmission of HIV Infection during an Invasive Dental Procedure — Florida.. MMWR 40(2):21—27, Jan 18, 1991a

CDC. Hepatitis B virus: A comprehensive strategy for eliminatng transmission in the

United States through universal childhood vaccination: recommendations of the

ACIP. Appendix A: Postexposure prophylaxis for hepatitis B. MMWR 40 (RR13):21-25, 1991b

CDC, Recommendations for Preventing Transmission of Human Immunodeficiency

Virus and Hepatitis B Virus to Patients During Exposure-prone Procedures.

MMWK 40(RR-08); 1-9, 1991c)

CDC. Case-control study of HIV seroconversion in health-care workers after percuta- neous exposure to HIV-infected blood France, United Kingdom, and United

States, January 1988—August 1994. MMWR 44:929—33, 1995

CDC. Update: Provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR 45(22):468—72, 1996

CDC/National Center for HIV, STD and TB Prevention, Fact Sheet, October 1998a

CDC. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR

47(RR-7):l-34, 1998b

CDC. Recommendations for prevention and control of hepatitis C 'virus (HCV) infection and HCV-related chronic disease. MMWR 47 (RR-19):1—39, Oct 16,1998c

Diaz RS, De OUveira CF, Pardini R, Operskalski E, Mayer AJ, Busch MR HIV type 1 tat gene heteroduplex mobility assay as a tool to establish epidemiologic relationships

among HIV type 1 -infected individuals. AIDS Res and Hum Retroviruses 15(13):

1151-6, 1999

Donnelly M, Duckworth G, Nelson S, Wehner H, GiU N, Nazareth B, Cummins A. Are

HIV lookbacks worthwhile? Outcome of an exercise to notify patients treated by

an HIV infected health care worker. Commun Dis Public Health. 2(2): 126—9, 1999

Grady GF, Lee VA, Prince AM et al. Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multicenter controlled trial. J

Infect Dis 138:625-38), 1978

Greco RJ, Garza JR. Use of double gloves to protect the surgeon from blood contact during aesthetic procedures. Aesthetic Plast Surg 19:265—267, 1995

Hammett TM. 1990 update: AIDS in correctional facilities. Washington; US. Department of Justice, 1991.

Imrie A, Beveridge A, Genn W, Vizzard J, Cooper DA, the Sydney Primary HIV Infection Study Group. Transmission of human immunodeficiency virus type 1 resist- ant to nevirapine and zidovudine. / DA 175: 1502—6, 1997

International Association of Fire Fighters. Guidelines to prevent transmission ofcommunicable disease during emergency care forfirefighters, paramedics, and emergency medical

technicians. International Association of Fire Fighters, New York City, New York,

1988.

U.S. Department of Health and Human Services, Health Resources and Services Administrahon, HW/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Occupational Exposure

Ippolito ( I, Puro Dc Carli G, the Italian Study Group on Occupational Risk of HIV

Infection. The risk of occupational human immunodeficiency virus infection in health care workers: Italian multicenter smdy. Arch Intern Med 153:1451—8, 1993

Ippolito G, Puro V, Heptonstall J, Jagger J, De CarU G, Petrosillo N. Occupational

1 luman Immunodeficiency Virus Infection in Health Care Workers: Worldwide

(iases Through September 1997. Clin Infectious Dis 28:365—83, 1999

lochimscn li,M. failures of zidovudine postexposure prophylaxis. Am J Med 102(suppl

5B):52-55, 1997

Konig M, Bruha M, Hirsch HA. Perforation of surgical gloves in gynecologic operations

and abdominal Cesarean section. Geburtshilfe Frauenheilkd 52\\Q9—W2, 1992

Mac(,)uarrie MD, h’orghani B, Wolochow DA. Hepatitis B transmitted by a human bite. JAMA 230:723^, 1974

Mitsui T, Iwano K, Masuko K et al. Hepatitis C virus infection in medical personnel

after needlestick accident. Hepatology 16:1109—14, 1992

Pinto LA, l.anday AL, Berzofsky JA, Kessler HA, Shearer GM. Immune response to human immunodeficiency virus (HIV) in healthcare workers occupationally

exposed to HIV-contaminated blood. Am J Med 102(suppl 5B):21—4, 1997

Puro V, Petrosillo N, IppoHto G. Italian Smdy Group on Occupational Risk of HIV and

Other Bllodborne Infections. Risk of hepatitis C seroconversion after occupational exposures in health care workers. Am J Infect Control 23:273—7, 1995

Ridzon R, Gallager K, Ciesielski C, Mast EE, Ginsberg MB, Robertson BJ, Luo CC,

DeMaria l\. Simultaneous Transmission of Human Immunodeficiency Virus and

I lepatitis C Virus from a Needle-Stick Injury. NEnglJ Med 336:919—22, 1997

Sartori M, La Terra G, Aglietta M, Manzin A, Navino C, Verzetti G. Transmission of

hepatitis C via blood splash into conjunctiva [letter]. ^/IMT 25:270—1, 1993

us. Department of Health and Human Services, Hf.alth Resources and Skrvicfls Adminis-i-r.viion, HIWAIDS Huri.ai 393
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XIV: Pharmacologic Considerations in

HIV-infected Pregnant Patients

Paul Pham, PharmD and Patricia Barditch-Crovo, MD

1. LIST OF TABLES

Table 14-1: Antiretrovirals 4—11

Table 14-2: Commonly Used Antimicrobials for the Treatment

and Prevention of Opportunistic Infections in

HIV-Infected Patients 12—30

Table 14-3: Safety of Commonly Used Antimicrobials 31-34

Table 14-4: Drug Interactions of Antimicrobials 35—56

Table 14-5: Clinically Pertinent Food-Drug Interactions 57

Table 14-6: Drugs of special consideration in women 57

Table 14-7: Alternative/ Complimentary Medication to Avoid

in Pregnancy 58-61

II. INTRODUCTION

The decision to administer drugs to a pregnant woman is largely based on the

therapeutic benefit to the mother and/or fetus versus the perceived risk to the

developing fetus. Clinicians are usually advised to avoid prescribing drugs for

pregnant patients since human safety data in pregnancy are lacking for many

medications. However in some clinical situations the benefits far outweigh the

risks. These are important considerations when selecting agents to treat patients with human immunodeficiency virus (HIV), to prevent its transmission, and to prevent associated opportunistic infections.

There is limited information concerning the safety of many antiretrovirals in

pregnancy. Mutagenicity and teratogenicity studies in animals are the basis for

most safety in pregnancy data. Animals are administered doses 5- to 20-times

higher that those given to humans; clinical applicability is not always evident.

It is now standard care to treat for HIV-infected patients with an “antiretroviral cocktail” making it increasingly difficult to assess the safety of a single

antiretroviral agent. More prospective clinical data are needed. Clinicians are

us. Department of Health and Human Services, Health Resources and Services ADMiNis-ncvnoN, fHV/.MDS Bure.m 395
A C'lUini'; 'I'o thI', ( j.iNicAi. (^\r|' oi' Womun wi th HIV

Pharmacologic (Considerations of ARV Therapy in HIV-Infected Pregnant Patients

encouraged to report all in utero exposures to The Antiretroviral Pregnancy

Registry (1-800-258-4263), a collaborative effort between the National Insti- tutes of Health, Centers for Disease Control and pharmaceutical companies:

Outcome data compiled from the Registry are used to monitor birth defects.

The Food and Drug Administration (FDA) has developed a classification

system to help clinicians choose agents safe for use in pregnancy. (Tables 14-1,

14-2, 14-3, and 14-6)

III. RISKS OF ANTIRETROVIRAL DRUGS IN PREGNANCY

Certain antiretroviral agents should be avoided during pregnancy, either

because of effects inherent to the drug itself, or the potential for dangerous

interactions. Administration of efavirenz to pregnant cynomolgus monkeys is associated with anenecephaly, unilateral anophthalmia, microopthalmia and

cleft palate in newborns'. Hydroxyurea produces mutagenesis and teratogenesis in many animal species; it should not be given during pregnancy-.

Antiretroviral therapy is often complicated by side effects in relatively

healthy HIV-infected nonpregnant adults which could be exacerbated in

pregnancy or put the fetus at risk. Protease inhibitors, for example, have been

associated with the development of glucose intolerance and even diabetes melUtus. Hyperglycemia in pregnancy leads to increased risk of macrosomia, fetal

distress, pre-eclampsia and stiUbirthk In patients taking indinavir, 10% develop

indirect bihrubinemia (i.e., > 2.5%) and nephrolithiasis has been reported in 5-

15%“’. Any of these adverse effects wiU complicate a pregnancy.

Because many patients turn to so-called complimentary or alternative therapies, it is important to take a complete medication history, including over-thecounter drugs and nutritional supplements . St John’s wort lowers trough

indinavir drug concentrations (Cmin) by 81% when administered concurrently

[Lancet 2000; 355(9203): 547-8]. Because St John’s wort induces cytochrome

P450 3A enzymes, it will likely decrease levels of other protease inhibitors and

non-nucleoside reverse transcriptase inhibitors. Therefore, St John’s wort

should not be taken with antiretroviral medications. Since safety data for

herbal alternative therapies are scarce, these agents should be avoided during

pregnancy. Table 14-6 summarizes data on alternative therapies to avoid

during pregnancy.

