Special Reviews

HIV/AIDS in Women: An Expanding Epidemic

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Science  10 Jun 2005:
Vol. 308, Issue 5728, pp. 1582-1583
DOI: 10.1126/science.1112489

Abstract

More than 20 years into the human immunodeficiency virus–type 1 (HIV-1) epidemic, women account for nearly half of the 40 million people living with HIV-1 worldwide, with an even higher proportion existing in developing countries. Social determinants of female vulnerability to HIV-1 include gender disparities, poverty, cultural and sexual norms, lack of education, and violence. Women are also more susceptible to HIV-1 because of hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sexually transmitted diseases. Prevention strategies must address the wide range of gender inequalities that promote the dissemination of HIV-1.

For the past two decades, HIV-1 infection and its consequent disease, acquired immunodeficiency syndrome (AIDS), have affected more women worldwide than any other life-threatening infectious disease. Women account for nearly half of the 40 million people living with HIV-1 (Fig. 1A) (1). In sub-Saharan Africa, females constitute 60% of those infected with HIV-1 (Fig. 1B) and 75% of infected individuals between the ages of 15 and 24 (2). In South Africa, Zambia, and Zimbabwe, young women aged 15 to 24 are three to six times more likely to be infected than young men. In South Africa, one in four women is HIV-1–infected by the age of 22. Women make up half of the adults living with HIV-1 in the Caribbean, and one-third in Latin America, with a higher burden in young women (1). In addition to the direct impact that HIV-1 infection has on these women, there is also the known high risk of HIV-1 transmission to their infants and a resulting plethora of consequences for the family.

Fig. 1.

(A) Estimated number of adult (age 15 to 49) women (red) and men (black) living with HIV/AIDS by region from 1985 to 2003 (1). (B) Estimated number of adult (age 15 to 49) women (red) and men (black) living with HIV-1 in sub-Saharan Africa from 1985 to 2003 (2). [Reproduced by permission of UNAIDS, the Joint United Nations Programme on HIV/AIDS.]

In the United States, the annual number of estimated AIDS cases increased 15% among women and only 1% among men from 1999 to 2003. The major burden of disease was in young women and women of color, particularly African-American and Hispanic women, who often have reduced access to health care (3). The rate of AIDS diagnoses for African-American women was approximately 25 times the rate for white women and four times the rate for Hispanic women. The majority of infections were due to heterosexual transmission (80%) or to injecting drug use (19%). These same risk factors, especially injecting drug use, have led to a 50% increase in infections in women in Asia and eastern Europe over the past 2 years (1, 2).

Physiologically, women are more susceptible to HIV infection than are men. Increased susceptibility among women has been linked to specific cofactors, including the use of hormonal contraceptives and the increased presence of sexually trasmitted diseases (STDs) (4, 5). The role of hormonal contraceptive use in increasing HIV-1 infection in women has been controversial, with one longitudinal study showing an association (5) but another not showing an effect (6). Hormonal contraceptive use has been linked to the infection of women with several viral strains from their partners, which in turn may accelerate disease progression (4). The role of hormonal contraceptives remains a key issue, given the common use of hormonal methods of contraception in at-risk populations, such as young females.

Much of our inability to define the biological role of these cofactors in HIV-1 susceptibility comes from a lack of understanding of the initial events in HIV-1 infection (7). HIV-1 is transmitted to women primarily via heterosexual contact, and the virus must therefore penetrate the mucosal barrier to establish a systemic infection. Ulcerative STDs increase the risk of HIV-1 infection, which implies that breaches in mucosa enhance HIV-1 transmission. Additionally, STDs increase the presence of inflammatory cells, a result that provides more potential targets for the virus. Fundamental questions regarding the biology of HIV-1 transmission have been difficult to answer, because it is hard to examine relevant cells and tissue at the time of HIV-1 acquisition, when the initial pivotal events are occurring.

Susceptibility to HIV-1 also varies throughout a woman's reproductive life. Adolescent girls appear to be the population most vulnerable to HIV-1, either because of behavioral high-risk activities or because of the physiological properties of an immature genital tract with increased cervical ectopy or exposed columnar epithelium. In addition, recent studies have shown a twofold increase in the risk of HIV-1 acquisition during pregnancy and the early postpartum period, even after adjustments have been made for changes in sexual behavior and social and demographic factors (8). Factors that could increase susceptibility during pregnancy include high levels of progesterone, which has been shown to enhance susceptibility in nonhuman primate models of HIV-1 (9), and increased ectopy. The mechanisms by which female hormones may affect HIV-1 susceptibility include increases in the number of target cells and the suppression of immune responses, but these mechanisms remain poorly defined.

If hormonal changes play a key role in HIV-1 susceptibility and the magnitude of the immune response to infection, then it is critical that vaccine trial design consider possible gender differences in outcome. Indeed, some preliminary findings from the only phase-III HIV-1 vaccine trial conducted to date suggested that there may be differences in the humoral immune responses to the vaccine generated in women and men (10). However, this difference was not detected in an analysis of smaller phase-I/II vaccine trials (11).

This growing “feminization” of the HIV-1 pandemic reflects women's greater social and biological vulnerability (12). Because gender norms shape attitudes toward information on sex, sexuality, sexual risk-taking, and fidelity, they play a critical role in determining the course of the epidemic. Because the risk of HIV-1 infection in women has been linked to the regional norms that affect power in interpersonal relationships (12), controlling the HIV-1 pandemic requires intensive attention to gender-related issues driving the epidemic. Interventions must be multifaceted and should include making both female and male condoms accessible to all in ways that do not stigmatize; prioritizing the development of female-initiated methods of protection such as microbicides; defining the influence of hormones on disease progression and response to treatment; and educating women and men about HIV-1 and other STDs, including how to negotiate safe sex, and encouraging them to seek testing and treatment.

References and Notes

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