Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa
Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa
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DOI：
10.1093/jac/dkw218
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发表时间：
2016-10-01
影响因子：
5.2
通讯作者：
Sigaloff, Kim C. E.
中科院分区：
文献类型：
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作者：
Boender, T. Sonia;Kityo, Cissy M.;Sigaloff, Kim C. E.
在撒哈拉以南非洲，艾滋病毒治疗方案中病毒载量（VL）监测的可用性有限，这可能会延迟转为二线抗逆转录病毒疗法，导致耐药性突变（DRM）的积累。本研究的目的是评估撒哈拉以南非洲地区成人和儿童在一线抗逆转录酶抑制剂治疗持续病毒学失败后逆转录酶抑制剂耐药的累积情况，包括接受基于非核苷类逆转录酶抑制剂的一线抗逆转录酶抑制剂治疗的HIV-1阳性成人和儿童。进行回顾性VL和pol基因型检测，如果VL为每千日元1000拷贝/mL的部分。在持续病毒学失败的参与者中（a parts per thousand yen 2 VL a parts per thousand yen 1000 copies/mL），评估耐药性。在首次病毒学失败时，在87%的参与者中检测到DRM：K103n（38.7%），G190A（21.8%），Y181C（20.2%），V106 M（8.4%），K101 E（8.4%），任何E138与NNRTI相关的M184 V（69.7%）、任何胸苷类似物突变（9.2%）、K65 R（5.9%）和K70 R（5.0%）。新DRM的平均累积速率为每年1.45（SD 2.07）DRM;每年分别为0.62（SD 1.11）NNRTI DRM和0.84（SD 1.38）NRTI DRM。在所有逆转录酶抑制剂持续病毒学失败后，预测的易感性显著下降（所有PaEuroS <aEuroS 0.001）。成人和儿童的获得性耐药模式相似，撒哈拉以南非洲的成人和儿童在一线抗逆转录病毒治疗失败后的耐药模式相似。需要改进VL监测以防止突变的积累，并需要新的药物类别以构建完全活性的方案。
Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa.HIV-1-positive adults and children on an NNRTI-based first-line ART were included. Retrospective VL and, if VL a parts per thousand yen1000 copies/mL, pol genotypic testing was performed. Among participants with continued virological failure (a parts per thousand yen2 VL a parts per thousand yen1000 copies/mL), drug resistance was evaluated.At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. New DRMs accumulated with an average rate of 1.45 (SD 2.07) DRM per year; 0.62 (SD 1.11) NNRTI DRMs and 0.84 (SD 1.38) NRTI DRMs per year, respectively. The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all PaEuroS < aEuroS0.001). Acquired drug resistance patterns were similar in adults and children.Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. Improved VL monitoring to prevent accumulation of mutations, and new drug classes to construct fully active regimens, are required.