Brief Report: Nicotine Metabolism Ratio Increases in HIV-Positive Smokers on Effective Antiretroviral Therapy: A Cohort Study

Abstract

Background: People with HIV (PWH) smoke tobacco at much higher rates than the general population. Previous research has shown that PWH have faster nicotine metabolism than HIVuninfected individuals, which may underlie this disparity, but the cause is unknown. We investigated whether higher nicotine metabolite ratio (NMR; 3-hydroxycotinine:cotinine), a validated biomarker of nicotine metabolism through CYP2A6, was associated with antiretroviral use among HIV-infected smokers. Methods:We conducted a retrospective cohort study of HIVpositive smokers in the University of Pennsylvania Center for AIDS Research cohort. We compared the NMR before viral suppression (.10,000 copies/mL) and after viral suppression on antiretroviral therapy (,200 copies/mL). We used mixed-effects linear regression to analyze the change in NMR after viral suppression and assessed for effect modification by efavirenz use.Results: Eighty-nine individuals were included in the study. We observed effect modification by efavirenz use (interaction term for efavirenz use, P , 0.001). Among those on nonefavirenz regimens, the mean NMR increased by 0.14 (95% confidence interval: 0.05 to 0.23, P = 0.002). Among those on efavirenz-containing regimens, the mean NMR increased by 0.53 (95% confidence interval: 0.39-0.66, P , 0.001). Conclusions:We observed a clinically and statistically significant increase in NMR after viral suppression among smokers with HIV, which more than doubled among those on efavirenz-based regimens. Higher NMR among HIV-positive smokers on antiretroviral therapy may help explain the higher rates of tobacco use and lower quit rates among PWH in care. These findings suggest that regimen choice and other modifiable factors may be targets for future attempts to increase success rates for tobacco cessation among PWH.

A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa

“…A handful of studies in the general population demonstrated a relationship between high NMR and older age [ 24 , 26 , 31 ]. However, studies in HIV populations did not report these associations [ 11 , 30 ], which was consistent with our findings. We also found no association with sex, which was inconsistent with existing evidence showing that women have a higher NMR than men [ 18 , 27 ].…”

“…Overall, the values of NMR found in our study sample were lower than what was reported in other populations of PWH in high-resource settings; however, the existing evidence came largely from more diverse Western settings, with a large proportion of participants of Caucasian descent. Mean values of NMR in literature among PWH range from 0.35 to 0.47 [ 11 , 25 , 27 , 30 ], whereas the mean in this study was 0.32. Given our sample was entirely Black South African, and given African Americans on average have a lower NMR than other racial/ethnic groups, the homogeneity of our population, with a genetic makeup closer to those with typically lower NMRs, aligned our findings with these other studies.…”

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

“…Interestingly, efavirenz is associated with a higher NMR in PWH. 12,16 Schnoll et al found that NMR in PWH on efavirenz-containing regimens was 0.67 compared with 0.44 in those on non-efavirenz-containing ART. As efavirenz is known to induce CYP2A6 24 -the predominant liver enzyme responsible for nicotine metabolism-our study adds further evidence that ART associated with HIV treatment, rather than HIV itself, may explain the higher nicotine metabolism rates seen in other cohorts of PWH.…”

“…Higher rates of nicotine metabolism among PWH may be due to direct viral effects of HIV itself, metabolic effects on the liver due to HIV infection or viral hepatitis, or pharmacologic effects of ART. [13][14][15][16] Direct virologic effects may induce CYP2A6 activity and thus increase NMR. CYP2A6 activity can be induced by inflammation and has been found to be higher in persons with hepatitis.…”

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

“…11 A recent study found that in PWH who achieved viral suppression on ART, those who took ART regimens including efavirenz had a higher mean NMR increase than those on regimens without efavirenz. 10 Given the likely effect of efavirenz on CYP2A6 activity, we hypothesized stopping efavirenz-based therapy would result in decreases in the NMR.…”