AIDS INFORMATION NEWSLETTER
                          Michael Howe, MSLS, Editor
                            AIDS Information Center
                       VA Medical Center, San Francisco
                            (415) 221-4810 ext 3305
                                 July 1, 1994

                      Women and HIV Infection (Part III)

      AIDS is the fourth leading cause of death for women aged 25
to 44 in the United States.  In fact, it is the primary cause of
death in women of this age group in nine major U.S. cities.  The
number of women infected by HIV is steadily increasing.  As of
Sept. 30, 1993, the U.S. Centers for Disease Control and Prevention
(CDC) reports that more than 40,700 adult women in the United
States have AIDS.  The majority are black or Hispanic. 
Epidemiologists believe that the actual number of women with AIDS
is greater because many women whose immune systems are severely
compromised by HIV infection remain undiagnosed and unreported. 
CDC revised the definition of AIDS in January 1993 to add three new
conditions, one of which is specific to women--invasive cervical
cancer.

NIAID Epidemiologic Studies of Women With HIV/AIDS

      For the National Institute of Allergy and Infectious Diseases
(NIAID), HIV infection in women is a major research focus.  NIAID
supports studies of the natural history, symptoms and transmission
of HIV infection in women to learn more about the disease and to
design better clinical trials of potential therapies and vaccines. 
Such studies are carried out in the United States and in 14 other
countries: Brazil, Dominican Republic, Jamaica, Mexico, Haiti,
India, Kenya, Malawi, Rwanda, Senegal, Thailand, Uganda, Zambia and
Zaire. 

More Information Needed 

      In December 1990, the U.S. Public Health Service (PHS)
sponsored a national conference on women and HIV infection.  A
steering committee, which included women living with HIV as well
as health and social service providers, made recommendations to the
PHS that have helped guide NIAID's research.   
      
      The conference attendees noted the increasing number of women
with HIV infection and underscored the need for targeted studies
of women.  Recognizing this need, CDC and NIAID have together
established a large-scale natural history study of women and HIV
infection.  The CDC sites opened in 1992, and the NIAID sites were
selected in 1993.  The NIAID study, called the Women's Interagency
HIV Study (WIHS), identifies clinical signs of HIV infection in
women, describes the pattern and rate of immune system decline and
examines potential co-factors that can affect disease progression.
The study investigators also are seeking further information on the
length of survival and quality of life for women with HIV
infection.  
      
      The CDC component of the study, called the HIV Epidemiology
Research Study (HERS) and co-sponsored by NIAID, tested many of the
processes and procedures used by WIHS.  Other components of PHS
have advised the sponsoring agencies on the study's design through
the PHS Women and AIDS Study Group.
      
      In both HERS and WIHS, researchers also consider the factors
influencing women's access to health care.  The majority of
American women with HIV infection live in inner cities and have
traditionally experienced great difficulty in obtaining access to
health services.  The information obtained from these studies will
be used to develop comprehensive social support programs for women
and their children participating in NIAID studies.

Observational Database 

      A large amount of information has been collected on HIV-
infected individuals since September 1990 through the
NIAID-supported Observational Database (ODB), a component of the
community-based clinical trials network, the Terry Beirn Community
Programs for Clinical Research on AIDS (CPCRA).
      
      Participating sites are attempting to characterize the full
spectrum of HIV infection, providing an epidemiological profile of
the infection in both men and women.  Information is collected on
transmission, symptoms, current treatments and factors associated
with disease progression.   
      
      Because participating women receive care from community
physicians, the ODB also offers a snapshot of routine clinical
practice.  Women enrolled in the ODB who meet eligibility
requirements have the opportunity to participate in CPCRA treatment
protocols.

HIV Transmission to Women 

      To date, the majority of women with HIV in the United States
became infected by using injection drugs.  Recently, however, the
number of women acquiring HIV through heterosexual contact with
infected men has risen dramatically.  During heterosexual
intercourse, women are more easily infected than men when one of
the partners is infected.
      
