Differences in the rate of nicotine metabolism among smokers with and without HIV

Abstract

Objective: HIV-infected smokers lose more life years to tobacco use than to HIV infection. The nicotine metabolite ratio (NMR), a biomarker of CYP2A6, represents individual variation in the rate at which nicotine is metabolized and is associated with response to smoking cessation treatments. We evaluated whether HIV-infected smokers metabolize nicotine faster than HIV-uninfected smokers, which may contribute to the disproportionate smoking burden and may have important treatment implications.

Design: We analysed baseline data from two clinical trials (NCT01710137; NCT01314001) to compare the NMR in HIV-infected smokers (N = 131) to HIV-uninfected smokers (N = 199).

Methods: Propensity scores were used to match the groups 2 : 1 on characteristics that influence NMR: sex, race, BMI and smoking rate. Nicotine metabolites were assessed via liquid chromatography-tandem mass spectrometry methods and the ratio of 3-hydroxycotinine:cotinine was used to compute the NMR.

Results: HIV-infected smokers had significantly higher NMR (mean = 0.47, SEM = 0.02) and were more likely to be in the highest NMR quartile compared with HIV-uninfected smokers (mean = 0.34, SEM = 0.02; Ps < 0.001).

Conclusion: The higher NMR observed among HIV-infected smokers may partially explain higher smoking rates and lower response to transdermal nicotine therapy. Understanding the mechanisms by which HIV and/or ART contribute to faster nicotine metabolism may guide the use of the NMR to personalize tobacco cessation strategies in this underserved population.

Conflict of interest statement

Conflicts of Interest: Dr. Schnoll receives medication and placebo free of charge from Pfizer for clinical trials and has provided consultation to Pfizer, GlaxoSmithKline, and Curaleaf. Dr. Gross serves on a Pfizer Data and Safety Monitoring Board for a drug unrelated to smoking or HIV. Dr. Ashare has an investigator-initiated grant from Novo Nordisk for a drug unrelated to the current study. Dr. Tyndale has consulted for Quinn Emmanual, Apotex and Ethismos.

Figures

Figure 1.. NMR Quartile by HIV Status in Matched Sample.

There were significantly more HIV-infected smokers (35%) characterized as fastest metabolizers (4th quartile) compared to HIV-uninfected smokers (17%). In contrast, 47% of HIV-uninfected smokers were characterized as the slowest metabolizers compared to 29% of HIV-infected smokers.