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（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（https://www.cancer.gov/about-nci/budget/plan/public-health）。第二，坚持吸烟 在普通人群中和PLWHA中，停止药物很少超过60％，不遵守 降低戒烟率2-3倍。我们开发了托管解决问题（地图）干预措施 由CDC（https://www.cdc.gov/hiv/research/interventionresearch/compendium/ma/index.html）认可为 PLWHA中的药物依从性的基于证据的干预措施。因此，申请的前提是 将干预组件纳入NMR来量身定制烟草使用药物（varenicline或patch） 并使用地图增加对药物的依从性将优化PLWHA的烟草处理。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量表的处理和地图是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/或地图干预措施对最终的影响 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泰式和地图干预的主持人 （探索目的）。我们的整体方法与已获得的多相优化策略一致 指导评估干预措施以增强烟草使用治疗效果的突出性。 解决这些目标将确定：使用吸烟的粘附和药物遗传学优化 PLWHA的停止处理，这些优化策略对这些优化策略的影响的机制对 停止结果，以及这些优化策略跨小组的影响的变化 plwha。最后，该审判将有助于了解是否将正确的药物送给合适的人并帮助 为了确保他们充分使用该药物优化该人群的戒烟治疗。