HIV Infection in Women

OVERVIEW
The number of women with HIV (human immunodeficiency virus) infection and AIDS (acquired immunodeficiency syndrome) has been increasing steadily worldwide. By the end of 2003, according to the World Health Organization (WHO), 19.2 million women were living with HIV/AIDS worldwide, accounting for approximately 50 percent of the 40 million adults living with HIV/AIDS.

By the end of 2002, 159,271 adolescent and adult women in the United States were reported as having AIDS. Based on cases reported to the Centers for Disease Control and Prevention (CDC) through December 2002, more than 57,376 women have been infected with HIV. Among adolescent and adult women, the proportion of AIDS cases more than tripled from 7 percent in 1985 to 26 percent in 2002. Nonetheless, AIDS cases in adolescent and adult women have declined by 17 percent and have plateaued in the past 4 years, reflecting the success of antiretroviral therapies in preventing the development of AIDS.

Worldwide, more than 90 percent of all adolescent and adult HIV infections have resulted from heterosexual intercourse. Women are particularly vulnerable to heterosexual transmission of HIV due to substantial mucosal exposure to seminal fluids. This biological fact amplifies the risk of HIV transmission when coupled with the high prevalence of non-consensual sex, sex without condom use, and the unknown and/or high-risk behaviors of their partners.

Younger women are also increasingly being diagnosed with HIV infection, particularly among African-Americans and Hispanics. Through December 2002, women aged 25 and younger accounted for 9.8 percent of the female AIDS cases reported to CDC.

HIV disproportionately affects African-American and Hispanic women. Together they represent less than 25 percent of all U.S. women, yet they account for more than 82 percent of AIDS cases in women.

Women suffer from the same complications of AIDS that afflict men but also suffer gender-specific manifestations of HIV disease, such as recurrent vaginal yeast infections and severe pelvic inflammatory disease, which increase their risk of cervical cancer. Women also exhibit different characteristics from men for many of the same complications of antiretroviral therapy, such as metabolic abnormalities.

Frequently, women with HIV infection have great difficulty accessing health care, and carry a heavy burden of caring for children and other family members who may also be HIV-infected. They often lack social support and face other challenges that may interfere with their ability to adhere to treatment regimens.

CURRENT RESEARCH
To confront the growing problem of HIV infection and AIDS in women, the National Institute of Allergy and Infectious Diseases (NIAID) has made woman-focused research an important component of the Institute's AIDS research program.

NIAID is studying the course of HIV/AIDS disease in women primarily through two cohort studies: the Women's Interagency HIV Study (WIHS) and the Women and Infant's Transmission Study. Clinical trials to investigate gender-specific differences in disease progression, complications and/or treatment are also being conducted by the Adult AIDS Clinical Trials Group (AACTG), the Pediatric AIDS Clinical Trials Group (PACTG), and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

Natural History and Epidemiological Research
NIAID supports studies in the United States and abroad of the natural history and manifestations of HIV infection in both non-pregnant and pregnant women, as well as the factors that influence the transmission of HIV to women. Investigators are studying the unique features of HIV/AIDS in women and developing treatment regimens for them.

The WIHS, a multi-site, prospective cohort of predominantly minority HIV-infected and uninfected women, is conducting research on the natural history of HIV among women and has increased the number of women enrolled in their study. The increase in participants will enable WIHS to evaluate the natural history and clinical outcomes in the era of highly active antiretroviral therapy, or HAART, such as

Time to AIDS
Impact of other infections such as hepatitis C
Therapy use and treatment effects in women
Impact of aging on HIV disease
Impact of hormonal factors on HIV disease
The expansion is now complete, and projects have 2,580 women under active follow-up.

A study conducted in the WIHS compared the rates of AIDS and/or death prior to (October 1994 to April 1996) and after (April 1996 to March 1999) the introduction of HAART (highly active antiretroviral therapy). Mortality declined 21 percent for women with AIDS and 11 percent for those without AIDS at the start of WIHS. The researchers also quantified the level of immune reconstitution and viral suppression. Women with AIDS at study entry saw the greatest improvements in their CD4+/CD8+ cells and viral load.

In another study, WIHS researchers showed that a baseline measurement of serum albumin (the main protein in the blood) was a strong predictor of 3-year survival in HIV-infected women. Women with serum albumin levels in the low-normal range had a higher risk of death compared to those with higher levels of serum albumin. This information could have important implications for women's treatment decisions, and given the low cost and availability of this measurement, it may have applications in resource-poor settings.

Moreover, another study showed that after adjusting for age, serum albumin levels, body mass index, CD4 lymphocyte counts, and HIV-1 RNA levels, higher C-reactive protein levels (> 0.4 mg/dL) were associated with shorter survival. C-reactive protein, an inflammatory marker, may be a useful and inexpensive predictor of HIV disease mortality in women.

In a study co-funded by the National Institute on Drug Abuse and NIAID, researchers found that the initial HIV viral load in women tends to be lower than in men regardless of CD4+ T cell count. Investigators need to do additional research to determine the significance of this finding because the rate of progression to AIDS in women appears to be similar to that in men.

Topical Microbicides
Because HIV is spread predominantly through sexual transmission, the development of chemical, biological, and physical barriers that can be used intravaginally or intrarectally to inactivate HIV and other sexually transmitted infection (STI) pathogens is critically important for controlling HIV infection.

Scientists are developing and testing new chemical and biological compounds that women could apply before intercourse to protect themselves against HIV and other sexually transmitted organisms. These include creams or gels, known as topical microbicides, which ideally would be non-irritating, inexpensive, and unobtrusive. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation. There are several promising investigational topical microbicides, such as PR02000/5 Gel (P), Cellulose Sulfate Gel, and PMPA Gel, currently in clinical trials in the HIV Prevention Trials Network (HPTN).

Less than 10 percent of the participants reported symptoms that could have been attributable to the product, and upon pelvic examination, approximately 90 percent had no visible vaginal or cervical abnormalities. Currently, researchers are planning a Phase III trial which will evaluate the effectiveness of Carraguard. (Carraguard is a gel derived from seaweed that prevents infection of appropriate target cells by HIV and other STIs.) In addition, HPTN has initiated several Phase I trials to study the safety and acceptability of other candidate microbicides and will be conducting a Phase II/IIb trial of two other promising microbicide candidates for vaginal use.

Scientists are no longer studying nonoxynol-9 (N9) as a potential microbicide due to safety concerns and the potential for increased risk of HIV infection as reported at the 13th International Conference on AIDS in Durban, South Africa, in July 2000.