IV. BENEFITS OF ANTIRETROVIRAL DRUGS IN

PREGNANCY: DRUGS TO CONSIDER

One example in which the benefit far outweighs the risk of drug administration during pregnancy is evident in the use of zidovudine (AZT) in preventing

perinatal HIV transmission (ACTG study 076)^ Administration of AZT to the

pregnant HIV-infected mother after the first trimester, during labor, after labor

us. Department of Health and Hum.\n Servicf.s, He.u.th Resources and Services Administration, HIV/AIDS Bure.\u
A Guide to the Clinical Care of Women with HIV

Pharmacologic Considerations of ARV Therapy in HIV-Infected Pregnant Patients

and to the newborn reduced the perinatal acquisition of HIV. In addition,

uninfected infants exposed to AZT in this study and followed to a median age

of 3.9 years, have not shown a significant difference in growth, neurological

tlevelopment or immune status when compared to uninfected infants exposed

to placebo*. The use of AZT during pregnancy and delivery has become the

standard of care in the United States; however due to its high cost, its administration during pregnancy is not feasible in developing countries.

The HIVNET 012 trial compared the administration of one dose of nevirapine given orally to the mother during labor followed by one dose of nevirapine to the infant within 72 hours after birth to the adrniriistration of AZT

during labor followed by AZT to the infant for 7 days. The 14-16 week post

delivery data showed that while both regimens were well tolerated, 25.1% of

infants in the AZT arm and 13.1% of infants in the nevirapine arm were

infected with HIV (p=0.0006)7 Although long-term safety data are not currendy

available for nevirapine, this regimen may provide a simple and inexpensive regimen to prevent perinatal transmission of HIV in less developed countries. The

current guidelines state that pregnancy per se should not preclude use of optimal therapeutic regimens. Therefore pregnant women should be treated according to standard guidelines for antiretroviral therapy in adults, with sustained

reducdon of viral load as the primary objective. (MMWR 1998; 47[RR-2])

V. PHARMACOKINETICS OF ANTIRETROVIRAL DRUGS

IN PREGNANCY

Although many physiologic changes occur during pregnancy, few trials have

been conducted to evaluate their clinical significance on the pharmacokinetics

of commonly used drugs. Physiologic changes that may affect drug pharmacokinetics include: delayed gastric emptying, decreased intestinal motility,

increased volume of distribution (an average increase of 8L), increased renal

blood flow (by 25-50%) and glomerular filtration rate (by 50%)® ’"’. The

serum half-life of nevirapine is reduced from 66 hours in non-pregnant

women to 45 hours in pregnant women; this decrease is not likely to be clini- cally significant". Pregnancy does not change the pharmacokinetics of AZT,

3TC and ddl.’^ " ’^

The absorption and pharmacokinetics of many of the anti-HIV drugs are affected by food. Table 14-5 lists pertinent food-drug interactions that are probably as valid for pregnant women as for a non-gravid population.

Table 14-1, on the following pages, provides a quick reference on dosing

recommendations, FDA Pregnancy Risk Classification, animal teratogenicity

and human experience in pregnancy for the most commonly prescribed drugs

in the treatment of HIV infection.

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450 us. DEP.WTNtENT OF Hf,.\LTH AND HUMAN SERVICES, HEALTH RESOURCES AND SERVICES ADMINISTR-ATION, HIV/AIDS BUREAU
A Guide 'ro the Clinical Care of Women with HIV

Pharmacologic Considerations of ARV Therapy in HIV-Infected Pregnant Patients

Table 14-5: Clinically Pertinent Food-Drug Interactions

Ganciclovir Capsule/ Itraconazole Capsule / Nelfinavir / Ritonavir:

Should be taken with food or within 2 hours of eating.

AZT:

Can be taken with food to decrease Gl side effects.

Saquinavir (Fortovase® and Invirase®) / Atovaquone:

Should be administered with a high fat meal

Efavirenz / Amprenavir:

High fat meal should be avoided

Didanosine / Indinavir / Itraconazole Solution:

Should be taken on an empty stomach (1 hour before or 2 hours after meals).

Grapefruit Juice: Increases saquinavir levels 40-100% but decreases indinavir AUC by 26%.

Table 14-6: Drugs of special consideration in women

Drug Name

FDA

Class Comments

Terbutaline B Terbutaline has produced significant increases in birth weights (Briggs et al, 1998). Follow-up studies did not

show increased adverse fetal outcomes (Acta Obstet

Gynecol Scand SuppI 1982; 108:67-70.)

Ritodrine B The manufacturer reports that ritodrine administration

after the 20th week of gestation has not been

associated with an increase in fetal abnormalities.

Methergine C Indicated for postpartum uterine bleeding. According

to the manufacturer, oral methylergonovine 0.2

milligram 3-to 4-times daily may be administered to nursing mothers for a MAXIMUM of 1 week

postpartum to control uterine bleeding

Pain Medication

Acetaminophen B Acetaminophen is considered safe for short term use

in all stages of pregnancy

Aspirin C Avoid in pregnancy.

However if absolutely needed, doses of 80 mg per day

may be used. Avoid full dose aspirin in third trimester

due to potential for bleeding complication in the

newborn and prolongation of gestation and labor. Non-steroidal

anti-inflammatory

drugs (NSAIDs)

C Avoid in pregnancy.

Due to the prostaglandin synthesis inhibition,

constriction of ductus arteriosus has been reported.

Persistent pulmonary hypertension in the newborn has

occurred when NSAIDs were used in 3rd trimester or near term. NSAIDs have been shown to inhibit labor

and prolong pregnancy.

Narcotic

analgesic

B Narcotic analgesics can be used short term in . pregnancy. Avoid the use of high doses for prolong

periods near term as neonatal withdrawal can occur.

us. Department of Health and Human Services, He,\lth Resources and Services ADMiNis-nuvnoN, IIIV/AIDS Hi ri.v 451
A (iuii)i'. I'o ini', CuNicAi. (A\ri{ oI' Womkn verm 1 IIV Pharmacologic Considerations of ARV 'I'hcrapy in I IIV Infected Pregnant Patients

US. Dhr\rtmknt of Health and Hum,\n Services, He.alth Resources and Services Administr.vi'ion, HI\’/AIDS Bureau
A Guide to the Clinic.\l C.\ue of Women 'xith

I^harmacologic Considerations of ARV Therapy in HIV-Infected Pregnant Patients

US. Department of He.\lth and Human Service.s, Health Resources and Services ADMiNisrRvnoN, IIIN'/MDS Hi re- 453
A duiDi': lo Till' Clink;.

\

i. C.\rl: ol Womiin with HIV

Pliarmacologic Considerations of AR\^ Therapy in Hl\'-lnfected Pregnant l^atients

US. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Pharmacologic Considerations of ARV Therapy in HIV-Infected Pregnant Patients

us. Department of Health and Hum^\n Services, Health Resources and Services ADMiNis’in.vnoN, HIV/ AIDS Hi ri .m 455
A CiL'ini', TO ’mii ('i.iNic \i, (^aui; op WomI';n with JilV

Pharmacologic (Considerations of ARV Therapy in HlV-lnfectcd Pregnant l^atients

REFERENCES

' Sustiva (Efavirenz) Capsules l^roduct Monograph. Wilmington: DE: DuPont Pharmaceutical; 1998.

“ Shepard TH, Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:JHU, Press. 1992:

206-7.

’ Ndiaye O, Gbaguidi A, Ba M et al. Newborn infant with macrosomia: etiologic factors and perinatal compUcarions. Dakar Med 1997: 42(2): 159-61.

* Crixivan (Indinavir) Capsules Product Monograph. West Point; Pa: Merck & Co; 1998.

^ Connor E and Mofenson L. Zidovudine for the reduction of perinatal human immunodeficiency virus transmission: Pediatric AIDS Clinical Trials Group Protocol 076-

results and treatment recommendations. Pediatric Infect Dis J, 1995; 14:536-41.

'' Hanson C, AntoneUi TA; Sperling RS et al. Lack of tumors in infants with perinatal

HIV exposure and fetal neonatal exposure to zidovudine. J

Acquir Immune Defic

Sjndr Hum Retrovirol 1999 Apr 15;20(5):463-7

^ Guay LA, Musoke P; Fleming T et al. Intrapartum and neonatal single-dose nevirapine

compared with zidovudine for prevention of mother-to-child transmission of

HIV-1 in Kampala, Uganda: HIVNET 012 randomized trial. Hancet 1999 Sep 4; 354(9181): 795-802.

* Dunihoo DR. Maternal physiology. In: Dunihoo DR, editor. Fundamentals of Gynecology

and Obstetrics. Philadelphia: J.B. Lippincott Co. 1992: 280-4

’ Parry E, Shields R, Turnbull A. Transit time in the small intestine in pregnancy. J

Obstet Gynaecol Br Commonw 1970; 77:900-1.

Davidson JM, Hytten EE. Glomerular filtration during and after pregnancy. JObstet Gynaecol \91A-, 81: 588-95.

" Mirochnick M; Fenton T; Gagnier P et al. Pharmacokinetics of nevirapine in human

immunodeficiency virus t5^e 1- infected pregnant women and their neonates.

Pediatric AIDS Clinical Trials Group Protocol 250 Team./ Infect Dis 1998

Aug;178(2):368-74.

Pharmacokinetic and antiretroviral acitivity of lamivudine alone or when coadrninistered with zidovudine in human immunodeficiency virus type 1 -infected pregnant

women and their offspring.

