Community tenofovir levels as a population adherence measure to understand the impact of oral PrEP on HIV acquisition among young women in sub-Saharan Africa

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PROJECT SUMMARY Pre-exposure prophylaxis (PrEP) works at an individual-level to prevent HIV acquisition and is currently being rolled out globally to people at high risk for HIV acquisition— particularly among the high priority population of young women in sub-Saharan Africa. With the UNAIDS goal of 3 million people receiving PrEP globally by 2020, population-level metrics are needed to understand if PrEP delivery programs are achieving effective HIV prevention. For antiretroviral therapy (ART), community viral load provides insight into infectiousness. Similarly, measures of community PrEP use and HIV risk may provide insight for PrEP delivery and identify gaps in client outreach and adherence support. In this R21 application, we will develop the first ever model of “community tenofovir levels”. We will build on our existing HIV transmission model (which includes HIV incidence, ART uptake, viral suppression, and assumptions of PrEP adherence and HIV risk) and leverage objective PrEP adherence data and multiple assessments of HIV risk from an ongoing cohort study of 350 young women taking PrEP in Kenya, called MPYA (Monitoring PrEP in Young Adult women). We propose the following aims: 1. Measure tenofovir diphosphate (TFV-DP) levels in archived and unanalyzed dried blood spots (DBS) from the MPYA cohort. Funding is currently available for a 15% random sample of participant visits. We propose to analyze additional 500 DBS that will enable a more complete characterization of the first year of PrEP use. 2. Adapt an existing HIV transmission model to use heterogeneity in community tenofovir levels and HIV risk to estimate the impact of PrEP on HIV acquisition in young women in sub-Saharan Africa. 2a. Building on our current HIV transmission model, we will add DBS TFV-DP levels (Aim 1) plus sexual behavior from the MPYA cohort to estimate an “effective community tenofovir level” (i.e., the proportion of condomless sex acts protected by tenofovir). This effort will involve parameterization of our HIV transmission model and validation with data from three other studies of PrEP in young African women. 2b. Use the new PrEP impact model (Aim 2a) to estimate the community tenofovir levels needed among young women by age and risk group to decrease HIV incidence at an individual and population level. Investigators for this proposal consist of leaders in the fields of PrEP adherence (Dr. Haberer) and HIV modeling (Dr. Barnabas) with critical contextual input from a PrEP delivery expert (Dr. Irungu). This proposal reflects a novel approach to population-level adherence estimation that could provide much needed guidance for the rollout of PrEP in sub-Saharan Africa. It builds and extends on the solid scientific premise of research showing the importance of adherence in PrEP effectiveness, as well as the potential for population-level information from objective biomarkers. The products of the proposal thus have great potential to both advance science and move the field of PrEP implementation research forward.