The overarching goal of this Mid-Career Investigator Award in HIV-related Patient-Oriented Research (K- 24) application is to make meaningful contributions to social and behavioral science research aimed at improving HIV treatment outcomes in sub-Saharan Africa. My specific goals are to 1) mentor students, post- doctoral fellows, and junior faculty in social-behavioral HIV research who will 2) conduct patient-based research to improve antiretroviral therapy adherence in a rural African setting. My mentoring activities will be primarily based at Mbarara University of Science and Technology (MUST) in Mbarara, Uganda, and Harvard University in Cambridge, Massachusetts. The mentoring program will leverage research and teaching infrastructure at these universities and will consist of direct one-on-one mentoring in the conduct of social-behavioral HIV research, as well as formal seminars on research methods, manuscript writing, and grant writing. A mentoring advisory committee will formally evaluate mentored junior investigators, on the basis of their productivity. The research program will test the feasibility of preventing antiretroviral therapy interruptions through novel real-time wireless adherence monitoring. This new direction is based on our finding that incomplete adherence, to the extent that it occurs in rural Uganda, is manifested as treatment interruptions due to structural and/or economic barriers to treatment access. We found that the duration of treatment interruption for patients on non-nucleoside reverse transcriptase inhibitor antiretroviral therapy is directly related to the risk of virologic rebound. While an interruption of 4 days poses little risk of virologic rebound, an interruption of 15 days poses a 50% risk of virologic rebound. These data suggest that there is a 3-5 day window to intervene after missed doses but before virologic failure. Because adherence is so closely associated with viral suppression, accurate adherence monitoring can provide a strategy to strategically limit viral RNA monitoring only to those patients at a defined risk for viral rebound. Novel wireless adherence monitoring tools combined with the well developed wireless communications network in many Sub-Saharan African countries creates the potential for a new paradigm of HIV treatment defined by strategic viral RNA monitoring and the proactive prevention rather than the reactive response to virologic failure.

Public Health Relevance

While there has been encouraging data on treatment adherence in sub-Saharan Africa, treatment options remain limited. Treatment success will require sustained adherence over decades of treatment. Novel approaches to adherence monitoring and intervention, as well as a strong cadre of investigators to build behavioral science research infrastructure, will help design effective, feasible, and culturally relevant antiretroviral adherence interventions to promote optimal HIV treatment response in sub-Saharan Africa.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24MH087227-10
Application #
8259204
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Stirratt, Michael J
Project Start
2004-09-27
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
10
Fiscal Year
2012
Total Cost
$155,220
Indirect Cost
$10,563
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Matthews, Lynn T; Bajunirwe, Francis; Kastner, Jasmine et al. (2016) ""I Always Worry about What Might Happen Ahead"": Implementing Safer Conception Services in the Current Environment of Reproductive Counseling for HIV-Affected Men and Women in Uganda. Biomed Res Int 2016:4195762
Musinguzi, Nicholas; Mocello, Rain A; Boum 2nd, Yap et al. (2016) Duration of Viral Suppression and Risk of Rebound Viremia with First-Line Antiretroviral Therapy in Rural Uganda. AIDS Behav :
Conroy, Amy A; Tsai, Alexander C; Clark, Gina M et al. (2016) Relationship Power and Sexual Violence Among HIV-Positive Women in Rural Uganda. AIDS Behav 20:2045-53
Matthews, Lynn T; Ribaudo, Heather B; Kaida, Angela et al. (2016) HIV-Infected Ugandan Women on Antiretroviral Therapy Maintain HIV-1 RNA Suppression Across Periconception, Pregnancy, and Postpartum Periods. J Acquir Immune Defic Syndr 71:399-406
Tsai, Alexander C; Wolfe, William R; Kumbakumba, Elias et al. (2016) Prospective Study of the Mental Health Consequences of Sexual Violence Among Women Living With HIV in Rural Uganda. J Interpers Violence 31:1531-53
Lee, Sulggi A; Mefford, Joel A; Huang, Yong et al. (2016) Host genetic predictors of the kynurenine pathway of tryptophan catabolism among treated HIV-infected Ugandans. AIDS 30:1807-15
Psaros, Christina; Haberer, Jessica E; Boum 2nd, Yap et al. (2015) The factor structure and presentation of depression among HIV-positive adults in Uganda. AIDS Behav 19:27-33
Palar, Kartika; Kushel, Margot; Frongillo, Edward A et al. (2015) Food Insecurity is Longitudinally Associated with Depressive Symptoms Among Homeless and Marginally-Housed Individuals Living with HIV. AIDS Behav 19:1527-34
Nieves, Christina I; Kaida, Angela; Seage 3rd, George R et al. (2015) The influence of partnership on contraceptive use among HIV-infected women accessing antiretroviral therapy in rural Uganda. Contraception 92:152-9
Mimiaga, Matthew J; Closson, Elizabeth F; Safren, Steven A et al. (2015) Inkwari: an emerging high-risk place potentiating hiv spread among young adults in a hyper-endemic South African setting. Arch Sex Behav 44:307-15

Showing the most recent 10 out of 122 publications