  The past decade has seen tremendous progress in the development of biomedical
agents that are effective as pre-exposure prophylaxis (PrEP) for HIV
prevention. To expand the choice of products and delivery methods, new
medications and delivery methods are under development. Future trials of
non-inferiority, given the high efficacy of ARV-based PrEP products as they
become current or future standard of care, would require a large number of
participants and long follow-up time that may not be feasible. This motivates
the construction of a counterfactual estimate that approximates incidence for a
randomized concurrent control group receiving no PrEP. We propose an approach
that is to enroll a cohort of prospective PrEP users and augment screening for
HIV with laboratory markers of duration of HIV infection to indicate recent
infections. We discuss the assumptions under which these data would yield an
estimate of the counterfactual HIV incidence and develop sample size and power
calculations for comparisons to incidence observed on an investigational PrEP
agent.