Schuman P; Kauffman R; Crane LR et al. Pharmacokinetics of zidovudine during

pregnancy. Int Conf AIDS. 1990 Jun 20-23; 6 (2): 94 (abstract no. EB.17)

Wang Y; Liningston E; Path S et al. Pharmacokinetics of didanosine in antepartum

and postpartum human immunodeficiency virus-infected pregnant women and

their neonates: an AIDS clinical trial group study. JID 1999 Nov; 180(5): 1536-41.

Briggs, Freeman and Yaffe; Drugs in Pregnancy and Factation: A P^ference Guide to Fetal and

Neonatal PJsks, Williams and Wilkins.

us. Department of Health and Hum.\n Services, Health Resources and Services Administration, HtV/AIDS Bureau
XV: Resources

Arranged According to Topic

Topics included in this section are:

I. Clinical care

II. Clinical trials /research

III. Consumer resources

IV. Adherence

V. Adolescents

VI. Psychosocial care

VII. Substance abuse

VIII. PaUiative care

IX. Prevention

X. Occupational exposure

XI. Professional associations

XII. International resources

If a resource is listed once, it is not listed under subsequent topics.

I. clinical care/primary care

AIDS Treatment Information Service (ATIS): Provides all the PHS

Treatment guidelines, updated as new data become available. ATIS also

provides documents on general treatment information, anergy skin testing,

nutrition and food safety, hepatitis C co-infection, and other relevant

clinical topics. • http://www.hivatis.org • Public Health Service Treatment guidelines:

http://wrww.hivatis.org/trtgdlns.html

Click on Adult and Adolescent Treatment Guidelines*

Click on Pediatric Treatment Guidelines*

Click on Perinatal Guidelines

Click on Health Care Worker Exposure Guidelines

Click on Nonoccupational Exposure Considerations

U.S. Department of Health and Human Services, Health Resources and Si;rvices Administrahon. III\7AIDS Hi ki m 457
A GuiOl- TO THE Cl.lNlCAl. CarE. OI' WoMI'N with HIV

Resources Arranged According to Topic

Click on Opportunistic Infection Guidelines

Click on Tuberculosis Guidelines

*This document is periodically updated as new data become available. • Other ATIS documents:

Click on General Treatment Information

Or click on Drug Treatment

Or click on Hepatitis C Co-infection

Or click on Nutrition and Food Safety

Or click on ATIS Publication List

Or click on Anergy Skin Testing • ATIS by phone: 1-800-HIV-0440 (Monday-Friday 9am-7pm ET, and in

Spanish); Fax: 301-519-6616; TTY: 800-480-3739

AIDS Education and Training Centers Warmline: Medical and health

care professionals can call with questions on any topic related to HIV care. • 1-800-933-3413 • Monday — Friday from 7:30 am to 5 pm, western standard time.

Johns Hopkins University AIDS Service: A comprehensive Web site of

HIV information and resources, including publications, medical education,

provider and consumer interactive forums for seeking answers to questions,

and resources and information on managed care, epidemiology, prevention

and treatment. • http://www.hopkins-aids.edu. • http:/ /wwvw.hopkins-aids.edu/pubUcations/index_pub.html:

Click on 1999 Medical Management ofHTVInfection, John G.

Bartlett, M.D (a comprehensive manual of HIV/AIDS treatment)

To order a copy of this manual, call 1-800-787-1254.

Or click on Hopkins HIVReport, a bimonthly newsletter for practitioners. A range of topics, such as: Update on STDsfrom IDSA.

To receive this newsletter free, write to The Hopkins HIVReport,

P.O. Box 5252, Baltimore MD 21224, Attn: Distribution.

University of CaUfornia at San Francisco: A comprehensive Web site of

HIV information and resources. • http: / /www.HIVInSite/ucsf.edu

Click on The AIDS Knowledge Base for the text of this comprehensive manual of HIV/AIDS treatment (http: //www.HIVInSite /ucsf.edu/ akb/1997 /)

The Body: A comprehensive Web site of HIV information and resources, including complete library on AIDS Basics and Prevention, Treatment,

Conferences, Quality of Life, and Government. • http://wnvw.thebody.com

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with

Resources Arranged According to Topic

Aegis: A comprehensive Web site of HIV information and resources. Clinical and treatment information as well as information on women and chiltlren. A very good source of up-to-date information from the mainstream

press, professional journals, and legal and legislative sources. • http://www.aegis.com

• Publications such as: Guidelines for the education andfoster care ofchildren infected with HIV.

American Foundation for AIDS Research (AMFAR) Treatment Directory: A list of treatments and treatment protocols, updated biannually (Online and book form) • http://www.amfar.org/td • Or order from National AIDS Clearinghouse (listed under Prevention).

Centers for Disease Control National Prevention Information Network: Offers up-to-date epidemiological information, including downloadable slides, daily updates on HIV/AIDS, and patient-oriented information. • http://www.cdcnpin.org/ • Daily news updates in both general media and professional journals • Numerous resources: distance learning, description of and contact

information for model centers, linkages to many other sites

NIAID Database for Anti-HIV Compounds: Computerized databases

containing chemical structures and biological data have been established at the Division of AIDS (DAIDS) NIAID to monitor developments in the

chemotherapy of HIV and opportunistic infections (OI’s) and to serve as an information source. A portion of the HIV database is presented, and

there are plans to make the entire database, consisting of more than 20,000

compounds, available on the Internet. • http://www.riiaid.nih.gov/daids/dtpdb

FDA Background on Protease Inhibitors: Profiles of the similarities and

differences of each approved protease inhibitor, and provide useful information about dosing, storage, potential drug interactions, and therapeutic

options. • http:/ /www.fda.gov/oashi/aids/piindex.html

HFV Medication Guide: A Web site providing drug information as well as software to assess for potential drug interactions. • http://www.jag.on.ca/asp_bin/Main.asp • Click on HIVMedication Guide 2.05 to download PC software with

which to store information about patients (schedules, laboratory values

including CD4+ and viral load, weight, etc. (in English and French) • Or click on pamphlets for patient information pamphlets on antiretroviral agents.

us. Department of Health and Human Services, Health Resources and Servicf.s Administration, HIV/AIDS Hi ri jM 459
A Glide to the Cunicai. Care of Women w ith HI\'

Resources Arranged According to Topic

• CD-ROM version for S20 USD call (705) 523-1782 or write: JAG

enterprises, 2408 South Shore Road, Sudbury, Ontario P3G 1M3

• This site is made possible by an unrestricted educational grant from

Glaxo Wellcome and BioChem Pharma

Resistance mutations: Web sites that deal with \tiral resistance to antiretroAirals. • http: //w^ww.viral-resistance, com

• http://www.hiv-web.lanl.gov

New York Online Access to Health (NOAH): The NY State Web site on health proGdes a range of topics relevant to HI\’^/AIDS and women.

• http:/ /www.noah.cuny.edu/about.html

Click on Health topics, then click on HIV/AIDS

Then click on Gender, age and race for numerous topics (such as menstrual problems) and resources AIDS Alliance for Children, Youth & Families (formerly the AIDS Policy Center for Children, Youth & Families): The national association providing advocacy, education and support for children and families affected by

HR7AIDS.

• http://www.aids-alliance.org

Health Care Financing Administration (HCFA): The federal agency that

adrniriisters the Medicare, Medicaid and Child Health Insurance Programs. • http://www.hcfa.gov

• Preventing HF\^ transmission:

http:/ /www.hcfa.gov/hiv/babies.htm • The Maternal AIDS Project:

http:/ /www.hcfa.gov/hiv/subpg6.htm

National Pediatric & Family HIV Resource Center (NPHRC): A comprehensive WUb site of HI\^ information and resources for professionals who

care for children, adolescents and families with HIV infection and AIDS. • http://www.pedHIVAIDS.org

• To order the Pediatric Treatment Guidelines and other documents:

http:/ /www.pedHIVAIDS.org/catalog

Or call: 1-800-448-0440 or (800) 362-0071

Or write to: University of Medicine and Dentistry', 30 Bergen

Street, ADMC #4, Newark, NJ 07107

Fax: (973) 972-0399 • Publications (in English and Spanish) include:

HTVand AIDS in Ghildren: Questions andAnswers

The Family Information Guide

us. Department of Health and Hl.man SER\acES, Health Resoluces and Sermces Ad.vontstration, HW/AIDS Bltieal
A Guide to the Clinical C.\re of Women with HR'

Resources Arranged According to Topic

What Women Need to Know: The HTV Treatment Guidelines for

Pregnant Women

Womens Initiative for HTV Care and Reduction ofPerinatal Transmission (WIN): Program Findings

Medication Adherence for Children and Families: Guidelines for

Assessment and Support

National Library of Medicine (NLM): Literature searches of the professional medical and HIV/AIDS-related literature including abstracts from

relevant conferences. • http://www.nlm.nih.gov

Then click on Medline-,

Then click on Internet Grateful Med.

HIV Dent: Information on the dental manifestations of and AIDS,

including informadon for persons living with HW/AIDS and their dental

care providers. • http://www.hivdent.org

The Journal of the American Medical Association: HIV/AIDS site with an extensive array of information for pro\iding clinical care to people

living with HIV and AIDS.

• http:/ /www.ama-assn.org/special/hiv/hivhome.htm

The Kaiser Family Foundation (KFF): Provides numerous publications

about HIV/AIDS policy and the healthcare system, such as Medicaid and

HIV/AIDS Policy: A Basic Primer • http: / /www.kff.org

The HRSA HIV/AIDS Bureau (HAB): The Web site of the Federal

agency that administers the Ryan White CARE Act funding (Health

Resources and Ser\tices Administration — HRSA). Numerous Ryjes of information related to models of care for women:

• http://www.hrsa.gov/HAB

Click on Title TV-Women, Infants, Children, and Youth

Click on SPNS-Special Projects ofNational Significance

Then click on SPNS Snapshots for model programs for

women, youth, and homeless youth;

Or click on New SPNS Initiatives:

Then click on adherence to anti-retroviral therapies,

Or palliative care/end-of-life treatmentfor HIVpositive

individuals.

