Incidence of Treatment-Limiting Toxicity with Stavudine-Based Antiretroviral Therapy in Cambodia: A Retrospective Cohort Study
Incidence of Treatment-Limiting Toxicity with Stavudine-Based Antiretroviral Therapy in Cambodia: A Retrospective Cohort Study
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DOI：
10.1371/journal.pone.0030647
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发表时间：
2012-01-27
期刊：
影响因子：
3.7
通讯作者：
van Griensven, Johan
中科院分区：
文献类型：
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作者：
Phan, Vichet;Thai, Sopheak;van Griensven, Johan
背景：尽管司他夫定 (D4T) 在亚洲低收入国家仍然经常使用，但相关的长期毒性数据却很少。本研究的目的是确定接受抗逆转录病毒治疗 (ART) 长达六年的 HIV 感染柬埔寨人中严重 D4T 毒性（需要药物替代）的长期发生率和相关危险因素。 方法/主要发现：这是对观察队列的回顾性分析，使用了 ART 项目的数据，并系统监测了 D4T 毒性。计算由于怀疑 D4T 毒性（治疗限制性 D4T 毒性）而进行 D4T 替代的时间概率，并使用多变量 Cox 回归模型进行危险因素分析。在 2581 名开始含 D4T 治疗方案的成年人中，276 名（10.7%）名患者因神经病变、14 名（0.5%）名因乳酸酸中毒和 957 名（37.1%）名因脂肪萎缩而被替换为 D4T。主要的早期副作用是周围神经病变（1 年时为 7.0%）。第一年后，脂肪萎缩占主导地位，3 年和 6 年的累积发生率分别为 56.1% 和 72.4%。年龄较大（aHR 1.8；95%CI：1.4-2.3）和基线血红蛋白较低（aHR 1.7；95%CI：1.4-2.2）与神经病变的发生相关。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）以及ART开始时的结核病治疗（aHR 8.6；95%CI：2.7-27.5）增加了乳酸性酸中毒的可能性。脂肪萎缩与女性性别（aHR 2.3；95%CI：2.0-2.6）、年龄较大（aHR 1.3；95%CI：1.1-1.4）和 CD4 计数呈正相关
Background: 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