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. Consequently, patients are
kept on failing ART regimens. Non-monitoring of LLV may result in an epidemic of resistance to
currently used antiretrovirals and poor clinical prognosis in PLWH. Thus, it is vital to understand the
predictors of LLV and its impact on PLWH, to inform improved clinical care of PLWH. Our proposed
aims are: 1).
To identify and characterize a cohort of from the IeDEA West Africa Database and
determine the epidemiology and predictors of low-level viremia (LLV) in the cohort (for HIV-1 and
HIV-2) and ii). Establish a prospective cohort of PLWH in Lagos, Nigeria, to estimate adherence to
ART, using 3 different adherence measures (pharmacy refill records (PRR), innovative urine tenofovir
POC test, and innovative TFV-DP in DBS). To accomplish this, We will assess the prevalence of LLV in a
large West African database (IeDEA West Africa) and also determine the relationship between adherence
with low-level viremia (LLV) in a cohort of 272 PLWH in Lagos, Nigeria and predict future LLV. This will be a
2-year follow-up prospective longitudinal study (3-monthly appointments for urine and DBS collection and 6-
monthly viral load testing).
