The number of women with human immunodeficiency virus (HIV) infection and AIDS has been increasing steadily worldwide. As of December 2000, according to the World Health Organization (WHO), 16.4 million women were living with HIV/AIDS worldwide, accounting for 47 percent of the 34.7 million adults living with HIV/AIDS.
As of June 2000, 124,911 adolescent and adult women in the United States were reported as having AIDS. The proportion of reported U.S. AIDS cases occurring among women increased from 7 percent to 23 percent from 1985 to 1998. This proportion remained at 23 percent in 1999, possibly reflecting the success of antiretroviral therapies in preventing the development of AIDS.
Worldwide, women face the greatest risk of acquiring HIV due to substantial mucosal exposure to seminal fluids, high prevalence of non-consensual sex, sex without condom use, and unknown, high-risk behaviors of their partners.
Nonetheless, in 1999 more than 8,000 new cases of AIDS were reported in adolescent and adult women between 13 and 24 years of age, and nearly 7,000 new cases were reported in women between the ages of 24 and 29. Women aged 45-64 and 65 and older are also increasingly being diagnosed with HIV infection. As of December 1999, women in these age groups accounted for 10 percent of the female cases.
HIV infection 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 77 percent of AIDS cases in women. HIV/AIDS is now the third leading cause of death among women ages 25 to 44 and the leading cause of death among African-American women in this age group.
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 lipodystrophy.
Frequently, women with HIV infection have great difficulty accessing health care, and carry a large 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.
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.
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.
For example, a recent study that was conducted in the Women's Interagency HIV Study (WIHS), a multi-site cohort study of HIV-infected and uninfected women, examined the level of virus in the female genital tract and its impact on transmission to sexual partners and infants. Researchers determined that women with high viral loads were more likely to have detectable levels of HIV in their genital tract and that reductions in HIV levels in the genital tract of women could have a significant impact on HIV transmission.
In another study, WIHS researchers showed that a baseline measurement of serum albumin (the main protein in the blood) was a strong predictor of three-year survival in HIV-infected women. Women with low serum albumin levels 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 widespread applications.
In one recent 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.
Because HIV is spread predominantly through sexual transmission, the development of chemical and physical barriers that can be used intravaginally or intrarectally to inactivate HIV and other sexually transmitted disease (STDs) pathogens is critically important for controlling HIV infection.
Scientists are developing and testing new chemical 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 and inexpensive. In addition, microbicides should be available in both spermicidal and non-spermicidal formulations so that women do not have to put themselves at risk for acquiring HIV and other STDs in order to conceive a child. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation.
A small study of low-risk women in the United States recently tested the safety of BufferGel, a microbicide that helps maintain the healthy acidic environment of the vagina in the presence of semen. This in turn helps protect women against HIV and other sexually transmitted pathogens. This U.S.-based study found BufferGel to be safe and generally accepted. A subsequent study was then conducted in India, Thailand, Malawi, and Zimbabwe and found that compliance and use of the BufferGel was high. Because there were no major safety concerns reported in either the domestic or international studies, research is underway to evaluate the effectiveness of BufferGel in preventing HIV infection.
Transmission of HIV from Mother to Infant
In the United States, approximately 25 percent of pregnant HIV-infected women who do not receive AZT or a combination of antiretroviral therapies pass on the virus to their babies. If women do receive a combination of antiretroviral therapies during pregnancy, however, the risk of HIV transmission to the newborn is below 5 percent.
The risk of mother-to-infant transmission is significantly increased if the mother has advanced HIV disease, large amounts of HIV in her bloodstream, or fewer-than-normal amounts of the immune system cells (CD4+ T cells) that are the main targets of HIV.
Other factors that may increase the risk include
· Drug use, such as heroin or crack/cocaine
· Severe inflammation of fetal membranes
· A prolonged period between membrane rupture and delivery
One NIAID-sponsored study found that HIV-infected women who gave birth more than four hours after rupture of the fetal membranes were nearly twice as likely to transmit HIV to their infants, as compared to women who delivered within four hours of membrane rupture. In the same study, HIV-infected women who used heroin or crack/cocaine during pregnancy were also twice as likely to transmit HIV to their babies as HIV-infected women who did not use drugs.
