Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Clin Infect Dis. 2012 Aug;55(3):432-40. doi: 10.1093/cid/cis433. Epub 2012 Apr 26.
Antiretroviral therapy (ART) in resource-limited settings (RLSs) is monitored clinically and immunologically, according to World Health Organization (WHO) or national guidelines. Revised WHO pediatric guidelines were published in 2010, but their ability to accurately identify virological failure is unclear.
We evaluated performance of WHO 2010 guidelines and compared them with WHO 2006 and Cambodia 2011 guidelines among children on ≥6 months of first-line ART at Angkor Hospital for Children between January 2005 and September 2010. We determined sensitivity, specificity, positive and negative predictive values, and accuracy using bootstrap resampling to account for multiple tests per child. Human immunodeficiency virus (HIV) resistance was compared between those correctly and incorrectly identified by each guideline.
Among 457 children with 1079 viral loads (VLs), 20% had >400 copies/mL. For children with WHO stage 1/2 HIV, misclassification as failure (met CD4 failure criteria, but VL undetectable) was 64% for WHO 2006 guidelines, 33% for WHO 2010 guidelines, and 81% for Cambodia 2011 guidelines; misclassification as success (did not meet CD4 failure, but VL detectable) was 11%, 12%, and 12%, respectively. For children with WHO stage 3/4 HIV, misclassification as failure was 35% for WHO 2006 guidelines, 40% for WHO 2010 guidelines, and 43% for Cambodia 2011 guidelines; misclassification as success was 13%, 24%, and 21%, respectively. Compared with WHO 2006 guidelines, WHO 2010 guidelines significantly increased the risk of misclassification as success in stage 3/4 HIV (P < .05). The WHO 2010 guidelines failed to identify 98% of children with extensive reverse-transcriptase resistance.
In our cohort, lack of virological monitoring would result in unacceptable treatment failure misclassification, leading to premature ART switch and resistance accumulation. Affordable virological monitoring suitable for use in RLSs is desperately needed.
在资源有限地区（RLS），抗逆转录病毒疗法（ART）根据世界卫生组织（WHO）或国家指南进行临床和免疫监测。修订后的 WHO 儿科指南于 2010 年发布，但它们准确识别病毒学失败的能力尚不清楚。
我们评估了 2010 年 WHO 指南的性能，并将其与 2006 年 WHO 和 2011 年柬埔寨指南进行比较，比较对象为 2005 年 1 月至 2010 年 9 月在吴哥窟儿童医院接受一线 ART 治疗至少 6 个月的儿童。我们使用自举重采样来确定敏感性、特异性、阳性和阴性预测值以及准确性，以考虑每个儿童的多次检测。比较了根据每个指南正确和错误识别的 HIV 耐药性。
在 457 名儿童的 1079 个病毒载量（VL）中，20%的儿童的 VL>400 拷贝/ml。对于 HIV 处于 1/2 期的儿童，WHO 2006 指南将失败（符合 CD4 失败标准，但 VL 不可检测）错误分类为 64%，WHO 2010 指南为 33%，柬埔寨 2011 指南为 81%；将成功（未达到 CD4 失败标准，但 VL 可检测）错误分类为 11%、12%和 12%，分别。对于 HIV 处于 3/4 期的儿童，WHO 2006 指南将失败错误分类为 35%，WHO 2010 指南为 40%，柬埔寨 2011 指南为 43%；将成功错误分类为 13%、24%和 21%，分别。与 WHO 2006 指南相比，WHO 2010 指南显著增加了将 3/4 期 HIV 错误分类为成功的风险（P<0.05）。WHO 2010 指南未能识别 98%具有广泛逆转录酶耐药性的儿童。
在我们的队列中，缺乏病毒学监测将导致不可接受的治疗失败错误分类，从而导致过早切换 ART 和耐药性积累。迫切需要负担得起的适合 RLS 使用的病毒学监测。
