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美国中南部一家大型诊所中初治的HIV-1感染者中传播的抗逆转录病毒药物耐药性发生率。

Incidence of transmitted antiretroviral drug resistance in treatment-naive HIV-1-infected persons in a large South Central United States clinic.

作者信息

Kleyn Thomas J, Liedtke Michelle D, Harrison Donald L, Lockhart Staci M, Salvaggio Michelle R, Ripley Toni L, Rathbun R Chris

机构信息

Western University of Health Sciences, Pomona, CA, USA.

出版信息

Ann Pharmacother. 2014 Apr;48(4):470-5. doi: 10.1177/1060028013519246. Epub 2014 Jan 28.

Abstract

BACKGROUND

Transmitted drug resistance (TDR) can limit effective treatment options to antiretroviral-naive HIV-infected persons and increase the risk of treatment failure. Limited estimates of TDR have been reported from the South Central United States.

OBJECTIVE

To describe the incidence of TDR in Oklahoma and to examine whether TDR rates have increased with time.

METHODS

This was a retrospective observational study of antiretroviral-naive patients at the Infectious Diseases Institute, a large infectious diseases clinic in Oklahoma City, Oklahoma, who had received baseline antiretroviral resistance testing. Mutations were screened using the 2011 International Antiviral Society-USA Drug Resistance Mutation (DRM) update, and categorized using the 2009 World Health Organization (WHO) Surveillance Drug Resistance Mutation (SDRM) list.

RESULTS

Genotypic sequences from 428 patients revealed a 6.0% to 13.6% incidence of SDRMs between 2007 and 2011, though no progression in the frequency was apparent during the study period. Primary DRMs were detected in 12.6% of the sampled patients, most commonly involving nonnucleoside reverse transcriptase inhibitors (NNRTIs; 8.2%), followed by protease inhibitors (PIs; 3.5%) and nucleoside reverse transcriptase inhibitors (NRTIs; 3.3%). The K103N/S and E138A reverse transcriptase mutations were the most common DRMs identified, both present in 3.5% of patients. The L90M mutation was the most frequently observed PI SDRM (1.6%), while the T215C/D/I mutation was the most common NRTI SDRM identified (1.9%). This study was limited by the fact that the WHO SDRM list was last updated in 2009.

CONCLUSIONS

The frequency of DRMs in central and western Oklahoma is similar to recently reported rates in the United States which lack data from this region. However, the frequency of second-generation NNRTI DRMs (4.4%) suggests the need to closely monitor epidemiologic trends for increasing resistance rates to individual classes of ARVs in order to predict the impact of TDR on therapeutic options.

摘要

背景

传播性耐药(TDR)会限制初治HIV感染者的有效治疗选择,并增加治疗失败的风险。美国中南部地区关于TDR的评估报告有限。

目的

描述俄克拉荷马州TDR的发生率,并探讨TDR发生率是否随时间增加。

方法

这是一项对俄克拉荷马城一家大型传染病诊所——传染病研究所初治抗逆转录病毒治疗患者的回顾性观察研究,这些患者接受了基线抗逆转录病毒耐药性检测。使用2011年美国国际抗病毒学会耐药突变(DRM)更新版筛查突变,并根据2009年世界卫生组织(WHO)监测耐药突变(SDRM)列表进行分类。

结果

428例患者的基因序列显示,2007年至2011年间SDRM的发生率为6.0%至13.6%,不过在研究期间发生率没有明显变化。在12.6%的抽样患者中检测到主要DRM,最常见的是涉及非核苷类逆转录酶抑制剂(NNRTIs;8.2%),其次是蛋白酶抑制剂(PIs;3.5%)和核苷类逆转录酶抑制剂(NRTIs;3.3%)。K103N/S和E138A逆转录酶突变是最常见的DRM,在3.5%的患者中均有出现。L90M突变是最常观察到的PI SDRM(1.6%),而T215C/D/I突变是鉴定出的最常见的NRTI SDRM(1.9%)。本研究的局限性在于WHO SDRM列表最后一次更新是在2009年。

结论

俄克拉荷马州中部和西部的DRM频率与美国最近报告的缺乏该地区数据的频率相似。然而,第二代NNRTI DRM的频率(4.4%)表明需要密切监测流行病学趋势,以了解对个别抗逆转录病毒药物类别耐药率的上升情况,从而预测TDR对治疗选择的影响。

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