Taniguchi Toshibumi, Nurutdinova Diana, Grubb Jessica R, Önen Nur F, Shacham Enbal, Donovan Michael, Overton Edgar Turner
Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
AIDS Res Hum Retroviruses. 2012 Mar;28(3):259-64. doi: 10.1089/aid.2011.0022. Epub 2011 Aug 30.
Trends in transmitted drug resistance-associated mutations (TDRM) in HIV-1infection vary depending on geographic and cohort characteristics. The impact of TDRM among patients receiving fully active combination antiretroviral therapy (cART) is poorly characterized. This was a retrospective study of 801 HIV-1-infected treatment-naive patients from 2001 to 2009 who had pre-cART genotype resistance test results available. The prevalence of TDRM was compared for each year strata. Multivariate Cox proportional hazards regression models were used to assess factors associated with virologic failure at 48 weeks. TDRM was detected in 136 (17%) patients with ≥2 class TDRM in 20 patients. K103N/S was the most frequent (n=77). There were no changes in the prevalence of mutations over time (P(trend)=0.67). Six hundred and eleven patients were started on cART. Virologic failure occurred in 38% of those with TDRM and 24% of those without (p<0.01). In multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance was associated with a 1.5-fold increased risk of virologic failure. TDRM remains common among treatment-naive HIV-1-infected patients, affecting one in six patients. Transmission of NNRTI drug resistance was associated with risk of virologic failure despite initiation of genotype-guided cART.
HIV-1感染中与传播相关的耐药性突变（TDRM）的趋势因地理和队列特征而异。在接受完全有效的联合抗逆转录病毒疗法（cART）的患者中，TDRM的影响尚不明确。这是一项对2001年至2009年间801例初治HIV-1感染患者的回顾性研究，这些患者有cART前基因型耐药性检测结果。比较了各年份分层中TDRM的患病率。使用多变量Cox比例风险回归模型评估与48周时病毒学失败相关的因素。在136例（17%）患者中检测到TDRM，其中20例患者有≥2类TDRM。K103N/S最为常见（n = 77）。随着时间推移，突变患病率没有变化（P（趋势）= 0.67）。611例患者开始接受cART。有TDRM的患者中38%发生病毒学失败，无TDRM的患者中24%发生病毒学失败（p<0.01）。在多变量分析中，非核苷类逆转录酶抑制剂（NNRTI）耐药性与病毒学失败风险增加1.5倍相关。TDRM在初治HIV-1感染患者中仍然很常见，每六名患者中就有一名受影响。尽管开始了基因型指导的cART，但NNRTI耐药性的传播与病毒学失败风险相关。
