A Guide to the Clinical Care of Women with HIV/AIDS

J. R. Anderson (Editor)
A Guide to the Clinical Care of Women with HIV/AIDS


EDITED BY JEAN R. ANDERSON, MD

Associate Professor
Departments of Gynecology, Obstetrics, and Medicine
The Johns Hopkins University School of Medicine
Departments of Population and Family Health Sciences
The Johns Hopkins University School of Public Health









U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau i
A GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION









Recommendations change rapidly in HIV care, so the care provider
is cautioned that this edition is dated 2005. For the most current
and continually updated HIV/AIDS treatment guidelines, contact
AIDSinfo at:
http://www.aidsinfo.nih.gov



This Guide contains information relating to general principles of medical
care which should not be construed as specific instructions for individual
patients. Some of the information may cite the use of a particular drug
in a dosage, for an indication, or in a manner other than recommended.
Therefore, the manufacturer’s package inserts should be consulted for
complete prescribing information.











DEPARTMENT OF HEALTH AND HUMAN SERVICES
HEALTH RESOURCES AND SERVICES ADMINISTRATION
HIV/AIDS BUREAU
PARKLAWN BUILDING, ROOM 7-13
5600 FISHERS LANE
ROCKVILLE MD 20857
http://www.hab.hrsa.gov

Publication date 2005



ii U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
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FORWARD
A GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION
A Guide to the Clinical Care of Women with HIV is a comprehensive clinical
manual that addresses the primary care needs unique to women with
HIV infection. The target audience is clinicians who provide primary care
to women as well as those seeking a more in-depth understanding of how
to care for women with HIV/AIDS. This 2005 edition of the guide, first
published in 2001, has been updated and chapters have been added on
international issues and nutrition.
A manual devoted specifically to the care of women with HIV is
important. Because women are often challenged by social isolation,
poverty, discrimination and lack of access to quality health care, they
tend to be diagnosed later and to have poorer health status than men.
They must contend with vulnerability related to reproductive and gender
issues and domestic violence. Finally, women living with HIV are usually
relied upon to meet the care needs of children and other family members,
many of whom are also HIV-positive.


DEDICATION
We want to acknowledge the women with HIV/AIDS who have been the
inspiration for this Guide. 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.


ACKNOWLEDGMENTS
A number of people made this Guide possible. Joan Holloway provided
the framework for the Guide’s inception and development. Magda Barini-
García, MD, MPH was the Project Officer who shepherded and oversaw the
project. Helen Schietinger, the project manager, coordinated the production
process and brought it to fruition. Laura Spofford designed the cover. For
the 2005 edition, Patrice Lincoln was the typographer and designer and Bill
Todd was the copyeditor and indexer.









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A GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION


For the 2005 Edition,
the chapters were reviewed by the following experts:
Dawn Averitt
Founder and CEO, The Well Project
Kirsten B. Balano, PharmD
University of California, San Francisco
John G. Bartlett, MD
The Johns Hopkins University School of Medicine
Gail V. Berkenblit, MD, PhD
The Johns Hopkins University School of Medicine
Jonathan Ellen, MD
The Johns Hopkins University School of Medicine
Thurma McCann Goldman, MD
HIV/AIDS Bureau, HRSA
Laura A. Guay MD
The Johns Hopkins University School of Medicine
Lisa Ruth Hirschhorn, MD
Harvard University Medical School
Gregory M. Lucas, MD, PhD
The Johns Hopkins University School of Medicine
Mary E. McCaul, PhD
The Johns Hopkins University School of Medicine
Howard L. Minkoff, MD
State University of New York at Stonybrook School of Medicine
Helen Miramontes, RN, MSN, FAAN
School of Nursing, University of California, San Francisco
(Emeritus)
Ila Mulasi, MD
University of Maryland School of Medicine
Eula W. Pines, PhD, APRN, BC
University of the Incarnate Word
Timothy R. Sterling, MD
Vanderbilt University School of Medicine
Glenn J. Treisman, MD, PhD
The Johns Hopkins University School of Medicine
Ruth Ellen Tuomala, MD
Harvard University Medical School
Jonathan Zenilman, MD
The Johns Hopkins University School of Medicine



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Contributing Authors
Silvia M. Abularach, MD, MPH
Assistant Professor
Department of Gynecology and Obstetrics
The Johns Hopkins University School of Medicine
Baltimore, MD, U.S.
Carla S. Alexander, MD
Assistant Professor of Medicine
University of Maryland School of Medicine
Baltimore, MD, U.S.
Jean R. Anderson, MD
Associate Professor
Departments of Gynecology, Obstetrics, and Medicine
The Johns Hopkins University School of Medicine
Departments of Population and Family Health Sciences
The Johns Hopkins University School of Public Health
Baltimore, MD, U.S.
Barbara Aranda-Naranjo, PhD, RN, FAAN
Scanlon Endowed Chair in Values Based Health Care
Nursing and Health Studies
Georgetown University
Washington, DC, U.S.
Jared M. Baeten, MD, PhD
Department of Medicine
Massachusetts General Hospital
Boston, MA, U.S.
Patricia Barditch-Crovo, MD
Assistant Professor
Division of Infectious Diseases
The Johns Hopkins University School of Medicine
Baltimore, MD, U.S.
Magda Barini-García, MD, MPH
Senior Medical Advisor
HRSA Center for Quality
HIV/AIDS Bureau, Health Resources and Services Administration
Rockville, MD, U.S.
Victoria A. Cargill, MD, MSCE
Director of Minority Research, Director of Clinical Studies
Office of AIDS Research
National Institutes of Health
Bethesda, MD, U.S.






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A GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION



Contributing Authors continued
Connie Celum, MD, MPH
Professor of Medicine and Adjunct Professor of Epidemiology
University of Washington
Seattle, WA, U.S.
Laura Cheever, MD, ScM
Deputy Associate Administrator
Chief Medical Officer
HIV/AIDS Bureau, Health Resources and Services Administration
Rockville, MD, U.S.
Rachel Davis, RN, ACRN
Field Nurse Case Manager
Concentra Integrated Services, Inc.
Pleasanton, TX, U.S.
Judith Y. Ellis, MS
Division of Training and Technical Assistance
HRSA Center for Quality
HIV/AIDS Bureau, Health Resources and Services Administration
Rockville, MD, U.S.
Judith Feinberg, MD
Professor of Medicine
University of Cincinnati College of Medicine
Cincinnati, OH, U.S.
Henry Francis, MD
Director, Center on AIDS and Other Medical Consequences
of Drug Abuse (CAMCODA)
National Institute on Drug Abuse, National Institutes of Health
Bethesda, MD, U.S.
Donna Futterman, MD
Professor of Clinical Pediatrics, Albert Einstein College of Medicine
Director, Adolescent AIDS Program, Montefiore Medical Center
Bronx, NY, U.S.
Monica Gandhi, MD, MPH
Assistant Professor
Division of Infectious Diseases
University of California, San Francisco
San Francisco, CA, U.S.
Ruth M. Greenblatt, MD
Professor of Medicine, Epidemiology and Biostatistics
University of California at San Francisco
San Francisco, CA, U.S.






