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菲律宾HIV感染者中与耐药相关突变的超深度测序分析:首份报告

Ultra-Deep Sequencing Analysis on HIV Drug-Resistance-Associated Mutations Among HIV-Infected Individuals: First Report from the Philippines.

作者信息

SahBandar Ivo N, Samonte Genesis, Telan Elizabeth, Siripong Nalyn, Belcaid Mahdi, Schanzenbach David, Leano Susan, Chagan-Yasutan Haorile, Hattori Toshio, Shikuma Cecilia M, Ndhlovu Lishomwa C

机构信息

1 Hawaii Center for AIDS, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii Manoa , Honolulu, Hawaii.

2 Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii Manoa , Honolulu, Hawaii.

出版信息

AIDS Res Hum Retroviruses. 2017 Nov;33(11):1099-1106. doi: 10.1089/AID.2016.0151. Epub 2017 Jul 5.

DOI:10.1089/AID.2016.0151
PMID:28569550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5749046/
Abstract

A sharp increase in the number of people living with HIV has been documented in the Philippines. In response, the government has instituted antiretroviral therapy (ART) nationwide through HIV treatment hubs. However, no data presently exist on the status of ART drug-resistance-associated mutations (DRMs). In this study, we aim at analyzing DRM profiles in the Philippines and at providing comprehensive data on DRMs to guide treatment decisions and prevent viral failures. We conducted a cross-sectional study in 119 volunteers who tested positive for HIV from more than 8,000 participants screened for HIV across the nation through the 2013 Integrated HIV Behavioral and Serologic Surveillance (IHBSS) program. Amplicons were generated from plasma RNA by using primers designed to analyze diverse HIV-1 isolates targeting the reverse transcriptase region and sequenced on a 454 ultra-deep sequencing (UDS) platform to assess DRMs. DRMs were defined by using the Stanford HIV drug resistance database, and we found only 2 from 110 evaluable individuals with major HIV variants (>20% prevalence) that were highly resistant to the non-nucleoside reverse transcriptase inhibitor (NNRTI: efavirenz and nevirapine). However, a larger fraction of individuals harbored minority drug-resistant HIV variants (0.5%-20% prevalence) and they were highly resistant to NNRTI nevirapine (89/110), rilpivirine (5/110), and efavirenz (49/110). This study is the first report on the presence of HIV drug resistance in the Philippines and demonstrates the utility of UDS in assisting the detection of HIV minor variants. Monitoring for ART-DRMs will assist in improving HIV management strategies in curtailing the evolving epidemic in the Philippines.

摘要

据记录,菲律宾感染艾滋病毒的人数急剧增加。作为应对措施,政府已通过艾滋病毒治疗中心在全国范围内推行抗逆转录病毒疗法(ART)。然而,目前尚无关于抗逆转录病毒疗法耐药相关突变(DRM)状况的数据。在本研究中,我们旨在分析菲律宾的DRM谱,并提供有关DRM的全面数据,以指导治疗决策并预防病毒治疗失败。我们对119名艾滋病毒检测呈阳性的志愿者进行了横断面研究,这些志愿者来自通过2013年综合艾滋病毒行为和血清学监测(IHBSS)计划在全国筛查艾滋病毒的8000多名参与者。通过使用设计用于分析靶向逆转录酶区域的多种艾滋病毒-1分离株的引物,从血浆RNA中生成扩增子,并在454超深度测序(UDS)平台上进行测序,以评估DRM。使用斯坦福艾滋病毒耐药数据库定义DRM,我们在110名可评估的主要艾滋病毒变体(流行率>20%)个体中仅发现2例对非核苷类逆转录酶抑制剂(NNRTI:依非韦伦和奈韦拉平)高度耐药。然而,更大比例的个体携带少数耐药艾滋病毒变体(流行率0.5%-20%),并且他们对NNRTI奈韦拉平(89/110)、利匹韦林(5/110)和依非韦伦(49/110)高度耐药。本研究是关于菲律宾艾滋病毒耐药情况的首份报告,并证明了UDS在协助检测艾滋病毒少数变体方面的实用性。监测抗逆转录病毒疗法相关DRM将有助于改进艾滋病毒管理策略,以遏制菲律宾不断演变的疫情。

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