Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use: A Randomized Clinical Trial

Abstract

Importance: 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.

Objective: 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.

Interventions: 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).

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02797587.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Tindle, Freiberg, Cheng, Gnatienko, Hahn, So-Armah, and Krupitsky reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Tindle reported volunteering scientific input on the early stages of design of a phase 3 trial conducted in the US testing cytisine for smoking cessation and serving as the principal investigator for smoking cessation trials for which medications were donated by the manufacturer. Dr Cheng reported receiving personal fees from Janssen outside the submitted work. Dr Hahn reported receiving personal fees from Pear Therapeutics outside the submitted work. . No other disclosures were reported.

Figures

Figure 1.. Trial Design

NRT indicates nicotine replacement therapy.

Figure 2.. Flow of Participants Through Trial

NRT indicates nicotine replacement therapy. aLost to follow-up includes participants who missed all follow-up visits (months 3, 6, and 12). bThere were 4 deaths in group 1, 3 deaths in group 2, and 2 deaths in group 3, and there was 1 death in group 4. Death counts include those who died before follow-up or after any follow-up visit. cAll participants randomized were included in analysis, per intention to treat. Multiple imputation was performed to impute outcomes for participants who missed follow-up interviews. Per-protocol analysis was limited to participants who were adherent to their assigned intervention. The per-protocol analysis used the imputed data set, thus making it possible to include adherent participants who were lost to follow-up after adherence had been determined in the first 10 weeks.