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Contributing Authors continued
Nancy A. Hessol, MSPH
Assistant Professor
Department of Medicine
University of California, San Francisco
San Francisco, CA, U.S.
Dorothy Kasonde, MBCHB, MMed
Antiretroviral Consultant
JHPIEGO/Zambia
Lusaka, Zambia
Joyce Seiko Kobayashi, MD
Associate Professor
University of Colorado Health Sciences Center
Denver, CO, U.S.
Rani Lewis, MD
Division Director for Maternal Fetal Medicine
Meharry School of Medicine
Nashville, TN, U.S.
Janine Maenza, MD
Clinical Assistant Professor
Division of Allergy and Infectious Diseases, Department of Medicine
University of Washington
Seattle, WA, U.S.
Paul Pham, PharmD
Research Associate
Division of Infectious Diseases
The Johns Hopkins University School of Medicine
Baltimore, MD, U.S.
Moses Pounds, PhD
Deputy Chief
Service Evaluation and Research Branch
Office of Science & Epidemiology
HIV/AIDS Bureau, Health Resources and Services Administration
Rockville, MD, U.S.
Helen Schietinger, MA, ACRN
HIV Policy Analyst
Washington, DC, U.S.










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Contributing Authors continued
Suniti Solomon, MD
Founding Director
Y.R.Gaitonde (YRG) Centre for AIDS Research and Education
Chennai, India
Valdiléa Gonçalves Veloso Dos Santos, MD, MSc
Associate Researcher
Evandro Chagas Clinical Research Institute
Oswaldo Cruz Foundation
Rio Di Janiero, Brazil
Chia C. Wang, MD, MS
Assistant Professor
Department of Medicine
Division of Infectious Diseases University of Washington
Seattle, WA, U.S.
































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TABLE OF CONTENTS
Abbreviations ................................................................................................x
I. Epidemiology and Natural History of HIV Infection in Women.............1
Nancy A. Hessol, MSPH, Monica Gandhi, MD, MPH,
and Ruth M. Greenblatt, MD
II. Approach to the Patient .............................................................................35
Jean R. Anderson, MD
III. Prevention of HIV.......................................................................................47
Jared M. Baeten, MD, PhD, Chia C. Wang, MD, MS,
and Connie Celum, MD, MPH
IV. Primary Medical Care ................................................................................ 91
Judith Feinberg, MD and Janine Maenza, MD
V. Adherence to HIV Therapies ................................................................... 167
Laura W. Cheever, MD, ScM
VI. Gynecologic Problems.............................................................................. 177
Silvia M. Abularach, MD, MPH and Jean R. Anderson, MD
Color Plates ............................................................................................... 231
VII. HIV and Reproduction ............................................................................. 241
Jean R. Anderson, MD
VIII. Addressing Cultural Issues to Improve Quality of Care ........................ 331
Barbara Aranda-Naranjo, PhD, RN, FAAN, Magda Barini-García, MD, MPH,
Moses Pounds, PhD, and Rachel Davis, RN, ACRN
IX. Psychiatric Issues...................................................................................... 347
Joyce Seiko Kobayashi, MD
X. Substance Abuse........................................................................................ 377
Henry Francis, MD and Victoria A. Cargill, MD, MSCE
XI. Adolescents................................................................................................ 405
Donna Futterman, MD
XII. Palliative Care and End-of-Life Care ....................................................... 419
Carla S. Alexander, MD
XIII. Occupational Exposure ............................................................................ 453
Rani Lewis, MD
XIV. Pharmacologic Considerations in HIV-Infected Pregnant Patients..... 469
Paul Pham, PharmD and Patricia Barditch-Crovo, MD
XV. Resources ................................................................................................... 547
Judith Y. Ellis, MS and Helen Schietinger, MA, ACRN
XVI. International Issues.................................................................................. 563
Dorothy Kasonde, MBCHB, MMed, Suniti Solomon, MD,
Valdiléa Gonçalves Veloso dos Santos, MD, MSc, and Jean R. Anderson, MD
XVII. Nutrition Counseling, Care and Support................................................ 577
World Health Organization
Index .......................................................................................................... 599



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ABBREVIATIONS


3TC Lamivudine
5-FU 5-fluorouracil
A-aDO2 Alveolar to arterial oxygen


CBC Complete blood count
CBV Combivir
CDC Centers for Disease Control
difference
ABC Abacavir
American College
and Prevention
CEA Carcinoembryonic antigen
CES-D Center for Epidemiological
ACOG of Obstetricians and
Gynecologists
ADC AIDS dementia complex
Studies Depression scale
CI Confidence interval
CIN1, -2, -3 Cervical intraepithelial
ADR Adverse drug reaction
AFB Acid-fast bacilli
AFI Amniotic fluid index

CLIA
neoplasia, grade 1 (2, 3)
Clinical Laboratory
Improvements
Amendments
AFP Alfa fetoprotein
AGC Atypical glandular cells
ALT Alanine aminotransferase
Cmax Peak serum concentration
Cmin Trough serum
Anti-HBc Hepatitis B core antibody
Anti-HBs Hepatitis B surface
concentration
CMV Cytomegalovirus
CNS Central nervous system
antibody
AP Antepartum
APAP Acetaminophen
APV Amprenavir
ARV Antiretroviral
ASA Aspirin (acetylsalicylic acid)
Anal squamous
ASC-H intraepithelial lesions—
cannot exclude HSIL
Anal squamous
ASCUS intraepithelial lesions—
undetermined significance
ASIL Anal squamous
CPK Creatinine phosphokinase
CrCl Creatinine clearance
CSF Cerebrospinal fluid
CST Contraction stress test
CT Computed tomography
CVD Cardiovascular disease
CXR Chest x-ray
d Day
d/c Discontinue
d4T Stavudine
ddC Zalcitibine
ddI Didanosine
intraepithelial lesions
ATV Atazanavir
DEXA Dual-energy X-ray
AUC Area under the
concentration-time curve
absorptiometry
DFA Direct fluorescent
AZT Zidovudine
bDNA Branched DNA
bid 2 times daily
biw 2 times weekly
BMI Body mass index
BV Bacterial vaginosis
antibody
DLV Delavirdine
Depo-
DMPA medroxyprogesterone
acetate
DOT Directly observed therapy
DRESS Drug rash, eosinophilia,
bx Biopsy
CASI Computer assisted self-
systemic symptoms
DS Double strength
dT Diphtheria/tetanus toxoid
interviewing

