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进展是一个基本的悬而未决的问题，具有深远的公共卫生影响。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普遍。动物研究表明，在感染早期大量饮酒有可能加速艾滋病毒疾病的进展。然而，人类饮酒对艾滋病毒疾病进展的观察性研究结果，除了对抗逆转录病毒治疗（ART）依从性的影响外，由于一些方法上的限制，一致性要差得多。我们提出了一项650人的前瞻性队列研究，以检查在ART之前大量饮酒对HIV疾病进展的影响。我们将在乌干达进行这项研究，乌干达有非常高的饮酒水平，HIV感染率高，许多HIV感染者尚未接受ART。在乌干达进行的一项210人前瞻性队列研究的扩展。主要目标是确定大量饮酒对HIV疾病进展的影响，通过尚未接受ART的患者中CD4细胞计数下降来衡量。我们将克服以前的方法学限制，将我们的研究限制在未接受ART的患者中，通过使用饮酒的生物标志物磷脂酰乙醇（PEth）来正确评估饮酒，并通过在乌干达进行研究，其他物质的使用很少。我们将对大量饮酒可能加速HIV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，我们将获得大量饮酒对未接受抗逆转录病毒治疗的人的HIV感染临床过程的影响的关键证据，这将为临床医生和患者提供明确的信息，并可能在美国和世界各地提供比以前认为必要的更早减少饮酒的动机。此外，更好地了解酒精引起的损害发生的机制将为制定有效的干预措施提供信息。

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.