广州市2008-2015年未接受抗病毒治疗的注射吸毒人群HIV-1感染者耐药分析

Prevalence of antiretroviral drug resistance in treatment-naive injecting drug users infected with HIV-1 in Guangzhou, 2008-2015

目的了解广州市未接受抗病毒治疗的注射吸毒人群(IDU)HIV-1感染者耐药株流行情况。方法收集2008-2015年新确证HIV-1抗体阳性、现住址为广州市、传播途径为注射吸毒、确证时未接受抗病毒治疗的IDU HIV-1感染者的血清样本,提取HIV-1 RNA,采用巢式PCR法扩增pol区蛋白酶(PR)基因全序列与反转录酶(RT)基因部分序列并测序后,提交到美国斯坦福大学HIV耐药数据库做耐药分析。结果 518例HIV感染者中,有407例(78.57%)血清样本成功获得pol区基因片段。年龄18~64(37.44±8.14)岁,男性占89.68%(365/407),汉族占89.93%(366/407),未婚者占55.28%(225/407),文化程度以初中及以下为主(83.78%,341/407)。HIV-1亚型以CRF07_BC为主(47.18%,192/407),CRF01_AE占23.83%(97/407)和CRF08_BC占22.85%(93/407),其他亚型占6.14%(25/407)。总耐药率为3.44%(14/407),蛋白酶抑制剂耐药率为1.47%(6/407),核苷类反转录酶抑制剂耐药率为0.25%(1/407),非核苷类反转录酶抑制剂耐药率为1.72%(7/407)。突变发生率为12.29%(50/407),蛋白酶区和核苷类反转录酶区未检出主要耐药突变,非核苷类反转录酶区中V179E突变率更高的是其他亚型和CRF07_BC亚型,其他亚型中的CRF55_01B亚型8例全部发生此突变;E138A突变率最高的是CRF08_BC亚型,为3.23%。有2例病例对NNRTIs的4种药物全都耐药。结论 2008-2015年广州市未接受抗病毒治疗的IDU HIV-1感染者的耐药率处于较低水平,大多数IDU HIV-1感染者对现有抗病毒治疗药物敏感。应加强IDU HIV-1感染者的耐药监测,控制耐药性毒株多重、交叉耐药的流行。

Objective To understand the prevalence of drug resistance in treatment-naive injecting drug users (IDUs) infected with HIV-1 in Guangzhou. Methods HIV-1 RNA were extracted from the serum specimens of the newly confirmed HIV-1 positive IDUs living in Guangzhou, being infected through injecting drug use and receiving no antiretroviral therapy at the time of confirmation during 2008-2015. Full sequence of pol protease (PR) gene and partial sequence of reverse transcriptase (RT) gene were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and sequenced. After that, data were submitted to the HIV resistance database of Stanford University for drug resistance analysis. Results Among the 518 HIV-1 infected IDUs, HIV-1pol gene segments were successfully obtained from the serum samples of 407 HIV-1 infected IDUs (78.57%) aged 18-64 (37.44±8.14) years. Among them, males accounted for 89.68%(365/407), those of Han ethnic group accounted for 89.93%(366/407), the unmarried accounted for 55.28%(225/407), and those with education level of junior high school or below accounted for 83.78%(341/407). The distribution of subtypes was predominated by CRF07_BC (47.18%, 192/407), followed by CRF01_AE (23.83%, 97/407), CRF08_BC (22.85%, 93/407), and other subtypes (6.14%, 25/407). The overall prevalence of drug resistance was 3.44%(14/407). The prevalence of drug resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors were 1.47%(6/407), 0.25%(1/407) and 1.72%(7/407) respectively. The mutation rate was 12.29%(50/407). No major drug resistance mutation was detected in protease and nucleoside reverse transcriptase regions. Higher rate of V179E mutation in the non-nucleoside reverse transcriptase region was detected in other subtypes and subtype CRF07_BC. Mutation seemed to have occurred in all 8 cases of subtype CRF55_01B in other subtypes. The highest mutation rate of E138A was detected in subtype CRF08_BC (3.23%). Two cases were resistant to all four drugs of NNRTIs. Conclusions The prevalence of drug resistance in treatment-naive HIV-1 positive IDUs remained at a relatively low level during 2008-2015, in Guangzhou. Most infections were sensitive to existing antiviral drugs. However, drug resistance surveillance in IDUs infected with HIV should be strengthened to prevent the prevalence of multi-drug resistance and cross drug resistance.