      The NIAID-supported Heterosexual AIDS Transmission Study
(HATS) is a collaborative project with CDC that began in April
1990.  HATS examines the risk factors influencing heterosexual
transmission of HIV to women.  In pursuit of an explanation for the
higher risk of HIV transmission among female cocaine users, HATS
researchers found that knowledge, perceptions and reported
behavioral changes did not differ between cocaine-using women and
non-users in an inner-city group.  However, the cocaine users had
more sexual partners and more cases of sexually transmitted
diseases (STDs).
      
      In a separate HATS investigation, scientists found higher
rates of human papilloma virus (HPV) infection in a group of
younger inner-city women than in older women with comparable sexual
practices.  More than 40 million Americans are infected with HPV,
which cause genital warts, making it one of the most common STDs
in the United States.  Age-related differences in younger women's
cervical tissue can facilitate HPV infection and may heighten
susceptibility to infection with HIV.
      
      The risk of becoming infected, or infecting others, with HIV
is substantially increased if one has an STD.  A 1992 study in
Brooklyn, N.Y., is tracking the acquisition of STDs in women with
HIV infection and following the natural course of their HIV
disease.  The study, called the Women's AIDS Cohort Study (WACS),
has enrolled 450 HIV-infected women.
      
      Thus far, the study finds that women with HIV, once diagnosed,
reduce their number of sex partners, increase condom use and show
a trend towards stopping use of illegal drugs.  STD control also
is very important in HIV-infected persons because they can develop
severe symptoms, which in turn may enhance the infectivity of HIV. 
Controlling STDs is, therefore, crucial to preventing the spread
of HIV infection.  NIAID is comparing different approaches to
detect and treat STDs to identify those methods with the greatest
potential for reducing HIV transmission.
      
      Additionally, NIAID supports basic research that will lead to
the development of topical antimicrobial agents, compounds that
might be used safely and effectively in the vagina to kill viruses. 
The Institute also supports studies assessing the ability of
nonoxynol-9, an agent found in many spermicides, to destroy the
bacteria that cause gonorrhea and chlamydia.

Symptoms and Diagnosis 

      Because many women do not perceive themselves at risk for HIV
infection, symptoms that could serve as warning signals of
infection may go unheeded.  Recurrent vaginal candidiasis often
occurs in the early stages of HIV infection in women.  Pelvic
inflammatory disease, abnormal changes or dysplasia in cervical
tissue that precede cancer, genital ulcers, genital warts and
severe mucosal herpes infections also may occur among women with
HIV infection.  These symptoms should signal doctors to offer women
HIV testing accompanied by counseling.
      
      Limited access to health care contributes to the late
diagnosis of HIV infection in women and their consequential higher
death rates.  Women whose infections are detected early survive as
long as infected men, according to preliminary findings from one
NIAID-supported study.  That study indicates that women and men
also receive HIV-related therapies at similar rates and show no
differences in their numbers of HIV-related illnesses.  This CPCRA
investigation is the first large study to show that men and women
share similar consequences of HIV disease.
      
      Early diagnosis of HIV infection allows women to take full
advantage of antiretroviral therapies and forestall the development
of AIDS-related infections and malignancies.  Health care workers
need to be alert to early signs of HIV infection in women and,
conversely, women need to consider HIV testing in light of their
risk status.

NIAID Clinical Studies

      NIAID supports three clinical trials networks through the
Division of AIDS to identify effective therapies for HIV infection
and the subsequent opportunistic infections that develop from it.
The AIDS Clinical Trials Group (ACTG) is a network of more than 50
sites based at major academic institutions with the ability to
carry out sophisticated large-scale research studies.  CPCRA
complements the ACTG by giving community providers and their
HIV-infected patients greater opportunities to participate in
clinical research, especially women and others traditionally
underrepresented in HIV-related studies.  The Division of AIDS
Treatment Research Initiative (DATRI) provides for rapid trials to
address critical questions about potential therapies and novel
treatment approaches to HIV disease.  NIAID also supports basic
research on the development of treatments and vaccines for men,
women and children with HIV infection.
      
