School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
J Acquir Immune Defic Syndr. 2011 Mar 1;56(3):270-8. doi: 10.1097/QAI.0b013e3182060610.
With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.
Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (2 consecutive unsuppressed viral loads with the second being >1000 copies/mL, after ≥24 weeks of therapy) and switch to second-line. Cox-proportional hazards models stratified by program were used to determine predictors of these outcomes.
The 3-year probability of virologic failure among 5485 children was 19.3% (95% confidence interval: 17.6 to 21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared with efavirenz) and exposure to prevention of mother to child transmission regimens were independently associated with failure [adjusted hazard ratios (95% confidence interval): 1.77 (1.11 to 2.83), 2.39 (1.57 to 3.64) and 1.40 (1.02 to 1.92), respectively]. Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (interquartile range) months between failure and switch was 5.7 (2.9-11.0).
Triple ART based on nevirapine or ritonavir as a single protease inhibitor seems to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.
随着扩大儿科抗逆转录病毒治疗(ART)的可及性,儿童将开始经历治疗失败,并需要二线治疗。我们评估了南非儿童发生病毒学失败和转换的概率和决定因素。
对 7 个南非治疗项目中接受 ART 治疗的儿童的常规个体数据进行汇总分析,这些项目每 6 个月进行一次病毒载量和 CD4 监测,使用 Kaplan-Meier 估计病毒学失败(治疗≥24 周后连续 2 次未抑制病毒载量,第二次>1000 拷贝/mL)和转换为二线治疗的概率。使用按项目分层的 Cox 比例风险模型来确定这些结果的预测因素。
5485 名儿童中,3 年病毒学失败的概率为 19.3%(95%置信区间:17.6%至 21.1%)。初始方案中使用奈韦拉平或利托那韦单药(与依非韦伦相比)和接触预防母婴传播方案与失败独立相关[调整后的危险比(95%置信区间):1.77(1.11 至 2.83),2.39(1.57 至 3.64)和 1.40(1.02 至 1.92)]。在 252 名随访时间≥1 年的失败儿童中,38%的儿童转换为二线治疗。失败与转换之间的中位(四分位距)时间为 5.7(2.9-11.0)个月。
基于奈韦拉平或利托那韦作为单一蛋白酶抑制剂的三药 ART 似乎与病毒学失败的风险较高相关。只有少数病毒学失败的儿童被转换。