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ABBREVIATIONS continued


DVT Deep venous thrombosis


HCSUS HIV Cost and Services
EBV Epstein-Barr virus
EC Enteric coated
EFV Efavirenz
ELISA Enzyme-linked
Utilization Study
HCV Hepatitis C virus
HDL High-density lipoprotein
HERS HIV Epidemiology
immunosorbent assay
EM Electron microscopy
EMG Electromyelogram
ERCP Endoscopic retrograde
cholangiopancreatography
ESR Erythrocyte sedimentation
Research Study
hgc Hard gel capsule
HLA Human leukocyte antigen
HPV Human papillomavirus
hr Hour
HRT Hormone replacement
rate
ETOH Ethyl alcohol
therapy
HSIL High-grade squamous
FA Fluorescent antibody
FDA Food and Drug
intraepithelial lesion
HSV Herpes simplex virus
Administration
HTLV Human T-cell lymphotropic
FSH Follicle stimulating
virus
hormone
IDSA Infectious Disease Society
FTA Fluorescent treponemal
of America
IDU Injection drug use/user
antibody
FTC Emtracitabine
FUO Fever of unknown origin
IDV Indinavir
IgA Immunoglobulin A (E, G,
G6PD Glucose-6-phosphate
M, etc.)
dehydrogenase
GBS Group B Streptococci
GBV-C GB virus type C
GC Gonorrhea culture
G-CSF Granulocyte-colony
im Intramuscularly
INH Isoniazid
INR International
normalization ratio
IP Intrapartum
IUD Intrauterine device
stimulating factor
GI Gastrointestinal
GTT Glucose tolerance test
H&E Hematoxylin and eosin
iv Intravenously
IVP Intravenous pyelogram
JC virus (Initials of index case of
HAART Highly active antiretroviral
PML)
KOH Potassium hydroxide
therapy
HAD HIV-associated dementia
HAV Hepatitis A virus
HBIG Hepatitis B
KS Kaposi sarcoma
LAAM L-a-acetyl-methadol
LCR Ligase chain reaction
LDH Lactic dehydrogenase
immunoglobulin
HbsAg Hepatitis B surface antigen
HBV Hepatitis B virus
HCG Human chorionic
LDL Low-density lipoprotein
LFT Liver function test
LIP Lymphoid interstitial
gonadotropin
pneumonia



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ABBREVIATIONS continued


LP Lumbar puncture
LPV Lopinavir
LTS Long-term survival
MAC Mycobacterium avium


O&P Ova and parasites
OC Oral contraceptive
OI Opportunistic infection
OR Odds ratio
complex
PACTG Pediatric AIDS Clinical
MCMD Minor cognitive-motor
Trials Group
disorder
Perinatal AIDS
MDD Major depressive disorder
MDMA Methylenedioxymethamph
PACTS
Collaborative Transmission
Study
etamine (ecstasy)
MMR Measles, mumps and
PaO2 Partial pressure of oxygen
PCN Penicillin
rubella
Pneumocystis jiroveci
mo Month
PCP
(formerly carinii)
pneumonia
MPA Medroxyprogesterone
PCR Polymerase chain reaction
acetate
MRI Magnetic resonance
PEP Postexposure prophylaxis
imaging
PGL Persistent generalized
MSM Men who have sex with
lymphadenopathy
men
MTCT Mother-to-child
PI Protease inhibitor
PID Pelvic inflammatory
transmission
MTPA Methoxy (trifluoromethyl)
disease
PK Pharmacokinetic
phenylacetic acid
N/V/D Nausea/vomiting/diarrhea
PLWHA People living with HIV/
N-9 Nonoxynol-9
AIDS
PML Progressive multifocal
NASBA Nucleic acid sequence-
leukoencephalopathy
based amplification
PMTCT Prevention of mother-to-
NFV Nelfinavir
NIDU Non-injection drug use
NIH National Institutes of
child transmission
po By mouth
PP Postpartum
Health
NIMH National Institute of
PPD Purified protein derivative
PSN Predominantly sensory
Mental Health
NNRTI Non-nucleoside reverse
neuropathy
PTSD Post-traumatic stress
transcriptase inhibitor
NOS Not otherwise specified
NRTI Nucleoside reverse
disorder
PV Vaginally
qd 1 time daily
transcriptase inhibitor
NSAID Nonsteroidal anti-
qm 1 time monthly
qod Every other day
inflammatory drug
NST Non-stress test
qw 1 time weekly






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ABBREVIATIONS continued


r/o Rule out TE Toxoplasmic encephalitis
RIBA Recombinant immunoblot TIBC Total iron binding capacity
assay
RNA Ribonucleic acid
RPR Rapid plasma reagin
RT-PCR Reverse transcriptase
tid 3 times daily
tiw 3 times weekly
TMP Trimethoprim
TSH Thyroid-stimulating
polymerase chain reaction
RTV Ritonavir
sc Subcutaneously
sgc Soft gel capsule
hormone
TSS Toxic shock syndrome
TST Tuberculin skin test
UNAIDS United Nations Program
SI Syncytium-inducing
SIL Squamous intraepithelial
on AIDS
USPHS United States Public
lesions
SIV Simian immunodeficiency
Health Service
VCT Voluntary counseling and
virus
SMX Sulfamethoxazole
testing
VDRL Venereal Disease Research
SOC States of Change behavior
Laboratory slide test
theory
SP Sulfadioxone
pyrimethamine
sq Subcutaneous
VZV Varicella zoster virus
WBC White blood cell
WHO World Health Organization
WIHS Women’s Interagency HIV
SQV Saquinavir
SS Single strength
Study
WITS Women and Infants
SSRI Selective serotonin
Transmission Study
yr Year
reuptake inhibitor
STI Sexually transmitted
infection
sx Symptom
TAM Thymidine-associated
mutation
TB Tuberculosis
Td Tetanus/diphtheria
TDM Therapeutic drug
monitoring











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A GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION



I. EPIDEMIOLOGY AND NATURAL HISTORY OF
HIV INFECTION IN WOMEN
Nancy A. Hessol, MSPH, Monica Gandhi, MD, MPH,
and Ruth M. Greenblatt, MD

I. INTRODUCTION
The successful introduction and spread of the human immuno-
deficiency virus (HIV) into the global human population has occurred
for many reasons. The discovery and widespread use of penicillin and
other antibiotics meant that there was treatment and cure for most
sexually transmitted infections. The existence of these new drugs
changed how people perceived risks associated with sexual activity.
The development of hormonal contraceptives hastened the pace of
change in sexual practices, as prevention of pregnancy without barrier
methods became a possibility. Lifestyles were also changing: people
were moving into regions that were previously uninhabited by man and
long-distance travel became easier and much more common, allowing
for greater social migration and sexual mixing. Although the virus may
have been first introduced to humans earlier in the 20th century (most
likely contracted from infected animals), it was in the 1970s 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
26% of adult cases in 2001 (CDC, 2002). Seventy-eight percent of AIDS
cases in women are in African Americans and Hispanics, as compared
with 52% of cases in men.
In developing countries, the AIDS epidemic manifested quite differently,
both because the signs and symptoms were harder to distinguish from
competing causes of morbidity and mortality, and because the epidemic
was more generalized, instead of seemingly limited to certain “high-
risk” groups. Worldwide, women now represent 50% of all adults living
with HIV and AIDS (Table 1-1), and this proportion had been steadily
increasing over time (UNAIDS, 2002).
This chapter reviews the epidemiology of HIV/AIDS, beginning with
how HIV is transmitted and the variables involved; the natural history
of HIV infection in women — both without treatment and in the era of
highly active antiretroviral therapy (HAART), and concludes with future
issues regarding the HIV/AIDS epidemic.