      CPCRA and ACTG each receive advice from members of communities
affected by HIV through Community Constituency Groups (CCGs). In
the case of the ACTG, CCG members are selected from community
advisory boards that provide direction to, and oversight of,
clinical trials at the local level.  CCG members serve as full and
active members on all committees of the ACTG and CPCRA to ensure
community input into NIAID's scientific agenda.
      
      No NIAID-sponsored studies exclude women.  However, some sites
experience difficulty recruiting and retaining women in clinical
studies.  The Women's Health Committee of the ACTG ensures that
women's issues are reflected in the ACTG scientific agenda.  As
part of their mandate, the Committee reviews the eligibility
requirements for ACTG studies to determine whether certain
criteria, such as weight or blood iron, contribute to the
difficulties in enrolling women in studies.
      
      The Patient Care Committee of the ACTG has evaluated other
possible barriers that may prevent women from participating in
clinical trials.  They found that many women with HIV lack access
to health care and have few options to support themselves and their
children. The Women, Children and People of Color Interest Group
of CPCRA also has explored this issue.  Researchers in both
networks work closely with church groups, social workers and others
at the grassroots level to find solutions to these problems.
      
      Additionally, funds are available to clinical trials sites for
ancillary services to do gynecologic assessments and to help
provide child care, transportation and linkage to social services
when needed.  Some measures of success of such efforts have been
seen in ACTG and CPCRA.  Since 1986, women's overall enrollment has
climbed greatly.  In 1992, women accounted for 20 percent of the
adults in CPCRA, and 23 percent of those in ACTG.  Currently, equal
numbers of men and women are enrolling in studies.

Antiretroviral Therapies

      Treatment for people with HIV infection consists of the use
of one or more of several antiretroviral drugs.  Treatment
guidelines are similar for women who are not pregnant and for men
with HIV infection.  Studies have shown that the drug zidovudine
(AZT) is as beneficial to women as men and should be considered by
physicians once a person's number of white blood cells, called CD4+
T cells, drop below 500 cells per cubic millimeter of blood.
Limited data are available on the use of the drug didanosine (ddI)
and other antiretroviral therapies in women.
      
      Ongoing studies will determine the effects of antiviral drugs
on pregnant women and their children.  Obstetricians from the ACTG
Women's Health Committee work closely with the ACTG's Pediatric
Committee to develop trials for pregnant women.  Thus far, AZT
seems to be well-tolerated when used by pregnant women and has not
caused malformations, fetal distress or premature birth in their
babies.

Other Studies

      Two ACTG studies address cervical dysplasia in women.  One
trial is comparing topical vaginal 5-Fluorouracil maintenance
therapy to standard therapy to prevent the recurrence of cervical
dysplasia in women with HIV infection.  Treatments to fight several
gynecologic conditions including genital ulcer disease, fungal
infections and pelvic inflammatory disease are under consideration
for future ACTG clinical trials.  NIAID-funded sites receive
resources and training for clinical staff to conduct routine
gynecologic exams.  Plans to include nested studies, as components
of a larger study, are under way to allow investigators to collect
additional information on participants' gynecologic conditions.
      
      CPCRA recently began a trial specifically for women.  This
protocol will determine if fluconazole can prevent yeast infections
of the mouth, throat and vagina of women with HIV infection. 
Candida infections of the mucous membranes may represent the
earliest recognized and most common opportunistic infections
afflicting women with HIV infection.  These infections, common and
easily treatable in most women, can be severe in women with HIV.
      
      DATRI coordinators plan to begin a pilot study of the effect
of treatment on the amount of HIV present in cervical secretions
compared to amount of virus in blood, immunological markers and
clinical status of women with HIV.  The study also assesses
gynecologic risk factors associated with the presence of HIV in
vaginal and cervical fluid.

Perinatal Transmission

      NIAID-supported studies have shown that, in the United States,
HIV is transmitted from mothers to infants about 24 percent of the
time. Researchers base their findings on blood samples taken from
babies through 6 months of age.  Other studies have documented
rates of transmission ranging from 13 to 40 percent.  Rates in
developing nations are higher.
      
