Sub-Saharan Africa (SSA) is home to two-thirds of all people living with HIV (PLHIV). Widely-adopted targets
such as “95-95-95” (diagnosing =95% of PLHIV, treating =95% of those diagnosed, and achieving viral load
suppression in =95% of those on treatment) have fueled tremendous progress in access and effective use of
HIV treatment, with surveillance from Population HIV Impact Assessments (PHIAs) used to monitor progress.
Although these efforts have reduced HIV incidence and mortality, HIV/AIDS remains the leading cause of
death among SSA adults, and HIV incidence remains high, with many regions not on track to achieve the
Sustainable Development Goal (SDG) of HIV incidence <0.1% per person-year by 2030. Pre-exposure
prophylaxis (PrEP) has been shown to dramatically reduce HIV acquisition risk when taken as directed.
However, at a population level, PrEP use in SSA is still limited. Several modeling studies, including our own,
suggest the SDG could be achieved in much of SSA with sufficient expansions in PrEP access and use.
A challenge for PrEP expansion in SSA is the lack of established targets, and lack of surveillance to monitor
progress toward targets. Such target-setting-and-tracking approaches have been remarkably successful in
driving scale-up of HIV treatment and monitoring progress through PHIAs. Our central hypothesis is that PrEP
research data can be used to derive setting-specific PrEP coverage targets corresponding to incidence
reduction goals, which can be monitored using population-based drug measurements as a “PHIA for PrEP.”
Several innovations are needed to enable a “PHIA for PrEP.” First (Aim 1), the relationship between drug
concentrations measured and reduction in HIV incidence needs to be established. This was previously
accomplished for men who have sex with men (MSM) in the Global North. We will determine this relationship
using pooled PrEP study data from SSA, where transmission is predominantly heterosexual. Second (Aim 2),
the totality of the effects of PrEP program participation need to be understood, which may extend beyond the
pharmacological effects of PrEP drugs. Several studies have measured HIV incidence reductions among non-
adherent participants and those taking placebos, suggesting PrEP program participation may serve as a
“gateway” to behavioral risk reduction. We will estimate these effects using pooled study results from post-
licensure SSA PrEP pilots and demonstration projects. Third (Aim 3), PrEP target-setting needs to account for
differential HIV risk across population groups and settings. We will use agent-based HIV transmission
modeling to estimate a range of PrEP coverage configurations that achieve epidemic targets, with trade-offs
between coverage vs. adherence and between overall coverage vs. targeting those most-at-risk. Cognizant of
stigma, accessibility, and other challenges, we will engage policy-makers, advocates, community advisory
boards, as well as experts in HIV trials, surveys, and bioethics, to weigh PrEP target options and design
monitoring strategies using a “PHIA for PrEP.”
