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: 10477202
• 负责人: ROBERT GROSS
• 金额: $ 61.67万
• 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/10477202
• 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; 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; psychiatric comorbidity; 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.

针对艾滋病毒/艾滋病患者的抗逆转录病毒疗法(ART)的出现极大地改善了生活 但现在，吸烟的PLWHA因吸烟而损失的寿命比他们因艾滋病毒而损失的寿命更多 感染。不幸的是，美国PLWHA的吸烟率约为40%。有限的烟草使用 PLWHA的治疗研究表明，行为治疗和药物(尼古丁贴片和 Varenicline)对戒烟有温和的影响，戒烟率明显低于 普通人口。因此，迫切需要确定优化戒烟治疗的新方法。 针对携带艾滋病毒的吸烟者。有两个因素对药物治疗的戒烟结果有高度预测作用 在一般人群中和在妇女解放运动中。首先，吸烟者的尼古丁代谢率，特征是 尼古丁代谢物比率(核磁共振，CYP2A6基因变异的标志)预示着varenicline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，使用核磁共振对吸烟者进行药物治疗可以提高疗效并减少毒性 美国国家情报局(https://www.cancer.gov/about-nci/budget/plan/public-health).第二，坚持吸烟 在普通人群和PLWHA中，戒断药物很少超过60%，而且不遵守 将戒断率降低2-3倍。我们开发了管理问题解决(MAP)干预，这是 由疾控中心(https://www.cdc.gov/hiv/research/interventionresearch/compendium/ma/index.html)认可为 PLWHA患者坚持用药的循证干预。因此，应用程序的前提是 结合干预成分以使用核磁共振定制烟草使用药物(varenicline或贴片) 使用MAP增加对药物的依从性将优化PLWHA的烟草治疗。为了测试这一点 前提下，我们将对488名HIV+吸烟者进行严格的多点随机临床试验，以评估 核磁共振定制治疗和MAP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验：1)核磁共振定制和/或MAP干预对末端的影响。 治疗后(EOT)和6个月的戒烟率(主要目标)；2)核磁共振的介体-量身定制和 MAP干预措施(次要目标)；以及3)核磁共振主持人--量身定制和MAP干预措施 (探索性目标)。我们的总体方法与多阶段优化策略是一致的，该策略已获得 突出指导提高烟草使用治疗有效性的干预措施的评价。 解决这些目标将决定：吸烟依从性的使用和药物遗传学的优化 PLWHA的戒断治疗，这些优化策略对 戒烟结果，以及这些优化策略在不同亚组中的效果差异 PLWHA。最终，这项试验将有助于理解是否将正确的药物提供给正确的人并帮助 为了确保他们充分使用这种药物，优化了这一人群的戒烟治疗。