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I Table 1-1: R egional HIV/AIDS St atistics and Featur es , December 2002 R egion Epidemic St arted # Per sons With Hiv Infection # Per sons With N ew Hiv Infection Pr ev alence Among A dults Per cent Of Infected A dults Who Ar e W omen Main Modes Of Tr ansmission For A dults Sub-Saharan Africa Late 1970s- early 1980s 29.4 million 3.5 million 8.8% 58% Heter osexual contact North Africa and Mid-East Late 1980s 550,000 83,000 0.3% 55% Heter osexual contact, injection drug use, South, South-East Asia Late 1980s 6.0 million 700,000 0.6% 36% Heter osexual contact, injection drug use East Asia, Pacific Late 1980s 1.2 million 270,000 0.1% 24% Injection drug use, heter osexual contact, male/male sex Latin America Late 1970s- early 1980s 1.5 million 150,000 0.6% 30% Male/male sex, injection drug use, heter osexual contact Caribbean Late 1970s- early 1980s 440,000 60,000 2.4% 50% Heter osexual contact, male/male sex Easter n Eur ope, Central Asia Early 1990s 1.2 million 250,000 0.6% 27% Injection drug use W ester n Eur ope Late 1970s- early 1980s 570,000 30,000 0.3% 25% Male/male sex, injection drug use North America Late 1970s- early 1980s 980,000 45,000 0.6% 20% Male/male sex, injection drug use, heter osexual contact Australia, New Zealand Late 1970s- early 1980s 15,000 500 0.1% 7% Male/male sex Total 42 million 5 million 1.2% 50% Source: Modified from (UNAIDS, 2002).LINICALA G
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Epidemiology and Natural History of HIV Infection in Women

II. HIV TRANSMISSION
Epidemiology and Natural History of HIV Infection in Women
Epidemiologic studies have demonstrated that HIV is transmitted by
three primary routes: sexual, parenteral (blood-borne), 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. Because HIV is a relatively large virus, has a short half-life
in vitro, and can only live within primates, HIV cannot be transmitted
from casual (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 female-to-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 41% of reported cases
as of December 2001 (CDC, 2002). This 41% is probably an underestimate
given that a large proportion of the women with AIDS who report no
identifiable risk (an additional 17% of AIDS cases in women) are actually
also infected via sexual transmission. While receptive anal 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 anal and vaginal) has also been associated with HIV infection
(approximately 0.06% and 0.1%, respectively, per episode) (Mastro, 1996;
Vittinghoff, 1999). 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%-0.10% per contact) (Lifson,
1990; Samuel, 1993; Vittinghoff, 1999; Page-Shafer, 2002) and female-to-
female transmission from oral-vaginal, oral-anal, sex toy–related, and
digital intercourse (Marmor, 1986; Monini, 1996; Monzon, 1987; Perry,
1989; Rich, 1993; Sabatini, 1983; Kwakwa, 2003).
Parenteral transmission of HIV has occurred in recipients of blood
and blood products, through transfusion of blood (estimated 95% risk
of infection from transfusion of a single unit of HIV-infected whole
blood [CDC, 1998a]) or clotting factors, in intravenous or injection drug
users through the sharing of needles (approximately 0.67% risk per
exposure [Kaplan, 1992]), in health care workers through needlesticks
(approximately 0.3–0.4% risk per exposure, depending on the size
and location of the inoculum [Tokars, 1993. Updated PHS guidelines,
2001]), and, less commonly, mucous membrane exposure (0.09% risk
per exposure (Updated PHS guidelines, 2001, Hessol, 1989). Among
cumulatively reported AIDS cases in U.S. women through December
2001, 39% had injection drug use as their exposure risk and 3% reported
receipt of infected blood, blood products, or tissue (CDC, 2002). Parenteral
transmission patterns vary by geographic region due to social and
economic factors. For instance, in regions where the prevalence of HIV

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Epidemiology and Natural History of HIV Infection in Women

infection is higher, the risk of occupational or nosocomial transmission of
HIV is greater than in 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. Recent data suggests
that medical injections may account for a large number of previously
unexplained HIV infections in the developing world (Gisselquist, et al.
2002; Gisselquist, 2002; Rosenthal, 2001).
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) overall in the absence of intervention, but
vary by maternal stage of disease, use of antiretroviral therapy, duration
of ruptured membranes, practice of breast-feeding, and other factors.
In the United States as of December 2001, 91% of cumulative pediatric
AIDS cases were attributed to perinatal transmission (CDC, 2002). 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 and the recipient, as
well as 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 HIV-infected 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
(Quinn, 2000; Vernazza, 1999; Gray, 2001). 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 but not to a second-born child (de
Martino, 1991), and temporal studies of semen from HIV-infected men
demonstrate waxing and waning viral titers over time (Krieger, 1991;
Tindall, 1992).
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Table 1-2: Biologic and Host-related Factors Affecting Sexual
Transmission Of HIV
Host-related Infectivity Factors
Biologic Factor

Mutation of chemokine-
receptor gene
Late stage of HIV
infection
Primary HIV infection
Anti-retroviral therapy
Local infection
Presence of cervical
ectopy*
Presence of foreskin*
Method of
contraception
Barrier
Hiv Concentration
In Genital
Secretions
?
▲▲
▲▲
▼
▲▲
▲▲
?


Not applicable
Infectiousness
(Transmission)
?
▲▲▲
▲▲
▼▼
▲
▲?
▲▲


▼▼▼
▲
Susceptibility
(Acquisition)
▼▼▼
Not applicable
Not applicable
▼?
▲▲
▲▲
▲▲


▼▼▼
▲
Hormonal contraceptives
Spermicidal agents
Intrauterine devices
Menstruation
Factors that lower
cervicovaginal pH*
Immune activation
Genital tract trauma*
Pregnancy
▲▲
?
?
?
▼?
▲?
▲?
▲▲
▼?
▼?
?
▲▲
▼?
▲
▲▲
▲?
▼
▲
▼
▲▲
▲
▼?
▲
▲▲
▲?
The degrees of positivity (▲ to ▲▲▲) 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. Coptright New England Journal of Medicene. Reprinted with permission.
*More recent data reveal that use of microbicides containing nonoxynol-9 are associated with a higher
susceptibility to HIV infection (Roddy, 1998).
Factors that decrease viral titers, including antiretroviral 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, 1998b). (See Chapter VII on HIV and Reproduction.) Individuals
receiving antiretroviral therapy have also shown reduced rates of HIV
transmission to their sex partners (Musicco, 1994). Several studies have
suggested that antiretroviral treatment reduces detection of HIV in
female genital secretions (Cu Uvin, 1998) and the concentration of HIV


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Epidemiology and Natural History of HIV Infection in Women

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 because not all treatments reduce
infectiousness, and transmissions have been reported among individuals
with undetectable HIV RNA levels (European Collaborative Study Group,
1999). The presence of HIV in seminal cells has been documented in
some individuals receiving highly active antiretroviral therapy and with
undetectable levels of HIV-RNA in plasma (Zhang, 1998).
Factors that increase the risk of exposure to blood, such as genital ulcer
disease (Cameron, 1989; Plummer, 1991), trauma during sexual contact
(Marmor, 1986), and menstruation of an HIV-infected woman during
sexual contact (European 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 protects both men and women
against HIV.

