Safety and Comparative Effectiveness of New Medications for Unhealthy Alcohol Use in HIV

描述(由申请人提供)：不健康的饮酒威胁艾滋病毒感染者的健康。Varenicline、加巴喷丁和托吡酯减少了未感染艾滋病毒患者的酒精消费，并显示出解决艾滋病毒感染患者使用不健康酒精的前景。这些药物中的每一种都被批准并用于治疗非酒精相关疾病(例如吸烟、神经性疼痛和癫痫)，可能会导致不良的临床结果。Varenicline可能与精神症状和心血管并发症有关。加巴喷丁和托吡酯会引起头晕和镇静。到目前为止，还没有研究这些药物的使用与不良临床结果之间的联系，或者这些药物对艾滋病毒感染患者使用不健康酒精的比较有效性。在广泛评估或使用这些药物治疗艾滋病毒感染患者的不健康饮酒行为之前，进行此类研究是至关重要的。大型临床数据集，如NIAAA资助的退伍军人老龄化队列-虚拟队列(VAS-VC)，包含有关处方、酒精消费、抑郁症状、化验值和诊断的信息，为研究这些药物在艾滋病毒感染患者和未感染对照患者中的安全性和比较有效性提供了机会。接受了varenicline(1235)、加巴喷丁(10,193)和托吡酯(914)的Vacs-VC艾滋病毒感染者的人数为检查安全性和比较有效性提供了一个独特的机会。这项研究的具体目的是：根据艾滋病毒状况，确定与使用varenicline、加巴喷丁和托吡酯相关的不良临床结局的发生率(目标1)，比较varenicline、加巴喷丁和托吡酯对艾滋病毒感染患者和未感染患者AUDIT-C评分的个体有效性(目标2)，以及比较varenicline、加巴喷丁和托吡酯对HIV感染患者的CD4、病毒载量和Vacs指数的个体有效性(目标3)。我们将进行倾向分数匹配分析(目标1-3)，对于目标3，我们将进行中介分析，以调查观察到的变化在多大程度上是由酒精变化所调节的。这一系列研究是在一大批感染艾滋病毒和未感染艾滋病毒的对照人群中进行的，这一系列研究将提供必要的关键信息，为艾滋病毒感染患者实施这些不健康的饮酒药物提供信息。

DESCRIPTION (provided by applicant): Unhealthy alcohol use threatens the health of HIV-infected individuals. Varenicline, gabapentin, and topiramate decrease alcohol consumption in HIV uninfected patients and show promise to address unhealthy alcohol use in HIV-infected patients. Each of these medications, approved and used for the treatment of non-alcohol-related conditions (e.g. smoking, neuropathic pain, and epilepsy), may cause adverse clinical outcomes. Varenicline may be associated with psychiatric symptoms and cardiovascular complications. Gabapentin and topiramate can cause dizziness and sedation. To date, studies have not examined the association between the use of these medications and adverse clinical outcomes or the comparative effectiveness of these medications for unhealthy alcohol use in HIV-infected patients. It is essential to conduct such studies prior to the widespread evaluation or use of these medications for unhealthy alcohol use in HIV-infected patients. Large clinical datasets, such as the NIAAA-funded Veterans Aging Cohort-Virtual Cohort (VACS-VC) with information on prescriptions, alcohol consumption, depressive symptoms, laboratory values and diagnoses provide the opportunity to investigate the safety and comparative effectiveness of these medications in HIV-infected patients and uninfected comparators. The number of VACS-VC HIV-infected individuals who have received varenicline (1235), gabapentin (10,193) and topiramate (914) presents a unique opportunity to examine safety and comparative effectiveness. The specific aims of this research are to: Determine the incidence of adverse clinical outcomes, by HIV status, associated with the use of varenicline, gabapentin and topiramate (Aim 1), Compare the individual effectiveness of varenicline, gabapentin and topiramate on AUDIT-C scores in HIV- infected and uninfected patients (Aim 2), and Compare the individual effectiveness of varenicline, gabapentin and topiramate on CD4, viral load and the VACS-Index in HIV- infected patients (Aim 3). We will conduct propensity score matched analysis (Aims 1-3) and for Aim 3 we will conduct mediation analyses to investigate the extent to which observed changes are mediated by changes in alcohol. This line of research, conducted in a large and well-characterized cohort of HIV-infected and HIV-uninfected comparators, will provide critical information that is necessary to inform implementation of these medications for unhealthy alcohol use in HIV-infected patients.