Mutwa Philippe R, Boer Kimberly R, Rusine John, Muganga Narcisse, Tuyishimire Diane, Schuurman Rob, Reiss Peter, Lange Joep M A, Geelen Sibyl P M
From the *Department of Pediatrics, Kigali University Teaching Hospital; †Academic Medical Centre/Amsterdam Institute for Global Health and Development, Kigali, Rwanda; ‡Academic Medical Centre/Amsterdam Institute for Global Health and Development; §Royal Tropical Institute (KIT), Biomedical Research, Epidemiology Unit, Amsterdam, The Netherlands; ¶National Reference Laboratory; ‖Treatment and Research on HIV/AIDS Centre (TRAC-plus), Outpatients clinic, Kigali, Rwanda; **Department of Virology, University Medical Centre; and ††Utrecht University Children's Hospital/University Medical Centre Utrecht, Utrecht, The Netherlands.
Pediatr Infect Dis J. 2014 Jan;33(1):63-9. doi: 10.1097/INF.0b013e31829e6b9f.
To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy.
A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed.
Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%).
Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.
确定接受联合抗逆转录病毒治疗的儿童和青少年的长期治疗结果及基因型耐药的流行情况。
一项横断面研究（2009年9月至2010年10月），在一次研究访视时以及通过一组感染HIV的儿童和青少年的患者记录来评估临床、免疫和病毒学结果。使用逻辑回归评估临床和免疫反应及病毒学结果的危险因素，并评估临床和免疫标准在识别病毒学失败方面的准确性。
共纳入424例患者，中位年龄为10.8岁（范围：1.7 - 18.8岁），联合抗逆转录病毒治疗的中位疗程为3.4年（范围：1.0 - 8.1年）。33%发育迟缓，17%体重不足。5岁以上儿童中84%（95%置信区间：79 - 87）的CD4≥350细胞/mm，年幼儿童中74%（95%置信区间：62 - 84）的CD4%≥25。开始联合抗逆转录病毒治疗时的CD4值和年龄与CD4结果独立相关；124例（29%）HIV-1 RNA≥1000拷贝/mL，无显著预测因素。年龄别体重、年龄别身高和CD4细胞（<350/mm）的敏感性仍低于50%（15 - 42%）；CD4细胞显示出最佳特异性，范围为91%至97%。在检测的52个样本中，91%（核苷类逆转录酶抑制剂）和95%（非核苷类逆转录酶抑制剂）观察到≥1个突变；16例（31%）检测到1至2个与胸苷类似物相关的突变，7例（13%）检测到≥3个与胸苷类似物相关的突变。
近三分之一的儿童出现病毒学失败，在进行基因分型的治疗失败儿童亚组中，超过10%显示出多种HIV耐药突变。临床状况和CD4细胞均不是治疗失败的良好指标。
