HIV-1 infection of women is a relatively rare outcome of sexual exposure to HIV-1. The risk may vary for each woman, and it may also vary for the same woman during different exposures. Susceptibility is determined by a complex set of factors, including the amount and properties of the virus to which a woman is exposed, individual host genetic factors, as well as multiple modifiable biological cofactors present at the time of exposure. In this program project grant, we proposed to examine the mechanisms by which biological cofactors increase susceptibility of women to HIV-1. The proposed studies will include women in multiple high-risk groups: sex workers, pregnant/postpartum women and women in HIV-1 discordant relationships. Specifically, we will examine the role of: 1) pregnancy and the postpartum effects (Project 1);2) vaginal flora and specific bacterial infections (Project 2);3) innate immune factors, including as they relate to hormones and genital tract infections (Project 3);and 4) mucosal HIV-1 antibodies induced in response to repeated HIV-1 exposure (Project 4) on susceptibility to HIV-1 infection in women. For these studies, we will take advantage of cohort studies, collaborative partnerships and infrastructure developed by our research team, the Seattle/Kenya collaborative research group, over the past ~ 15 years. Our research group, which includes virologists, immunologists, bacteriologists, epidemiologist, statisticians and clinical scientists, has a long and productive history of collaboration, and is known for its focus on translational research in women. Here we will build on that foundation to conduct multiple collaborative projects within this program grant. We expect that each of these projects will draw on the expertise of others in the team, and in some cases, will include parallel studies that address synergistic biological questions in the same populations.

Public Health Relevance

Collectively, these studies are designed to provide a comprehensive picture of the biological factors that contribute to increased risk of HIV-1 infection in women. Such studies will be critical for understanding unique aspects of HIV-1 transmission in women, and for finding approaches to decrease transmission that consider issues that are relevant to women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD064915-04
Application #
8312551
Study Section
Special Emphasis Panel (ZAI1-TP-A (J2))
Program Officer
Mofenson, Lynne M
Project Start
2009-09-15
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$1,767,383
Indirect Cost
$284,842
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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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