Mondleki Enkosi, Banda Clifford G, Chandiwana Nomathemba C, Sokhela Simiso, Wiesner Lubbe, Venter Francois, Maartens Gary, Sinxadi Phumla Z
Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
South Afr J HIV Med. 2022 Dec 13;23(1):1452. doi: 10.4102/sajhivmed.v23i1.1452. eCollection 2022.
Dolutegravir, a component of the preferred first-line antiretroviral therapy regimen, has been associated with increased weight gain. South Africa has a high prevalence of obesity, especially among women. Understanding dolutegravir exposure in patients with obesity is important for dose optimisation.
We compared the pharmacokinetic parameters of dolutegravir in Southern African adults living with HIV with and without obesity.
Blood samples were collected at various time points over a 24 h-period for dolutegravir assays. Non-compartmental analysis was conducted and geometric mean ratios (GMRs), with 90% confidence intervals (CIs), were generated to compare dolutegravir pharmacokinetic parameters between the groups. Regression analyses to assess predictors of dolutegravir exposure were done.
Forty participants were enrolled, 26 were women and 10 had obesity. Dolutegravir area under the concentration-time curve to 24-h and the maximum concentrations were not statistically significantly lower in participants with obesity: GMR 0.91 (90% CI: 0.71-1.16) and GMR 0.86 (90% CI: 0.68-1.07), respectively. In a multivariate linear regression analysis adjusting for age, gender, body mass index, creatinine clearance and randomisation arm (tenofovir alafenamide or tenofovir disoproxil fumarate), a unit increase in body mass index was associated with 1.2% lower dolutegravir area under the concentration-time curve to 24-h ( = 0.035).
Dolutegravir exposure was marginally lower in participants with obesity, but this is not clinically significant. Our findings suggest that there is no need to dose adjust dolutegravir in people with obesity.
多替拉韦是首选一线抗逆转录病毒治疗方案的组成部分，与体重增加有关。南非肥胖患病率很高，尤其是在女性中。了解肥胖患者的多替拉韦暴露情况对于剂量优化很重要。
我们比较了有肥胖和无肥胖的南非成人艾滋病毒感染者中多替拉韦的药代动力学参数。
在24小时内的不同时间点采集血样进行多替拉韦检测。进行非房室分析，并生成具有90%置信区间（CI）的几何平均比（GMR），以比较两组之间的多替拉韦药代动力学参数。进行回归分析以评估多替拉韦暴露的预测因素。
招募了40名参与者，其中26名是女性，10名患有肥胖症。肥胖参与者的多替拉韦24小时浓度-时间曲线下面积和最大浓度在统计学上没有显著降低：GMR分别为0.91（90%CI：0.71-1.16）和0.86（90%CI：0.68-1.07）。在一项针对年龄、性别、体重指数、肌酐清除率和随机分组组（替诺福韦艾拉酚胺或富马酸替诺福韦二吡呋酯）进行调整的多元线性回归分析中，体重指数每增加一个单位，多替拉韦24小时浓度-时间曲线下面积降低1.2%（P = 0.035）。
肥胖参与者的多替拉韦暴露略低，但这在临床上无显著意义。我们的研究结果表明，肥胖者无需调整多替拉韦的剂量。
