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Varenicline vs Placebo for Smoking Cessation: ANRS 144 Inter-ACTIV Randomized Trial
Patrick Mercie3, Caroline Roussillon1, Christine Katlama4, Aurélie Beuscart1, Samuel Ferret2, Nathalie Wirth5, David Zucman6, Xavier Duval7, Genevieve Chene1
1 Inserm U897, Bordeaux, France. 2 Hosp. Saint-Louis, Paris, France. 3 Hosp. Saint-André, Bordeaux, France. 4 Hosp. La Pitié-Salpêtrière, Paris , France. 5 Hosp. De Brabois, Vandoeuvre les Nancy, France. 6 Hosp. Foch, Suresnes, France. 7 CIC 1425, Paris , France.
Background: About half of HIV-infected patients are regular tobacco smokers in Europe, a higher prevalence than the general population. Tobacco is an important determinant of non AIDS morbidity and mortality (including vascular diseases and malignancies), a major reason to promote tobacco cessation. It is unclear whether varenicline is safe and efficacious for smoking cessation in HIV-infected patients. We evaluated varenicline at 48 weeks in regular smokers motivated to quit smoking.
Methods: Randomized (1:1), placebo-controlled clinical trial with a 12-week treatment period (from 0.5 mg once daily to 1 mg twice daily at the end of the first week) and a further 36-week follow-up, including smoking cessation counseling in both arms, conducted in 30 ANRS centers from Oct. 2009 to Jan. 2014. Self-reported tobacco abstinence was confirmed by exhaled carbon monoxide measurements at 9 weeks and at intervals up to 48 weeks. The primary endpoint was continuous abstinence rate from week 9 to 48. Secondary endpoints included continuous abstinence rate from week 9 to 12 and adverse events.
Results: 248 smokers were randomized; 213 included in the modified intention-to-treat analysis (102 varenicline, 111 placebo), others did not start trial treatment. Median age was 45 years, 83% male, median nadir CD4+ 213/mm3, baseline CD4+ 617/mm3 and undetectable HIV RNA 73%. Varenicline was associated with a higher continuous abstinence rate at 48 weeks than placebo: 17.6% vs 7.2% (p=0.02) and 34.3% vs 12.6% at 12 weeks (p=0.0002). At 48 weeks, median CD4+ was 615/mm3 and 80% had undetectable HIV RNA, without difference between arms. Grade 3/4 drug-related effects were reported in 7 patients in each arm, including 9 psychiatric side effects (5 in the varenicline arm vs 4 in the placebo arm) and 3 gastrointestinal side effects (1 and 2, respectively). At least one depressive episode related to trial treatment was reported in 1 and 7 patients, respectively. Among 7 grade 3/4 cardiovascular events, 4 occurred in the varenicline arm (not treatment related) and 3 in the placebo arm. No neurovascular event was reported.
Conclusions: Varenicline is safe and effective in HIV infected patients with a 34% rate of tobacco abstinence at 12 weeks (end of treatment) and 18% at 48 weeks. These results are in the range of those reported in the HIV uninfected population. Varenicline should be considered as part of the standard of care in HIV-infected patients motivated to quit smoking.