Most mother-to-infant transmission, an estimated 50 to 70 percent, probably occurs late in pregnancy or during birth. Although the exact ways the virus is transmitted are unknown, scientists think it may happen when the mother's blood enters the fetal circulation, or by mucosal exposure to virus during labor and delivery. Research is underway to identify the mechanisms of mother-to-child transmission of HIV and to develop interventions to reduce it. Notably, NIAID-funded investigators have identified two regimens that reduce mother-to-infant transmission of HIV. The first regimen to prevent mother-to-infant transmission of HIV was identified in a landmark study conducted in 1994 by the Pediatric AIDS Clinical Trials Group. It involved a specific regimen of AZT given to an HIV-infected woman during pregnancy and to her baby after birth and was shown to reduce mother-to-infant HIV transmission by two thirds.
In another NIAID-sponsored study in Uganda, researchers identified a highly effective and safe drug regimen for preventing transmission of HIV from an infected mother to her newborn that is also more affordable and practical than any other examined to date. The study demonstrated that a single oral dose of the antiretroviral drug nevirapine given to an HIV-infected woman in labor and another dose given to her baby within three days of birth reduces the transmission rate by about half compared with a course of AZT given only during labor and delivery. This study suggests that women in the United States who are identified very late in pregnancy or at the time of labor and delivery could also have lower rates of transmission of HIV to their infants by following a nevirapine-containing regimen.
HIV also may be transmitted from a nursing mother to her infant. A series of studies have determined that breastfeeding increases the risk of HIV transmission by about 14 percent. Currently, the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommends that HIV positive women be educated and counseled so they can make an informed decision about how to best feed their infant. Research is underway in areas of the world where the benefits of breastfeeding outweigh the risks to identify effective strategies for reducing the risk of transmission through breastfeeding. This includes early weaning strategies, as well as the evaluation of drugs or vaccines to reduce the risk of transmission from breastfeeding.
Transmission of HIV to Women Worldwide, WHO estimates that more than 80 percent of adult HIV infections are due to heterosexual transmission of the virus through sexual intercourse. In the United States, the majority of women are infected with HIV during sex with an HIV-infected man or while using HIV-contaminated syringes for the injection of drugs such as heroin, cocaine, and amphetamines. Of the new AIDS cases reported among women in the United States in December 1999, 40 percent were attributed to heterosexual contact and 27 percent to injection drug use. The majority of the remaining cases had no identifiable risk.
In the United States, studies have shown that during unprotected heterosexual intercourse with an HIV-infected partner, women have a greater risk of becoming infected than do uninfected men who have heterosexual intercourse with an HIV-infected woman. In other parts of the world, however, this is not necessarily true. In Uganda, for example, one study demonstrated that the risk of HIV transmission from a woman to man was the same as from a man to woman. This difference may be due to the lack of circumcision in Ugandan men.
Studies in both the United States and abroad have demonstrated that STDs, particularly infections that cause ulcerations of the vagina (e.g., genital herpes, syphilis, and chancroid), greatly increase a woman's risk of becoming infected with HIV. NIAID-sponsored cohort studies in the United States have also found a number of other factors to be associated with an increased risk of heterosexual HIV transmission, including alcohol use, history of childhood sexual abuse, current domestic abuse, and use of crack/cocaine.
The consistent and correct use of male latex condoms greatly reduces the risk of becoming infected with HIV. In studies of heterosexual couples, in which one individual was HIV-positive and the other uninfected and regular condom use was reported, the rate of HIV transmission has been extremely low.
SIGNS AND SYMPTOMS OF HIV
Many manifestations of HIV disease are similar in men and women. Both men and women with HIV may have non-specific symptoms even early in disease, including low-grade fevers, night sweats, fatigue, and weight loss. Anti-HIV therapies, as well as treatments for other infections associated with HIV, appear to be similarly effective in men and women. Other conditions, however, occur in different frequencies in men and women. HIV-infected men, for instance, are eight times more likely than HIV-infected women to develop a skin cancer known as Kaposi's sarcoma. In some studies, women had higher rates of herpes simplex infections than men.
Data from several studies conducted by NIAID's Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) found that HIV-infected women were also more likely than HIV-infected men to develop bacterial pneumonia. This finding may be explained by factors such as a delay in seeking care among HIV-infected women as compared to men, and/or less access to anti-HIV therapies or preventive therapies for Pneumocystis carinii pneumonia (PCP).
WOMAN-SPECIFIC SYMPTOMS OF HIV INFECTION
Women also experience HIV-associated gynecologic problems, many of which occur in uninfected women but with less frequency or severity.
Vaginal yeast infections, common and easily treated in most women, often are particularly persistent and difficult to treat in HIV-infected women. Data from WIHS suggest that these infections are considerably more frequent in HIV-infected women. A drug called fluconazole is commonly used to treat yeast infections. A CPCRA study demonstrated that weekly doses of fluconazole can also safely prevent oropharyngeal and vaginal but not esophageal yeast infections, without resulting in resistance to the drug.
