摘要目的 了解广东省2015年抗病毒治疗失败的艾滋病患者非核苷类逆转录酶抑制剂(NNRTIs)耐药相关基因突变的流行情况及特点.方法 连续收集2015年1月至12月广东省艾滋病诊疗控制中心收治的广东省(除深圳)抗病毒治疗1年以上且病毒载量>1000拷贝/mL患者的血浆样本.用实验室自建方法扩增获得612条HIV-1基因片段.构建系统进化树确定基因亚型,提交美国斯坦福大学HIV-1耐药数据库获得与NNRTIs耐药相关的突变位点,分析NNRTIs耐药情况,相关耐药突变与患者基线CD4+T淋巴细胞计数、传播途径、抗HIV治疗方案和病毒基因型之间的关系.采用SPSS17.0软件对数据进行分析.结果 612例病毒抑制失败患者中,与NNRTs相关的耐药突变位点以K103(26.80%)、Y181(14.71%)、V179(13.73%)、G190(11.44%)和V106(10.62%)为主.310例(50.65%)患者对NNRTIs的敏感性发生变化,其中对奈韦拉平(NVP)的高度耐药率(49.51%)高于依非韦伦(EFV,43.14%)、依曲韦林(ETR,5.56%)和利匹韦林(RPV,12.25%),差异具有统计学意义(χ2=5.00、296.3和198.0,P值<0.05);基线CD4+T淋巴细胞计数>200个/μL的患者耐药发生率低于<200个/μL患者(χ2=17.93,P<0.01);静脉注射毒品患者耐药发生率低于性传播患者(χ2=44.21,P<0.01);含NVP治疗方案的耐药发生率高于含EFV治疗方案人群(χ2=8.93,P<0.01);CRF01_AE型患者耐药发生率高于CRF07_BC和CRF08_BC型患者(χ2=8.46和8.47,P<0.01).结论 建议对基线CD4+T淋巴细胞计数较高及静脉注射毒品人群加强随访和依从性教育,合并肝脏疾病患者应避免使用含NVP的治疗方案.

abstractsObjective To investigate the prevalence and characteristics of non-nucleoside reverse transcriptase inhibitors (NNRTIs)resistance-related gene mutations among the AIDS patients with virological suppression failure in Guangdong Province 2015.Methods Plasma samples from AIDS patients receiving highly active antiretroviral therapy for more than one year with viral loads > 1000 copies/mL from Guangdong province (except Shenzhen)were collected from January to December 2015.Total 612 HIV-1 gene fragments were amplified from plasma samples using self-developed lab method.Sub-genotypes were determined by phylogenetic tree according to the sequences,NNRTIs resistance-related mutations were determined in Stanford University HIV-1 Drug Resistance Database. The NNRTIs-resistance, the relationships of NNRTIs resistance-related mutations with baseline CD4 +T lymphocyte counts,transmission routes,antiviral regimens and HIV-1 genotypes were analyzed.SPSS 17.0 software was used to analyze the data.Results In 612 patients with virological suppression failure,the main NNRTIs resistance-related mutations were K103 (26.80%),Y181 (14.71 %),V179 (13.73%),G190 (11 .44%) and V106 (10.62%).The susceptibility rate of 310 patients (50.65%)to NNRTIs had changed,the highly resistant rate to nevirapine was 49.51 %,which was higher than that of efavirenz (43.14%),etravirine (5.56%) and rilpivirine (12.25%),respectively,and the differences were statistically significant (χ2 =5.00,296.3 and 198.0,all P <0.05).The incidence rate of drug resistance in patients with baseline CD4 +T lymphocyte counts >200 cells/μL was lower than that in those with baseline CD4 +T lymphocyte counts <200 cells/μL (χ2 =17.93,P <0.01 );the incidence rate of drug resistance was lower in intravenous drug abusers than that of sexually transmitted patients (χ2 =44.21 ,P <0.01 );while the incidence of drug resistance in patients receiving NVP-containing regimens was higher than that in those receiving EFV-containing regimens (χ2 =8.93,P <0.01 ),and the incidence rate was higher in patients with CRF01 _AE than that in those with CRF07_BC and CRF08 _BC (χ2 =8.46 and 8.47,P <0.01 ).Conclusions The results suggest that compliance education and follow-up should be strengthened in patients with high baseline CD4 +T lymphocyte counts and intravenous drug users,and patients with liver diseases should avoid using drugs containing NVP regimens.