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.

针对艾滋病毒/艾滋病感染者的抗逆转录病毒疗法（ART）的出现大大改善了生活