Impact of Heavy Alcohol Use on Pre-ART HIV Disease - Uganda ARCH Cohort

描述(由申请人提供)：大量饮酒是否会加速艾滋病毒疾病的发展是一个具有深远公共卫生影响的基本问题，尚未得到解答。酒精是世界上最常用的药物之一，大量饮酒在艾滋病毒感染者中非常常见。动物研究表明，在感染早期大量饮酒可能会加速艾滋病毒疾病的进展。然而，除了对抗逆转录病毒治疗(ART)坚持的影响外，人类对饮酒对艾滋病毒疾病进展的观察研究的结果由于几个方法学的限制而不太一致。我们建议进行一项650人的前瞻性队列研究，在抗逆转录病毒治疗前检查大量饮酒对HIV疾病进展的影响。我们将在乌干达进行这项研究，乌干达的酒精消费水平非常高，艾滋病毒感染率很高，许多艾滋病毒感染者尚未接受抗逆转录病毒治疗。参与者进行前瞻性研究，将从乌干达的8000名患者艾滋病毒治疗计划中招募，作为新启动的210人前瞻性队列研究的扩展。主要目标是确定大量饮酒对艾滋病毒疾病进展的影响，这是通过尚未接受抗逆转录病毒治疗的人的CD4细胞计数下降来衡量的。我们将克服以前的方法局限性，将我们的研究限制在那些不使用ART的人，通过使用酒精消费的生物标记物磷脂酰乙醇(PEH)，正确地评估酒精消费，以及通过在乌干达进行这项研究，那里很少使用其他物质。我们将对大量饮酒可能加速艾滋病毒疾病进展的几种生物和行为途径进行探索性分析。在进行这项研究时，我们将获得关键证据，证明在美国和世界各地，大量饮酒对非抗逆转录病毒治疗患者的HIV感染临床过程的影响，将为临床医生和患者提供明确的信息，并可能提供比之前认为必要的更早减少酒精消费的动力。此外，更好地了解酒精引起的损害发生的机制将有助于开发有效的干预措施。

DESCRIPTION (provided by applicant): Whether heavy alcohol consumption accelerates HIV disease progression is a fundamental unanswered question with far-reaching public health implications. Alcohol is one of the most commonly used drugs in the world, and heavy alcohol consumption is very common among those infected with HIV. Animal studies suggest that heavy alcohol consumption early in infection has the potential to accelerate HIV disease progression. However, the results of human observational studies of alcohol consumption on HIV disease progression, beyond the effect on antiretroviral therapy (ART) adherence, have been much less consistent due to several methodological limitations. We propose a 650-person prospective cohort study to examine the effect of heavy alcohol consumption on HIV disease progression prior to ART. We will conduct this research in Uganda, which has very high levels of alcohol consumption, high prevalence of HIV infection, and many HIV-infected persons not yet on ART. Participants, studied prospectively, will be recruited from an 8,000 patient HIV treatment program in Uganda as an expansion of a newly initiated 210 person prospective cohort study. The main goal is to determine the impact of heavy alcohol consumption on HIV disease progression, as measured by CD4 cell count decline among those not yet on ART. We will overcome previous methodological limitations by limiting our study to those not on ART, by using a biomarker of alcohol consumption, phosphatidylethanol (PEth), to correctly assess alcohol consumption, and by conducting the study in Uganda, where other substance use is rare. We will conduct exploratory analyses of several biological and behavioral pathways by which heavy alcohol consumption may accelerate HIV disease progression. In conducting this study, we will gain critical evidence of the impact of heavy alcohol use on the clinical course of HIV infection among persons not on ART that will provide clinicians and patients with clear information and may provide motivation to reduce alcohol consumption earlier than previously thought necessary, both in the US and around the world. In addition, better understanding of the mechanisms by which alcohol-induced damage occurs will inform the development of effective interventions.