Department of Medicine, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
J Med Virol. 2013 Feb;85(2):194-9. doi: 10.1002/jmv.23452. Epub 2012 Nov 14.
Antiretroviral therapy (ART) has increased in resource-limited settings. This study determined the prevalence of HIV-1 drug resistance-associated mutations (DRAMs) among patients with chronic HIV-1 infections and compare DRAMs between CRF01_AE and B subtypes. ART-naive Thai patients who had ART initiation between 2010 and 2011 were enrolled prospectively. Genotypic assays were performed on viral reverse transcriptase and protease genes within 4 weeks before starting ART. DRAMs were assessed using the International AIDS Society-USA 2011 list. A total of 330 patients were included. HIV-1 subtypes included CRF01_AE (73%), B (23.9%), and others (3.1%). Median (IQR) CD4+ was 66 (23-172) cells/mm(3) and median (IQR) HIV-1 RNA was 5.2 (4.6-5.8) log copies/ml. The prevalence of patients with ≥1 DRAMs for any antiretroviral agents was 17.6%. DRAM prevalence was 17% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.6% for NRTIs, and 0.6% for protease inhibitors (PIs). DRAMs to NNRTIs were V106I (7%), V179D (4.2%), V179T (1.8%), E138A (1.5%), V90I (1.2%), K103N (0.9%), Y181C (0.9%), and P225H (0.3%). DRAMs to NRTIs were M184V (0.3%) and T215S (0.3%). The only major DRAM for PIs was M46L (0.6%). Minor DRAMs to PIs including I13V, M36I, H69K, and L89M were observed more frequently in CRF_01 AE. By multivariate analysis, the factors "HIV-1 subtype B" and "low pretreated CD4+ cell count" were associated with a higher rate of DRAMs. HIV-1 DRAMs, especially to NNRTIs, are emerging in a middle-income country after widespread use of NNRTI-based ART. HIV genotypic assays before ART initiation in patients with chronic HIV-1 infection should be considered.
抗逆转录病毒疗法(ART)在资源有限的环境中有所增加。本研究旨在确定慢性 HIV-1 感染者中 HIV-1 耐药相关突变(DRAMs)的流行率,并比较 CRF01_AE 和 B 亚型之间的 DRAMs。2010 年至 2011 年间开始接受 ART 的泰国初治患者前瞻性入组。在开始 ART 前 4 周内,对病毒逆转录酶和蛋白酶基因进行基因分型检测。使用国际艾滋病协会-美国 2011 年列表评估 DRAMs。共纳入 330 例患者。HIV-1 亚型包括 CRF01_AE(73%)、B(23.9%)和其他(3.1%)。中位数(IQR)CD4+为 66(23-172)细胞/mm3,中位数(IQR)HIV-1 RNA 为 5.2(4.6-5.8)log 拷贝/ml。任何抗逆转录病毒药物耐药 DRAMs 发生率为 17.6%。NNRTIs 耐药 DRAMs 发生率为 17%,NRTIs 耐药 DRAMs 发生率为 0.6%,PI 耐药 DRAMs 发生率为 0.6%。NNRTIs 耐药 DRAMs 包括 V106I(7%)、V179D(4.2%)、V179T(1.8%)、E138A(1.5%)、V90I(1.2%)、K103N(0.9%)、Y181C(0.9%)和 P225H(0.3%)。NRTIs 耐药 DRAMs 包括 M184V(0.3%)和 T215S(0.3%)。PI 中唯一的主要耐药 DRAMs 是 M46L(0.6%)。PI 中的次要耐药 DRAMs 包括 I13V、M36I、H69K 和 L89M,在 CRF_01 AE 中更为常见。多因素分析显示,“HIV-1 亚型 B”和“低预处理 CD4+细胞计数”是 DRAMs 发生率较高的相关因素。在广泛应用基于 NNRTI 的 ART 后,中等收入国家出现了 HIV-1 DRAMs,尤其是对 NNRTIs 的耐药。在慢性 HIV-1 感染者开始 ART 前,应考虑进行 HIV 基因分型检测。