Low-Frequency HIV-1 Drug Resistance Mutations and Risk of NNRTI-Based Antiretroviral Treatment Failure
Low-Frequency HIV-1 Drug Resistance Mutations and Risk of NNRTI-Based Antiretroviral Treatment Failure
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2011
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通讯作者：
R. Paredes;H. Ribaudo;E. Svarovskaia;K. Metzner;M. Kozal;K. H. Hullsiek;M. Balduin;M. Jakobsen;A. Geretti;R. Thiébaut;L. Ostergaard;B. Masquelier;Jeffrey A Johnson;Michael D. Miller;D. Kuritzkes
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作者：
R. Paredes;H. Ribaudo;E. Svarovskaia;K. Metzner;M. Kozal;K. H. Hullsiek;M. Balduin;M. Jakobsen;A. Geretti;R. Thiébaut;L. Ostergaard;B. Masquelier;Jeffrey A Johnson;Michael D. Miller;D. Kuritzkes
人类免疫缺陷病毒1型(HIV-1)耐药性的基因分型测试使用聚合酶链式反应(PCR)扩增和群体测序技术，检测至少15%至25%的病毒群体中存在与耐药性相关的突变。使用这些传统检测方法，在北美和欧洲的HIV-1感染者中，传播耐药突变的流行率估计在8%到16%之间。这些检测方法无法检测到感染个体中HIV-1准种种群中存在低频或少数抗药性突变。与标准群体测序相比，一些超灵敏的分析方法，包括等位基因特异性聚合酶链式反应和深度测序，可以检测突变，作者在文章的结尾列出了这些突变。通讯作者：Jonathan Z.Li，MD(jli22@partners.org)和Daniel R.Kuritzkes，MD(dkuritzkes@partners.org)，哈佛医学院布里格姆和妇女医院逆转录病毒治疗科，65 Landsdown St，435室，剑桥，MA 02139。背景：人类免疫缺陷病毒1型(HIV-1)耐药低频率或少数突变的存在可能会对抗逆转录病毒治疗(ART)的反应产生不利影响，但关于此类突变对一线ART有效性的影响的证据相互矛盾。
GENOTYPIC TESTS FOR HUMAN immunodeficiency virus type 1 (HIV-1) drug resistance use polymerase chain reaction (PCR) amplification and population sequencing techniques that detect resistance-associated mutations present in at least 15% to 25% of the viral population. Using these traditional assays, the prevalence of transmitted drug resistance mutations is estimated to be between 8% and 16% among HIV-1 infected persons in North America and Europe. These assays fail to detect the presence of low-frequency, or minority, drug resistance mutations within the population of HIV-1 quasispecies in an infected individual. Compared with standard population sequencing, a number of ultrasensitive assays, including allele-specific PCR and deep sequencing, can detect mutations Author Affiliations are listed at the end of this article. Corresponding Authors: Jonathan Z. Li, MD (jli22 @partners.org), and Daniel R. Kuritzkes, MD (dkuritzkes @partners.org), Section of Retroviral Therapeutics, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne St, Room 435, Cambridge, MA 02139. Context Presence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting.