Antiretroviral (ARV)-based HIV-1 prevention - including 1) ARV treatment (ART) to reduce the infectiousness of HIV-1 infected persons and 2) oral and topical pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition - is one of the most promising approaches for dramatically decreasing HIV-1 spread. Critical unanswered questions for successful delivery of ARV-based HIV-1 prevention include how to target ART and PrEP to realize maximum population HIV-1 prevention benefits, and for those targeted, whether HIV-1 infected persons at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1, highest-risk HIV-1 negative persons would use PrEP, and both would sustain high adherence needed to achieve high effectiveness. Stable, heterosexual, African HIV-1 serodiscordant couples (i.e., in which one member is HIV-1 infected and the other uninfected) face high risk of HIV-1 transmission and will be a prime target for ARV-based prevention. Since 2004, we have recruited >8500 African HIV-1 serodiscordant couples into prospective HIV-1 prevention studies, including 4700 couples from Kenya and Uganda into the Partners PrEP Study, an ongoing trial of oral tenofovir-based PrEP. HIV-1 serodiscordant couples will be a primary target globally for ARV-based prevention interventions, with the opportunity to use ARVs as treatment or as PrEP for prevention. Successful implementation of ARV-based HIV-1 prevention among HIV-1 serodiscordant couples will need to target delivery to highest risk couples, define optimal strategies for targeting for ART for HIV-1 infected partners versus PrEP for HIV-1 uninfected partners, respond to couples'preferences for prevention interventions, especially preferences for ART versus PrEP, and achieve high uptake and sustained adherence. We propose a series of integrated studies to optimize targeted delivery and sustained use of ARV-based HIV-1 prevention in African HIV-1 serodiscordant couples. We will analyze data from our previous cohorts of HIV-1 serodiscordant couples, implement additional data collection in our ongoing Partners PrEP Study, and test our hypotheses in a new cohort of highest-risk couples from Kenya and Uganda. We have assembled a multinational and multidisciplinary project team has the expertise and experience to complete the proposed work. We will: 1) develop a prediction risk score to identify priority HIV-1 serodiscordant couples to target for ARV-based HIV-1 prevention, based on highest risk for HIV-1 seroconversion, 2) use mathematical modeling to define optimal targeting of early ART of HIV-1 infected partners versus PrEP for HIV-1 uninfected partners for prevention in couples, 3) assess user preferences among high-risk HIV-1 serodiscordant couples about earlier ART initiation for HIV-1 infected partners versus PrEP for HIV-1 uninfected partners, and 4) prospectively ascertain initiation of and adherence to, ARV-based HIV-1 prevention strategies, including facilitators and barriers, among high-risk HIV- 1 serodiscordant couples. The proposed project offers an unprecedented opportunity to explore the critical public health questions surrounding ARV-based HIV-1 prevention in a target population for implementation. The project is novel and significant in its integration of biobehavioral and sociocultural research, focus on primary HIV-1 prevention and prevention of transmission from persons with HIV-1, target of dyads to identify appropriate prevention approaches, and aim to identify barriers and facilitators for dissemination of effective HIV-1 prevention.

Public Health Relevance

The use of antiretroviral medications for HIV-1 prevention, including antiretroviral therapy (ART) for HIV-1 infected persons to decrease their infectiousness and pre-exposure prophylaxis (PrEP) for HIV-1 uninfected persons to decrease HIV-1 acquisition, has the potential to dramatically decrease HIV-1 spread. There are many unanswered questions about how to implement preventive ART for HIV-1 infected persons and PrEP for high-risk HIV-1 uninfected persons as complementary HIV-1 prevention strategies. Stable, heterosexual, African HIV-1 serodiscordant couples (i.e., in which one member is HIV-1 infected and the other uninfected) face high risk of HIV-1 transmission and are a priority for antiretroviral-based HIV-1 prevention. We propose a series of integrated studies to optimize targeted delivery and sustained use of antiretroviral-based HIV-1 prevention in African HIV-1 serodiscordant couples.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH095507-03
Application #
8476276
Study Section
Special Emphasis Panel (ZMH1-ERB-F (04))
Program Officer
Stirratt, Michael J
Project Start
2011-08-10
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$518,045
Indirect Cost
$100,207
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Hancuch, Kerry; Baeten, Jared; Ngure, Kenneth et al. (2018) Safer conception among HIV-1 serodiscordant couples in East Africa: understanding knowledge, attitudes, and experiences. AIDS Care 30:973-981
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Mugwanya, Kenneth K; Baeten, Jared M; Wyatt, Christina et al. (2018) Brief Report: Frequency of Monitoring Kidney Function in HIV-Uninfected Persons Using Daily Oral Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis. J Acquir Immune Defic Syndr 77:206-211
Velloza, Jennifer; Baeten, Jared M; Haberer, Jessica et al. (2018) Effect of Depression on Adherence to Oral PrEP Among Men and Women in East Africa. J Acquir Immune Defic Syndr 79:330-338
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Mugwanya, Kenneth K; Irungu, Elizabeth; Bukusi, Elizabeth et al. (2018) ScaleĀ up of PrEP integrated in public health HIV care clinics: a protocol for a stepped-wedge cluster-randomized rollout in Kenya. Implement Sci 13:118
Heffron, Renee; Mugo, Nelly; Hong, Ting et al. (2018) Pregnancy outcomes and infant growth among babies with in-utero exposure to tenofovir-based preexposure prophylaxis for HIV prevention. AIDS 32:1707-1713
Pyra, Maria; Anderson, Peter L; Hendrix, Craig W et al. (2018) Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis. AIDS 32:1891-1898

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