Biomarkers for Alcohol/HIV Research (BAHR) Study

酒精/艾滋病毒研究生物标志物 (BAHR) 研究

• 批准号: 10615910
• 负责人: JUDITH ALISSA HAHN
• 金额: $ 59.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615910
• 关键词: Affect; Age; Aging; Agreement; Alcohol consumption; Alcohols; Biological Markers; Biometry; Blood; Blood Tests; Cohort Studies; Consumption; Data; Data Pooling; Diagnostic; Dryness; Ethnic Origin; Failure; Future; Glucuronides; Goals; HIV; Harm Reduction; Health; Individual; Intervention; Intervention Studies; Intervention Trial; Laboratories; Measurement; Measures; Meta-Analysis; Metabolism; Metadata; Modification; Observational Study; Outcome; Participant; Patient Self-Report; Pattern; Persons; Population Heterogeneity; Populations at Risk; Predictive Value; Race; Randomized, Controlled Trials; Regimen; Reporting; Research; Research Design; Resources; Risk; Social Desirability; Spottings; Testing; Treatment Efficacy; Uncertainty; Urine; Veterans; Viral Load result; Whole Blood; alcohol intervention; alcohol measurement; alcohol misuse; alcohol risk; antiretroviral therapy; carbohydrate-deficient transferrin; clinical care; cohort; cost; efficacy evaluation; experience; indexing; mortality; mortality risk; phosphatidylethanol; predictive modeling; randomized trial; reduced alcohol use; research study; sex; stem; substance use; therapy adherence; tool

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.

摘要 饮酒在艾滋病毒感染者中很常见，是抗逆转录病毒效果不佳的一致预测因素 治疗（ART）依从性。它也与HIV病毒学失败和死亡率有关，但这些结果 有些混合，酒精使用水平与这些结果之间的关系不是 定义明确。减少PWH中酒精使用的干预措施显示出适度或混合的结果。因此 对PWH造成伤害所需的酒精使用水平以及减少伤害的干预措施的有效性 不确定这种不确定性部分源于人们几乎普遍依赖自我报告来测量酒精含量 使用，这可能是不准确的，由于回忆偏见或社会期望偏见，并导致虚假或模糊 结果，以及不一致的酒精测量。可以利用客观生物标志物来补充 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（PEth）， 可以在全血或干血斑中发现，检测之前2-4周的酒精使用，并与 总酒精消耗量PWH的几项研究已经进行或计划进行PEth测试， 这使得汇集大量PEth和HIV数据的观察结果成为可能， 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 （BAHR）收集和汇总这些数据的研究，其中将包括8，000多个PWH和15，000个 观察，并使用PEth来解决过去的酒精/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PEth之间的关系- 使用以下数据测量接受抗逆转录病毒治疗的PWH中的酒精使用和艾滋病毒病毒学失败及死亡风险： 6项研究（目标1）。我们将对酒精/艾滋病干预的个体参与者数据进行荟萃分析 研究（15项已同意参与），以检查干预措施降低PEth的有效性的证据， 测量的酒精使用，以及它们对病毒学失败的进一步影响（目标2）。为了实现这两个目标，我们将 将单独使用PEth的结果与单独使用自我报告以及自我报告与 PEth，以指导未来的酒精测量研究。最后，由于PEth价格昂贵， 低资源和非研究设置，我们将研究的预测价值的组合，共同 实验室测试作为PEth测试的低成本替代品，利用在 6000-个人研究（目标3）。这些分析将为酒精/艾滋病毒领域提供切实的进展， 即关于饮酒与艾滋病毒学失败和死亡风险之间关系的明确答案; 酒精干预研究对减少酒精使用和减少病毒学失败的有效性; 使用生物标志物与自我报告测量酒精使用的结果的可比性;以及 低成本酒精风险评分对进一步测试的预测能力和潜在的增加可用性， 低资源和非研究环境。