      How perinatal transmission occurs is still unclear.  Studies
indicate that babies can be infected during pregnancy, during birth
and postpartum.  In a large European study, breast feeding was
associated with a 14 percent increase in the risk of transmission. 
In developing countries, the World Health Organization recommends
that women with HIV infection continue to breast feed because the
benefits outweigh the risks of HIV transmission to their children. 
Breast feeding is discouraged in the United States for women with
HIV infection.
      
      Other questions regarding women who have HIV and are pregnant
include the effects of anti-HIV drugs on both the mother and the
fetus, the influence of HIV on pregnancy and the effects of
pregnancy on the course of HIV infection.  Current NIAID studies
such as the Women and Infants Transmission Study (WITS) will answer
many of these questions.
      
      NIAID established WITS in conjunction with the National
Institute of Child Health and Human Development (NICHD) in
September 1989.  The study addresses specific questions relating
to the natural history of HIV in pregnant and nonpregnant women,
including gynecologic complications, changes in the immune system,
and progression of disease.  WITS has successfully recruited a
population of women of many ethnicities with HIV from the mainland
United States and Puerto Rico.
      
      A large number of social, demographic and behavioral risk
factors among these women make it difficult to assess HIV-specific
effects on pregnancy.  However, one WITS analysis indicates that,
regardless of the babies' HIV status, those whose mothers used
cocaine during pregnancy had shorter gestations, lower birth
weights, and smaller head circumference, and were shorter in
length.
      
      Investigators at the University of Medicine and Dentistry of
New Jersey, funded by NIAID and the Walter Reed Army Institute of
Research in Washington, D.C., are comparing the natural history of
the pregnancies of women with HIV compared to women who do not have
HIV.  The scientists also are examining any effects of illegal drug
use on the pregnancies.  This study is coordinated with a
CDC-sponsored perinatal study at the same site.

Strategies to Prevent Perinatal Transmission

      As more women of childbearing age become infected with HIV,
experts expect a concurrent rise in the number of infected
children. Preliminary results from ACTG study 076 have shown that
AZT reduced the risk of transmission of HIV from infected pregnant
women to their newborns by two-thirds.  HIV-infected women in their
14th to 34th week of pregnancy who did not need AZT as part of
their medical care received either AZT or placebo during pregnancy
and labor.  At birth, infants in the study continued their mother's
treatment until six weeks of age.  AZT produced no serious side
effects, but long-term follow-up of the infants and mothers is
essential to learn more about the risks and benefits of treatment.
Under NIAID sponsorship, early clinical trials of two experimental
AIDS vaccines are under way.  Investigators will assess whether the
vaccines will reduce the amount of virus present in the pregnant
women and improve their health, while simultaneously stimulating
antibodies that will prevent the women from passing HIV infection
to their babies.  A third candidate vaccine is scheduled to be
tested in pregnant women later this year.
      
      Another strategy to prevent transmission is to administer
antibodies in the form of immune globulin injections to bolster the
immune system.  A three-year study, sponsored by NIAID, NICHD and
the National Heart Lung and Blood Institute, evaluates HIVIG, an
immunoglobulin preparation containing large quantities of
antibodies to HIV.  Participants also receive AZT.  A control group
in the study will receive IVIG, an intravenous immunoglobulin
preparation that contains many other types of antibodies, and AZT. 
In an earlier study on chimpanzees, HIVIG prevented infection after
the animals were exposed to the virus.

For More Information About Trials

      NIAID provides major support for the AIDS Clinical Trials
Information Service, at 1-800-TRIALS-A, to advise callers of the
status of HIV clinical trials being conducted throughout the United
States.  The service operates from 9 a.m. to 7 p.m. Eastern Time,
Monday through Friday.  English and Spanish-speaking specialists
are available.
      
      NIAID, a component of the National Institutes of Health,
supports research on AIDS, tuberculosis and other infectious
diseases as well as allergies and immunology.  NIH is an agency of
the U.S. Public Health Service, U.S. Department of Health and Human
Services.

(NIAID BACKGROUNDER, April 1994.  Prepared by: Office of
Communications, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD 20892.)