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（PWH）的患者中很常见，并且是抗逆转录病毒较差的一致预测指标治疗（艺术）依从性。它也与HIV病毒学衰竭和死亡率有关，但是这些结果有些混杂，酒精使用水平与这些结果之间的关系不是定义很好。减少PWH中饮酒的干预措施显示出适度或混合的结果。因此，造成PWH危害所需的饮酒水平以及减少危害的干预措施的功效是不确定。这种不确定性部分源于对自我报告的几乎无处不在的依赖，以衡量酒精使用，由于召回偏见或社会可取性偏见而可能不准确，并导致虚假或掩盖结果，以及不一致的酒精测量。客观的生物标志物可以被利用以补充自我报告或作为自我报告的替代方案。领先的酒精生物标志物是磷脂酰乙醇（Peth），它可以在全血或干血处发现，检测到之前2-4周的酒精使用，并与总酒精消耗。 PWH的几项研究已经进行或计划进行Peth测试，通过Peth和HIV数据汇总大量观察的前所未有的机会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）收集和汇集这些数据的研究，其中包括8,000多个PWH，15,000 观察并使用Peth解决过去的酒精/艾滋病毒研究不确定性，以指导未来的干预措施，并为将来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PWH，使用来自ART的PWH的酒精使用和HIV病毒衰竭和死亡风险六项研究（目标1）。我们将进行酒精/艾滋病毒干预的单个参与者数据荟萃分析研究（15项同意参加），以检查干预措施减少Peth-的功效的证据测量的酒精使用及其对病毒学衰竭的进一步影响（AIM 2）。对于这两个目标，我们都会比较单独使用Peth的结果与单独使用自我报告获得的结果，并与自我报告合并 Peth，指导研究中未来的酒精测量。最后，因为佩斯很昂贵且无法访问低资源和非研究设置，我们将研究共同组合的预测价值实验室测试是Peth测试的低成本替代方案，利用在A中进行的广泛测试 6000人研究（AIM 3）。这些分析将为酒精/艾滋病毒领域提供切实的进步，即关于酒精使用与HIV病毒学衰竭和死亡率风险的关系的确切答案；这酒精干预研究的功效减少酒精使用并减少病毒学衰竭；信息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；和证据低成本酒精风险评分进一步测试的预测能力和潜在的增加的可用性低资源和非研究设置。