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

测试新型药物遗传学和依从性优化治疗，以提高艾滋病毒吸烟者戒烟治疗的有效性

• 批准号: 10818945
• 负责人: ROBERT GROSS
• 金额: $ 14.45万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818945
• 关键词: 7alpha hydroxylase; Address; Adherence; Behavior Therapy; Behavioral; Effectiveness; Evaluation; Evidence based intervention; General Population; HIV; HIV Infections; HIV/AIDS; Health; Intervention; Life; Life Expectancy; Literature; Mediator; Metabolism; Nicotine; Outcome; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Population; Problem Solving; Public Health; Risk; Site; Smoke; Smoker; Smoking; Smoking Cessation Intervention; Subgroup; Testing; Tobacco; Tobacco Dependence; Tobacco use; Toxic effect; Treatment Effectiveness; Variant; Virus; antiretroviral therapy; design; genetic variant; improved; individualized medicine; medication compliance; multiphase optimization strategy; nicotine patch; novel; pharmacologic; randomized, clinical trials; smoking cessation; tobacco cessation intervention; treatment optimization; treatment research; varenicline

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.

针对艾滋病毒/艾滋病（PLWHA）的人的抗逆转录病毒疗法（ART）实质上改善了生活 期待，但是现在，吸烟的Plwha因烟草的使用而损失了更多的寿命 感染。不幸的是，美国PLWHA的吸烟率约为40％。有限的烟草使用 使用PLWHA的治疗研究表明行为治疗和药物（尼古丁斑块和 varenicline）对戒烟产生适度的影响，其戒烟率大大低于对 一般人口。因此，迫切需要确定新的方法来优化烟草戒烟处理 对于艾滋病毒的吸烟者。两个因素高度可预测药物治疗的停止结果， 普通人群和PLWHA。首先，吸烟者的尼古丁代谢速​​率为特征 尼古丁代谢物比（NMR，CYP2A6基因变体的标记）预测了抗性素和静止 尼古丁补丁。我们对普通人群和艾滋病毒感染者的研究表明，个性化选择 使用NMR的吸烟者药物可以提高功效并降低毒性，这种方法突出显示了 由NCI。其次，遵守戒烟药物，一般人群以及 PLWHA很少超过60％，不遵守降低戒烟率为2-3倍。我们开发了 托管解决问题（地图）干预措施被疾病预防控制中心作为循证 PLWHA中的药物依从性干预。因此，申请的前提是合并 干预措施以量身定制烟草使用药物（varenicline或patch），并增加 使用地图遵守药物将优化PLWHA的烟草处理。为了测试这个前提，我们 将使用488 HIV+吸烟者进行严格的多站点随机临床试验，以评估NMR- 量身定制的处理和地图作为PLWHA烟草依赖治疗的优化策略。我们 将使用阶乘设计来检查：1）NMR-Tailored和/或MAPS干预措施对 - 治疗（EOT）和6个月的戒烟率（主要目的）； 2）NMR-Tailored和 地图干预措施（次要目的）； 3）NMR泰式和地图的主持人 干预措施（探索目的）。我们的整体方法与多相优化策略一致 这已经获得了指导评估干预措施以增强烟草使用的重要性 治疗效率。解决这些目标将确定：使用依从性和药物遗传学 优化对PLWHA的戒烟处理的优化，这是这些作用的基础的机制 关于停止结果的优化策略以及这些优化影响的变化 跨PLWHA子组的策略。最后，该审判将有助于了解是否正确 给合适的人的药物，并帮助确保他们充分利用药物优化 该人群的烟草戒烟治疗。