학술논문

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz‐Based Therapy in People With HIV Who Smoke
Document Type
article
Source
Clinical Pharmacology & Therapeutics. 115(1)
Subject
Medical Biochemistry and Metabolomics
Biomedical and Clinical Sciences
Tobacco Smoke and Health
Tobacco
Infectious Diseases
Sexually Transmitted Infections
Clinical Research
HIV/AIDS
Good Health and Well Being
Humans
Nicotine
Cotinine
Cigarette Smoking
HIV Infections
Pharmacology and Pharmaceutical Sciences
Pharmacology & Pharmacy
Pharmacology and pharmaceutical sciences
Language
Abstract
Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P