Follmann Dean, Duerr Ann, Tabet Stephen, Gilbert Peter, Moodie Zoe, Fast Patricia, Cardinali Massimo, Self Steve
National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
J Acquir Immune Defic Syndr. 2007 Jan 1;44(1):49-60. doi: 10.1097/01.qai.0000247227.22504.ce.
A successful HIV vaccine would have a substantial impact on acquisition of infection, progression of disease among the infected, or infectiousness of the infected. Current vaccine candidates are anticipated to have their major effect on viremia, however, with the expectation that this would induce or be concordant with a reduced rate of AIDS, death, or infectiousness. Although direct assessment of disease progression or infectiousness may be impractical, available potential surrogates for these endpoints may be misleading. This article summarizes the proceedings of a National Institute of Allergy and Infectious Disease-sponsored workshop to explore the use of surrogate endpoints for licensure of an HIV vaccine. Early, medium, and late endpoints were discussed, along with challenges such as surrogate validity, the confounding effect of antiretroviral therapy initiation, and potential selection bias in the vaccine and placebo recipients who become infected. Results from 5 hypothetic HIV vaccine clinical trials with ambiguously successful results were presented to an expert panel for interpretation and discussion of next steps. Key recommendations included assessing magnitude and durability of surrogate effects, generalization across populations, and directed improvement of vaccines. Use of acquisition and a postinfection surrogate as coprimary endpoints was supported, along with use of composite endpoints and exploration of heterogeneity in vaccine efficacy by characteristics of the host and virus.
一种成功的HIV疫苗将对感染的获得、感染者疾病的进展或感染者的传染性产生重大影响。然而，目前的候选疫苗预计主要作用于病毒血症，期望这将诱导艾滋病发病率、死亡率或传染性降低，或与之相一致。尽管直接评估疾病进展或传染性可能不切实际，但这些终点的现有潜在替代指标可能会产生误导。本文总结了美国国立过敏和传染病研究所主办的一次研讨会的会议记录，该研讨会旨在探讨使用替代终点来批准HIV疫苗。讨论了早期、中期和晚期终点，以及诸如替代指标有效性、抗逆转录病毒治疗开始的混杂效应，以及疫苗和感染的安慰剂接受者中潜在的选择偏倚等挑战。将5项结果模棱两可的假设性HIV疫苗临床试验的结果提交给一个专家小组，以供解释和讨论下一步措施。主要建议包括评估替代效应的大小和持续性、在不同人群中的普遍性，以及针对性地改进疫苗。支持将感染获得和感染后替代指标用作共同主要终点，同时支持使用复合终点，并按宿主和病毒特征探索疫苗效力的异质性。
