title: What constitutes efficacy for a human immunodeficiency virus vaccine that ameliorates viremia: issues involving surrogate end points in phase 3 trials.
abstract: Initial human immunodeficiency virus (HIV) vaccines are unlikely to prevent acquisition of HIV in all recipients. 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 transmission. 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 moderately durable effects to delay therapy and to ameliorate viremia merits consideration for licensure.
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, University of Washington, 1100 Fairview Avenue North, Seattle, WA 98109, USA. pgilbert@scharp.org
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: Victor G
authors.initials: VG
authors.lastname: DeGruttola
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003657:Decision Making; D018450:Disease Progression; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D008004:Licensure; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D016915:AIDS Vaccines; D015415:Biomarkers