The potential role of biomarkers in HIV preventive vaccine trials.
The potential role of biomarkers in HIV preventive vaccine trials.
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DOI：
10.1097/qai.0b013e3181adcbbe
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Duerr A
中科院分区：
文献类型：
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作者：
Maclachlan E;Mayer KH;Barnabas R;Sanchez J;Koblin B;Duerr A
成功开展艾滋病毒疫苗功效试验需要确定和纳入高危人群，评估作为预防艾滋病毒感染和改善受感染疫苗接种者疾病进程的疫苗功效措施的适当终点，以及确定潜在的混杂因素或效果修饰因素。虽然并非总是有用的，并且在测量和验证方面带来了自己的成本，但各种生物标志物可能在试验进行的每个阶段提供帮助。根据质量、生物标志物与艾滋病毒疫苗试验的相关性以及出版物的可得性，对选定的文章进行了审查。作者还从目前的试验和其他计划中的或正在进行的试验中吸取了经验。生物标志物可用于评估潜在研究人群中的HIV发病率，但在解释这些检测结果时需要注意。在试验过程中，诸如HSV-2之类的性传播感染可能作为主要和次要终点的效果调节剂，包括HIV发病率和设定点病毒载量。性传播感染生物标志物的使用可能在很大程度上取决于临床试验点的当地流行病学。最近大型艾滋病毒疫苗疗效试验的分析指出了解释试验结果的复杂性，并强调了生物标志物在评估混淆和效果修饰方面的潜在效用。
Successful conduct of HIV vaccine efficacy trials entails identification and enrollment of at-risk populations, assessment of appropriate endpoints as measures of vaccine efficacy for prevention of HIV acquisition and amelioration of disease course among infected vaccinees, as well as identification of potential confounders or effect modifiers. While not invariably useful and bringing their own cost in terms of measurement and validation, a variety of biomarkers may aid at each stage of trial conduct. A review of selected articles, chosen based on quality, relevance of the biomarker to HIV vaccine trials, and availability of the publication, was conducted. The authors also drew experience from current trials and other planned or ongoing trials. Biomarkers are available to assess HIV incidence in potential study populations but care is needed in interpreting results of these assays. During trial conduct, STIs such as HSV-2 may act as effect modifiers on primary and secondary endpoints, including HIV incidence and set point viral load. The utility of STI biomarkers will likely depend heavily on local epidemiology at clinical trial sites. Analyses from recent large HIV vaccine efficacy trials point to the complexities in interpreting trial results and underscore the potential utility of biomarkers in evaluating confounding and effect modification.