Department of Psychiatry, University of Pennsylvania Perelman School of Medicine.
Pulmonary, Allergy, & Critical Care Division, University of Pennsylvania Presbyterian Medical Center.
AIDS. 2019 May 1;33(6):1083-1088. doi: 10.1097/QAD.0000000000002127.
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.
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).
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.
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).
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.
感染 HIV 的吸烟者因吸烟而损失的寿命比因 HIV 感染而损失的寿命更多。尼古丁代谢比（NMR）是细胞色素 P4502A6 的生物标志物，代表尼古丁代谢率的个体差异，与戒烟治疗的反应相关。我们评估了感染 HIV 的吸烟者是否比未感染 HIV 的吸烟者更快地代谢尼古丁，这可能导致吸烟负担不成比例，并可能对治疗产生重要影响。
我们分析了两项临床试验（NCT01710137；NCT01314001）的基线数据，以比较感染 HIV 的吸烟者（N=131）与未感染 HIV 的吸烟者（N=199）的 NMR。
采用倾向评分匹配两组 2：1 的特征，这些特征会影响 NMR：性别、种族、BMI 和吸烟率。通过液相色谱-串联质谱法评估尼古丁代谢物，并用 3-羟基可替宁/可替宁的比值计算 NMR。
感染 HIV 的吸烟者的 NMR 明显更高（平均值=0.47，SEM=0.02），且更有可能处于 NMR 最高四分位数（平均值=0.34，SEM=0.02；P<0.001）。
感染 HIV 的吸烟者观察到的更高 NMR 可能部分解释了更高的吸烟率和对经皮尼古丁治疗的较低反应。了解 HIV 和/或 ART 如何促进更快的尼古丁代谢的机制，可能有助于指导在这一服务不足的人群中使用 NMR 来制定个体化的戒烟策略。
