Division of Infectious Diseases, Department of Internal Medicine, Chris Hani Baragwanath Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Clinical HIV Research Unit, Department of Internal Medicine, Helen Joseph Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
HIV Med. 2014 Jan;15(1):3-12. doi: 10.1111/hiv.12074. Epub 2013 Aug 28.
Low-dose stavudine therapy may have a lower toxicity profile compared with standard dose. A randomized controlled trial comparing these two doses of stavudine with tenofovir disoproxil fumarate (tenofovir DF) was performed to assess the effects on anthropometry, markers of inflammation, and lipid and glucose metabolism in Black South African patients.
Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or tenofovir DF (300 mg), each combined with lamivudine and efavirenz, for 48 weeks. Anthropometry, markers of inflammation, and lipid and glucose metabolism were assessed using standard techniques.
In all three treatment arms, there was a significant increase in lipid levels over the study period. At 48 weeks, fasting glucose level (P < 0.005) and homeostasis model assessment (HOMA) score (P < 0.05) increased significantly in the standard-dose stavudine arm, as did insulin and C-peptide levels in both the standard- and low-dose stavudine arms. At week 48, a significant decrease (P < 0.05) in adiponectin was noted in the standard-dose stavudine arm, but there was an increase (P < 0.005) in the tenofovir DF arm. In both the stavudine arms, significant increases in anthropometric measures occurred at 24 weeks but these decreased by week 48. Mitochondrial toxicities occurred in both the stavudine arms. Immunological and virological outcomes were similar for all three arms.
This study highlights the occurrence of metabolic abnormalities with both stavudine and tenofovir DF treatment. Awareness of the potential increased cardiovascular risk should be of concern with the use of both these therapies.
与标准剂量相比，低剂量司他夫定治疗可能具有更低的毒性。本研究进行了一项随机对照试验，比较了这两种剂量的司他夫定与富马酸替诺福韦二吡呋酯（替诺福韦酯）在南非黑人患者中的疗效，评估了它们对人体测量、炎症标志物以及脂质和糖代谢的影响。
60 名患者按 1:1:1 的比例随机分为标准剂量（30-40mg）、低剂量（20-30mg）司他夫定或替诺福韦酯（300mg）组，每组联合拉米夫定和依非韦伦治疗 48 周。采用标准技术评估人体测量、炎症标志物以及脂质和糖代谢。
在所有 3 个治疗组中，研究期间脂质水平均显著升高。在第 48 周，标准剂量司他夫定组的空腹血糖水平（P<0.005）和稳态模型评估（HOMA）评分（P<0.05）显著升高，标准剂量和低剂量司他夫定组的胰岛素和 C 肽水平也升高。在第 48 周，标准剂量司他夫定组的脂联素水平显著下降（P<0.05），但替诺福韦酯组的脂联素水平显著升高（P<0.005）。在司他夫定的两个剂量组中，人体测量指标在 24 周时显著增加，但在第 48 周时下降。两种司他夫定组均发生线粒体毒性。所有 3 个组的免疫和病毒学结果相似。
本研究强调了司他夫定和替诺福韦酯治疗均会发生代谢异常。鉴于这两种治疗方法均有潜在的心血管风险增加，应引起重视。
