Yuan Dan, Du Zonglun, Zhou Junmin, Ye Li, Su Ling, Yang Hong, Yuan Fengshun, Li Yiping, Liu Honglu, Zhai Wenwen, Liang Shu, Yang Shujuan
Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention.
School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China.
Medicine (Baltimore). 2019 Oct;98(43):e17585. doi: 10.1097/MD.0000000000017585.
This study sought to examine the human immunodeficiency virus type 1 (HIV-1) genetic diversity on drug resistance among men who have sex with men (MSM) with virologic failure in antiretroviral therapy (ART), and investigate linking-associated factors for genetic transmission networks.Seven hundred and thirty-four HIV-positive MSM with virologic failure in ART were recruited into our study from 2011 to 2017. HIV-1 pol gene sequences were used for phylogenetic and genotypic drug resistance analyses. The drug resistance mutations were determined using the Stanford University HIV Drug Resistance Database. The genetic transmission networks were analyzed for CRF01_AE and CRF07_BC sequences by the genetic distance-based method.Of 734 subjects, 372 (50.68%) showed drug resistance, in which CRF01_AE and CRF07_BC were the predominating subtypes. Drug resistance more frequently occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) treatment (48.64%), and followed by nucleoside reverse transcriptase inhibitors (NRTIs) (36.51%) and PIs (4.03%). The most common drug resistance-associated mutations in protease inhibitors (PIs), NRTIs and NNRTIs were K20I/R, M184V/I and K103N/KN, respectively. For 283CRF01_AE sequences, 64 (22.61%) fell into clusters at a genetic distance of 0.011, resulting in 17 clusters ranging in size from 2 to 16 individuals. For 230 CRF07_BC sequences, 66 (28.69%) were connected to at least one other sequence with 0.005 genetic distances, resulting in 8 clusters ranging in size from 2 to 52 individuals. Individuals who showed drug resistance to ART were less likely to fall into clusters than those who did not. The genetic linkage was robust by the exclusion of sites associated with drug resistance.CRF01_AE and CRF07_BC were the main strains among MSM with virologic failure in ART, and the drug resistance more frequently occurred in NNRTIs, followed by NRTIs and PIs. Genetic transmission networks revealed a complexity of transmission pattern, suggesting early-diagnosis and in-time intervention among MSM.
本研究旨在探讨接受抗逆转录病毒治疗(ART)出现病毒学失败的男男性行为者(MSM)中,人类免疫缺陷病毒1型(HIV-1)的耐药基因多样性,并调查基因传播网络的相关影响因素。2011年至2017年,734例接受ART出现病毒学失败的HIV阳性MSM被纳入本研究。HIV-1 pol基因序列用于系统发育和基因型耐药性分析。使用斯坦福大学HIV耐药数据库确定耐药突变。通过基于遗传距离的方法分析CRF01_AE和CRF07_BC序列的基因传播网络。734名受试者中,372例(50.68%)出现耐药,其中CRF01_AE和CRF07_BC是主要亚型。耐药在非核苷类逆转录酶抑制剂(NNRTIs)治疗中更常见(48.64%),其次是核苷类逆转录酶抑制剂(NRTIs)(36.51%)和蛋白酶抑制剂(PIs)(4.03%)。蛋白酶抑制剂(PIs)、核苷类逆转录酶抑制剂(NRTIs)和非核苷类逆转录酶抑制剂(NNRTIs)中最常见的耐药相关突变分别为K20I/R、M184V/I和K103N/KN。对于283条CRF01_AE序列,64条(22.61%)在遗传距离为0.011时聚为簇,形成17个簇,大小从2至16人不等。对于230条CRF07_BC序列,66条(28.69%)与至少一条其他序列在遗传距离0.005时相连,形成8个簇,大小从2至52人不等。对ART耐药的个体比未耐药的个体聚为簇的可能性更小。通过排除与耐药相关的位点,基因连锁关系较为稳固。CRF01_AE和CRF07_BC是接受ART出现病毒学失败的MSM中的主要毒株,耐药在NNRTIs中更常见,其次是NRTIs和PIs。基因传播网络揭示了传播模式的复杂性,提示对MSM进行早期诊断和及时干预。