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 #
5R01MH095507-04
Application #
8665491
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
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$576,601
Indirect Cost
$125,875
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
Mujugira, Andrew; Celum, Connie; Tappero, Jordan W et al. (2016) Younger Age Predicts Failure to Achieve Viral Suppression and Virologic Rebound Among HIV-1-Infected Persons in Serodiscordant Partnerships. AIDS Res Hum Retroviruses 32:148-54
Mujugira, Andrew; Celum, Connie; Coombs, Robert W et al. (2016) HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy. J Acquir Immune Defic Syndr 72:579-84
Carroll, Jennifer J; Heffron, Renee; Mugo, Nelly et al. (2016) Perceived Risk Among Human Immunodeficiency Virus Serodiscordant Couples in East Africa Taking Oral Pre-Exposure Prophylaxis. Sex Transm Dis 43:471-5
Roberts, Sarah T; Haberer, Jessica; Celum, Connie et al. (2016) Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study. J Acquir Immune Defic Syndr 73:313-322
Mujugira, Andrew; Coombs, Robert W; Heffron, Renee et al. (2016) Seminal HIV-1 RNA Detection in Heterosexual African Men Initiating Antiretroviral Therapy. J Infect Dis 214:212-5
Irungu, Elizabeth M; Heffron, Renee; Mugo, Nelly et al. (2016) Use of a risk scoring tool to identify higher-risk HIV-1 serodiscordant couples for an antiretroviral-based HIV-1 prevention intervention. BMC Infect Dis 16:571
Carroll, Jennifer J; Ngure, Kenneth; Heffron, Renee et al. (2016) Gendered differences in the perceived risks and benefits of oral PrEP among HIV-serodiscordant couples in Kenya. AIDS Care 28:1000-6
Baeten, Jared; McCormack, Sheena (2016) Welcome to the preexposure prophylaxis revolution. Curr Opin HIV AIDS 11:1-2
Ngure, Kenneth; Heffron, Renee; Curran, Kathyrn et al. (2016) I Knew I Would Be Safer. Experiences of Kenyan HIV Serodiscordant Couples Soon After Pre-Exposure Prophylaxis (PrEP) Initiation. AIDS Patient Care STDS 30:78-83
Mugo, Nelly R; Ngure, Kenneth; Kiragu, Michael et al. (2016) The preexposure prophylaxis revolution; from clinical trials to programmatic implementation. Curr Opin HIV AIDS 11:80-6

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