Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.
Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.
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2007 - 2013年原发性HIV-1感染的抗逆转录病毒 - 不属性受试者中缺乏对整合酶抑制剂的抗性。
DOI：
10.3851/imp2780
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发表时间：
2015
影响因子：
1.2
通讯作者：
Collier AC
中科院分区：
文献类型：
--
作者：
Stekler JD;McKernan J;Milne R;Tapia KA;Mykhalchenko K;Holte S;Maenza J;Stevens CE;Buskin SE;Mullins JI;Frenkel LM;Collier AC
美国指南建议对新诊断的HIV感染者进行基因分型，以确定与NRTI、NNRTI和PI敏感性降低相关的传播性耐药突变。到目前为止，还没有常规推荐检测整合酶链转移抑制剂（CITI）突变。我们的目的是评估在华盛顿州西雅图原发性HIV-1感染者中传播的HIV-1基因突变的患病率。自1992年以来，患有原发性HIV-1感染的人在华盛顿大学原发性感染诊所参加了一个观察队列。我们对从2007年至2013年入组的82名未经抗逆转录病毒治疗的受试者中前瞻性收集的血浆标本进行了回顾性分析，这些受试者是在FDA批准第一种抗逆转录病毒药物后。通过共识测序进行耐药性检测。在估计HIV-1感染日期后中位数24天（lQR 18-41，范围8-108）获得用于分析的标本。除1例受试者感染C亚型外，所有受试者均感染HIV-1 B亚型。共有测序未发现有主要的cDNAI突变（T66 I、E92 Q、G140 S、Y143 C/H/R、S147 G、Q148 H/K/R、N155 H）的受试者。使用精确二项置信区间，95% CI的上限为4.4%。虽然我们的样本量很小，但这项研究不支持在新诊断为HIV-1感染的患者中评估整合酶突变作为常规共识测序的一部分的必要性。然而，随着最近更多INSTI的商业化引入，以及HIV-1感染者中可能更多的INSTI使用，传播的INSTI突变的流行率可能会增加。
U.S. guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to NRTIs, NNRTIs, and PIs. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA. Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007–13, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing. Specimens for analysis had been obtained a median of 24 (lQR 18–41, range 8–108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial confidence intervals, the upper bound of the 95% CI was 4.4%. Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INST1 use among persons living with HIV-1.