Bbosa Godfrey S, Kyegombe David B, Anokbonggo William W, Ogwal-Okeng Jasper, Musoke David, Odda John, Lubega Aloysius, Ntale Muhammad
J Basic Clin Physiol Pharmacol. 2014 Jan 27:1-12. doi: 10.1515/jbcpp-2013-0089.
Abstract Background: Chronic ethanol use is a global problem including among HIV-infected patients on stavudine/lamivudine/nevirapine (d4T/3TC/NVP) regimen. The study determined the effect of chronic ethanol use on the therapeutic window of d4T, 3TC and NVP in HIV-infected patients using alcohol-use biomarkers to screen patients for chronic ethanol use. Methods: A case-control study using repeated measures design with serial measurements was used to quantify drugs in plasma. The WHO alcohol use disorder identification test (AUDIT) tool was initially used to screen patients for chronic alcohol use, and then they were further sorted using alcohol-use bioamarkers (γ-glutamyl transferase ≥55.0 IU; mean corpuscular volume, ≥96 fl, aspartate amino transferase/alanine aminotransferase ratio ≥2.0 value). A total of 41 patients (26 in the alcohol group and 15 in the control group) were followed up for 9 months with blood sampling done at 3-month intervals. Plasma drug concentrations were quantified using a Shimadzu Class-VP™ HPLC data system version 6.1. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed model. Means were compared using Student's t-test. Results: The mean steady-state plasma drug concentrations of d4T and 3TC in the alcohol group were lower than that in the control group during the 9-month period of follow-up. For 3TC, there was a statistical difference in the mean steady-state plasma drug concentrations between the alcohol group and the control group (p≤0.05) in the 6- and 9-month period of follow-up. For NVP, in both groups they were within the reference ranges, although the drug plasma concentrations were higher in the alcohol group compared to the control group and were statistically significant (p<0.05) in 0, 3 and 6 months of follow-up. Conclusions: Chronic ethanol use by HIV-infected patients reduced the therapeutic steady-state plasma drug concentrations of d4T and 3TC and increased the NVP drug concentrations in the HIV-infected patients.
摘要 背景：长期饮酒是一个全球性问题，在接受司他夫定/拉米夫定/奈韦拉平（d4T/3TC/NVP）治疗方案的HIV感染患者中也存在。本研究通过使用酒精使用生物标志物筛查慢性饮酒患者，确定了长期饮酒对HIV感染患者中d4T、3TC和NVP治疗窗的影响。方法：采用重复测量设计的病例对照研究，通过系列测量来定量血浆中的药物。最初使用世界卫生组织酒精使用障碍识别测试（AUDIT）工具筛查慢性饮酒患者，然后使用酒精使用生物标志物（γ-谷氨酰转移酶≥55.0 IU；平均红细胞体积≥96 fl，天冬氨酸氨基转移酶/丙氨酸氨基转移酶比值≥2.0）进一步分类。共41例患者（酒精组26例，对照组15例）随访9个月，每3个月采集一次血样。使用岛津Class-VP™ HPLC数据系统6.1版对血浆药物浓度进行定量。使用SAS 2003版9.1统计软件包和重复测量固定模型分析数据。采用学生t检验比较均值。结果：在9个月的随访期内，酒精组d4T和3TC的平均稳态血浆药物浓度低于对照组。对于3TC，在随访的6个月和9个月时，酒精组和对照组的平均稳态血浆药物浓度存在统计学差异（p≤0.05）。对于NVP，两组均在参考范围内，尽管酒精组的药物血浆浓度高于对照组，且在随访的0、3和6个月时具有统计学意义（p<0.05）。结论：HIV感染患者长期饮酒会降低d4T和3TC的治疗稳态血浆药物浓度，并增加HIV感染患者中NVP的药物浓度。
