哮喘联盟

   摘要
   背景：HIV人群中吸烟者并不少见，但高质量戒烟干预资料较少。本研究旨在评价伐尼克兰联合戒烟咨询对于HIV人群的戒烟安全性和有效性。
   方法：ANRS 144 Inter-ACTIV一项随机、平行、双盲、多中心、安慰剂对照III期临床研究在全法国30多个临床中心进行。HIV患者吸烟至少每天10支持续至少1年以上，被动员戒烟，且不依赖于其他精神活性药物，没有抑郁或自杀倾向则可以考虑入选研究。应用计算机随机按照1：1进行分配，或接受伐尼克兰逐步过渡至1.0mg 每天2次，或接受每天2次安慰剂治疗，持续12周，同时给予面对面的戒烟咨询。患者和研究者对于治疗分组双盲。在24周未戒断患者则接受额外12周揭盲后的伐尼克兰治疗。首要研究终点为从第9周至48周的持续戒断比例。吸烟状态通过呼出气一氧化碳评价。ITT人群和mITT人群进行有效性分析，其中包括至少服用1片研究药物的患者。安全性分析尽在mITT人群进行。
   结果：自2009年10月16日至2012年12月20日，303名患者符合入选条件，248名经过随机分配进入伐尼克兰治疗组（n=123）和安慰剂组（n=125）。随机后，1名初始接受安慰剂治疗的受试者因故（无法国医保）从ITT分析中退出。伐尼克兰组102名患者和安慰剂组111名患者接受至少1次治疗，并被纳入mITT分析。在ITT分析中，伐尼克兰与研究期内（9-48周）患者持续戒断率相关:18名(15%, 95% CI 8-21)接受伐尼克兰治疗患者v.s. 8名(6%, 2-11)接受安慰剂治疗患者，调整后OR为2.5(95% CI 1.0-6.1; p=0.041)。在mITT分析中，伐尼克兰应用于更高的戒断率相关：18 名(18%, 95% CI 10-25) 接受伐尼克兰治疗患者v.s. 8名(7%, 2-12) 接受安慰剂治疗患者(调整后OR为2.7, 95% CI 1.1-6.5; p=0.029)。关于抑郁发生率，接受伐尼克兰治疗组为2.4/每100人·年 (95% CI 0·6-9·5; 2位患者[2%])，接受安慰剂治疗组为12.4/每100人·年 (95% CI 6·9-22·5; 11位患者[10%])。213名受试者中14名（7%）出现心血管事件：接受伐尼克兰治疗组为6人（6%），接受安慰剂治疗组为8人（7%）。
   结论：伐尼克兰可以安全、有效用于HIV患者戒烟，可以推荐作为标准治疗。
 

（上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译）
（Lancet HIV. 2018 Mar;5(3):e126-e135.）

Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial.  

 
Mercié P, et al.
 
 
Abstract
BACKGROUND:Tobacco smoking is common in people living with HIV, but high-quality evidence on interventions for smoking cessation is not available in this population. We aimed to assess the efficacy and safety of varenicline with counselling to aid smoking cessation in people living with HIV.
METHODS:The ANRS 144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo-controlled phase 3 trial was done at 30 clinical hospital sites in France. People living with HIV who had smoked at least ten cigarettes per day for 1 year or longer, were motivated to stop smoking, were not dependent on another psychoactive substance, and had no history of depression or suicide attempt were eligible. Using a computer-generated randomisation sequence, we allocated (1:1) the patients to receive either varenicline titrated to two 0·5 mg doses twice daily or placebo twice daily for 12 weeks, plus face-to-face counselling. Patients and investigators were masked to treatment group allocation. Patients who were not abstinent at week 24 were offered open-label varenicline for 12 additional weeks. The primary outcome was the proportion of smokers continuously abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide in exhaled air. Primary analyses were done in both the intention-to-treat (ITT) population and modified ITT (mITT) population, which comprised all patients who took at least one tablet of their assigned study treatment. The safety analyses were done in the mITT populatio
FINDINGS:From Oct 26, 2009, to Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were randomly assigned to the varenicline group (n=123) or the placebo group (n=125). After randomisation, one participant initially assigned to the placebo group was excluded from the ITT analysis for a regulatory reason (no French health-care coverage). 102 patients in the varenicline group and 111 patients in the placebo group received at least one dose of their assigned treatment and were included in the mITT analysis. In the ITT analysis, varenicline was associated with a higher proportion of patients achieving continuous abstinence over the study period (week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight (6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2·5 (95% CI 1·0-6·1; p=0·041). In the mITT analysis, varenicline was also associated with higher continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of 111 in the placebo group (adjusted OR 2·7, 95% CI 1·1-6·5; p=0·029). The incidence of depression was 2·4 per 100 person-years (95% CI 0·6-9·5; two [2%] of 102) in the varenicline group and 12·4 per 100 person-years (95% CI 6·9-22·5; 11 [10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18 cardiovascular events: six (6%) of 102 people in the varenicline group and eight (7%) of 111 people in the placebo group.

INTERPRETATION:Varenicline is safe and efficacious for smoking cessation in people living with HIV and should be recommended as the standard of care.