Alcohol use and ARV treatment outcomes in Uganda

乌干达的饮酒和抗逆转录病毒治疗结果

• 批准号: 6942266
• 负责人: DAVID Roy BANGSBERG
• 金额: $ 37.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6942266
• 关键词: AIDS therapy; Africa; African; Asians; HIV infections; alcoholic beverage consumption; clinical research; combination chemotherapy; drug interactions; drug resistance; ethanol; human subject; lamivudine; nevirapine; patient oriented research; pharmacokinetics; stavudine; therapy compliance

DESCRIPTION (provided by applicant): Suboptimal antiretroviral exposure is an important predictor of clinical outcome and may be due to incomplete adherence or pharmacokinetic variability. Alcohol is one of the most consistent predictors of non-adherence in resource rich-settings and is the drug of choice in resource-limited settings. Alcohol may also impact antiretroviral drug exposure through adherence and/or changes in CYP 3A metabolism of antiretroviral medications. Inadequate viral suppression through impaired adherence, treatment discontinuation/rationing, or pharmacokinetic alterations may lead to rapid viral resistance. While the predictors of adherence are well known in resource-rich settings, little is known about the correlates of adherence behavior in resource-limited settings, particularly sub-Saharan Africa. Less is known about the pharmacokinetics of generic antiretroviral therapy in African patients. There is no data on how alcohol may impact adherence, treatment duration, or pharmacokinetics and development of resistance in resource-limited settings. Since it is the most commonly abused substance in resource-limited settings, it is important to know how alcohol may impact these important treatment outcomes. We have developed valid and objective adherence measures in patients receiving HIV antiretroviral therapy in Kampala, Uganda, and we propose to recruit 174 patients in three alcohol strata to determine the impact of alcohol use on adherence and pharmacokinetics of generic Triomune (D4T/3TC/NVP) antiretroviral therapy over 12 months of observation. Triomune is an ideal medication to study adherence, may have important pharmacokinetic interactions with alcohol, and possesses an adherence resistance relationship not seen with other antiretrovirals. The specific aims of this study are to: 1) determine whether increased severity of alcohol use is associated with lower levels of adherence to and treatment interruptions/discontinuations of Triomune therapy, 2) determine the effect of alcohol use on pharmacokinetics of Triomune therapy, 3) determine the impact of alcohol use on HIV viral suppression mediated through adherence to and pharmac0kinetics of Triomune therapy, and 4) determine the impact of alcohol use on Triomune antiretroviral drug resistance mediated through adherence, treatment duration, and pharmacokinetics. This research will be an essential first step to determine the impact of alcohol on treatment outcomes to expanding antiretroviral therapy in sub-Saharan Africa.

描述（由申请人提供）：次优的抗逆转录病毒暴露是临床结果的重要预测指标，可能是由于不完全依从性或药代动力学变异性所致。酒精是资源丰富储备中不遵守的最一致性预测因素之一，并且是资源有限环境中首选的药物。酒精还可以通过依从性和/或CYP 3A代谢的抗逆转录病毒药物的变化影响抗逆转录病毒药物。通过依从性受损，治疗停止/配给或药代动力学改变可能导致病毒抗性的迅速抗性，病毒抑制不足。尽管依从性的预测因素在资源丰富的环境中是众所周知的，但对于资源有限的环境，尤其是撒哈拉以南非洲的依从性行为的相关性知之甚少。对于非洲患者的通用抗逆转录病毒疗法的药代动力学知之甚少。没有关于酒精如何影响依从性，治疗持续时间或药代动力学的数据，以及在资源有限的环境中的耐药性发展。由于它是在资源有限的环境中最常见的滥用物质，因此重要的是要知道酒精如何影响这些重要的治疗结果。我们已经在乌干达坎帕拉接受HIV抗逆转录病毒疗法的患者制定了有效和客观的依从性指标，我们建议在三个酒精阶层招募174名患者，以确定酒精使用对依从性和药代动力学对通用Tromune的影响（D4T/3TC/NVP）Antiretroviral Therapy以外的预疗法。 Triomune是研究依从性的理想药物，可能与酒精具有重要的药代动力学相互作用，并且具有与其他抗逆转录病毒的依从性关系。这项研究的具体目的是：1）确定饮酒的严重程度是否与较低的依从性和治疗中断和治疗中断有关/三位一治疗的中断/不连续性，2）确定酒精使用对三膜治疗的药代动力学对通过对HIV病毒抑制的影响和药物抑制作用的影响和药物抑制的影响，并确定Trii Accriencation trii trii trii trii trii trii trii trii a）的影响，Trii trii trii sysics tri trii tri trii tri trii tri tri trii tri tri tri tri tri tri tri tri a）trii for tri a）通过依从性，治疗持续时间和药代动力学介导的三元抗逆转录病毒耐药性。这项研究将是确定酒精对撒哈拉以南非洲抗逆转录病毒疗法的治疗结果影响的重要第一步。