SUSCEPTIBILITY OF THE RECIPIENT
Characteristics of the uninfected individual may increase the likelihood
of infection for a given exposure to HIV. Specifically, inflammation
or disruption of the genital or rectal mucosa (which can occur with
sexually transmitted infections 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 a
woman’s risk of acquiring HIV infection (Lazzarin, 1991) as may bleeding
during sexual intercourse (Seidlin, 1993). In women, both ulcerative and
nonulcerative sexually transmitted infections have been shown to be risk
factors for acquiring HIV infection (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 all (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; Sturm-Ramirez, 2000).
Nonbarrier contraceptive methods have also been investigated in
association with risk of HIV acquisition. 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 of HIV.) Traditional vaginal agents,
used in African women for sexual enhancement and self-treatment
of vaginal symptoms, have also been investigated as potential cofactors
for HIV transmission (Dallabetta, 1995). Use of hormonal contraceptives
does not seem to be associated with increased susceptibility to HIV
infection after adjustment for behavioral factors (Kiddugavu, 2003).
The use of a popular vaginal and rectal microbicide, nonoxynol-9,
has been shown to have no protective efficacy against the acquisition


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of HIV (Roddy, 1998) and may even increase susceptibility to HIV
infection due to mucosal barrier disruption, particularly with frequent
use (Stephenson, 2000). The utility of other microbicidal agents for
reducing the susceptibility to HIV infection is currently under active
investigation.
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 U.S. homosexual
men (Dean, 1996), in which both sets of study subjects remained
uninfected despite multiple sexual exposures to HIV. Individuals who
are homozygous for a null 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. However,
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
overproduction of ß-chemokines 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 “fitness” of the virus, and resistance to
antiretroviral 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 phenotype is the nonsyncytia-inducing,
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, T-tropic viral phenotype can
be found and this is often a precursor to the development of AIDS.
While some researchers have suggested that nonsyncytia-inducing
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
distribution of HIV subtypes differs 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.



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The transmission characteristics of a viral strain that is resistant to
certain antiretroviral agents may differ from transmission of wild-type
virus. Recent data indicates that resistant virus may be transmitted less
efficiently than wild-type virus (Leigh Brown, 2003), but further research
on the characteristics of drug-resistant virus is underway.


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 sex on the
manifestations and progression of HIV disease is still being investigated.
HIV infects and induces cell death in a variety of human cell lines.
T-helper lymphocytes (also known as CD4 cells) are a major target of
viral infection, and circulating CD4 cells 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 cell depletion is unusual
in persons who do not have HIV infection and is usually iatrogenic
or associated with severe illnesses, such as chemotherapy-induced
leukopenia (Aldrich, 2000). Other immunologic 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. The plasma HIV-RNA level or viral load quantifies the
amount of virus circulating in the bloodstream and reflects the level of
HIV replication.
Untreated HIV infection is a chronic illness that progresses through
characteristic clinical stages; AIDS is an endpoint of HIV infection,
resulting from severe immunologic damage, loss of an effective immune
response to specific opportunistic pathogens, and tumors. AIDS is
diagnosed by the occurrence of these specific infections and cancers or
by CD4 cell depletion to less than 200/mm3.
A. STAGING
HIV can cause a wide range of symptoms and clinical conditions that
reflect the level of immunologic 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 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 and Prevention in 1992 (CDC, 1992).


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The case definition (Table 1-3) begins first with confirmation of HIV
infection via either serologic testing (combination of a screening method
such as enzyme immunoassay and a 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/mm3) to severe CD4 depletion (<200 cells/mm3). 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 cells/mm3 (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. Because lymphocyte subset quantitation is not widely available in many countries, the Global Program on AIDS of the World Health Organization (WHO) proposed a clinically based staging system that is more broadly applicable than the CDC system (WHO, 1993). The system uses clinical historical data, laboratory measures (optional), and indices of physical activity to assess level of infirmity to establish four clinical stages, summarized in Table 1-4. Laboratory measures include a single-assessment absolute CD4 cell count, with the option of replacing this test with total lymphocyte count, both 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; Jacobson, 2003; Badri, 2003). 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 WHO system requires fewer 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 Southeast 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. U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau8 9 IA GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION Epidemiology and Natural History of HIV 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 1. 500 cells/mm3 2. 200–499 cells/mm3 3. < 200 cells/mm3 Clinical Category A A1 A2 A3 Clinical Category B B1 B2 B3 Clinical Category C C1 C2 C3 Category A Conditions Category B Conditions Category C Conditions • No symptoms • Acute HIV infection (resolves) • Generalized lymphadenopathy Source: CDC, 1992. • 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 leukoplakia
• Herpes zoster: multiple episodes
or involving > 1 dermatome
• 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 mo duration)
• Cytomegalovirus disease
(excluding liver, spleen or lymph
nodes)
• HIV-related encephalopathy
•
> 1 mo duration, or bronchitis,
pneumonitis, or esophagitis
• Histoplasmosis: disseminated or
extrapulmonary
• Isosporiasis: > 1 mo duration
• Kaposi’s sarcoma
• Burkitt’s lymphoma
• Immunoblastic lymphoma
• Primary lymphoma of the brain
•
or M. kansasii: disseminated or
extrapulmonary
•
•
unknown species, disseminated
or extrapulmonary
• Pneumocystis carinii pneumonia
• Recurrent pneumonia
• Progressive multifocal
leukoencephalopathy
•
• Toxoplasmosis of the brain
• Wasting syndrome due to HIV






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Table 1-4: The World Health Organization Clinical HIV
Staging System and Proposed Modifications




A
Laboratory Component
Cd4 Cell Total
Count Lymphocyte
Count
>=500 >=2000

1


A1
Clinical Group
2 3


A2 A3

4


A4
B
200-499 1000-1999
B1
B2
B3
B4
C
<200 <1000 C1 C2 C3 C4 Clinical Stage One: Asymptomatic Two: Mild Disease Three: Moderate Disease Clinical History 1. Asymptomatic infection 2. Persistent generalized lymphadenopathy 3. Acute retroviral infection 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 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 Criteria Normal functional level in performance scales Performance scale level at which symptoms are present but patients are almost fully ambulatory Performance scale level at which patients remain in bed <50% of daytime, but more than normal Proposed Modifications None 1. Substitution of weight loss with BMI 19–21 kg/m2* 2. Specify addition of acute oral or genital ulcers as one of the minor mucocutaneous manifestations* 3. ESR ? 65 mm/hr defines Kigali stage II 4. ESR > 65 mm/hr defines
Kigali stage III
1. Suggest exclusion of
oral candidiasis and
pulmonary tuberculosis*
2. Recommend
substitution of weight
loss with BMI ? 19
kg/m2*
3. Differentiation of
ambulatory vs.
hospitalized patients
improved correlation
with laboratory markers
(Kassa, 1999)
4. ESR ? 65 mm/hr defines
Kigali stage II
5. ESR > 65 mm/hr defines
Kigali stage III









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Table 1-4 (continued)
Clinical Stage Clinical History Performance
Scale Criteria





