Recent events have lowered the cost barrier to antiretroviral therapy in sub-Saharan Africa, where millions of people could benefit from such treatment. In addition to prolonging lives, antiretrovirals could provide a powerful tool for decreasing the spread of the virus. However, cofactors that enhance viral replication or an increase in sexual risk taking could mitigate the benefits of antiretrovirals on HIV-1 transmission. The objective of the proposed research is to define the complex interplay of these factors in order to understand how the introduction of antiretrovirals will influence sexual transmission of HIV-1. We propose a series of studies utilizing genital HIV-1 as a marker for infectiousness in a core transmitter group of women in Mombasa, Kenya. This research will address the following key hypotheses. First, that antiretroviral therapy will produce a rapid and sustained reduction in genital HIV-1 levels. Second, that there are modifiable cof actors that increase genital HIV-1 shedding even in the face of antiretrovirals. These cof actors represent attractive targets to augment the benefits of antiretroviral therapy for reducing HIV-1 infectivity. Finally, we hypothesize that the introduction of antiretrovirals may adversely influence sexual risk, which could offset the benefit of decreased HIV-1 shedding. This hypothesis will be evaluated by measuring changes in the incidence of communicable genital tract infections before and after the introduction of antiretrovirals. One hundred HIV-1 seropositive women will be recruited from an existing cohort. Women initiating long-term antiretroviral therapy will have serial examinations to determine the effects of antiretrovirals, CD4 count, plasma viral load, adherence to therapy, genital tract infections, and hormonal contraceptives on HIV-1 shedding. These studies will help to guide the development of interventions to address infectious, hormonal, immunologic, virologic, and pharmacologic cof actors for HIV-1 infectivity among women on antiretrovirals, and will identify changes in sexual risk that may occur as access to antiretroviral therapy increases.
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