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，个性化的选择 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。 国家癌症研究所（https：//www.cancer.gov/about-nci/cancert/plan/public-health）。二、坚持吸烟 在一般人群和PLWHA中，停止用药很少超过60%， 降低戒烟率2-3倍。我们开发了管理问题解决（MAPS）干预， 经疾病预防控制中心（https：//www.cdc.gov/hiv/research/interventionresearch/compendium/ma/index.html）认可， 对艾滋病毒/艾滋病感染者的药物依从性进行循证干预。因此，应用程序的前提是 将干预成分与核磁共振结合， 使用MAPS增加对药物的依从性将优化PLWHA的烟草治疗。为了验证这一 在此前提下，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）NMR定制和/或MAPS干预对最终结果的影响， 治疗结束（EOT）和6个月戒烟率（主要目的）; 2）NMR定制和 MAPS干预措施（次要目标）;以及3）国家监测报告定制干预措施和MAPS干预措施的调节人 （探索性目标）。我们的整体方法与多阶段优化策略一致， 在指导评估提高烟草使用治疗有效性的干预措施方面具有突出地位。 实现这些目标将决定：使用依从性和药物遗传学优化吸烟 停止治疗PLWHA，这些优化策略的作用机制， 停止结果，以及这些优化策略在不同的子组中的影响的变化。 PLWHA。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， 以确保他们充分使用这种药物，优化这一人群的戒烟治疗。

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 (https://www.cancer.gov/about-nci/budget/plan/public-health). 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 (https://www.cdc.gov/hiv/research/interventionresearch/compendium/ma/index.html) 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.