Proposed
Modifications
Four: Severe
Disease


























* Lifson, 1995.
† >1 mo duration.
‡ De Cock, 1993.
Source: WHO, 1993.
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 atypical
Mycobacterium spp. infection
13. Nontyphoidal Salmonella
septicemia
14. Extrapulmonary tuberculosis
15. Lymphoma
16. Kaposi’s sarcoma
17. HIV-related encephalopathy
Performance scale
level at which
patients remain
in bed > 50% of
daytime
1. Addition of oral
candidiasis
2. Substitution of weight
loss with BMI ? 19
kg/m2*
3. Addition of chronic†
oral or genital ulcer
4. Addition of pulmonary
tuberculosis
5. ESR > 65 mm/hr defines
Kigali stage III
6. Addition of positive HIV
serology‡
7. Addition of invasive
cervical cancer‡

The four clinical stages in the WHO system correlated well with CD4
cell counts and HIV RNA levels in a study of 750 Ethiopians (including
336 women) by Kassa and others (Kassa, 1999). Other studies of patient
populations have also demonstrated correlation of WHO clinical stage
with CD4 cell count and clinical outcome (Morgan, 1997; 1998; Schechter,
1995). When compared with the CDC staging, the WHO clinical stages
demonstrated a high degree of specificity, but a lower level of sensitivity
(35–65%) for HIV infection (Gallant, 1992; 1993). 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; De Cock, 1991). Modifications (Table 1-4) have been


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proposed that improve the prognostic accuracy of the WHO 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 (weight (kg) divided
by height (m2)) for weight loss and use of erythrocyte sedimentation rate
as a laboratory indicator of infirmity (Lifson, 1995). Body mass index
was significantly better than percentage of body weight lost over two
measurements taken in 1 year at predicting mortality. Both erythrocyte
sedimentation rate and hematocrit were highly predictive of mortality
over a 36-mo 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 WHO systems.

B. UNTREATED NATURAL HISTORY
PRIMARY OR ACUTE INFECTION
Acute HIV infection is a transient symptomatic illness 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 cubic millimeter of
plasma), and initiation of an HIV-specific immune response. The amount
of virus present in blood and tissues begins to fall after the 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 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 missed. Because early treatment at the time
of acute infection is actively being investigated (Rosenberg, 2000) (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


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a steady state between viral replication and elimination (Henrad,
1995). A variable level of viremia is attained that 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), most patients establish a
relatively stable viral load after recovering from acute infection, and
this viral set point is highly predictive of the rate of future progression
of illness. In the case of a high viral load set point (i.e., values ranging
up from 40000 copies/mm3), more rapid decline in CD4 cell counts and
more rapid occurrence of Clinical Class B and C conditions will occur.
Some patients have low viral load set points (below 500 copies/mm3),
which indicates 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 sex (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, tuberculosis, and even routine vaccinations, have resulted in
10–1000-fold increases in viral load; these increases are transient and
most often resolve within 2 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 over time.
Transition for the nonsyncytia-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 have been observed to coincide with key clinical
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 individual’s immune response or other 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 still be detected with
more sophisticated techniques (Hockett, 1999). Thus HIV replication
continues at varying pace among infected persons, even those who
control viremia well.





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HIV is also frequently present in the genital tract (Fiore, 1999; Iversen,
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 those in 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
(Di Stefano, 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). Almost half of seroconverters will die (due to any cause)
after 10 years of infection if the disease is left untreated (Vella, 1992).
Increasing age is the factor most consistently associated with rate of
progression and death in most groups of patients studied to date (Alioum,
1998; UK Register of HIV Seroconverters Steering Committee, 1998;
Pezzotti, 1999b; 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 have
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 is generally not specific
to HIV infection. Table 1-5 summarizes these laboratory measures, their
outcomes, and 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 lymphocyte function (cytotoxic
lymphocyte response to HIV) (Spijkerman, 1997; Vlahov, 1998).









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Table 1-5: Laboratory Indicators of prognosis and/or stage of
illness in HIV infection (blood specimen)
Group
Test
Interpretation
in HIV
Advantages Disadvantages
A HIV RNA level Higher level,
greater rate of viral
Direct measure
of current viral
Requires freshly
frozen and separated
replication, poorer
activity, excellent sample, expensive and
prognosis
prognostic
indicator. Useful
as indicator
of treatment
response.
technically demanding.
(O’Brien, 1996; Saag,
1996)
A P24 antigen
level
Higher level indicates Simple and
greater level of relatively
viremia, poorer inexpensive
prognosis
Of less prognostic
value than most other
assays (Coombs, 1989;
Fahey, 1990)
A Syncytium-
Emergence of
An indicator of
Requires viral culture
inducing
SI strains is an
viral virulence for or DNA assay, which
(SI) HIV
phenotype



B Lymphocyte
count


B CD4 subset
(absolute
count, % or
CD8 ratio)
independent
predictor of
progression to AIDS


Lymphopenia
suggests greater
immune injury

Depletion of CD4
cells suggests
immune injury and
poorer prognosis,
CD4 cells, adds
to prognostic
information
provided by CD4
and HIV RNA
level
Indicates
current status,
cumulative over
variable time
Indicates
current status,
cumulative over
variable time,
is cumbersome and
costly. (Koot, 1993)



Nonspecific, can be
influenced by large
number of concurrent
conditions and
treatments
Large range of
variation (some
introduced by
differences among


B Lymphocyte
markers of
excellent prognostic
indicator.
Presence of
specific sets of
severe depletion labs) expensive, must
relatively specific be performed on fresh
for HIV (not frozen) specimen
Highly specific Methods not
marker of long standardized, costly
immunologic
activation



B HIV-specific
cytotoxic
lymphocytes

C B-2
activation markers
on lymphocytes,
depending on type,
indicates favorable
or unfavorable
prognosis. Excellent
prognostic indicators.
Strong cytotoxic
responses to HIV
indicate favorable
prognosis.
Higher B-2
term stability or
decline.



Highly specific
marker of long
term stability.

Simple to
and has limited
availability. (Giorgi,
1994)



Methods not
standardized, costly
and has limited
availability. (Harrer,
1996)
General marker
microglobulin microglobulin levels
associated with risk
of progression
C Neopterin Higher neopterin
perform

Perhaps best
of inflammation,
nonspecific. (Planella,
1998)
Not as good a
levels associated with prognostic
prognostic indicator as
risk of progression
indicator among CD4 cell count. (Fahey,
group C. Simple 1990)
to perform assay.



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Epidemiology and Natural History of HIV Infection in Women

LONG-TERM NONPROGRESSORS
Epidemiology and Natural History of HIV Infection in Women
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 (Buchbinder, 1994; Munoz, 1995),
a phenomenon that has been named long-term survival (LTS). These
individuals are often called long-term nonprogressors. Among these
individuals who remain clinically stable 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
longterm 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
patients was markedly less than in perhipheral blood mononuclear cells
taken from healthy HIV-uninfected donors (Cao, 1995).
SEX EFFECTS
Concerns about sex-based differences in the course of HIV infection
were expressed early in the epidemic. Women appeared to have more
rapid progression of illness than men and to present with a different
constellation of opportunistic conditions than men. However, current
data suggests that the incidence and distribution of HIV-related illnesses
are similar by sex, with the exception of Kaposi’s sarcoma, which is
uncommon in women, and gynecologic manifestations of HIV. When
sophisticated statistical methods were applied that controlled for the
tendency of women to receive less care and to present with more
advanced disease, sex-based differences in HIV disease course appeared
to be eliminated. 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 predictors
of progression and survival in women (Anastos, 1999b). Several recent
reports, however, describe sex-based differences in HIV RNA level and
in rate of CD4 cell depletion; women had HIV RNA levels 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 (Lyles, 1998; Sterling, 1999; Sterling, 2001). A
recent epidemiologic review of 13 studies, 4 of which were longitudinal,
confirmed these findings, which were unchanged after adjustment for
potential confounding variables, such as age, race, mode of transmission,
and antiretroviral treatment (Gandhi, 2002). Intuitively, lower levels of
circulating HIV RNA, which suggest lower steady-state levels of viremia,
should be associated with better outcome. However, the lower HIV RNA


