Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
J Int AIDS Soc. 2012 Mar 12;15(1):13. doi: 10.1186/1758-2652-15-13.
As stavudine remains an important and widely prescribed drug in resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.
We analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six- and/or 12-month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.
Between 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13-2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86-5.25), lipoatrophy (OR 11.8; 95% CI 3.2-43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83-18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.
Lower stavudine dosage is associated with fewer reports of several stavudine-associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.
在资源有限的环境中，司他夫定仍然是一种重要且广泛应用的药物，因此，使用较低剂量的司他夫定（从 40 毫克降至 30 毫克）对高效抗逆转录病毒治疗（HAART）结果的影响仍然是一个重要的公共卫生问题。
我们对南非约翰内斯堡 Themba Lethu 诊所前瞻性收集的数据进行了分析。我们评估了司他夫定剂量与司他夫定替代治疗的 6 个月和/或 12 个月结果之间的关系，包括病毒载量未能抑制到低于 400 拷贝/ml、外周神经病变、脂肪萎缩和乳酸性酸中毒的发生。由于预期体重低于 60 公斤的个体在整个研究期间将接受相同剂量的司他夫定，因此，分析仅限于基线体重为 60 公斤或以上的个体。数据采用逻辑回归进行分析。
2004 年 4 月 1 日至 2009 年 9 月 30 日，共有 3910 名接受抗逆转录病毒治疗（ART）的患者记录了司他夫定剂量，纳入了分析。其中，2445 名（62.5%）患者接受了 40 毫克司他夫定剂量，1565 名（37.5%）患者接受了 30 毫克司他夫定剂量。多变量分析显示，与接受 30 毫克剂量的患者相比，接受 40 毫克剂量的患者在接受 ART 治疗 12 个月时更有可能停止使用司他夫定（调整后的优势比，OR 1.71；95%置信区间，CI 1.13-2.57）。此外，接受 40 毫克剂量司他夫定的患者在同一时间内更有可能报告外周神经病变（OR 3.12；95%CI 1.86-5.25）、脂肪萎缩（OR 11.8；95%CI 3.2-43.8）和乳酸性酸中毒（OR 8.37；95%CI 3.83-18.29）。在开始 HAART 治疗后 12 个月内，病毒载量未能得到抑制的情况在接受 40 毫克剂量的患者中更为常见（OR 1.62；95%CI 0.88, 2.97），尽管这一结果缺乏精度。考虑到死亡和失访的敏感性分析通常支持这些估计。
较低剂量的司他夫定与较少报告几种司他夫定相关不良反应以及在开始接受 ART 治疗后的第一年更可能停止使用司他夫定有关。
