Vanderbilt Center for Tobacco, Addiction and Lifestyle, Vanderbilt University Medical Center, Division of Internal Medicine and Public Health, Nashville, Tennessee.
Vanderbilt Center for Clinical Cardiovascular Trials Evaluation, Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tennessee.
JAMA Netw Open. 2022 Aug 1;5(8):e2225129. doi: 10.1001/jamanetworkopen.2022.25129.
Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions.
To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT.
DESIGN, SETTING, AND PARTICIPANTS: This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022.
Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4).
The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months.
Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking.
This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups.
ClinicalTrials.gov Identifier: NCT02797587.
重要性：吸烟和危险饮酒经常同时发生且未得到充分治疗。尼古丁受体部分激动剂和尼古丁替代疗法（NRT）可治疗吸烟，但对酒精无效，且临床试验很少纳入 HIV、物质使用和精神健康状况的个体。
目的：比较烟碱型乙酰胆碱受体部分激动剂伐伦克林和烟碱与 NRT 对饮酒和吸烟的影响。
设计、地点和参与者：这是一项 4 组随机、双盲、安慰剂对照的临床试验，于 2017 年 7 月至 2020 年 12 月在俄罗斯圣彼得堡进行。纳入了 400 名患有 HIV 的个体，这些个体存在危险饮酒（≥5 个过去 30 天的大量饮酒日 [HDD]）和每日吸烟的情况，并在入组后随访 12 个月。数据分析于 2021 年 5 月至 2022 年 6 月进行。
干预措施：参与者接受酒精和烟草咨询，4 组中的每组接受 1 种活性药物和 1 种安慰剂，分别为：活性伐伦克林和安慰剂 NRT（第 1 组）、安慰剂伐伦克林和活性 NRT（第 2 组）、活性烟碱和安慰剂 NRT（第 3 组）或活性烟碱和安慰剂 NRT（第 4 组）。
主要结局和测量：主要结局是 3 个月时的过去 30 天 HDD 数量。次要结局包括 3 个月时的生物化学验证的酒精戒断和 6 个月时的吸烟情况。
结果：在 400 名参与者（263 名[65.8%]男性；平均[SD]年龄，39[6]岁）中，97 名（24.3%）使用阿片类药物，156 名（39.1%）有抑郁症状。这些个体的 CD4 计数平均（SD）为 391（257）个细胞/mm3，平均（SD）每天吸烟 21（8）支，过去 30 天报告的平均（SD）HDD 为 9.3（5.8）个。与基线相比，所有组在 3 个月时的平均（SD）HDD 数量均减少（第 1 组：2.0[3.8] HDD 与 9.5[6.1] HDD；第 2 组：2.1[4.3] HDD 与 9.3[5.7] HDD；第 3 组：1.5[3.3] HDD 与 8.9[5.0] HDD；第 4 组：2.4[5.2] HDD 与 9.6[6.3] HDD）。在 3 个月时，各组之间的平均（SD）HDD 无显著差异，包括第 1 组与第 2 组（发病率比[IRR]，0.94；95%CI，0.49-1.79）、第 3 组与第 4 组（IRR，0.60；95%CI，0.30-1.18）和第 1 组与第 3 组（IRR，1.29；95%CI，0.65-2.55）。在 6 个月时，各组之间的吸烟戒断率无显著差异，包括第 1 组与第 2 组（100 名个体中有 15 名[15.0%]与 99 名个体中有 17 名[17.2%]；比值比[OR]，0.89；95%CI，0.38-2.08）、第 3 组与第 4 组（100 名个体中有 19 名[19.0%]与 101 名个体中有 19 名[18.8%]；OR，1.00；95%CI，0.46-2.17）和第 1 组与第 3 组（OR，0.79；95%CI，0.35-1.78）。事后分析表明，与继续吸烟的个体相比，那些戒烟的个体的平均（SD）HDD 更低（例如，在 3 个月时：0.7[1.8]HDD 与 2.3[4.6]HDD），酒精戒断率更高（例如，在 3 个月时：85 名个体中有 30 名[35.3%]与 315 名个体中有 54 名[17.1%]）。
结论和相关性：这项研究发现，在患有 HIV 且存在危险饮酒和吸烟的个体中，伐伦克林和烟碱与 NRT 相比，治疗危险饮酒和吸烟的效果并不更好，但所有组的行为改变率都很高。
试验注册：ClinicalTrials.gov 标识符：NCT02797587。
