A SMART Approach to Treating Tobacco Use Disorder in Persons Living with HIV

摘要 吸烟是艾滋病毒感染者（PLWH）健康的主要威胁。不幸的是， 艾滋病毒感染者烟草使用障碍的治疗落后于艾滋病毒本身。2016年科克伦荟萃分析数据来自 12项临床试验涉及2，087名接受药物和行为支持的参与者， 短期（<6个月）改善禁欲的证据，但不是长期的。这些研究的一个缺点是， 治疗方案不包括对吸烟无反应或复吸的计划。一个更新的临床试验设计， 序贯多分配随机试验（SMART），包括一个动态的治疗策略，其中， 指定的决策规则指导应答者和无应答者的持续治疗。这种方法允许 SMART设计，以更好地反映慢性复发性疾病的管理，如烟草使用障碍。我们， 因此，建议对622名吸烟并接受治疗的成年PLWH进行两组、两阶段随机试验 三个卫生系统之一。开始时，受试者将随机接受尼古丁 替代治疗（NRT）（贴剂和口香糖或锭剂）或联合NRT+应急管理（CM）。在12 两组中的应答者（通过呼出的一氧化碳[eCO]确认的非吸烟受试者）将 再接受12周同样的治疗无应答者（通过自我报告持续吸烟的受试者 和/或eCO）将被重新随机分配至12周治疗， varenicline（VAR）或varenicline+CM（VAR+CM）。干预措施将由经过培训的临床药剂师提供。 主要结局将是入组后24周时经eCO证实的禁欲。的具体目标 建议的研究是：（1）研究动态治疗方法的有效性，以减少患病率 吸烟在PLWH队列中的作用，并确定最佳方法;（2），研究各种动态 治疗方案对CD 4计数、HIV病毒抑制和VACS指数（发病率和死亡率风险的有效测量）的影响; 以及（3）以实施科学为基础，使用混合主动性-实施类型I设计，确定 阻碍和促进我们采取干预措施，为今后的执行工作提供信息的因素。研究团队包括 具有烟草使用障碍治疗、艾滋病毒和艾滋病毒感染者成瘾、临床试验、CM、 实施科学和SMART设计。研究组成部分易于扩展，所有干预措施都具有丰富的 循证该提案提供了创新，因为在针对吸烟的干预中首次使用了以下内容 PLWH：（1）一线烟草治疗药物的SMART设计;（2）临床药师作为关键 干预者;（3）VACS指数2.0作为吸烟的PLWH一般样本的结果;以及（4） 以实施为重点的烟草干预过程评估，包括艾滋病毒诊所的药剂师和CM。这 这项研究为在全国范围内改变艾滋病毒治疗环境中的烟草使用障碍治疗带来了特殊的希望。

ABSTRACT Smoking is the leading threat to health of patients living with HIV (PLWH). Unfortunately, the evidence-base for tobacco use disorder treatment in PLWH lags behind that of HIV itself. A 2016 Cochrane meta-analysis of data from 12 clinical trials involving 2,087 participants receiving both medications and behavioral support found modest evidence of improved abstinence in the short term (<6 months), but not long-term. A short-coming of these studies is that treatment algorithms did not include plans for non-response, or relapse to smoking. A newer clinical trial design, the Sequential Multiple Assignment Randomized Trial (SMART), includes a dynamic treatment strategy in which pre- specified decision rules guide the ongoing treatment of both responders and non-responders. This approach allows SMART designs to better mirror the management of chronic relapsing conditions, such as tobacco use disorder. We, therefore, propose a two-arm, two-stage randomized trial of 622 adult PLWH who smoke cigarettes and receive care in one of three health systems. At inception, participants will be randomized to either combination nicotine replacement therapy (NRT) (patch and gum or lozenge) or combination NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed by exhaled carbon monoxide [eCO]) in both arms will receive 12 more weeks of the same treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with varenicline (VAR) or varenicline+CM (VAR+CM). The intervention will be delivered by trained clinical pharmacists. The primary outcome will be eCO-confirmed abstinence at 24 weeks post-enrollment. The specific aims of the proposed study are to: (1) study the effectiveness of a dynamic treatment approach to reduce the prevalence of smoking in a cohort of PLWH, and to identify the optimal approach; (2), study the effectiveness of various dynamic regimens on CD4 count, HIV viral suppression, and VACS index (validated measure of morbidity and mortality risk); and (3) grounded in implementation science and using a Hybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation. The study team includes individuals with expertise in tobacco use disorder treatment, HIV and addiction in PLWH, clinical trials, CM, implementation science, and SMART designs. Study components are readily scalable and all interventions are richly evidence-based. This proposal offers innovation as the first use of the following in a smoking intervention targeting PLWH: (1) a SMART design with first-line tobacco treatment medications; (2) clinical pharmacists as key interventionists; (3) VACS Index 2.0 as an outcome among a general sample of PLWH who smoke; and (4) implementation-focused process evaluation of tobacco intervention including pharmacists and CM in HIV clinics. This study holds exceptional promise to transform tobacco use disorder treatment in HIV treatment settings nationally.