Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline.
Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline.
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马拉维抗逆转录病毒计划中的二线治疗：早期死亡率很高，但幸存者的结果良好，尽管基线时具有广泛的耐药性。
DOI：
10.1111/j.1468-1293.2010.00825.x
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发表时间：
2010-09
期刊：
影响因子：
3
通讯作者：
van Oosterhout JJ
中科院分区：
文献类型：
--
作者：
Hosseinipour MC;Kumwenda JJ;Weigel R;Brown LB;Mzinganjira D;Mhango B;Eron JJ;Phiri S;van Oosterhout JJ
马拉维的抗逆转录病毒疗法方案采用公共卫生办法来查明抗逆转录病毒疗法失败的情况。晚期疾病进展可能发生在转换为二线ART之前。我们报告了马拉维评估和开始二线治疗患者的结局。在两个大型城市ART诊所中，对符合马拉维ART失败免疫学或临床标准的患者进行病毒学失败（病毒载量>400 HIV-1 RNA拷贝/mL）评估，如果证实失败，则开始二线ART（齐多夫定/拉米夫定/替诺福韦/洛匹那韦/利托那韦）。患者每月就诊一次，每季度和根据需要进行实验室评价。我们进行了逻辑回归建模，以确定与死亡率，死亡率或新的艾滋病毒疾病，以及在12个月的病毒学抑制相关的因素。在确认病毒学失败的109例患者中，5例患者在开始治疗前死亡，3例患者拒绝转换，101例患者开始二线治疗。在12个月内，另有10名患者死亡，34名患者发生了45起艾滋病毒相关事件，19名患者发生了3级或4级毒性。在存活者中，85.2%在12个月时HIV-1 RNA<400拷贝/mL。虽然区分差异的能力有限，但无论基线耐药水平如何，应答率均相似。中位CD 4计数增加为142个细胞/μL。基线时世界卫生组织临床失败[比值比（OR）3.47; 95%置信区间（CI）1.14-10.59]和体重指数<18.5（OR 4.43; 95% CI 1.15-17.12）是死亡的危险因素。基线CD 4计数<50个细胞/μL与12个月时死亡或发病风险增加相关（OR 2.57; 95% CI 1.01-6.52）。马拉维的二线治疗与大量死亡率、发病率和毒性有关，但在幸存者中，病毒学结果是有利的。
The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/μL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14–10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15–17.12) were risk factors for death. Baseline CD4 count <50 cells/μL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01–6.52). Second-line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.