Biomarkers for Alcohol/HIV Research (BAHR) Study

摘要 酗酒在艾滋病毒(PWH)携带者中很常见，并且是抗逆转录病毒能力差的一贯预测指标 坚持治疗(ART)。它还与艾滋病毒病毒学失败和死亡率有关，但这些结果 有些复杂，酒精使用水平和这些结果之间的关系并不是 定义得很清楚。在威斯康星医院中减少酒精使用的干预措施显示出适度或喜忧参半的结果。因此， 对威尔斯亲王造成伤害所需的酒精使用水平和减少伤害的干预措施的效果是 不确定。这种不确定性部分源于人们几乎无处不在地依赖自我报告来测量酒精含量 使用，可能由于回忆偏差或社会合意性偏差而不准确，并导致虚假或模糊 结果，以及不一致的酒精测量。客观的生物标志物可以用来补充 自我报告或作为自我报告的替代方案。主要的酒精生物标志物是磷脂酰乙醇酯(Peth)，它 可在全血或干血斑点中发现，检测到之前2-4周饮酒，并与 总饮酒量。威尔斯亲王医院的几项研究已经或计划进行PEH测试， 这是一个前所未有的机会，可以将大量的观察结果与peth和HIV数据结合在一起 为这些问题提供明确的答案。我们提出了酒精/艾滋病毒研究的生物标志物 (巴赫尔)研究收集和汇集这些数据，其中将包括8,000多个威尔斯亲王医院和15,000个 观察，并使用PEH来解决过去酒精/艾滋病毒研究的不确定性，以指导未来的干预措施， 并为今后的研究提供测量指导。我们将确定佩斯和佩斯之间的关系- 使用以下数据在接受抗逆转录病毒治疗的PWH患者中测量酒精使用和艾滋病毒病毒学失败和死亡风险 六项研究(目标1)。我们将进行酒精/艾滋病毒干预的个体参与者数据荟萃分析 研究(15项已同意参与)，以检查干预措施有效性的证据，以减少心肺疾病。 量度酒精使用及其对病毒学失败的进一步影响(目标2)。为了这两个目标，我们将 将单独使用PEH和仅使用自我报告以及将自我报告与 Peth，以指导未来研究中的酒精测量。最后，因为佩斯价格昂贵，而且在 在低资源和非研究背景下，我们将结合常见的预测价值进行考察 实验室测试作为peth测试的低成本替代方案，利用在 6000人研究(目标3)。这些分析将为酒精/艾滋病毒领域提供切实的进展， 即关于酒精使用与艾滋病毒病毒学失败和死亡风险的关系的明确答案； 减少酒精使用和减少病毒学失败的酒精干预研究的有效性；关于 使用生物标记物和自我报告来测量酒精使用的结果的可比性； 低成本酒精风险评分对进一步测试的预测能力和潜在的可获得性 低资源和非研究环境。

ABSTRACT Alcohol use is common among people living with HIV (PWH) and is a consistent predictor of poor antiretroviral therapy (ART) adherence. It has also been associated with HIV virologic failure and mortality, but these results have been somewhat mixed and the relationships between level of alcohol use and these outcomes are not well defined. Interventions to reduce alcohol use among PWH have shown modest or mixed results. Thus, the level of alcohol use needed to cause harm for PWH and the efficacy of interventions to reduce the harm are uncertain. This uncertainty stems in part from the near ubiquitous reliance on self-report to measure alcohol use, which may be inaccurate due to recall bias or social desirability bias and lead to spurious or obscured results, and from inconsistent alcohol measurement. Objective biomarkers can be leveraged to supplement self-report or as alternatives to self-report. The leading alcohol biomarker is phosphatidylethanol (PEth), which can be found in whole blood or dried blood spots, detects prior 2-4 weeks alcohol use, and is correlated with total alcohol consumed. Several research studies of PWH have conducted or plan to conduct PEth testing, making possible an unprecedented opportunity to pool a large number of observations with PEth and HIV data to provide definitive answers to these questions. We propose the Biomarkers for Alcohol/HIV Research (BAHR) Study to gather and pool these data, which will include more than 8,000 PWH with 15,000 observations, and use PEth to resolve past alcohol/HIV research uncertainties, to guide future interventions, and to provide measurement guidance for future research. We will determine the relationship between PEth- measured alcohol use and HIV virologic failure and mortality risk among PWH who are on ART using data from six studies (Aim 1). We will conduct individual participant data meta-analyses of alcohol/HIV intervention studies (15 have agreed to participate) to examine evidence of the efficacy of the interventions to reduce PEth- measured alcohol use, and their further impact on virologic failure (Aim 2). For both these aims, we will compare the results using PEth alone to those obtained using self-report alone, and self-report combined with PEth, to guide future alcohol measurement in research. Lastly, because PEth is expensive and inaccessible in low-resource and non-research settings, we will examine the predictive value of a combination of common laboratory tests as a low-cost alternative to PEth testing, leveraging the extensive testing being conducted in a 6000-person study (Aim 3). These analyses will provide tangible advancements for the alcohol/HIV field, namely definitive answers on the relationship of alcohol use to HIV virologic failure and mortality risk; the efficacy of alcohol interventions studies to reduce alcohol use and decrease virologic failure; information on the comparability of results using biomarkers versus self-report to measure alcohol use; and evidence on the predictive ability of a low-cost alcohol risk score for further testing and potential increased availability in low-resource and non-research settings.