Use of Pharmacoepidemiology to Understand Predictors and Impact of Low-level Viremia in Persons with HIV in West Africa - PROJECT SUMMARY/ABSTRACT With this K43 Career Development Award, I will develop the skills necessary to reach my ultimate goal of becoming an independent investigator focused on the use of pharmacoepidemiology and experimental pharmacology to inform improved strategies for achieving sustained viral suppression in HIV treatment. Career Development Plan: My long-term career goal is to become an independently funded researcher with expertise in pharmacoepidemiology (epidemiology and clinical pharmacology) to inform improved strategies for achieving sustained viral suppression in HIV treatment. In the short-term during this K43 period, my goals are to Identify and characterize a retrospective cohort of PLWH in the IeDEA West Africa Database and determine the epidemiology and predictors of HIV-1, HIV-2 low-level viremia (LLV) in the cohort; and to determine the relationship between low-level viremia (LLV) and adherence to ART in a prospective cohort using 3 different adherence measures (pharmacy refill records (PRR), innovative urine-tenofovir POC test, and innovative TFV-DP in DBS). To attain these goals, I will be mentored during this K43 award period by a group of experienced career scientists: Dr. Cecile Lahiri, a clinician scientist whose focus is on HIV cure/eradication; Dr. Oliver Ezechi, a specialist in reproductive and population health whose focus is on the clinical impact of infectious diseases on women and adolescent health; Dr Antoine Jaquet, a clinician/epidemiologist with focus on the epidemiology of HIV and related chronic comorbidities; Dr. Igho Ofotokun an HIV translational clinician scientist with focus on women’s health and Dr. Castillo-Mancilla, a translational researcher focused on applied clinical pharmacology. For this K43 award, I will complete coursework and hands-on training in large data analysis and experimental pharmacology, I will also conduct research that exemplifies the undetectable = untransmissible (U=U) agenda with the goal of learning new ways of monitoring adherence to achieve effective HIV treatments that will stop transmission and eliminate HIV eventually. Merging my background in pharmacy practice in HIV care and infectious diseases, with advanced analytic skills, mathematical modelling, epidemiology, and experimental pharmacology from this K43, will give me the capacity for a career as an independent researcher. Research Plan: Emerging evidence suggests that persistent low-level viremia (LLV) in persons with HIV (PLWH) on antiretroviral therapy (ART) is a barrier to achieving the goal of zero transmission and eradication of HIV1-8, but not much is known about the impact of LLV on attaining the goal of viral suppression in West Africa; thus, this proposal aims to provide information vital to understand the impact of LLV in ART outcomes in West Africa. It will also be important to understand if differences exist between HIV-1 and HIV-2 treatment outcomes in the presence of LLV, since West Africa is one of the few regions in the world where HIV-2 is endemic. While literature is unanimous that sub-optimal adherence results in LLV, controversy surrounds the prognostic value of LLV for clinical outcomes. Some studies attribute the cause of LLV to drug resistance and reactivation of viral reservoirs, but other studies name these factors as consequences of LLV9-11. The ‘Undetectable=Untransmissible (U=U)’ concept is hinged on exploring pharmacologic, psycho- socio-economic, and other interventions to improve adherence and achieve undetectable viral load12,13. Individuals with LLV have been shown to be significantly less likely to subsequently achieve complete undetectable viral load. The upper limit of LLV (200-1000 copies/ml), has also been shown to be associated with virologic failure, development of resistance to ARVs, AIDS events and AIDS-related deaths1. Current WHO guidelines do not advise monitoring or treatment interventions even after repeated measurements of low-level viraemia. Consequen
