Panichsillapakit Theppharit, Smith Davey M, Wertheim Joel O, Richman Douglas D, Little Susan J, Mehta Sanjay R
*Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; †Department of Medicine, University of California, San Diego, CA; ‡Veterans Affairs San Diego Healthcare System, San Diego, CA; and §Department of Pathology, University of California, San Diego, CA.
J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):228-36. doi: 10.1097/QAI.0000000000000831.
Transmitted drug resistance (TDR) remains an important concern when initiating antiretroviral therapy (ART). Here, we describe the prevalence and phylogenetic relationships of TDR among ART-naive, HIV-infected individuals in San Diego from 1996 to 2013.
Data were analyzed from 496 participants of the San Diego Primary Infection Cohort who underwent genotypic resistance testing before initiating therapy. Mutations associated with drug resistance were identified according to the WHO-2009 surveillance list. Network and phylogenetic analyses of the HIV-1 pol sequences were used to evaluate the relationships of TDR within the context of the entire cohort.
The overall prevalence of TDR was 13.5% (67/496), with an increasing trend over the study period (P = 0.005). TDR was predominantly toward nonnucleoside reverse transcriptase inhibitors (NNRTIs) [8.5% (42/496)], also increasing over the study period (P = 0.005). By contrast, TDR to protease inhibitors and nucleos(t)ide reverse transcriptase inhibitors were 4.4% (22/496) and 3.8% (19/496), respectively, and did not vary with time. TDR prevalence did not differ by age, gender, race/ethnicity, or risk factors. Using phylogenetic analysis, we identified 52 transmission clusters, including 8 with at least 2 individuals sharing the same mutation, accounting for 23.8% (16/67) of the individuals with TDR.
Between 1996 and 2013, the prevalence of TDR significantly increased among recently infected ART-naive individuals in San Diego. Around one-fourth of TDR occurred within clusters of recently infected individuals. These findings highlight the importance of baseline resistance testing to guide selection of ART and for public health monitoring.
启动抗逆转录病毒疗法(ART)时,传播耐药性(TDR)仍是一个重要问题。在此,我们描述了1996年至2013年期间圣地亚哥未接受过ART治疗的HIV感染者中TDR的流行情况及其系统发育关系。
分析了圣地亚哥原发性感染队列中496名参与者的数据,这些参与者在开始治疗前接受了基因型耐药性检测。根据世界卫生组织2009年监测清单确定与耐药性相关的突变。利用HIV-1 pol序列的网络分析和系统发育分析来评估整个队列背景下TDR的关系。
TDR的总体患病率为13.5%(67/496),在研究期间呈上升趋势(P = 0.005)。TDR主要针对非核苷类逆转录酶抑制剂(NNRTIs)[8.5%(42/496)],在研究期间也呈上升趋势(P = 0.005)。相比之下,对蛋白酶抑制剂和核苷(酸)类逆转录酶抑制剂的TDR分别为4.4%(22/496)和3.8%(19/496),且不随时间变化。TDR患病率在年龄、性别、种族/民族或危险因素方面无差异。通过系统发育分析,我们确定了52个传播簇,其中8个簇中至少有2人共享相同突变,占TDR个体的23.8%(16/67)。
1996年至2013年期间,圣地亚哥近期感染且未接受过ART治疗的个体中TDR患病率显著上升。约四分之一的TDR发生在近期感染个体的簇中。这些发现凸显了基线耐药性检测对于指导ART选择和公共卫生监测的重要性。