Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Amsterdam Institute of Global Health Development (AIGHD), Amsterdam, The Netherlands.
J Antimicrob Chemother. 2018 Dec 1;73(12):3471-3475. doi: 10.1093/jac/dky348.
Drug resistance mutations (DRMs) increasingly jeopardize paediatric HIV programmes in sub-Saharan Africa. As individual monitoring of DRMs and viral loads has limited availability, population data on DRMs are essential to determine first-line susceptibility. Paediatric data from sub-Saharan Africa are scarce and unavailable for Malawi.
To determine the prevalence of virological failure (VF) and DRMs among ART-naive HIV-infected Malawian children during the first year of first-line ART.
In a prospective cohort of HIV-infected Malawian children, on first-line treatment, children were followed monthly; blood was collected for viral load testing (6 and 12 months) and genotypic resistance testing (12 months). VF was defined as at least one viral load >1000 copies/mL or death after 6 months of ART. DRMs were identified and susceptibility to NRTIs and NNRTIs was scored using the Stanford algorithm and by calculating genotypic susceptibility scores (GSSs).
VF occurred in 66% (23/35) of the children during 12 months of follow-up. DRMs were detected in 44% (15/34); all had NNRTI resistance and 12% (4/34) had dual-class NNRTI/NRTI resistance. Reduced susceptibility (DRMs and GSS <3) was seen in 41% (14/34) to their current first-line regimen. High-level resistance was most common for nevirapine [26% (9/34)].
In this first report on VF and DRMs in children on first-line ART in Malawi, the rates of VF and DRMs were alarmingly high. Paediatric HIV programmes in sub-Saharan Africa should emphasize programmatic evaluation of VF and include detection of DRMs to adjust and design adequate first- and second-line regimens and prevent widespread resistance in children.
耐药突变（DRMs）日益威胁着撒哈拉以南非洲的儿科艾滋病毒项目。由于对 DRMs 和病毒载量的个体监测可用性有限，因此需要人群数据来确定一线药物敏感性。撒哈拉以南非洲的儿科数据稀缺，马拉维没有相关数据。
确定在接受一线抗逆转录病毒治疗（ART）的首年内，感染艾滋病毒的马拉维儿童中出现病毒学失败（VF）和耐药突变的比例。
在一项前瞻性队列研究中，对感染艾滋病毒的马拉维儿童进行了研究，这些儿童正在接受一线治疗，每月进行随访；在 6 个月和 12 个月时采集血液进行病毒载量检测，在 12 个月时进行基因耐药性检测。VF 定义为至少一次病毒载量>1000 拷贝/ml 或在 ART 治疗 6 个月后死亡。通过斯坦福算法和计算基因型耐药评分（GSS）来识别耐药突变并评估 NRTIs 和 NNRTIs 的耐药性。
在 12 个月的随访期间，66%（23/35）的儿童出现 VF。34 例儿童中有 44%（15/34）检测到耐药突变；所有儿童均对 NNRTIs 耐药，12%（4/34）对 NNRTI/NRTI 双重耐药。当前一线方案中，41%（14/34）的儿童存在耐药性（DRMs 和 GSS<3）。对奈韦拉平的高耐药率最为常见[26%（9/34）]。
在马拉维首例儿童接受一线 ART 治疗的 VF 和耐药突变报告中，VF 和耐药突变的发生率非常高。撒哈拉以南非洲的儿科艾滋病毒项目应强调对 VF 的方案评估，并包括耐药突变的检测，以调整和设计适当的一线和二线方案，防止儿童中广泛耐药。