Or HTVcare for incarcerated populations,

Or care for HTVpositive substance abusers

us. Dep.artment of Health .\nd Human Services, Health Resources jVND Services Administration, |II\ / AIDS Bi ki m 461
A CAm)i', TO i Hi': Ci.iNiCAi. Cari{ ob WoMi'N vn't'ii HIV

Resources Arranged According to Topic

• Publications: Numerous publications such as the ones listed below can be obtained by calling (301) 443-6652 or writing HIV/AIDS Bureau

Office of Communications, 5600 Fishers Lane, Room 7-46, Rockville,

Maryland 20857 or faxing (301) 443-0791

Helping Adolescents with HIVAdhere to HAART— 1999

HIVDisease in Women of Color — May 1999

Hispanics Living with HIVDisease: Barriers to Care — April 1999

HIV!AIDS in Racial and Ethnic Minorities — February 1999

Women and HIV!AIDS — December 1998

National Maternal and Child Health Clearinghouse: Provides publications on topics related to maternal and child health, including HIV/AIDS. • Write: 2070 Chain Bridge Road, Suite 450,Vienna, VA 22182-2536 • Phone: (703) 356-1964

II. CLINICAL TRIALS/RESEARCH

AIDS Chnical Trials and Women: The ATIS Web site provides womenspecific information. • http: / /www.hivatis.org/womninfo.html

Click on NIAID Resources for Studying HIV/AIDS in Women

AIDS Clinical Trials Information Service (ACTIS): Nationwide access

to NIH-funded clinical trials at this Web site and phone number. • http://www.actis.org • 1-800-874-2572, TDD 1-800-243-7012

Pediatric AIDS Clinical Trials: Nationwide access to Pediatric AIDS

Clinical Trials. • http://www.pactg.s-3.com

AIDS Clinical Trials Group: The Web site for the NIH-funded AIDS

Clinical Trials Groups. No. • http://www.actg.s-3.com

Terry Beirn Community Programs for Clinical Research on

AIDS(CPCRA): A network of research units composed of communitybased health care providers who offer their patients the opportunity to participate in research where they get their health care. • http://www.cpcra.org

The Bulletin of Experimental Treatments for AIDS (BETA), is published four times a year by the San Francisco AIDS Foundation: • http://www.sfaf.org/treatment

us. Departoent of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HW

Resources Arranged According to Topic

• Or Contact BETA, 10 U.S. Plaza No. 660, San Francisco, CA 94102. • 1-800-959-1059 or 415-487-8060.

III. CONSUMER RESOURCES

Project Inform: A national project targeting consumers with up-to-date

treatment informadon, strategies for adherence, and other tools for people

living with HIV. • http://www.Projectinform.org

Click on Wise Women for the newsletter WISE Words

Or click on Fact Sheets for topics such as gynecological problems

Or click on other categories of information, such as treatment

information and an extensive list of consumer organizations

around the country. • Phone: 1-800-822-7422 • Project WISE EMail Address: WISE@projin£org

Women Alive: An organization by and for women living with HIV

• http://www.women-alive.org • National treatment hot Une: 1-800-554-4876 • Phone: 323-965-1564 . • e-mail: info@women-alive.org • Now available free: “Knowledge, Action, Health A woman’s guide to

HIV treatments” (Tambien en espanol)

The Community AIDS Treatment Information Exchange (CATIE): A

Canadian network that provides information on the treatment options available to people living with HIV/AIDS, including drugs, other medical treat- ments and complementary therapies, in English and French • http://www.catie.ca

New Jersey Women and AIDS Network: A hotiine staffed by women with

HIV. Also provides information and advocacy for women with HIV/AIDS. • 1-800-747-1108 M-F 9-5 ET

• Publications include NJWANNewsletter; Pregnancy and You; Me First;

Medical Manifestations ofHTV in Women.

Women Organized to Respond to Life-threatening Disease

(WORLD): Organization for women with HIV that provides peer advocacy, treatment education training and retreats for HIV positive women

(HIV University). • http://www.womenhiv.org

• 1-510-986-0340 M-F 10-6 PST

• Newsletter: WORLD.

U.S. Department OF Health and Human Services, Health Resources and Sp.rvicf.s Admimstraiion, IIIV/AIDS Bi ri ai 463
A CiLMDI- TO THi; Cl.INlCAL CaRI: Ol- WOMHN WITH HIV

Resources Arranged According to Topic

Seattle Treatment Education Project (STEP): Agency that provides

treatment information for people with HIV/AIDS, healthcare providers,

and ASOs, including a peer-staffed Treatment TalkLine. • http:/ /www.thebody.com/step/ steppage.html • 1-206-329-4857 M-F 1-5 PST

• Or call (877) 597-STEP [7837] toll-free, from the Pacific Northwest:

Washington, Oregon, Idaho, Alaska, and Montana. • Publications include Step Perspective; Babes Perspective (for women)

PWA Health Group: Organization that provides treatment education and

support, advocacy, policy and early treatment programs, and information

about alternative treatments. It started as an AIDS buyers’ when there were no approved drugs for AIDS, to import promising therapies from other

countries. The PWA Health Group was founded in 1987 by Thomas Hannan and Michael CaUen, both people with AIDS, and their doctor, Joseph

Sonnabend, as a not-for-profit organization. • http: / /www.aidsinfonyc.org/pwahg

• 1-212-255-0520 M-F 10-6, Sa 12-4 ET

• Publications include Notes from the Underground; Smart Women

Critical Path AIDS Project: Comprehensive HIV/AIDS Web site. Founded by Persons With AIDS (PWAs) to provide treatment, resource,

and prevention information in wide-ranging levels of detail — for

researchers, service providers, treatment activists, but first and foremost, for

other PWAs who often find themselves in urgent need of information

quickly and painlessly. Hosts other HIV/AIDS organizations.. • http://www.critpath.org

HIV/AIDS Phone resources: • National AIDS Hotiine: 1-800-342-2437, Spanish 1-800-344-7432,

TDD 1-800-243-7889 • AIDS Clinical Trials Information Service (ACTIS) : 1-800-874-2572,

TDD 1-800-243-7012 • HIV/AIDS Treatment Information Service (ATIS): 1-800-448-0440,

TDD 1-800-243-7012, 1-888-480-3739 • CDC National Prevention Information Network: 1-800-458-5231,

TDD 1-800-243-7012 • AIDS Treatment Data Network: 1-800-734-7104 • National AIDS Treatment Advocacy Project (NATAP): 212-219-0106 • 1-888-26 NATAP

• Treatment Action Group: 212-260-0300 • National Minority AIDS Council: 202-483-6622

us. Department of Health and Hu.man Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clixic\l Care of Women utth HR

Resources -Arranged According to Topic

• National Association of People \Atith -ALDS: 202-898-0414 • Latino Commission on -AIDS (CIEST): 212-675-3288 • The Mother’s Initiative: 1-800-828-3280 (Mothers available to talk) • Communin' Prescription Seruice: 1-800-842-0502 • Direct AIDS -Alternative Information Resources: 1-888-951-5433

Other Phone resources: • STD Hotline: 1-800-22^-8922, TDD 1-800-243-^889 • National Instimte on Drug Abuse Hotline: 1 -800-662-HELP (4357), 1- 800-66-A\X DA (662-9832) • National Drug and Alcohol Treatment Referral Sem-ice: 1-800-662-435” • Cocaine Treatment: 1-800-COC-ACNE

• M-A-Teen: 1-800-344-2666 • Marijuana treatment: l-800-”66-6’^’^9 • Domestic \-iolence local phone numbers of domestic violence hotlines:

l-800-S-\EE, TDD l-800-78'^-3224

IV. ADHERENCE

The HIV/AIDS Project Development and Evaluation Unit

(HAPDEU) Online and downloadable guide for the development of HI\^

antiretroA'iral treatment adherence programs • http: / /www.hapdeu.org/adherence • HRV-kIDS Client Ser\-ices and Earlv Inten'ention Program, P.O. Box

4"841, Olympia, WA 98504 • Or caU: Audie Lemke at (206) 685-1679.

University of San Francisco HIVInSite Adherence Resources: • http:/ /www.HrVTnSite.ucsf.edu/topics/adherence/2098.

4504.html • Resources include:

-AIDS Education and Training Center Adherence Curriculum bv

Helen Miramontes and Linda Erank, 1999.

ACTG Adherence Baseline Questionnaire

-\CTG Adherence FoUow L p

Questionnaire

The Body: Treatment Strategies for HIV/AIDS

• http:/ /WWW.thebody.com/treat/ adherence.html

ES Der\i!tment w Health .lsd HiAiAN Sermces, He.\lth Resoi rces and Serntces •V HI\ MDS H - 465
A Cii'iDi-: TO TUF. Ci.iNiCAF CarI' oi' Womi:n with I IIV

Resources Arranged According to Topic

V. ADOLESCENTS

Health Initiatives for Youth (HIFY): Adolescent health information, and

youth education and advocacy. • http:/ /www.hify.com • 1-415-487-5777

Publications:

Chabon, B and Futterman, D. Adolescents and HIV. AIDS Clinical Care 11(2):9-16.

