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 #
5P01HD064915-05
Application #
8500412
Study Section
Special Emphasis Panel (ZAI1-TP-A (J2))
Program Officer
Russo, Denise
Project Start
2009-09-15
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$1,674,581
Indirect Cost
$286,074
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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