The majority of adult HIV infections in sub-Saharan Africa occur in women, highlighting the importance of understanding HIV risk in this population. Numerous studies have suggested that perturbations of vaginal bacterial flora, including bacterial vaginosis (BV), may increase women's risk of HIV acquisition. Recently, molecular techniques for characterization of vaginal flora have enhanced our knowledge of the central role of uncultivated organisms in the microbial ecology of BV. Indeed, several novel bacterial species appear to be substantially more predictive of BV than bacteria previously identified through culture. Understanding the role of vaginal flora in mediating HIV risk is an important HIV prevention goal. The overarching aim of this proposal is to use cutting-edge molecular approaches to test the hypothesis that the presence of specific bacteria in the vaginal flora is associated with increased risk for HIV acquisition. To accomplish this objective, we will conduct a nested case-control study utilizing prospectively collected data from NIH-funded cohorts of women at risk for HIV in Mombasa and Kisumu, Kenya. Vaginal bacterial flora will be evaluated using two distinct and complementary molecular techniques: (1) quantitative 16S ribosomal DNA polymerase chain reaction (PCR) to identify and quantify species that are frequently associated with BV, and (2) broad range PCR with pyrosequencing (deep sequencing) to identify minority species and broad patterns of vaginal bacterial communities in women who acquire HIV versus those who remain HIV-seronegative. The proposed studies will be conducted by an experienced multidisciplinary team including basic scientists, clinicians, epidemiologists, and biostatisticians with an established record of collaborative HIV research in women.
The findings from the proposed studies will be highly relevant to public health, holding great promise for the development of a vaginal health approach to HIV prevention based on eradication of high-risk vaginal bacteria. Successful completion of these studies could help to inform the development of urgently needed female-controlled, non-coitally linked HIV prevention strategies.
|Roxby, Alison C; Fredricks, David N; Odem-Davis, Katherine et al. (2016) Changes in Vaginal Microbiota and Immune Mediators in HIV-1-Seronegative Kenyan Women Initiating Depot Medroxyprogesterone Acetate. J Acquir Immune Defic Syndr 71:359-66|
|Pintye, Jillian; Drake, Alison L; Kinuthia, John et al. (2016) A risk assessment tool for identifying pregnant and postpartum women who may benefit from pre-exposure prophylaxis (PrEP). Clin Infect Dis :|
|Masese, Linnet; Baeten, Jared M; Richardson, Barbra A et al. (2015) Changes in the contribution of genital tract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012. AIDS 29:1077-85|
|McClelland, R Scott; Richardson, Barbra A; Cherutich, Peter et al. (2015) A 15-year study of the impact of community antiretroviral therapy coverage on HIV incidence in Kenyan female sex workers. AIDS 29:2279-86|
|Odem-Davis, K; Fleming, T R (2015) A simulation study evaluating bio-creep risk in serial non-inferiority clinical trials for preservation of effect. Stat Biopharm Res 7:12-24|
|Kinuthia, John; Drake, Alison L; Matemo, Daniel et al. (2015) HIV acquisition during pregnancy and postpartum is associated with genital infections and partnership characteristics. AIDS 29:2025-33|
|Unger, Jennifer A; Matemo, Daniel; Pintye, Jillian et al. (2015) Patient-Delivered Partner Treatment for Chlamydia, Gonorrhea, and Trichomonas Infection Among Pregnant and Postpartum Women in Kenya. Sex Transm Dis 42:637-42|
|Strauss-Albee, Dara M; Fukuyama, Julia; Liang, Emily C et al. (2015) Human NK cell repertoire diversity reflects immune experience and correlates with viral susceptibility. Sci Transl Med 7:297ra115|
|Lehman, Dara A; Ronen, Keshet; Blish, Catherine A et al. (2014) Systemic cytokine levels show limited correlation with risk of HIV-1 acquisition. J Acquir Immune Defic Syndr 66:135-9|
|Drake, Alison L; Wagner, Anjuli; Richardson, Barbra et al. (2014) Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: a systematic review and meta-analysis. PLoS Med 11:e1001608|
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