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 (selfreported 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%;.2[1]= 2.80, p= 0.09) and adherent (35% vs. 15%;.2[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%;.2[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%;.2[1] = 4.43, p = 0.04). Conclusions: Increasing varenicline adherence and ensuring that fast nicotine metabolizers receive varenicline may increase quit rates for PLWHA.

Automated summary

In a randomized controlled trial of varenicline for smoking among PLWHA, adherence to treatment and rate of nicotine metabolism were found to be associated with smoking cessation rates. Higher adherence and faster nicotine metabolism were related to higher quit rates, especially among adherent and fast metabolizers. Increasing adherence to varenicline and providing it to fast nicotine metabolizers may increase quit rates for PLWHA.