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

Ashare, Rebecca L.a; Thompson, Morgana; Leone, Frankb; Metzger, Davida; Gross, Robertc,d; Mounzer, Karame; Tyndale, Rachel F.f; Lerman, Caryna; Mahoney, Martin C.g; Cinciripini, Paulh; George, Tony P.i; Collman, Ronald G.j; Schnoll, Roberta

doi: 10.1097/QAD.0000000000002127
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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.

aDepartment of Psychiatry, University of Pennsylvania Perelman School of Medicine

bPulmonary, Allergy, & Critical Care Division, University of Pennsylvania Presbyterian Medical Center

cDivision of Infectious Diseases, University of Pennsylvania Perelman School of Medicine

dCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania

ePhiladelphia FIGHT, Philadelphia, Pennsylvania, USA

fCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Pharmacology and Toxicology, and Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

gDepartments of Medicine and Health Behavior, Roswell Park Cancer Institute, Buffalo, New York

hDepartment of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

iAddictions Division, Centre for Addiction and Mental Health and Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

jPulmonary, Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Correspondence to Rebecca L. Ashare, Department of Psychiatry, University of Pennsylvania, 3535 Market Street, 4th Floor, Philadelphia, PA 19104, USA. Tel: +1 215 746 5789; e-mail: rlashare@pennmedicine.upenn.edu

Received 14 August, 2018

Revised 3 October, 2018

Accepted 11 October, 2018

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