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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
1P01HD064915-01
Application #
7683462
Study Section
Special Emphasis Panel (ZAI1-TP-A (J2))
Project Start
Project End
Budget Start
2009-09-15
Budget End
2010-06-30
Support Year
1
Fiscal Year
2009
Total Cost
$588,271
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Heffron, Renee; McClelland, R Scott; Balkus, Jennifer E et al. (2017) Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study. Lancet HIV 4:e449-e456
Pintye, Jillian; Drake, Alison L; Unger, Jennifer A et al. (2017) Male partner circumcision associated with lower Trichomonas vaginalis incidence among pregnant and postpartum Kenyan women: a prospective cohort study. Sex Transm Infect 93:137-143
Kinuthia, John; Richardson, Barbra A; Drake, Alison L et al. (2017) Sexual Behavior and Vaginal Practices During Pregnancy and Postpartum: Implications for HIV Prevention Strategies. J Acquir Immune Defic Syndr 74:142-149
Lokken, Erica M; Balkus, Jennifer E; Kiarie, James et al. (2017) Association of Recent Bacterial Vaginosis With Acquisition of Mycoplasma genitalium. Am J Epidemiol 186:194-201
Pintye, Jillian; Drake, Alison L; Kinuthia, John et al. (2017) A Risk Assessment Tool for Identifying Pregnant and Postpartum Women Who May Benefit From Preexposure Prophylaxis. Clin Infect Dis 64:751-758
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
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
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
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
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

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