Institute of Human Virology, University of Maryland School of Medicine, MD, USA.
AIDS. 2013 Feb 20;27(4):553-61. doi: 10.1097/QAD.0b013e32835b0f59.
In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns.
Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list.
One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4).
At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.
在资源有限的环境下，无法进行 HIV-1 耐药性检测以指导抗逆转录病毒治疗（ART）的选择。我们回顾性地对接受靶向病毒载量检测以确认治疗失败的尼日利亚患者的存档样本进行了基因分型分析，并报告了他们的耐药突变模式。
对 349 名接受非核苷类逆转录酶抑制剂（NNRTI）方案治疗的成年患者的储存血浆进行 HIV-1 RNA 病毒载量检测，对病毒载量超过 1000 拷贝/ml 的样本进行 pol 基因测序。耐药突变分析采用 IAS-US 2011 耐药突变列表。
对 175 个样本进行了基因分型；主要亚型为 G（42.9%）和 CRF02_AG（33.7%）。患者接受 ART 的中位时间为 27 个月。90%的患者存在 M184V/I 突变，62%的患者至少有一种胸苷类似物突变，14%的患者存在 K65R 突变。97%的患者存在 NNRTI 耐药突变，47%的患者至少存在两种依曲韦林相关突变。多变量分析表明，在调整亚型、既往 ART、CD4 和 HIV 病毒载量后，基于替诺福韦的方案发生至少三种核苷逆转录酶抑制剂（NRTI）突变的可能性较小[P<0.001，比值比（OR）0.04]。与基于齐多夫定的方案（40%）相比，基于替诺福韦的方案中 70%的患者有至少两种可供二线方案使用的敏感 NRTI[P=0.04，OR=3.4]。
在识别治疗失败时，基于替诺福韦的一线方案患者的 NRTI 耐药突变较少，可供二线方案使用的活性 NRTI 药物更多。这些发现可以为 ART 方案排序策略提供信息，以优化资源有限环境下的长期 HIV 治疗结果。