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Epidemiology and Natural History of HIV Infection in Women

level seen in women does not appear to provide benefit in terms of
disease progression or survival. Viral load differences tend to dissipate
several years after seroconversion and rates of progression to AIDS are
similar by sex (Sterling, 1999; Sterling, 2001) when examined in men and
women followed from seroconversion. [Studies have also suggested that
CD4 cell counts are higher in women at onset of AIDS (Prins, 1999) but
that CD4 cell depletion may occur more rapidly in women as compared
to men (Anastos, 2000).]
Determination of the effect of sex 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 biologic sex. Women tend to have lower income,
be un- or underinsured for health care, 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 factors 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 cell count and drug use are taken into consideration
(Alioum, 1998; UK Register of HIV Seroconverters Steering Committee,
1998; Pezzotti, 1999a; 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
(Melnick, 1994; Weisser, 1998).
Factors that influence disease progression are summarized in Table 1-6.
Table 1-6: Factors that influence rate of HIV-disease progression
Host Factors
Age





Sex


Race

Chemokine
receptor
and ligand
mutations:
CCR5, CCR2,
SDF-1
Effect
Increasing age
associated with more
rapid progression



Lower HIV RNA level
among women,
without progression
benefit (Sterling 2001).
No consistent effect in
various studies
Homozygous mutation
protective versus
primary infection,
heterozygotes appear
to have slower
progression
Notes
Increasing age at
the time of infection
is consistently
associated with rate
of progression to
AIDS and survival
after AIDS diagnosis






These mutations are
much more common
among Caucasians
Reference
(UK, 1998;
Del Amo,
1998; van
Benthem,
1998)


(Sterling,
2001)


(Del Amo,
1998)
(Winkler,
1998;
Zimmerman,
1997;
Martin,
1998)


18 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
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Epidemiology and Natural History of HIV Infection in Women


Table 1-6 Factors that influence rate of HIV-disease progression (continued)
Host Factors
HLA Type



HIV risk
behavior

Viral Factors
Effect
HLA differences
associated with
differing HIV RNA
levels and rate of
progression
Higher CD4 cell counts
in persons with a
history of IDU
Effect
Notes
Not currently of
clinical utility, may
provide clues to
immunopathogenesis

This effect seen in
several studies

Notes
Reference
(Saah,
1998)


(Brettle,
1995)

Reference
Clade/location Mixed evidence,
possible impact of viral
subtype (or clade) on
rate of progression
No clinical application
currently
(Prins,
1999;
(Kanki,
1999)
Mutations




Clinical
Indicators
Oral candidiasis
and hairy
leukoplakia
Mutation of viral
genes can produce
attenuated viral strains
that are associated
with slowed disease
progression
Effect

The presence of oral
candidiasis or hairy
leukoplakia suggests
HIV infection and
progression to impaired
immunological
function. Oral
candidiasis adds to the
predictive value of HIV
RNA in persons with
low CD4 cell counts
Mutation resulting in
attenuation appears
relatively rare.


Notes

Accuracy of diagnosis
varies with clinician
experience, but oral
manifestations are
particularly useful
prognostic indicators
in resource-poor
environments and
important points
of HIV recognition
world-wide
(Deacon,
1995;
Learmont,
1999)


Reference

(Carre,
1998;
Greenspan,
1996)


C. NATURAL HISTORY IN HAART ERA
INDUSTRIALIZED COUNTRIES
In countries that are able to provide highly active antiretroviral therapy
(HAART), HIV-associated morbidity and mortality have declined
significantly (Michaels, 1998; Miller, 1999a; Miller 1999b; Palella, 1998;
Pezzotti, 1999b). (See Primary 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; Collier, 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


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Epidemiology and Natural History of HIV Infection in Women

treatment before initiation of HAART (Ledergerber, 1999). Viral resistance
to HAART components can occur via several mechanisms, which for
the most part involve mutation of viral target proteins (Richman, 1996;
Schapiro, 1999). The 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 (Gulick, 1998; Ledergerber,
1999; Shafer, 1998). Multiple daily doses, side effects, and, in some
cases, dietary restrictions aggravate the problem of achieving optimal
drug levels because protease inhibitor agents are relatively poorly
bioavailable. Suppression of viral replication and prevention of resistance
are directly related to the levels of antiretroviral medications. Persistent
viral replication provides an opportunity for resistant mutations to occur,
and selective pressure to support the 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; Grant, 2002).

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 HAART in the developing
world. Thus the reductions in morbidity and gains in survival in HIV
patients that have been demonstrated in many industrialized countries
do not consistently extend to developing countries in which the majority
of HIV cases occur worldwide. 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 antiretroviral therapy; antiretroviral therapy 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; treatment of pregnant women to prevent perinatal transmission
must be a priority; and new drug development should focus on less
costly medications (International AIDS Society, 1999). In December
2002, the World Health Organization launched a new initiative called “A
Commitment to Action for Expanded Access to HIV/AIDS Treatment”
to promote international cooperation in expanding access to HIV
treatments to resource-poor settings.



20 U.S. Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau
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Epidemiology and Natural History of HIV Infection in Women

IV. FUTURE ISSUES
A. GLOBAL IMPACT
Epidemiology and Natural History of HIV Infection in Women
The HIV/AIDS epidemic continues to spread without full control in any
country. Over 58 million people have been infected worldwide. By the end
of 2002, the United Nations Program on AIDS (UNAIDS) estimated that 42
million people were living with HIV, a figure that includes 19.2 million adult
women (UNAIDS, 2002) (Table 1-1). In 2002 it is estimated that 5 million
new HIV infections occurred, with 2 million of these occurring in women.
After steady increases of the prevalence of disease among women during
the 1990s, currently 46% of all persons over the age of 15 living with HIV
are women. Globally, AIDS is now the fourth leading cause of mortality; 3.1
million deaths have been attributable to AIDS in 2002 alone, of which 1.2
million 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 where 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
2002 took place in this epicenter. The region has also experienced 83% of
all 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 yr) are infected; in
some regions 20–50% of pregnant women are infected and are likely to
transmit infection to one third of their offspring. In four southern African
countries, HIV prevalence in adults now exceeds 30%: Botswana (38.8%),
Lesotho (31%), Swaziland (33.4%), and Zimbabwe (33.7%). The declining
mortality rate and population growth taking place in other regions cannot
be extended to Sub-Saharan Africa, because of 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 yr
by 2015. AIDS will cost, on an average, 17 yr 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,
2002). Within 1 yr, 2400 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 former United States
Surgeon General, David Satcher, notes that “the progress of decades of work
immunizing children, controlling diseases, and improving nutrition is being
negated by HIV” (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.


