Goldenthal K L, Vaillancourt J M, Geber A, Lucey D R
Division of Vaccines and Related Products Applications,Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA.
AIDS Res Hum Retroviruses. 1998 Oct;14 Suppl 3:S333-40.
The clinical development of a human immunodeficiency virus (HIV) vaccine should be planned so that adequate safety and efficacy data can be obtained in an efficient manner to permit a risk/benefit assessment. Phase 1 and 2 studies should support the selection of an appropriate vaccine formulation, dose and schedule for evaluation in efficacy trials. Evaluation of the immune response(s) elicited by an HIV vaccine has an important role, even early in clinical development. Immune assay results and viral detection/quantitation technology may be used to identify and characterize HIV infections occurring during the trials. Thus, information about the performance parameters of these assays is important. Considerable research and development may be needed in this regard, especially when multiple endemic HIV-1 subtypes (clades) are expected. Prior to initiating an efficacy trial, background epidemiological information (e.g., recent seroincidence, endemic clades), as well as safety and immunogenicity data with the candidate vaccine, should be obtained in the intended efficacy trial population. The effects of antiretroviral therapy use and sensitive viral detection assays on the evaluation of the primary efficacy end point (as well as secondary end points) are important considerations. The detailed statistical plan for an efficacy trial should consider the 95% confidence limits on the estimate of vaccine efficacy; this may be of exceptional importance when relatively low point estimates of efficacy are expected.
人类免疫缺陷病毒（HIV）疫苗的临床开发应进行规划，以便能够高效获取充分的安全性和有效性数据，从而进行风险/效益评估。1期和2期研究应为选择合适的疫苗配方、剂量和给药方案以进行疗效试验评估提供支持。即使在临床开发早期，评估HIV疫苗引发的免疫反应也具有重要作用。免疫测定结果以及病毒检测/定量技术可用于识别和表征试验期间发生的HIV感染。因此，了解这些测定的性能参数很重要。在这方面可能需要进行大量的研发工作，尤其是当预计存在多种地方性HIV-1亚型（分支）时。在启动疗效试验之前，应在预期的疗效试验人群中获取背景流行病学信息（例如，近期血清发生率、地方性分支）以及候选疫苗的安全性和免疫原性数据。抗逆转录病毒疗法的使用和灵敏的病毒检测测定对主要疗效终点（以及次要终点）评估的影响是重要的考虑因素。疗效试验的详细统计计划应考虑疫苗效力估计值的95%置信区间；当预计效力的点估计值相对较低时，这可能尤为重要。
