Perceived relationships regarding adherence, risk of resistance, and clinical impact of resistance drive concerns about providing HIV therapy to impoverished populations. While these debates first focused on drug users and the homeless, now they focus on resource-constrained countries. Critical factors that determine drug resistance and treatment failure such as adherence, stage of disease at treatment initiation, T cell activation, viral subtype and pharmacogenomic determinants of drug resistance likely differ in resource-rich and resource-constrained settings. Our group has characterized adherence and resistance to non-boosted protease inhibitor antiretroviral therapy in San Francisco and we have begun to characterize adherence and treatment response to HIV antiretroviral therapy in Uganda. We propose to study the behavioral and biologic determinants of HIV antiretroviral drug resistance and disease progression in two prospective 500-person observational cohorts on HIV antiretroviral therapy: the Research in Access to Care in the Homeless (REACH) Cohort and the Uganda Antiretroviral Treatment Outcomes (UARTO) Cohort. We will leverage an R-21 NIAAA funded study to characterize adherence, treatment response and drug resistance in Uganda. We will continue to follow the REACH Cohort to characterize adherence-resistance relationships to new antiretroviral medications and to determine the extent that resistant virus speeds disease progression and death. Using comparable measures of objective adherence, T cell activation, viral suppression, viral subtype and immunologic response, we will utilize the behavioral and biologic variation in the two cohorts to characterize fundamental pathways of treatment failure and drug resistance. To better guide therapy in both settings, these studies will further our understanding of drug resistance, including its causes, its extent and the role it plays in disease progression and death.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH054907-11
Application #
7046128
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Stirratt, Michael J
Project Start
1995-07-01
Project End
2010-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
11
Fiscal Year
2006
Total Cost
$1,533,566
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Mwimanzi, Francis; Toyoda, Mako; Mahiti, Macdonald et al. (2018) Resistance of Major Histocompatibility Complex Class B (MHC-B) to Nef-Mediated Downregulation Relative to that of MHC-A Is Conserved among Primate Lentiviruses and Influences Antiviral T Cell Responses in HIV-1-Infected Individuals. J Virol 92:
Muiru, Anthony N; Bibangambah, Prossy; Hemphill, Linda et al. (2018) Distribution and Performance of Cardiovascular Risk Scores in a Mixed Population of HIV-Infected and Community-Based HIV-Uninfected Individuals in Uganda. J Acquir Immune Defic Syndr 78:458-464
Castillo-Mancilla, Jose R; Morrow, Mary; Boum, Yap et al. (2018) Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression. J Acquir Immune Defic Syndr 77:507-513
Dunkley, Emma; Ashaba, Scholastic; Burns, Bridget et al. (2018) ""I beg you…breastfeed the baby, things changed"": infant feeding experiences among Ugandan mothers living with HIV in the context of evolving guidelines to prevent postnatal transmission. BMC Public Health 18:188
Lee, Guinevere Q; Bangsberg, David R; Mo, Theresa et al. (2017) Prevalence and clinical impacts of HIV-1 intersubtype recombinants in Uganda revealed by near-full-genome population and deep sequencing approaches. AIDS 31:2345-2354
McCluskey, Suzanne M; Boum 2nd, Yap; Musinguzi, Nicholas et al. (2017) Brief Report: Appraising Viral Load Thresholds and Adherence Support Recommendations in the World Health Organization Guidelines for Detection and Management of Virologic Failure. J Acquir Immune Defic Syndr 76:183-187
North, Crystal M; Valeri, Linda; Hunt, Peter W et al. (2017) Cooking fuel and respiratory symptoms among people living with HIV in rural Uganda. ERJ Open Res 3:
Lee, Guinevere Q; McCluskey, Suzanne; Boum 2nd, Yap et al. (2017) Brief Report: Should Abacavir Be a First-Line Alternative for Adults With HIV in Sub-Saharan Africa? J Acquir Immune Defic Syndr 76:188-192
Haberer, Jessica E; Musinguzi, Nicholas; Tsai, Alexander C et al. (2017) Real-time electronic adherence monitoring plus follow-up improves adherence compared with standard electronic adherence monitoring. AIDS 31:169-171
Musinguzi, Nicholas; Mocello, Rain A; Boum 2nd, Yap et al. (2017) Duration of Viral Suppression and Risk of Rebound Viremia with First-Line Antiretroviral Therapy in Rural Uganda. AIDS Behav 21:1735-1740

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