DiClemente, Ralph J. Adolescents and AIDS: A Generation in Jeopardy. Newbury Park, CA: SAGE Publications, 1992.

Hoffman ND, Futterman D, Myerson A. Treatment Issues for

HIV+ Adolescents. AIDS Clinical Care 11 (3): 17-24.

Ryan, C. and Futterman, D. Lesbian and Gay Youth: Care and

Counseling. New York: Columbia University Press, 1998.

Also see Substance Abuse Resources related to adolescents.

VI. PSYCHOSOCIAL CARE

National directory of state and local hotlines for rape crisis centers and

other services for women in distress: • http:/ /www.feminist.org/911/harass_af.html

National Domestic Violence Hotline • http:/ /www.feminist.org/911/crisis.html • Telephone: 1 -800-799-SAFE (7233), or 1-800-787-3224 (TDD)

• Staffed 24 hours a day by trained counselors who can provide crisis assistance and information about shelters, legal advocacy, health care

centers, and counseling.

National Clearinghouse on Child Abuse and Neglect Information • http: / /www.caUb.com/nccanch

• Telephone: (800) 394-3366 or (703) 385-7565 • A national resource for professionals seeking information on the prevention, identification, and treatment of child abuse and neglect and

related child welfare issues.

The American Psychological Association Office on AIDS: Information, training, and technical assistance on a wide range of HIV/AIDSrelated topics associated with coping, mental health services, prevention,

technology transfer, community collaboration, public policy, and ethics. • http: / /www.apa.org/pi/aids/ activities.html • Provides the APA HOPE Program: Federally funded program for

us. Department of Health and Human Services, Health Resources ;\nd Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of XX'omen with HIV

Resources Arranged According to Topic

training mental health providers about working with people with

HIV\AIDS.

• Also publications such as the Psychology and AIDS Exchange

Newsletter.

The Invisible Epidemic: The Story ofWomen andAIDS. By Gena Corea.

NY: HarperCollins, 1992.

VII. SUBSTANCE ABUSE

National Clearinghouse for Alcohol and Drug Information (NCADI):

Numerous documents on diagnosis and treatment of substance abuse,

including specific to people living with HIV and vulnerable populations,

including youth. • http: / /www.health.org/pubs/hivaids.htm • http://www.health.org/pubs/catalog/intr.htm or call 1-800-729-

6686 • 1-800-729-6686, TDD 1-800-487-4889

VIII. PALLIATIVE CARE

A Handbookfor Palliative Care By Linda Wrede-Seaman, MD

• Published by InteUicard 2nd Edition: 1999, ISBN: 188841107-4 • Decision algorithms for assessment and management of pain and

common symptoms in terminal illness.

Recoveringfrom the Loss ofa Loved One to AIDS Help for Surviving Family, Friends, and Lovers Who Grieve By Katherine Fair Donnelly. Fawcett

Books,1995

Growth House Search Engine: Comprehensive database for end of life issues, including death with dignity, hospice, palliative care, grief, bereavement, and related topics. • http:/ /www.growthhouse.org/search.htm

The Oxford Textbook ofPalliative Medicine, 2nd edition.

IX. PREVENTION

The National AIDS Clearinghouse • 1-800-458-5231 • Provides numerous free prevention documents on specific topics such

as: What are adolescents prevention needs? And How do HIV, STD and

unintendedpregnancy prevention work together?

U.S. Department of Health and Human Services, Health Resourcf.s and Sf.rvicf.s Administration, HIV/AIDS Hi ri m 467
A Ciuinis TO THi': (j.inicai. CakI'. oi' Womi'.n wrni 1 IIV

Resources Arnmgetl Acconling to 'I'opic

Nonoccupational HIV Exposure Guidelines: • http:/ /www.hivatis.org/ trtgdlns.html

Click on Non-occupational exposure

Perinatal HIV prevention: • http:/ /www.hivatis.org/trtgdlns.html

Click on Perinatal Guidelines • http:/ /www.hivatis.org/womninfo.html

Click on National Pediatric and Family HIVResource Center

Then click on Perinatal prevention

Then click on Research Literature Updates:

What Women Need to Know: The HIV Treatment Guidelines for

Pregnant Women

Reduction ofPerinatal HIV Transmission: Guidefor Providers

(May 1997)

Reducing the Odds: Preventing Perinatal Transmission ofHIV in the United

States: National Academy of Science Report on perinatal transmission. • http:/ /www.nap.edu/readingroom/books/rto

X. OCCUPATIONAL EXPOSURE

HRSA/CDC National Clinicians’ Post-Exposure Prophylaxis Hotline

(PEPline) • National toll-free hotline to help counsel and treat health care workers

with job-related exposure to blood-borne diseases and infections,

including hepatitis and HIV infection. • i_888-448-4911

PHS Guidelinesfor the Management ofHealth Care Worker Exposures to HIVand Recommendationsfor Post Exposure Prophylaxis. • http: / /www.cdc.gov/epo/mmwr/preview/mmwrhtml/

00052722.htm • Guidelines published 15 May 1998

XL PROFESSIONAL ASSOCIATIONS

International Association of Physicians in AIDS Care (lAPAC) This

organization provides on its Web site policy information about ongoing

efforts to expand access to healthcare services and life-saving drugs and

technologies. • http://Tvww.iapac.org • Phone: 312 795-4930

U.S. Department of Health and Human Servicf.s, Health Resources and Services Administr/\tion, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Resources Arranged According to Topic

• I^ublications include the monthly Journal ofthe International Association

ofPhysicians in AIDS Care

Association of Nurses in AIDS Care (ANAC) Professional association

that provides information and advises members about clinical and policy

issues related to nursing and HIV care. • http://www.anacnet.org • 1-800-260-6780 • Publications include the monthly Journal ofNurses in AIDS Care. • ANAC is responsible for development of the HIV/AIDS Nursing

Certification Board, which provides nationally recognized HIV/AIDS

Certification (ACRN), based on eligibility requirements and successful

completion of the certification exam. • http: / /www.ptcny.com

• Call 202-356-0660

American College of Obstetricians and Gynecologists (ACOG) Professional association that provides resources to and advises members about

a range of issues such as domestic violence and cultural competency. • http://www.acog.org • Resource center: 1-800-762-2264 • Publications include a newsletter and an annual compendium of

selected publications, including educational and technical bulletins.

XII. INTERNATIONAL RESOURCES

The Panos Institute: • http:/ /www.oneworld.org/panos

Click on HIV/AIDS

Or click on Women and Health

Integrated Regional Information Network

Click on Publications

Then click on Non-U. S. Groups

Then click on IRIN for publications such as: “UN says violence against women linked to HIV/AIDS”

“New research Unks high HIV rates in teenage girls”

Womens Experiences: An International Perspective. Long, Lynellyn D and

Ankrah, E Maxine, Eds. NY: Columbia University Press, 1996.

The Joint UN Programme on AIDS (UNAIDS): Offers up-to-date

epidemiological and other data that can be downloaded. • http://www.unaids.org

U.S. Department of Health and Human Services, Health Resourcfs and Servici^ Administration, IIIX'/AIDS Hi hi 469
This Guide is a

PRELIMINARY EDITION.

We need YOUR HELP

to make the

NEXT EDITION

as useful as possible!

Please send your

comments

criticisms

corrections

suggested changes, and

other guidance

to one of the addresses below. Be sure to include in your

letter/note an address (fax, e-mail, or postal) where you can

be reached for follow-up.

Translation Partners Needed

Write to us if you can help us find partners to help us have

this Guide translated Into your native language. For

instance, provide us with a contact who works with translation in your country's Ministry of Health, or tell us about a

group at a medical school that translates medical texts.

Send Us Your Comments

E-mail: womencare@hrsa.gov

Fax to the attention of "Womencare": 301-443-0791 (USA)

Postal address: Womencare

Parklawn Building, Room 11A-33

5600 Fishers Lane

Rockville, Maryland 20857

USA

Note that this and subsequent editions of

A Guide to the Clinical Care of Women with HIV

will be available online.

Go to the HIV/AIDS Bureau Web site

and click on the publication Women's Guide:

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

Note: Because this is a preliminary editon, this

Index is also preliminary. It's future development

depends on you, and we welcome your input.

