Brief Report: HIV Infection Does Not Explain Higher Nicotine Metabolism in People Living With HIV

Arens, Yotam; Bilker, Warren B.; Han, Xiaoyan; Plankey, Michael; Ware, Deanna; Friedman, M. Reuel; D’Souza, Gypsyamber; Stosor, Valentina; Shoptaw, Steven; Schnoll, Robert A.; Tyndale, Rachel F.; Ashare, Rebecca L.; Gross, Robert

doi:10.1097/qai.0000000000003089

Cited by 2 publications

(3 citation statements)

References 39 publications

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“…Our team has previously found that PWH who smoke have a higher NMR than those without HIV who smoke 8 . Although we found that HIV infection itself (i.e., pre‐ vs. post‐HIV infection change in NMR) does not appear to be the mechanism responsible for the higher NMR in PWH who smoke, 9 we did find a small increase in the NMR after viral suppression (0.14, P = 0.002). However, there was a marked increase for those taking efavirenz‐based regimens (0.53, P < 0.001) 10 .…”

Section: Discussioncontrasting

confidence: 77%

“…We previously demonstrated that HIV acquisition had no discernable effect on the NMR. 9 In contrast, specific ART medications may alter the NMR through effects on CYP2A6. Efavirenz, a key component of ART globally, may upregulate CYP2A6 10 (CYP2A6 contributes to efavirenz metabolism) as it does CYP2B6, the primary enzyme involved in its metabolism.…”

Section: How Might This Change Clinical Pharma-cology or Translationa...mentioning

confidence: 99%

“…Differences in the NMR may be affected by HIV infection or its treatment, among other factors. We previously demonstrated that HIV acquisition had no discernable effect on the NMR 9 . In contrast, specific ART medications may alter the NMR through effects on CYP2A6.…”

mentioning

confidence: 97%

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Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz‐Based Therapy in People With HIV Who Smoke

Medaglio,

Bilker,

Han

et al. 2023

Clin Pharma and Therapeutics

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Rates of cigarette smoking in people with HIV (PWH) are 2‐3 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: 1) active cigarette smoking, 2) ART switched from efavirenz‐based to non‐efavirenz‐based regimen, 3) plasma available at pre‐ and post‐ART switch, and 4) 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 2010‐2019 in 72 PWH. The mean NMR difference after switching to a non‐efavirenz‐based regimen was ‐0.24 (SD:0.37, p<0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates.

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Section: Discussioncontrasting

confidence: 77%

Section: How Might This Change Clinical Pharma-cology or Translationa...mentioning

confidence: 99%

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Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz‐Based Therapy in People With HIV Who Smoke

Medaglio,

Bilker,

Han

et al. 2023

Clin Pharma and Therapeutics

Self Cite

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PharmVar GeneFocus: CYP2A6

Langlois,

Chenoweth,

Twesigomwe

et al. 2024

Clin Pharma and Therapeutics

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The Pharmacogene Variation Consortium (PharmVar) provides nomenclature for the human CYP2A gene locus containing the highly polymorphic CYP2A6 gene. CYP2A6 plays a role in the metabolism of nicotine and various drugs. Thus, genetic variation can substantially contribute to the function of this enzyme and associated efficacy and safety. This GeneFocus provides an overview of the clinical significance of CYP2A6, including its genetic variation and function. We also highlight and discuss caveats in the identification and characterization of allelic variation of this complex pharmacogene, a prerequisite for accurate genotype determination and prediction of phenotype status.

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Brief Report: HIV Infection Does Not Explain Higher Nicotine Metabolism in People Living With HIV

Cited by 2 publications

References 39 publications

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz‐Based Therapy in People With HIV Who Smoke

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz‐Based Therapy in People With HIV Who Smoke

PharmVar GeneFocus: CYP2A6

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