Gilbert Peter B, DeGruttola Victor G, Hudgens Michael G, Self Steven G, Hammer Scott M, Corey Lawrence
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, University of Washington, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
J Infect Dis. 2003 Jul 15;188(2):179-93. doi: 10.1086/376449. Epub 2003 Jul 1.
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.
最初的人类免疫缺陷病毒（HIV）疫苗不太可能在所有接种者中预防HIV感染。此外，有几种HIV疫苗正在评估中，其设计目的是在感染后降低病毒血症。这类疫苗对于延缓HIV病情发展和减少传播可能具有重要益处。在疗效试验中，基于观察到的对病毒载量及其他感染后替代终点的影响来决定疫苗是否获批，这一过程因疫苗效果能否持续并可靠地预测临床效果存在不确定性，以及在解释某些血清转化者接受抗逆转录病毒药物治疗所带来的数据挑战而变得复杂。在此，我们评估如何利用对某些替代终点的分析来推断具有临床意义的疫苗效果，并提出可在疗效试验中评估以支持获批的终点指标。评估表明，一种能展现出适度持久效果以延缓治疗并改善病毒血症的疫苗值得考虑获批。