Send Us Your Comments

E-mail: womencare@hrsa.gov

Fax to the attention of "Womencare": 301-443-0791 (USA)

Postal address: Womencare

Parklawn Building, Room 11A-33

5600 Fishers Lane

Rockville, Maryland 20857

USA

A

A Demographic Comparison of HIVpositive Women and Men: 273

Abnormal bleeding, What is considered:

149

Abnormal Pap smear: 1 53

Abnormal Pap Smears, Recommended

Management for : 158

Abnormal uterine bleeding/Amenorrhea:

149

Acceptability of male and female

condoms: 66

Access to care: 41

Acute Diarrhea in Patients with AIDS:

128

Adherence: 238

Adherence and Viral Load <400: 140

Adherence in Special Populations: 142

Adherence to HIV Therapies: 139

Adolescents, Immunizations for : 321

Adolescents 1: 313

Advance Care Planning: 348

Advanced HIVInfection Plus Altered

Status, New Seizures, Headache

(Severe or Persistent), or Focal

Neurologic Deficits: 134

Adverse Pregnancy Outcomes and

Relationship to HIV Infection: 208

Aegis: 459

African American, Case Study: : 262

African-American Culture: 260

AIDS Alliance for Children, Youth &

Families: 460

AIDS Clinical Trials and Women: 462

AIDS Clinical Trials Group: 462

AIDS Clinical Trials Information Service

(ACTIS): 462

AIDS Dementia Complex (ADC)/1 1I\’

Encephalopathy: 121 AIDS Education and Training Centers

Warmline: 458

AIDS Risk Reduction Model: 50

471 us. Department of Health and Human Service's, Health Resource's and Secrvici-.s Ai>NEiNis'iR,vnos, I lIV/AIDs Ui k;

INDEX
A CJuiOl'. TO rUF. Cl.lNlCAl. (^\RF. Ol' WOMl'N WITH HIV

Index

AIDS Treatment Information Service

(ATIS): 457

Alcohol Addiction: 303

Alcohol Use Estimates by Age, Gender,

and Ethnicity in the U.S.: 293

Algorithms for Diagnosis and

Management of Symptoms: 126

Allergic /irritative reaction: 183

Alternative/Complementary Therapy:

109

Alternative/Complimentary Medication

to Avoid in Pregnancy: 436

American College of Obstetricians and

Gynecologists (ACOG): 469

American Foundation for AIDS

Research (AMFAR) Treatment

Directory: 459

American Psychological Association

Office on AIDS: 466

Amniocentesis: 223

Amprenavir: Amprenavir: 227

Anemia: 125

Anovulation: 151

Antepartum: 218

Antepartum Fetal SurvetUance/Testing:

220

Antibiotic prophylaxis: 239

Antimicrobials: 390

Antiretroviral Agents: 96, 216

Antiretroviral Pregnancy Registry: 233

Antiretroviral resistance: 374

Antiretroviral Therapy: 95

Antiretroviral Therapy in Substance

Abusers: 308

Antiretroviral Treatment: 223

Antiretrovirals: 382

Aphthous Genital Ulcerations: 164

Approach to the Patient: 35

Assess healing: 240

Assessment of Pain: 338

Association of Nurses in AIDS Care

(ANAC): 469

Azole resistance: 168

B

B vaccine: 236

Bacterial urinary tract infection: 178

Bacterial vaginosis: 61

Bacterial Vaginosis (BV): 165, 208

Bacterial Vaginosis, Recommended

Management for : 166

Barrier contraceptives: 69

Barriers to Pain Relief: 335

Bartholin’s abscess: 181

Basehne laboratory evaluation: 87

Becoming Symptomatic: 324

Behavioral intervention models: 50

Behavioral Intervention trials: 51

Behavioral Interventions, Results of

Large Randomized Trials of : 52

Behavioral Risk: 315

Behavioral Theories Relevant to Sexual

Risk Reduction Counseling: 50

Behcet’s Syndrome: 163

Benefits of antiretroviral drugs in pregnancy: 380

Benefits to HIV testing: 46

Benign breast tumor: 185

Benign or malignant ovarian neoplasm:

177

Bereavement: 353

Biologic and Host-related Factors Affecting Sexual Transmission of

HIV: 5 Biologic growth characteristics

(phenotype): 214

Biological Risk: 315

Biopsy: 180

Body Fluids: 362

Body: Treatment Strategies for HIV/AIDS: 465

Breaking Bad News: 346

Breast cancer: 185

Breast Lump: 184

Breastfeeding: 217

Bulletin of Experimental Treatments for AIDS (BETA): 462

c

Cancer: 151

Candidiasis: 116

Care Provider Issues: 286

CBC, platelet count: 152

CD4 cell count: 215

CD4 lymphocyte count: 87

Centers for Disease Control National

Prevention Information Network:

459

us. Dep.artment of He.\lth and Hum.\n Services, Health Resources and Services Administration, HW/AIDS Bureau
A Guide to the Clinic.\l Care of Women with HIV

Index

(icntral Nervous System (CNS)

l.ymphoma: 123

cervical cancer: 154

cervical dysplasia; 154

cervical lesions: 157

(Cervical testing: 152

(!!hancroid: 162

Characteristics of bleeding: 150

(Checklist for the Behavioral Intervention

Counseling Session: 59

(Childhood Sexual Abuse and Adult

Victimization; 274

Children and Adolescents: 143

Chlamydia; 171

Chorionic villous sampling (CVS); 223

Chronic Diarrhea (CD4 Count

<300/mm3): 129

Chronic Hepatitis B and C: 123

Cigarette smoking: 216

Clinical and Psychosocial Care: 321

Clinician discomfort: 44

Clinician fear; 44

CMV: 236

Coagulation profile: 152

Cocaine Addiction: 303

Coccidiomycosis: 236

Cognitive/Behavioral Interventions: 304

Colposcopy: 180

Common Clinical Misperceptions

Regarding Psychiatric Issues: 281

Common Psychiatric Medications: 284

Common Symptoms in HIV Disease:

330

Communication: 35

Community: 262

Community AIDS Treatment

Information Exchange (CATIE);

463

Co-morbidity related to substance abuse:

293

Comparison of Genotypic and

Phenotypic Assays: 107

Complications: Opportunistic Diseases:

109

Components of HIV Pre- and Post-test Counseling: 47

Condom use during pregnancy: 238

Condom Use, Factors Associated with : 319

Condoms: 65

Condoms and prevention of HIV

infection: 63

Confidentiality: 37

Confidentiality and Legal Issues: 316

Containing the epidemic: 23

Contraception: 196

Contraception use postpartum: 238

Contraception/ condom use: 241

Contraceptive Methods: 197

Coping with HIV: 268, 324

Correlation of Complications with CD4

Cell Counts: 110

Cough, Fever, Dyspnea: 131

Counseling: 195

Counseling and Support: 237

Counseling and Testing: 317

Crirninal Justice Settings: 308

Critical Path AIDS Project: 464

Crohn’s Disease: 163

Cr5^tococcal Meningitis: 117

Cryptosporidiosis and Jvlicrosporidiosis:

120

Crytococcosis:: 236

Cultural Issues: 258

Cultural Setting/Background: 38

Cytomegalovirus: 119

Cytomegalovirus (CMV): 91, 163

D

Death: 352

Death, Guidelines for After the : 355

Delivery, Mode of: 238

Detoxification; 303

Developing Countries; 21

Developing World: 1

0

Disseminated MAC: 236

Disseminated Mycobacterium Avium

Complex (MAC): 119

DNA PCR: 86

Drug Abuse, Relapse: 306

Drug Reaction: 1 64

Drug Use, Prevalence of : 292

Drug use/treatment: 238

Drugs: 272

Drugs of special consideration in women: 435

Dry Mouth: 344

DSMIVDrug Addiction Oiteria: 298

us. Department of He.\lth .and Hunlan Services, He.\i,th Resources .and Services .VuMiNi.sTR.vnoN, HIXV.MDs lli i i ' 473

INDEX
A CiUlDl-: TO THi; (j.INICAI. (L\KU Ol- WoMliN WITH 1 nv

Index

Duration of Drug Detection: 299

Duration of membrane rupture: 216

Dysmenorrhea: 175

Dyspnea: 344

E

EARS: 323

Economic Issues: 254

Ectopic pregnancy: 177

Education and Counseling: 41

Efavirenz: 227

Emotional Milestones: 268

End-of-Ufe Care: 327

End-of-Life Issues: 349

Endometrial biopsy: 1 52

Endometrioma: 177

Endometriosis: 175

enhanced potency inactivated poHo

vaccine: 237

Epidemiology and Namral History of

HIV Infection in Women: 1 Episiotomy, forceps: 217

Established Infection: 14

Estrogen and Progestin Preparations,

Commonly Used : 187

Ethnic and Gender Considerations in Risk Reduction Counseling: 59

Evaluation of the HIV-Infected Woman:

37

Exposure Associated with Transmission:

361

Eyes: 83

F

Factors Associated with Condom Use

and Non-use: 68

Factors facilitating transmission: 4

Factors That Influence Rate of HIVdisease Progression: 18

Family-centered care: 40

Fatigue: 332

Fatigue, Treatable Causes of : 333

FDA Background on Protease Inhibitors:

459

Female Condom Insertion and

Positioning: 67

Fertility: 206

b’etal surveillance: 220

Fetal/infant adverse effects: 226

Fetal/ maternal monitoring: 238

Eetal/Neonatal Factors: 217

Fever of Unknown Origin in Patients

with AIDS: 127

Fibrocystic change: 185

Follicle stimulating hormone (FSH): 152

Follow-up Visits: 40

Food-Drug Interactions: 435

Frequency of Visits: 237

Fungal infection: 1 82

Future Issues: 21

G

G6PD: 92

Gastrointestinal masses: 177

Gastrointestinal pathology: 176

Gender Differences: 341

Gender Effects: 17

Genital herpes simplex (HSV): 209

Genital Itching/Irritation: 1 82

Genital Masses/Nodules: 181

Genital tract infections: 61, 151

Genital ulcers: 158

Genital Warts: 179

Genital Warts, Recommended

Management for : 1 80

Genitalia/perineum: 83

Genotypic resistance: 215

Gestational age: 216

Global Impact: 21

Goal Setting: 348

Gonorrhea (GC): 170

Granuloma Inguinale: 163

Grief: 353

Grieving Process: 356

Growth House Search Engine: 467

Guidelines for Gynecologic Referral: 189

Guidelines For Use of Erythropoietin in the Anemic HIV Patient: 124

Gynecologic evaluation: 188

Gynecologic Problems: 149

H

Handbook for Palliative Care: 467

us. Dep,\rtment of Health and Human Services, Health Resources and Services Administr-oton, HIV/AIDS Bureau
A Guide to the Clinical C.are of Women 'kith HIV

