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泰国儿童接受非核苷类逆转录酶抑制剂为基础的抗逆转录病毒治疗后病毒学失败的预测因素和基因型耐药突变模式。

Predictors of virologic failure and genotypic resistance mutation patterns in thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

机构信息

Department of Pediatric, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

出版信息

Pediatr Infect Dis J. 2009 Sep;28(9):826-30. doi: 10.1097/INF.0b013e3181a458f9.

DOI:10.1097/INF.0b013e3181a458f9
PMID:19654564
Abstract

BACKGROUND

Nonnucleoside reverse transcription inhibitor (NNRTI)-based antiretroviral therapy (ART) has been widely used as a first-line regimen for the treatment of HIV. This study aimed to determine the rate and predictors of virologic failure and describe patterns of resistance mutation.

METHODS

The inclusion criteria were children who were <18 years and receiving NNRTI-based ART. Plasma HIV-1 RNA and CD4 were monitored every 6 months. Virologic failure was defined as plasma HIVRNA >1000 copies/mL.

RESULTS

Forty (20%) of 202 children had virologic failure, of whom 33 (16%) failed in the first year of therapy. By multivariate analysis, the children who received nevirapine were 3.7 times more likely to develop virologic failure than those receiving efavirenz (P = 0.006). The prevalence's of patients with >or=1 major mutations conferring drug resistance to nucleoside reverse transcription inhibitors (NRTIs) and NNRTIs were 89% and 97%, respectively. The common NNRTI mutations were Y181C/I (58%) and K103N (34%). The NRTI mutations were M184V/I (84%), K65R (11%), Q151M (5%), and >or=3 TAMs (3%).

CONCLUSIONS

The virologic failure rate in children was high and mostly occurred in the first year of treatment. The most common resistance mutations were those conferring resistance to NNRTIs and lamivudine. There were few instances of multiNRTI resistance. Early detection of virologic failure might allow more options for second-line regimens.

摘要

背景

非核苷类逆转录酶抑制剂(NNRTI)为基础的抗逆转录病毒疗法(ART)已被广泛用作治疗 HIV 的一线方案。本研究旨在确定病毒学失败的发生率和预测因素,并描述耐药突变模式。

方法

纳入标准为接受 NNRTI 为基础的 ART 的<18 岁儿童。每 6 个月监测血浆 HIV-1 RNA 和 CD4。病毒学失败定义为血浆 HIVRNA >1000 拷贝/ml。

结果

202 名儿童中有 40 名(20%)发生病毒学失败,其中 33 名(16%)在治疗的第一年失败。多变量分析显示,接受奈韦拉平的儿童发生病毒学失败的可能性是接受依非韦伦的儿童的 3.7 倍(P=0.006)。>或=1 种对核苷逆转录酶抑制剂(NRTIs)和 NNRTIs 具有耐药性的主要突变的患者患病率分别为 89%和 97%。常见的 NNRTI 突变是 Y181C/I(58%)和 K103N(34%)。NRTI 突变是 M184V/I(84%)、K65R(11%)、Q151M(5%)和>或=3 TAMs(3%)。

结论

儿童的病毒学失败率较高,且大多发生在治疗的第一年。最常见的耐药突变是对 NNRTIs 和拉米夫定具有耐药性的突变。很少有多重 NRTI 耐药的情况。早期发现病毒学失败可能为二线方案提供更多选择。

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