Regulatory Perspectives for Streamlining HIV Prevention Trials

Abstract Designing and conducting active-controlled trials of HIV pre-exposure prophylaxis (PrEP) therapeutics are becoming challenging due to inconsistency of adherence across trials and the need for increasingly larger trials to assess efficacy. In the United States (US), trials evaluating oral contraceptives (OC) use the Pearl Index to assess efficacy in single-arm trials. This article explores the possibility of using an index (“HIV Incidence Index”) analogous to the Pearl Index to assess preventive efficacy in active-controlled HIV prevention trials in sexually-acquired HIV. One proposal for constructing an HIV Incidence Index is to use the incidence of sexually transmitted infections (STIs) during a trial to serve as a marker for HIV risk behavior and to estimate what the HIV seroconversion rate would have been had the participants not been on efficacious PrEP. In addition, a consensus of expert opinion will be needed to define clinically acceptable HIV seroconversion rates for populations at risk of HIV-infection receiving active PrEP.