Index

I Icadachc in l^aticnts with Aids: 133

I Icalth Belief Model: 50

1 lealth (iare h’inancing Administration

(1 ICI'A): 460

1 lealth Initiatives for Youth (HIFY): 466

Health Maintenance Issues: 188

1 leightened Vulnerability for Infection:

315

Hematology and Chemistry Panels: 91

1 lepatitis: 91

hepatitis A vaccine: 236

Hepatitis B (HBV): 212

Hepatitis C (HCV): 213

Hepatosplenomegaly: 83

Herpes Simplex Virus: 118

Herpes Simplex Virus (HSV): 159

Hiccoughs: 343

Hiccups: 343

Hidradenitis Suppurativa: 164

Hispanic, Case Study: : 259

HISPANICCULTURE: 258

1 listoplasmosis: 236

History of gynecologic problems/other

symptoms: 150

HIV and Reproduction: 195

HIV Counseling and Testing: 46

HIV Dent: 461

HIV Diagnosis, Receiving an : 323

HIV Experience: 37

HIV Infection following Occupational

Exposure: 370

HIV Medication Guide: 459

HIV seropositive HCW: 374

HIV Status, Disclosure of : 324

HIV/AIDS Phone resources: 464

HIV/AIDS Project Development and

Evaluation Unit (HAPDEU): 465

HIV-exposed Infant: 241

HIV-related Factors: 214

HIV-RNA level: 214

Home testing: 86

Homeless Patients: 142

Hormonal contraceptives: 69

Hormone Replacement Therapy (HRT):

186

HRSA HIV/AIDS Bureau (HAB): 461

HRSA/CDC National Clinicians’ Post- Exposure Prophylaxis Hotline

(PEPUne): 468

HRT, Alternatives to : 1 88

HSV, Recommended Management for: 160

Human papilloma virus (HPV): 210

Human Relationship Issues: 254

Hydrosalpinx/Pyosalpinx and

tuboovarian abscess: 177

Hydroxyurea: 227

IIdentifying support systems/disclosure:

39

lUicit Drug Use: 276

Illicit Drug Use Estimates by Age,

Gender, and Ethnicity in the U.S.: 292

immune globulins: 237

Immune-Based Therapy: 109

Immunizations: 236

Impact of HIV Counseling and Testing on Prevention: 49

Impact of Societal Perceptions and

Beliefs: 295

Important Issues for Patients Being

Counseled on Condom Use: 64

Improving Adherence: 143

Incarcerated Patients: 142

Indications for Colposcopy: 1 56

Indications for Consideration of Change

in Therapy: 104

Indications for Hospitalization in Patients with PID: 175

Indications for Initiation of

Antiretroviral Therapy in the

Chronically HIV-Infected Patient: 99

Indications for Plasma HIV RNA

Testing: 90

Indinavir: 227

Industrialized Countries: 20

Infant feeding: 240

Infectiousness of the Host: 4

Inflammatory Conditions: 1 63

influenza vaccine: 236

Initial Diagnosis: 84

Initial Evaluation: 39, 80

Injuries Sustained by Case Patients: 368

Insomnia: 341

Integrated Regional Information

Network: 469

us. Department of Health and Human Services, Health Resources and Servicils ADMiNis-iHAnoN, HIV/AID.S Hi kim' 475

INDEX
A (JuiDi' i() rill' (j.iNicAi. Caki', oI' WoMivN wrni HIV

1 ndcx

International Association of Physicians

in AIDS Care (lAPAC): 468

Interrelationship of HIV and Human

Papillomavirus (HPV): 153

Interstitial cystitis: 178

Interventions to Improve Adherence:

145

Intrapartum: 238

Intrapartum ARV prophylaxis: 239

Intrapartum/Postpartum Regimens: 230

Invasive fetal monitoring: 216

Itching: 343

J

Johns Hopkins University AIDS Service:

458

Joint UN Programme on AIDS

(UNAIDS): 469

Journal of the American Medical

Association: 461

K

Kaiser Family Foundation (KFF): 461

Kaposi’s Sarcoma (KS): 122

L

Laboratory Evaluation in the HIVInfected Pregnant Woman: 219

Laboratory Indicators and Predictors: 15

Laboratory Indicators of Prognosis

and/or Stage of Illness in HIV

Infection (Blood Specimen): 16

Laboratory Testing: 84

Laboratory Tests for Hepatitis Viruses:

92

Life's end: 356

Likelihood of Developing AIDSwithin

Three Years: 89

Linking Youth to Care: 320

Lipid Profile: 92

Lipodystrophy (Fat Redistribution

Syndromes): 98

Logistic-Regression Analysis of Risk

Factors: 367

Loss: 354

Lower Extremity Symptoms: Pain: 135

Lower Extremity Symptoms: Pain and

Numbness: 136

Lower Extremity Symptoms: Weakness

and Numbness: 135

Lungs: 83

Lymph nodes: 83

Lymphogranuloma Venereum (LGV):

163

M

Maintaining hope: 348

Major Depressive Disorder: 281

Major Depressive Disorder (MDD): 282

Male Condoms: 63

Mammography: 188

Maternal immune response: 215

Maternal/Obstetrical Factors: 215

Measures to Reduce Sexually Transmitted

Diseases (STDs): 62

Measuring Adherence: 143

Medical conditions: 151

Medical evaluation: 39

Medications: 151

Menopause: 186

Mental Illness: 324

Microbicides: 71

Mitochondrial toxicity: 228

Mittelschmerz: 176

MoUuscum contagiosum: 181

Multiservice Clinical Programs: 278

Mutations Associated with Resistance to

Specific Agents: 106

N

National AIDS Clearinghouse: 467

National Clearinghouse for Alcohol and

Drug Information (NCADI): 467

National Clearinghouse on Child Abuse

and Neglect Information: 466

National directory of state and local hotlines: 466

National Domestic Violence Hotline:

466

National Library of Medicine (NLM):

461

National Maternal and Child Health

Clearinghouse: 462

us. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
A Guide to the Clinical Care of Women with HIV

Index

National Pediatric & P'amily HIV

Resource (Center (NPHRC): 460

Natural history and HIV disease

progression: 7

Natural history in HAART era: 20

Natural History of HRHnfection

without the Use of Antiretroviral

Therapy: 88

Neoplastic: 164

Neurologic: 84

New jersey Women and AIDS Network:

463

New York Online Access to Health

(NOAH): 460

NIAID Database for Anti-HIV

Compounds: 459

Non-nucleoside Reverse Transcriptase

Inhibitors: 97

Nonoccupational HIV Exposure

(juideUnes: 468

Non-pharmologic Drug Addiction

Treatments: 305

Nucleic acid amplification: 85

Nucleoside Analog Reverse Transcriptase

Inhibitors: 97

Nucleoside Analogs: 96

0

Occupational Exposure: 361

Odynophagia in Patients with AIDS: 137

01 Prophylaxis: 111

Opiate Addiction: 302

Opioid Analgesics: 339

Opioid Conversions: 339

Opportunistic Disease in the HAART

Era: 125

Oropharynx: 83

Other bleeding sources: 150

Other forms of contraception and the

risk of HIV infection: 69

Ovarian functional cyst: 177

Ovarian torsion: 175

Oxford Textbook of PaUiative Medicine:

467

P

Pain: 334

Pain Intensity Scales: 332

Palliative Care: 327

Panos Instimte: 469

Pap smear: 152

Pap Smear Report Eormat for Bethesda

System: 155

Pap smears: 188

Patient Factors Associated with NonAdherence: 141

Patient Intake Flow Sheet: 94

Pediatric AIDS Clinical Trials: 462

Pediatric Classification System: 243

Pelvic examination: 83

Pelvic Inflammatory Disease (PID): 173

Pelvic Mass: 176

Pelvic ultrasound: 152

Pelvic/Abdominal Pain: 172

Percutaneous umbilical blood sampling

(PUBS): 223

Perimenopause: 151

Perinatal HIV prevention: 468

Perinatal Transmission: 214, 223

Peripheral Neuropathy: 120

Personal goals: 349

Personal Protective Equipment: 369

Pharmacokinetics: 223

Pharmacokinetics of antiretroviral drugs

in pregnancy: 381

Pharmacologic Considerations in HIVinfected Pregnant Patients: 379

PHS Guidelines for the Management of

Health Care Worker Exposures to HIV and Recommendations for

Post Exposure Prophylaxis: 468

Physical Comfort: 349

Physical Examination: 83

Placental disruption-abruption,

chorioamnionitis: 216

Plasma HIV-RNA: 86

Plasma vs genital tract viral load: 214

pneumococcal vaccine: 236

Pneumocystis carinii pneumonia: 233

Pneumocystis Carinii Pneumonia (PCP):

116

Post-exposure management: 371

Post-Exposure Prophylaxis: 71, 108

Postexposure Prophylaxis Regimens: 363

Postpartum: 240

Potential Variables in Transmission: 214

Poverty: 272

us. DeP.\RTNENT of HE.U.TH AND HUMAN SERVICES, HEALTH RI'-SOURCILS ,\ND SERVICI-.s AnMINIMR M|( i',. 1 ll\ / \ll)-> Ui 477