Other vaginal infections may occur more frequently and with greater severity in HIV-infected women, including bacterial vaginosis and common STDs such as gonorrhea, chlamydia, and trichomoniasis.
Severe herpes simplex virus ulcerations, which are sometimes unresponsive to therapy with the standard drug acyclovir, can severely compromise a woman's quality of life.
Idiopathic genital ulcers, with no evidence of an infectious organism or cancerous cells in the lesion are a unique manifestation of HIV disease. These ulcers, for which there is no proven treatment, are sometimes confused with those caused by herpes simplex virus.
Human papillomavirus (HPV) infections, which cause genital warts and can lead to cervical cancer, occur with increased frequency in HIV-infected women. A precancerous condition associated with HPV, called cervical dysplasia, is also more common and more severe in HIV-infected women, and more apt to recur after treatment.
Pelvic inflammatory disease (PID) appears to be more common and more aggressive in HIV-infected women than in uninfected women. PID may become a chronic and relapsing condition as a woman's immune system deteriorates.
Menstrual irregularities frequently are reported by HIV-infected women and are being actively studied by NIAID-supported scientists. Although menstrual irregularities were equally common in HIV-infected women and at-risk HIV-negative women in a WIHS survey, women with CD4+ T-cell counts below 50 per cubic millimeter (mm3) of blood were more likely to report no periods than were uninfected women, or HIV-infected women with higher CD4+ T-cell counts.
The U.S. Centers for Disease Control and Prevention (CDC) currently recommends that HIV-positive women have a complete gynecologic evaluation, including a Pap smear, as part of their initial HIV evaluations, or upon entry to prenatal care, and another Pap smear six months later. If both smears are negative, annual screening is recommended thereafter in asymptomatic women. More frequent screening-every six months-is recommended for women with symptomatic HIV infection, prior abnormal Pap smears, or signs of HPV infection.
Some women in the United States have poor access to health care. In addition, women may not think they are at risk for HIV infection. Symptoms that could serve as warning signals of HIV infection, they may not heed such as recurrent yeast infections. PID and the other symptoms discussed above should signal health care providers to offer women HIV testing accompanied by counseling.
Early diagnosis of HIV infection allows women to take full advantage of antiretroviral therapies and preventive drugs for opportunistic infections when their health care providers think it is appropriate. Both appropriate therapy and preventive drugs can forestall the development of AIDS-related symptoms and prolong life in HIV-infected men and women. Early diagnosis also allows women to make informed reproductive choices. Health care providers should be alert to early signs of HIV infection in women. In addition, all women should consider HIV testing if they have engaged in behaviors that put them at-risk of infection.
SURVIVAL AMONG HIV-INFECTED WOMEN
Women whose HIV infections are detected early and receive appropriate treatment survive as long as infected men. There are several studies that have shown HIV-infected women to have shorter survival times than men. Women may be less likely than men to be diagnosed early, which may account for shorter survival times.
In an analysis of several studies involving more than 4,500 people with HIV infection, women were one-third more likely than men to die within the study period. The investigators could not definitively identify the reasons for excess mortality among women in this study, but they speculated that poorer access to or use of health care resources among HIV-infected women as compared to men, domestic violence, homelessness, and lack of social supports for women may have been important factors.
FOR MORE INFORMATION
For information about FDA-approved HIV-related clinical trials being conducted throughout the United States, call the AIDS Clinical Trials Information Service:
1-800-TRIALS-A (1-800-874-2572) 1-800-243-7012 (TDD/Deaf Access) www.actis.org
For federally approved treatment guidelines on HIV/AIDS, call the HIV/AIDS Treatment Information Service:
1-800-HIV-0440 (1-800-448-0440) 1-800-243-7012 (TDD/Deaf Access) www.hivatis.org
Both services operate from 9 a.m. to 7 p.m. Eastern Time, Monday through Friday. Spanish-speaking specialists are available.
To obtain information specifically about clinical trials conducted by the NIAID Intramural AIDS Research Program, call 1-800-243-7644.
To obtain materials for women with HIV, or more information about women and HIV, contact the CDC National Prevention Information Network at 1-800-458-5231 or 1-800-243-7012 (TDD/Deaf Access).
REFERENCES FOR STATISTICS
UNAIDS/WHO AIDS Epidemic Update: December 2000
CDC HIV/AIDS Surveillance Report, Vol. 12, No. 2, 2000
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Prepared by: Office of Communications and Public Liaison National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892
U.S. Department of Health and Human Services