Impact of HIV Type 1 Subtype on Drug Resistance Mutations in Nigerian Patients Failing First-Line Therapy
Impact of HIV Type 1 Subtype on Drug Resistance Mutations in Nigerian Patients Failing First-Line Therapy
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DOI：
10.1089/aid.2010.0050
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发表时间：
2011-01-01
影响因子：
1.5
通讯作者：
Kanki, P.
中科院分区：
文献类型：
--
作者：
Chaplin, B.;Eisen, G.;Kanki, P.
多种非B亚型的HIV - 1病毒在非洲传播，并在全球大流行中占主导地位。了解非B亚型中的耐药突变如何与B亚型中所描述的模式不同是很重要的。对338名一线抗逆转录病毒治疗（ART）方案失败患者的HIV - 1逆转录酶和蛋白酶序列进行了评估。采用多变量逻辑回归分析来检验亚型对每种突变的影响，同时控制治疗方案、治疗时间和总突变数。HIV - 1亚型分布包括CRF02_AG（45.0%）、G（37.9%）、CRF06_cpx（4.4%）、A（3.3%）以及其他亚型或重组序列（9.2%）。最常见的核苷类逆转录酶抑制剂（NRTI）突变是M184V（89.1%）和胸苷类似物突变（TAMs）。最常见的非核苷类逆转录酶抑制剂（NNRTI）突变是Y181C（49.7%）、K103N（36.4%）、G190A（26.3%）和A98G（19.5%）。多变量分析表明，与其他亚型相比，CRF02_AG出现M41L突变的可能性较小[调整后的优势比（AOR）= 0.35；p = 0.022]。A亚型患者出现L210W突变的风险增加了42.5倍（AOR = 42.5，p = 0.001）。在NNRTI突变中，G亚型患者出现A98G（AOR = 2.40，p = 0.036）和V106I（AOR = 6.15，p = 0.010）的风险增加，而CRF02_AG亚型患者出现V90I（AOR = 3.16；p = 0.003）的风险增加，出现A98G（AOR = 0.48，p = 0.019）的风险降低。发现5种逆转录酶突变在不同的西非非B亚型之间存在显著差异。进一步研究以了解亚型特异性多样性对耐药性的临床影响，对于在资源有限的环境中扩大抗逆转录病毒治疗的持续成功至关重要。
A diverse array of non-subtype B HIV-1 viruses circulates in Africa and dominates the global pandemic. It is important to understand how drug resistance mutations in non-B subtypes may develop differently from the patterns described in subtype B. HIV-1 reverse transcriptase and protease sequences from 338 patients with treatment failure to first-line ART regimens were evaluated. Multivariate logistic regression was used to examine the effect of subtype on each mutation controlling for regimen, time on therapy, and total mutations. The distribution of HIV-1 subtypes included CRF02_AG (45.0%), G (37.9%), CRF06_cpx (4.4%), A (3.6%), and other subtypes or recombinant sequences (9.2%). The most common NRTI mutations were M184V (89.1%) and thymidine analog mutations (TAMs). The most common NNRTI mutations were Y181C (49.7%), K103N (36.4%), G190A (26.3%), and A98G (19.5%). Multivariate analysis showed that CRF02_AG was less likely to have the M41L mutation compared to other subtypes [adjusted odds ratio (AOR) = 0.35; p = 0.022]. Subtype A patients showed a 42.5-fold increased risk (AOR = 42.5, p = 0.001) for the L210W mutation. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR = 2.40, p = 0.036) and V106I (AOR = 6.15, p = 0.010), whereas subtype CRF02_AG patients had an increased risk for V90I (AOR = 3.16; p = 0.003) and a decreased risk for A98G (AOR = 0.48, p = 0.019). Five RT mutations were found to vary significantly between different non-B West African subtypes. Further study to understand the clinical impact of subtype-specific diversity on drug resistance will be critically important to the continued success of ART scale-up in resource-limited settings.