INDEX
A CiUini'. I'o I'liii Ci.iNicAi, (Ari' oi' Women wrm lllV

I ndcx

Practical Aspects of Counseling: 54

Practical aspects of counseling patients

about sexual risk reduction: 54

Pre- and Posttest HIV Counseling: 46

Predictors of Adherence: 140

Predictors of Drug Treatment Retention

and the Durability of Treatment

Gains: 306

Pregnancy: 151

Pregnancy Counseling Issues: 196

Pregnancy Course and Outcome: 207

Pregnancy on HIV Infection, Effects of: 207

Pregnancy test: 152

Pregnancy Testing: 206

Pregnancy Tests: 206

Pregnancy, CD4 count and HIV-RNA

levels in : 207

Pregnancy, General Principles for Antiretroviral Treatment in ; 228

Pregnancy, Use of Antiretrovirals in : 224

Pregnant HCW: 374

Pregnant Women, Opportunistic

Infections and Primary Prophylaxis

in : 234

Preparing for Death: 324

Presentation and Management of the

Most Common Complications of

Advanced HIV Disease (AIDS):

111

Preterm delivery: 227

Prevention of HIV: 43

Prevention of Occupational Exposure:

369

Primary Medical Care: 79

Primary or Acute Infection; 13

Principles of Pain Management: 335

Progressive Multifocal

Leukoencephalopathy (PML): 123

Project Inform: 463

Prophylaxis to Prevent First Episode of

Opportunistic Disease in Adults

and Adolescents Infected with

Human Immunodeficiency Virus;

112

Protease Inhibitors: 98

Providing HIV Care at Emotional

Milestones; 269

Pruritus: 343

Psychiatric Disorders: 279

Psychiatric Issues: 267

Psychological Issues: 256

Psychopharmacology for the HIVpositive woman: General

Guidelines: 283

Psychosocial and Cultural

Considerations: 253

Psychosocial Issues: 323

PWA Health Group: 464

Q

Quality of Life: 328

Quantitative virology/Viral load assays: 90

R

Rapid Tests: 48, 86

Reasons Patients Cite for Missing

Medication: 142

Recommendations for Antiretroviral

Therapy in the Treatmentexperienced Patient: 103

Recommendations for Initial Treatment

Regimens: 101

Recommended Antiretroviral Agents for

Initial Treatment of Established

HIV Infection: 102

Recovering from the Loss of a Loved

One to AIDS: 467

Recurrent candidiasis: 169

Reduction of Secondary Risk Factors: 237

Regional HIV/AIDS Statistics and

Features: 2

Relationships: 268

Renal/ureteral stones: 178

Resistance mutations: 460

Resistance Testing: 105

Resources: 457

Respect: 36

Retroperitoneal lymphadenopathy: 1 77

Revised Classification System for HIV

Infection and Expanded

Surveillance Case Definition for AIDS Among Adults and

Adolescents: 9

Risk Assessment for STD/HIV for Women: 45

us. Department of Hf.alth and Human Services, Health Resources and Services Administra'hon, HtV/AIDS Bureau
A Guide to the Clistc\l Care of Women vhth HR

Index

Risk assessment for STD/HR’

infections; 44

Risk Factors and Considerations in the

Evaluation of Suicidalit}': 285

Risk factors for HI\' infection

specifically relevant to women: 45

Risk F’actors for Occupational

Transmission; 366

Risk of Progression to AIDS Defining

Illness in a Cohort of

Homosexual Men Predicted by

Baseline CD4 + T Cell Count and

Viral Ixiadl: 100

Risks and Benefits of Early Initiation of

Antiretroviral Therapy in the

Asymptomatic HT\^-Infected

Patient: 108

Risks of antiretroviral drugs in pregnancy: 380

Ruptured/hemorrhagic ovarian cyst

rupture; 175

s

Saliva test: 86

Scabies/lice; 183

Screening strategies; 46

Screening tests: 155

Seattle Treatment Education Project

(STEP): 464

SensitixTt}" 36

Serology: 85

Sexual Abuse; 272

Sexual behaxtior: 216

Sexual risk: 314

Sexually transmitted diseases and

pregnanc}-: 314

Sexually transmitted diseases and the risk of infection: 61

Shortened Life Expectanq-: 346

Shormess of Breath: 344

Sigmoidoscopy/colonoscopy: 189

Singultus: 343

Sites of Action of Antiretroxiral Agents:

96

Sleep Disturbance: 341

Sleep Problems: 342

Smear/STD screening: 93

Socioeconomic Risk; 316

Speculum and bimanual pehic

examination: 84

Spiritual Assessment; 353

Spirituality: 38

Stage of Change (SOQ beha\ioral

theor}': 50

Staging: 8

STD screening: 188

Sterilizarion: 70

Strain variation (genotype): 214

Strategies for Prevention of Perinatal

Transmission: 218

Substance abuse; 151, 216, 291, 340

Substance Abuse in Pregnancy: 307

Substance Abuse in Vibmen: 295

Substance Abuse, Epidemiolog}’ of : 292

Substance Abuse, Treatment of : 300

Substance Use: 324

Substance Use, Identification of : 296

Substance Use, Medical Conditions and

Sequelae Associated with : 293

Suggested frequency of Pap smears: 156

Suicide Risk: 285

Surviting: 2~2

Susceptibilit}" of the Recipient: 6

Symptoms throughout Disease: 330

Syphilis: 91, 160, 210

Syphilis, Recommended Management for

: 161

Systemic Lymphoma: 122

T

Team Approach: 37

Teen .AIDER: 318

terine leiomyomas (fibroids): Ri

Terr}- Beirn Communin' Programs for

Clinical Research on

AIDS(CPCR.\): 462

tetanus-diphtheria (Td) vaccine: 236

The World Health Organisation Clinical

HR" Staging System and Proposed

Modifications: 11 Three Perspectives on the lUxperience of

Being a Woman with HR’: 268

Thyroid stimulating hormone (TSH): 152

Time Course: 1

5

Toxoplasmic encephalitis: 233

Toxoplasmosis: 91, 1 18, 21

Transmission: 3

Transmission, Modes of: 3

Trauma: 165

us. DeP.\RTMEST OF HE.\LTH ,\ND HL'St\N SERMCES, He\LTH RFiOETlCES -\ND SeRVKJ-.-. .KOMINSrp ' HIV MI5' B< i 479

INDEX
A Guide to the Clinical C.\re of Women with HIV

Index

Treatment Guidelines: 99

Treatment in Pregnancy: 1 09

Treatment of Acute HIV Infection: 107

Treatment Readiness/Harm Reduction:

300

Trichomoniasis: 170

Truth-teUing: 346

Tuberculosis: 92, 163

Tuberculosis (TB): 120

Tumors: 179

Tumors, other masses: 182

u

Ultrasound: 222

Unforgiving Nature of HIV and the

Medications to Treat It: 139

University of California at San Francisco:

458

University of San Francisco HI\TnSite

Adherence Resources: 465

Unprotected sex: 44

Untreated natural history: 13

Urethral syndrome: 178

Urinary incontinence: 179

Urinary retention: 179

Urinary symptoms: 177

Urinary tract pathology: 176

Urinary tuberculosis: 178

Urine test: 87

Uterine fibroids: 151

Uterine leiomyomas (fibroids): 177

V

Vaccines: 71

Vaginal cleansing: 240

Vaginal Discharge: 165

Vaginal versus cesarean delivery: 217

Varicella: 91

Viral detection: 85

Viral isolation: 86

Viral Properties: 7

Vitamin A deficiency: 216

Vulvovaginal Candidiasis: 166, 208

Vulvovaginal Candidiasis, Recommended

Management for : 167

w

W.H.O. Three-step Ladder: 337

Wasting Syndrome (“Slim Disease”): 121

Women Alive: 463

Women Organized to Respond to Lifethreatening Disease (WORLD):

463

Women’s Experiences: An International

Perspective: 469

X

Xerostomia: 344

Y

ytomegalovirus (CMV-^: 211

z

7.DY carcinogenicity: 226

ZDV exposure: 226

Zidovudine Perinatal Transmission

Prophylaxis Regimen: 229

480 us. Department op Hp;ai,th ,\nd Hum.vn Sp.rvk'.es, Hp:.\i.th Rj^soi'rcp-s ,\nd Spirvk'.e.s Ar)MiNisTR.vncPN, HI\’/.UDS Bi'ri:.\t
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ant editions of

? of Women with HIV

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I Women's Guide:
*IA

IIIA

XI

X

IX

MX

IIIX

AIX

AX

I: Epidemiology and Natural History of

HIV Infection in Women I Ruth M Greenhlatt, MD and Nancy A Hessol, M, ||

II: Approach to the Patient

Jean Anderson, MD

III: Prevention of HIV

Chia Wang, MD, MS and Connie Celum, MD, MPH

IV: Primary Medical Care

Judith Feinberg, MD andJanine Maenza, MD

V: Adherence to HIV Thera

Laura WCheever, MD

VI: Gynecologic Problems

Silvia Abularach, MD andJean

Color Plates

NIHIWBABY

496 00888 6056

VII: HIV and Reproduction

Jean Anderson, MD

VIII: Psychosocial and Cultural

Barbara Aranda-Naranjo PhD, R

IX: Psychiatric Issues

Joyce Kobayashi, MD

X: Substance Abuse

Henry L Francis, MD and Victoria

XI: Adolescents

Donna Futterman, MD

XII: Palliative Care and End-of-i^

Carla Alexander^ MD

XIII: Occupational Exposure

Rani Lewis, MD

XIV: Pharmacologic CoNSIDERATIO^

HIV-infected Pregnant Patie3

Paul Pham, PharmD and Patricia Ba

XV: Resources