司他夫定暴露与脂肪萎缩、糖代谢异常、乳酸性酸中毒和高三酰甘油血症之间缺乏关联：一项前瞻性横断面研究。

Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study.

机构信息

Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, K45 Old Main Building, Groote Schuur Hospital, Observatory, 7925, Cape Town, South Africa.

出版信息

AIDS Res Ther. 2010 Jul 14;7:23. doi: 10.1186/1742-6405-7-23.

DOI:10.1186/1742-6405-7-23

PMID:20630064

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2914641/

Abstract

BACKGROUND

Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides.

METHODS

Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy.

RESULTS

There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m2 and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79).

CONCLUSIONS

There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities.

摘要

背景

尽管司他夫定具有毒性，但在资源匮乏的环境中仍被广泛应用。我们的目的是确定司他夫定的血浆浓度与脂肪萎缩、葡萄糖、乳酸和甘油三酯浓度之间的关联。

方法

参与者参与了一项横断面研究，评估脂肪萎缩、口服葡萄糖耐量试验、空腹甘油三酯、指尖刺血乳酸和司他夫定浓度。使用群体药代动力学方法获得个体预测的浓度曲线下面积（AUC）。拟合逻辑回归模型，以评估司他夫定几何均数比值>1 与空腹血糖受损、糖耐量受损、高乳酸血症、高甘油三酯血症和脂肪萎缩之间的关系。

结果

共有 47 名研究参与者，中位年龄为 34 岁，83%为女性。中位体重指数和腰臀比分别为 24.5kg/m2 和 0.85。中位司他夫定治疗时间为 14.5 个月。脂肪萎缩、空腹血糖受损、糖耐量受损、高乳酸血症和高甘油三酯血症的患病率分别为 34%、19%、4%、32%和 23%。估计的中位数（四分位间距）司他夫定 AUC 为 2191（1957 至 2712）ng*h/mL。22 名参与者的司他夫定几何均数比值>1。单变量逻辑回归分析显示，司他夫定几何均数比值>1 与空腹血糖受损（比值比（OR）2.00，95%置信区间（CI）0.44 至 9.19）、糖耐量受损（OR 1.14，95%CI 0.07 至 19.42）、高乳酸血症（OR 2.19，95%CI 0.63 至 7.66）、高甘油三酯血症（OR 1.75，95%CI 0.44 至 7.04）和脂肪萎缩（OR 0.83，95%CI 0.25 至 2.79）无关。