Testing Novel Pharmacogenetic and Adherence Optimization Treatments to Improve the Effectiveness of Smoking Cessation Treatments for Smokers with HIV

针对艾滋病毒/艾滋病感染者的抗逆转录病毒疗法的出现大大改善了生活 但是，现在，吸烟的艾滋病毒感染者由于烟草使用而失去的生命年数超过了他们的艾滋病毒 感染不幸的是，美国艾滋病毒感染者中吸烟率约为40%。限制烟草使用 对PLWHA的治疗研究表明，行为治疗和药物（尼古丁贴片和 伐尼克兰）对戒烟产生中度影响，戒烟率大大低于 一般人口。因此，迫切需要确定优化戒烟治疗的新方法 吸烟者携带艾滋病病毒。两个因素高度预测药物治疗的戒烟结果， 一般人群和艾滋病毒/艾滋病感染者。首先，吸烟者的尼古丁代谢率，其特征在于 尼古丁代谢物比率（NMR，CYP 2A 6基因变异的标志物）预测伐尼克兰和 尼古丁贴片我们对普通人群和感染艾滋病毒的吸烟者的研究表明， 一种强调的方法是，使用核磁共振技术为吸烟者提供药物治疗可以提高疗效并减少毒性。 由NCI。第二，在一般人群和 艾滋病毒/艾滋病感染者和艾滋病患者很少超过60%，不坚持治疗会使戒烟率降低2-3倍。我们开发了 管理问题解决（MAPS）干预，这是由疾病预防控制中心作为一个基于证据的认可 对艾滋病毒感染者/艾滋病患者服药依从性的干预。因此，申请的前提是， 干预成分，以调整烟草使用药物（伐尼克兰或贴剂）与核磁共振，并增加 坚持使用MAPS的药物治疗将优化PLWHA的烟草治疗。为了验证这个假设，我们 将对488名HIV阳性吸烟者进行严格的多中心随机临床试验，以评估NMR- 定制治疗和MAPS作为PLWHA烟草依赖治疗的优化策略。我们 将使用析因设计来检查：1）针对国家监测报告和/或MAPS干预措施对 治疗（EOT）和6个月戒烟率（主要目的）; 2）NMR定制和 3）国家监测报告和MAPS干预措施的主持人 探索性目标（Exploration Objective）。我们的总体方法与多阶段优化策略一致 在指导评估促进烟草使用的干预措施方面， 治疗效果。实现这些目标将决定：使用依从性和药物遗传学 优化PLWHA的戒烟治疗，这些效果的机制 戒烟结果的优化策略，以及这些优化效果的变化 艾滋病毒/艾滋病感染者和艾滋病患者各亚组的战略。最后，这项试验将有助于了解，如果得到正确的 药物给正确的人，并帮助确保他们充分使用药物优化 为这一人群提供戒烟治疗。

The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life expectancy but, now, PLWHA who smoke lose more life-years due to tobacco use than they do to their HIV infection. Unfortunately, the rate of smoking among PLWHA in the US is about 40%. The limited tobacco use treatment research with PLWHA indicates that behavioral treatments and medications (nicotine patch and varenicline) yield moderate effects on cessation, with quit rates that are considerably lower than they are for the general population. Thus, there is a critical need to identify novel ways to optimize tobacco cessation treatment for smokers with HIV. Two factors are highly predictive of cessation outcomes with pharmacotherapy, in the general population and among PLWHA. First, a smoker's rate of nicotine metabolism, characterized by the nicotine metabolite ratio (NMR, a marker of CYP2A6 gene variants), predicts cessation both for varenicline and nicotine patch. Our studies with general population and HIV-infected smokers show that personalizing the choice of medications for smokers using the NMR can increase efficacy and reduce toxicities, an approach highlighted by the NCI. Second, adherence to smoking cessation medications, in the general population and among PLWHA, rarely exceeds 60% and non-adherence lowers cessation rates 2-3 fold. We developed the Managed Problem Solving (MAPS) intervention which is endorsed by the CDC as an evidence-based intervention for medication adherence among PLWHA. Thus, the application's premise is that incorporating intervention components to tailor tobacco use medications (varenicline or patch) with the NMR and increase adherence to the medication using MAPS will optimize tobacco treatments for PLWHA. To test this premise, we will conduct a rigorous multi-site randomized clinical trial with 488 HIV+ smokers to evaluate NMR- tailored treatment and MAPS as optimization strategies for tobacco dependence treatment for PLWHA. We will use a factorial design to examine: 1) The effects of the NMR-tailored and/or MAPS interventions on end-of- treatment (EOT) and 6-month smoking cessation rates (primary aim); 2) Mediators of the NMR-tailored and MAPS interventions (secondary aim); and 3) Moderators of the NMR-tailored and MAPS interventions (exploratory aim). Our overall approach is consistent with the Multiphase Optimization Strategy which has gained prominence for guiding the evaluation of interventions for enhancing tobacco use treatment effectiveness. Addressing these aims will determine: the use of adherence and pharmacogenetic optimization of smoking cessation treatment for PLWHA, the mechanisms that underlie the effects of these optimization strategies on cessation outcomes, and the variation in the effects of these optimization strategies across sub-groups of PLWHA. In the end, this trial will help understand if getting the right medication to the right person and helping to make sure they sufficiently use that medication optimizes tobacco cessation treatment for this population.