Medication adherence and rate of nicotine metabolism are associated with response to treatment with varenicline among smokers with HIV

Introduction: PLWHA who smoke have shown lower cessation rates within placebo-controlled randomized trials of varenicline. Adherence and rate of nicotine metabolism may be associated with quit rates in such clinical trials. Methods: This secondary analysis of a randomized placebo-controlled trial of varenicline for smoking among PLWHA (N = 179) examined the relationship between varenicline adherence (pill count, ≥80% of pills), nicotine metabolism (based on the nicotine metabolite ratio; NMR) and end-of-treatment smoking cessation (self-reported 7-day point prevalence abstinence, confirmed with carbon monoxide of ≤ 8 ppm, at the end of treatment; EOT). Results: Combining varenicline and placebo arms, greater adherence (OR = 1.011, 95% CI:1.00–1.02, p = 0.051) and faster nicotine metabolism (OR = 3.08, 95% CI:1.01–9.37, p = 0.047) were related to higher quit rates. In separate models, adherence (OR = 1.009, 95% CI:1.004–1.01, p < 0.001) and nicotine metabolism rate (OR = 2.04, 95% CI:1.19–3.49, p = 0.009) interacted with treatment arm to effect quit rates. The quit rate for varenicline vs. placebo was higher for both non-adherent (19% vs. 5%; χ²[1] = 2.80, p = 0.09) and adherent (35% vs. 15%; χ²[1] = 6.51, p = 0.01) participants, but the difference between treatment arms was statistically significant only for adherent participants. Likewise, among slow metabolizers (NMR < 0.31), the varenicline quit rate was not significantly higher vs. placebo (14% vs. 5%; χ²[1] = 1.17, p = 0.28) but, among fast metabolizers (NMR ≥ 0.31), the quit rate for varenicline was significantly higher vs. placebo (33% vs. 14%; χ²[1] = 4.43, p = 0.04). Conclusions: Increasing varenicline adherence and ensuring that fast nicotine metabolizers receive varenicline may increase quit rates for PLWHA.