Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia.
PLoS One. 2012;7(1):e30647. doi: 10.1371/journal.pone.0030647. Epub 2012 Jan 27.
Although stavudine (D4T) remains frequently used in low-income countries in Asia, associated long-term toxicity data are scarce. The aim of this study was to determine the long-term incidence of severe D4T-toxicity (requiring drug substitution) and associated risk factors in HIV-infected Cambodians up to six years on antiretroviral treatment (ART).
METHODOLOGY/PRINCIPAL FINDINGS: This is a retrospective analysis of an observational cohort, using data from an ART program with systematic monitoring for D4T-toxicity. Probabilities of time to D4T substitution due to suspected D4T toxicity (treatment-limiting D4T toxicity) were calculated, a risk factor analysis was performed using multivariate Cox regression modelling. Out of 2581 adults initiating a D4T-containing regimen, D4T was replaced in 276 (10.7%) patients for neuropathy, 14 (0.5%) for lactic acidosis and 957 (37.1%) for lipoatrophy. The main early side effect was peripheral neuropathy (7.0% by 1 year). After the first year, lipoatrophy became predominant, with a cumulative incidence of 56.1% and 72.4% by 3 and 6 years respectively. Older age (aHR 1.8; 95%CI: 1.4-2.3) and lower baseline haemoglobin (aHR 1.7; 95%CI: 1.4-2.2) were associated with the occurrence of neuropathy. Being female (aHR 3.8; 95%CI: 1.1-12.5), a higher baseline BMI (aHR 12.6; 95%CI: 3.7-43.1), and TB treatment at ART initiation (aHR 8.6; 95%CI: 2.7-27.5) increased the likelihood of lactic acidosis. Lipoatrophy was positively associated with female gender (aHR 2.3; 95%CI: 2.0-2.6), an older age (aHR 1.3; 95%CI: 1.1-1.4), and a CD4 count <200 cells/µL (aHR 1.3; 95%CI: 1.1-1.5).
Stavudine-based treatment regimens in low-income countries are associated with significant long-term toxicities, predominantly lipoatrophy. Close clinical monitoring for toxicity with timely D4T substitution is recommended. Phasing-out of stavudine should be implemented, as costs allows.
尽管在亚洲的低收入国家中仍经常使用司他夫定（D4T），但有关其长期毒性的数据却很少。本研究的目的是在接受抗逆转录病毒治疗（ART）长达六年的时间内，确定感染艾滋病毒的柬埔寨人发生严重 D4T 毒性（需要药物替代）的长期发生率以及相关的危险因素。
方法/主要发现：这是一项观察性队列的回顾性分析，使用了具有系统性 D4T 毒性监测的 ART 计划中的数据。使用多变量 Cox 回归模型进行了风险因素分析，计算了因疑似 D4T 毒性（治疗受限的 D4T 毒性）而导致 D4T 替代的时间概率。在 2581 名开始使用 D4T 治疗的成年人中，有 276 名（10.7％）患者因周围神经病，14 名（0.5％）患者因乳酸酸中毒和 957 名（37.1％）患者因脂肪萎缩而更换 D4T。主要的早期副作用是周围神经病（1 年内为 7.0％）。第一年之后，脂肪萎缩变得更为普遍，其累积发生率分别为 3 年和 6 年时的 56.1％和 72.4％。年龄较大（aHR 1.8；95％CI：1.4-2.3）和较低的基线血红蛋白（aHR 1.7；95％CI：1.4-2.2）与周围神经病的发生有关。女性（aHR 3.8；95％CI：1.1-12.5），较高的基线 BMI（aHR 12.6；95％CI：3.7-43.1）和 ART 开始时的结核病治疗（aHR 8.6；95％CI：2.7-27.5）增加了乳酸酸中毒的可能性。脂肪萎缩与女性（aHR 2.3；95％CI：2.0-2.6），年龄较大（aHR 1.3；95％CI：1.1-1.4）和 CD4 计数<200 个/µL（aHR 1.3；95％CI：1.1-1.5）呈正相关。
在低收入国家中，基于司他夫定的治疗方案会导致严重的长期毒性，主要是脂肪萎缩。建议进行密切的临床监测，以发现毒性并及时更换 D4T。应逐步淘汰司他夫定，费用允许的情况下。
