What Constitutes Efficacy for a Human Immunodeficiency Virus Vaccine that Ameliorates Viremia: Issues Involving Surrogate End Points

Initial human immunodeficiency virus (HIV) vaccines are unlikely to prevent acquisition of HIV in all recipi-ents. Moreover, several HIV vaccines are under evaluation that are designed to reduce viremia after acquisition of infection. Such vaccines could provide important benefits to delay HIV progression and to reduce trans-mission. The decision to license a vaccine on the basis of observed effects on virus load and other postinfection surrogate end points in an efficacy trial is complicated by uncertainty about whether the vaccine effects will persist and reliably predict clinical effects, and by the challenge in interpreting the data posed by treatment of some seroconverters with antiretroviral drugs. Here, we evaluate how analyses of certain surrogate end points can be used for inferring clinically significant vaccine effects and propose end points that could be evaluated in efficacy trials to support licensure. The assessment suggests that a vaccine demonstrating mod-erately durable effects to delay therapy and to ameliorate viremia merits consideration for licensure. Applied widely, a vaccine highly effective in durably preventing acquisition of most human immunodefi-ciency virus (HIV) strains would extinguish the HIV epidemic [1–3]. However, initial vaccines designed to reduce HIV acquisition are likely to demonstrate mod