Response of Genital Tract HIV-1 to HAART: Role of HSV-2?

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DESCRIPTION (provided by applicant): The applicant's long-term goals are to conduct clinical trials related to HIV prevention, care, and treatment in the African context, particularly with respect to women's health. Genital ulcer disease (GUD) plays an important role in fueling the HIV-1 epidemic. Herpes simplex virus type 2 (HSV-2) is an increasingly important cause of GUD around the world and has been associated with increased HIV-1 genital tract shedding and increased risk of HIV-1 acquisition and transmission. It is not known whether HSV-2 influences HIV-1 genital tract shedding even in the context of highly active antiretroviral therapy (HAART). This information is needed to determine factors influencing HIV-1 infectiousness among women on HAART as well as to formulate recommendations regarding genital herpes suppression among co-infected individuals on HAART. This proposed prospective observational cohort study will test the hypothesis that the effect of HAART on decreasing the presence and quantity of genital tract HIV-1 DMA is reduced by the presence of HSV-2 disease and/or genital tract shedding. Specific aims include: (i) Evaluating the association between HSV-2 serostatus and presence and quantity of genital tract cell-associated HIV-1 DNA among women at baseline and at 6 months post-HAART initiation, (ii) Evaluating the association between genital tract HSV-2 DNA and HIV-1 DNA among HSV-2 / HIV-1 coinfected women at baseline and at 6 months post-HAART initiation, and (iii) Determining HSV-2 seroprevalence among women with advanced HIV-infection. The study plans to enroll 400 HIV-infected women preparing to initiate HAART in Botswana (200 HSV-2 seronegative and 200 HSV-2 seropositive). Blood and genital tract specimens will be collected and analyzed at baseline and 6 months after HAART initiation.