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: 10225475
• 负责人: ROBERT GROSS
• 金额: $ 62.05万
• 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/10225475
• 关键词: AIDS/HIV problem; Address; Adherence; Affect; Aftercare; Age; Area; Behavior Therapy; Biochemical; Biological; Budgets; CD4 Lymphocyte Count; Cardiovascular Diseases; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical; Combined Modality Therapy; Control Groups; Counseling; Data; Dependence; Effectiveness; Evaluation; Evidence based intervention; Expectancy; Gender; General Population; HIV; HIV Infections; Health; Hepatitis C Therapy; Individual; Intervention; Life; Life Expectancy; Literature; Malignant Neoplasms; Mediating; Mediator of activation protein; Mental Depression; Metabolism; Methodology; Modeling; Motivation; Nicotine; Outcome; Outcome Assessment; Participant; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Population; Prevalence; Problem Solving; Public Health; Race; Randomized; Randomized Clinical Trials; Reporting; Research; Risk; Risk Factors; Safety; Sex Orientation; Site; Smoke; Smoker; Smoking; Smoking Cessation Intervention; Speed; Subgroup; Testing; Time; Tobacco; Tobacco Dependence; Tobacco Use Cessation; Tobacco smoking behavior; Tobacco use; Toxic effect; Treatment Effectiveness; Treatment Efficacy; Treatment outcome; Underserved Population; Variant; Virus; Work; antiretroviral therapy; base; behavioral pharmacology; comorbidity; design; efficacious intervention; follow-up; genetic variant; improved; indexing; individualized medicine; medication compliance; modifiable risk; multiphase optimization strategy; nicotine patch; nicotine replacement; nicotine use; novel; personalized approach; personalized medicine; placebo controlled trial; population health; prospective; side effect; smoking cessation; standard care; substance use; systematic review; therapy adherence; tobacco abstinence; 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 (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.

抗逆转录病毒疗法 (ART) 的出现显着改善了艾滋病毒/艾滋病患者 (PLWHA) 的生活 预期，但现在，吸烟的艾滋病毒感染者因吸烟而损失的寿命比因艾滋病毒而损失的寿命还要多 感染。不幸的是，美国艾滋病病毒感染者中的吸烟率约为 40%。限制烟草使用 针对 PLWHA 的治疗研究表明，行为治疗和药物治疗（尼古丁贴片和 伐尼克兰）对戒烟产生中等影响，戒烟率远低于戒烟率 一般人群。因此，迫切需要找到优化戒烟治疗的新方法 对于感染艾滋病毒的吸烟者。有两个因素可以高度预测药物治疗的戒烟结果： 一般人群和艾滋病病毒感染者中。首先，吸烟者的尼古丁代谢率，其特征是 尼古丁代谢物比率（NMR，CYP2A6 基因变异的标记），预测伐尼克兰和 尼古丁贴片。我们对一般人群和感染艾滋病毒的吸烟者的研究表明，个性化选择 一种强调使用 NMR 为吸烟者提供药物的方法可以提高疗效并减少毒性 由 NCI (https://www.cancer.gov/about-nci/budget/plan/public-health) 制定。二、坚持吸烟 在一般人群和 PLWHA 中，戒烟药物很少超过 60%，且不依从 戒烟率降低 2-3 倍。我们开发了管理问题解决 (MAPS) 干预措施 经 CDC (https://www.cdc.gov/hiv/research/interventionresearch/compendium/ma/index.html) 认可为 针对 PLWHA 服药依从性的循证干预措施。因此，应用的前提是 结合干预措施，通过 NMR 定制烟草使用药物（伐尼克兰或贴片） 使用 MAPS 提高药物依从性将优化 PLWHA 的烟草治疗。为了测试这个 前提是，我们将对 488 名 HIV+ 吸烟者进行严格的多中心随机临床试验来评估 NMR 定制治疗和 MAPS 作为 PLWHA 烟草依赖治疗的优化策略。 我们将使用因子设计来检查：1) NMR 定制和/或 MAPS 干预措施对最终的影响 治疗结束率 (EOT) 和 6 个月戒烟率（主要目标）； 2) NMR 定制的介体和 MAPS 干预（次要目标）； 3) NMR 定制和 MAPS 干预措施的主持人 （探索性目标）。我们的总体方法与多阶段优化策略一致，该策略已获得 指导评估提高烟草使用治疗效果的干预措施的重要性。 解决这些目标将决定：吸烟的依从性和药物遗传学优化的使用 PLWHA 的戒断治疗，这些优化策略对患者的影响的机制 戒烟结果，以及这些优化策略在不同亚组中的效果差异 感染者。最后，这项试验将有助于了解是否为正确的人提供正确的药物并帮助 确保他们充分使用该药物，优化针对该人群的戒烟治疗。