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Currently 7.2 million Asians are infected with HIV. Rapidly accelerating
epidemics are occurring in China, Cambodia, Vietnam, and India. For
instance, the US Intelligence Council estimates that 20 to 25 million
people in India will be infected by the year 2010. Whereas 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.
Although 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, and implementation of educational and
condom promotion programs. The incidence of HIV 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. Increasing rates of HIV incidence in men who
have sex with men have been reported from large urban centers in the
US over the past several years [Chen, 2002; Koblin, 2003]. In Mexico the
incidence of infection among men who have sex with men continues to
be high, whereas 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, 2002).
Rapid spread of infection among injection drug users in Eastern Europe
and Central Asia is 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 infections.

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 infections, and now hinder
control of HIV itself. Global disparities in economic status have limited
efforts to control sexually transmitted infections that are much simpler to
diagnose and treat than HIV. The effect of limited monetary resources is
compounded by stigmatization of HIV and sexually transmitted infections
that affect willingness to seek care, social support of afflicted individuals,


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Epidemiology and Natural History of HIV Infection in Women

and health policy decision making. Traditional cultural values regarding
the role of women also tend to intensify the problems. Lack of acceptance
of the right of women to make decisions about childbearing and work
outside the home limits options for individuals who wish to reduce the
risk of infection via sexual exposures. Economic independence is a crucial
factor enabling women to make decisions for 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 the risk of HIV and other
sexually transmitted infections (Gollub, 1999).
To control the HIV epidemic, societies need to make 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 21st century and
the third decade of the HIV pandemic.


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A GUIDE TO THE CLINICAL CARE OF WOMEN WITH HIV - 2005 EDITION



II. APPROACH TO THE PATIENT
Jean R. 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, education, cultural background, and income level, and
have all 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 provider–patient 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 all 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 clear and
nonjudgmental communication. Language and terminology used should
be sensitive, inoffensive, and easily understood by the 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. This anxiety and vulnerability may be particularly
pronounced in women with history of sexual abuse, rates of which are
increased in some popluations of women living wth HIV. It is important


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to adequately prepare each woman verbally for the exam, and 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
you see or feel, and reassure her 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. The
gynecologic exam may need to be postponed until a subsequent visit in
some women in order to develop trust and to ensure there is adequate
time for those with special anxiety about the exam.
Patients should be given written instructions on how to reach their
providers when there are problems or questions and how to make
appointments. Whenever possible, written information about HIV and
its treatment, and other health issues, should be available to supplement
face-to-face discussions.

B. RESPECT
Every person deserves respect. Do not be condescending, patronizing, or
judgemental. 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” or
“dear”) is usually inappropriate and often offensive.
Respect for the individual includes respect for her beliefs and values.
The use of complementary 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 ensure ongoing follow-up. It requires attention to
how words are used and 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



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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 in
choosing her treatment regimen when possible 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 vulnerable 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 of 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 partners and
health care providers. It is important to note that all states are required to
report cases of AIDS and some also have mandatory HIV reporting. The
need to report and the safeguards (such as anonymous reporting in some
states) which are in place should be discussed with each woman.


II. EVALUATION OF THE HIV-INFECTED WOMAN
A. TEAM APPROACH
Because of the medical and social complexity of HIV disease, a team
approach to the care of women with HIV is essential and care should
be both coordinated and integrated with different members of the
team. Furthermore, as the time available for the primary care provider
to spend with each patient becomes increasingly limited, the role of
other team members in assistance with education and support becomes
even more important. 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



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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. HIV EXPERIENCE
Care by a medical provider with HIV experience is one of the few
specific provider or health care system-related factors that has been
shown to prolong the life of HIV-infected individuals (Kitahata, 1996;
Laine, 1998). This is increasingly important as antiretroviral treatment
becomes steadily more complicated and recommendations change
almost monthly. 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 HIV-
positive individual. Primary providers with little or no HIV experience
should link with providers with HIV expertise to provide optimal care
by referral or regular consultation. If a woman requires referral to an
HIV expert, it is important that the primary care provider assure the
woman that she is not being abandoned; furthermore, as women live
longer with HIV, the primary care provider’s involvement in caring for
other medical conditions remains critical for the overall health of the
woman. Current U.S. Public Health Service treatment guidelines, several
as living documents with regular online updating, can be accessed at
http://www.aidsinfo.nih.gov. 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 AND 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. Potential barriers to care that may be
encountered include difficulties in speaking, understanding, or reading
English, culturally based fears and mistrust of the health care system,
and undocumented immigration status.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.






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D. SPECIAL POPULATIONS
In addition to cultural setting or background, women living with HIV/
AIDS may have other life circumstances that require special approaches
to care and unique sensitivity. These include incarcerated women;
women with alcohol or drug addiction; women with psychiatric illness;
lesbians and transgendered women; women who are victims of domestic
violence; and others. Certain circumstances may arouse strong emotions
in care providers because of the provider’s own background or beliefs. It
is essential that the provider be willing and able to separate themselves
from whatever personal connotations or associations they may assign to
certain lifestyles or life circumstances, and provide care that is unbiased,
sensitive, kind, and empathetic. If this is not possible, the patient should
be referred to another provider who can give such care.

E. SPIRITUALITY
The spiritual dimension of a person’s life encompasses her beliefs
and values and what gives her life meaning and a sense of wholeness
(Puchalski, 2000). 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 she views illness and its treatment. Some
women may view HIV as a punishment and this belief may lessen their
acceptance of treatment or may put them at risk of nonadherence. Major
spiritual questions that 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, 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.
F. IDENTIFYING SUPPORT SYSTEMS AND 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 visit. To
whom has she disclosed her HIV status and what was the response? Many

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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. Many communities
still attach enormous stigma to HIV and the individual woman’s fears about
ostracism and abandonment should be openly addressed. Their sense of
isolation is harmful to both their physical and emotional well-being, and
may result in avoiding clinic visits and nonadherence to 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 providers. 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 violence, should be identified and
addressed. The provider 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.

G. LIMITED RESOURCE SETTINGS
Currently, in limited resource settings the foundations of HIV care are
services to provide basic medical care, treat sexually transmitted infections
(STIs), identify HIV infection through voluntary counseling and testing
(VCT), and provide primary and secondary HIV prevention services,
including prevention of mother-to-child transmission. Prevention and
treatment of TB and other opportunistic infections are needed as
patients with HIV become more immunosuppressed, but require greater
resources in terms of medications, laboratory monitoring, patient and
provider education and training, and community engagement. In
settings with few resources the ability to use antiretroviral drugs is still
limited by issues of cost, accessibility, and health care infrastructure,
but this is beginning to change with the growing global consensus that
there is a moral imperative to provide these life-sustaining therapies. The
Clinical Services Pyramid (Figure 2-1) (JSI/WEI Center for HIV/AIDS.
2001) illustrates the inter-relatedness of the community, laboratory
infrastructure, and patient and provider education that is essential at all
levels of HIV care. These components of the health care system must
exist and be strengthened for both prevention and care and treatment
services to succeed and use of anti-retroviral therapy (ARV) to reach
those most in need.








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Figure 2-1
Clinical Services Pyramid




ART

TB OIs
Prevention/Treatment