Biomarkers for Alcohol/HIV Research (BAHR) Study

酒精/艾滋病毒研究生物标志物 (BAHR) 研究

基本信息

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
项目类别：
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

项目摘要

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.

抽象的饮酒在艾滋病毒感染者 (PWH) 中很常见，并且是抗逆转录病毒治疗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，但这些结果酒精使用水平与这些结果之间的关系有些复杂定义明确。减少感染者饮酒的干预措施显示出适度或好坏参半的结果。因此，对感染者造成伤害所需的饮酒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几乎普遍依赖自我报告来测量酒精含量使用，由于回忆偏差或社会期望偏差可能不准确，并导致虚假或模糊结果，以及酒精测量不一致。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)，它可以在全血或干血斑中发现，检测之前 2-4 周的饮酒情况，并与饮酒总量。 PWH 的多项研究已经进行或计划进行 PEth 测试，为将大量观察结果与 PEth 和 HIV 数据汇集在一起提供了前所未有的机会为这些问题提供明确的答案。我们提出用于酒精/艾滋病毒研究的生物标志物 (BAHR) 研究收集和汇总这些数据，其中将包括 8,000 多名感染者和 15,000 名感染者观察，并利用 PEth 解决过去酒精/艾滋病毒研究的不确定性，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- 之间的关系使用来自 ART 的数据测量了接受 ART 的 PWH 的饮酒情况以及 HIV 病毒学失败和死亡风险六项研究（目标 1）。我们将对酒精/艾滋病毒干预措施的个体参与者数据进行荟萃分析研究（15 项已同意参与）旨在检验干预措施对减少 PEth-的有效性的证据测量酒精使用情况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 PEth 的结果与单独使用自我报告以及自我报告与自我报告相结合获得的结果进行比较 PEth，指导未来研究中的酒精测量。最后，由于 PEth 价格昂贵且难以获得在资源匮乏和非研究环境中，我们将检查常见的组合的预测价值实验室测试作为 PEth 测试的低成本替代方案，利用在实验室进行的广泛测试 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步，即饮酒与艾滋病毒病毒学失败和死亡风险之间关系的明确答案；这酒精干预研究对减少饮酒和减少病毒学失败的功效；有关的信息使用生物标志物与自我报告测量酒精使用情况的结果的可比性；和证据低成本酒精风险评分的预测能力，用于进一步测试和潜在增加的可用性资源匮乏和非研究环境。