2019-2020年地坛医院HIV-1感染者治疗前耐药及影响因素

Analysis on the prevalence and influencing factors of pretreatment HIV drug resistance among adults at Ditan Hospital in Beijing(2019-2020)

目的分析北京市地坛医院HIV-1感染者治疗前耐药(PDR)流行情况及影响因素。方法收集2019年1月至2020年12月首都医科大学附属北京地坛医院就诊的未经ART的HIV-1感染者人口学特征、实验室检查结果及血浆标本,通过巢式反转录聚合酶链反应扩增HIV-1 pol基因,将测序结果与美国斯坦福大学HIV耐药数据库比对,分析HIV-1 PDR特征。结果1489例初治HIV-1感染者中,扩增成功1372例,扩增成功率为92.1%。2019-2020年总体耐药率为5.6%。其中NNRTIs的耐药率为4.6%,主要的突变位点为E138A/G和V179D/E,其次为K103 N/T/R和V106M/I;NRTIs的耐药率为1.5%,主要突变位点为M184V/I;PIs的耐药率为0.1%。2019年耐药率为3.8%,2020年为7.8%,2020年耐药率有上升趋势。NNRTI中NVP和EFV耐药率为6.3%,其中2019年为4.5%,2020年为8.4%。总体潜在耐药率为10.7%,其中NNRTIs、NRTIs和PIs的潜在耐药率分别为10.0%、0.3%和0.4%。2020年、CD4细胞计数<50个/μL为PDR的危险因素。与CRF01_AE亚型相比,B亚型和CRF55_01B亚型和其他亚型发生PDR的风险较高。结论2020年PDR发生率比2019年明显增高,以NNRTIs耐药为主,且NVP和EFV耐药率上升明显。发生PDR的风险因素与B亚型、CRF55_01B亚型、其他亚型、年度和低CD4细胞计数有关。因此应加强监测,有条件时应在治疗前实施耐药检测,指导临床选择最优抗病毒治疗方案,避免治疗失败并减少耐药株的传播。

Objective To analyze the prevalence of pretreatment drug resistance(PDR)and risk factors associated with PDR in HIV-1 infected patients in Beijing.Methods Demographic,laboratory test results,and blood samples were collected from ART-naïve HIV-1 infected patients from January 2019 to December 2020 in Beijing DiTan Hospital,Capital Medical University,Beijing,China.The HIV-1 pol gene was amplified using a nested polymerase chain reaction,and the results were compared with the Stanford University HIV DRUG RESISTANCE DATABASE to analyze the characteristics of PDR.Results Among the 1489 ART-naïve HIV-1 infected patients,1372 were successfully amplified,and the amplification success rate was 92.1%.The overall incidence of PDR from 2019 to 2020 was 5.6%.Among them,the incidence of non-nucleoside reverse transcriptase inhibitors(NNRTIs)was 4.6%,and the primary mutation was E138A/G和V179D/E,followed by K103 N/T/R and V106M/I.The incidence of nucleoside reverse transcriptase inhibitors(NRTIs)was 1.5%,and the primary mutation was M184V/I.The incidence of protease inhibitor(PIs)resistance was 0.1%.The incidence of PDR was 3.8% in 2019,and 7.8% in 2020,the incidence rate of PDR in 2020 had increased significantly compared with 2019.In NNRTI,the resistance rate of nevirapine(NVP)and efavirenz(EFV)was 6.3%,4.5% in 2019 and 8.4%in 2020.The overall potential low-level resistance rate was 10.7%,among which the possible drug resistance rates of NNRTIs,NRTIs,and PIs were 10.0%,0.3%,and 0.4%,respectively.The higher detection rate in 2020 and CD4 cell count<50/uL were risk factors for PDR.Compared with CRF01_AE,subtype B,CRF55_01B,and Others had higher risks of PDR.Conclusion The incidence of PDR in 2020,is significantly higher than that in 2019,and mainly resistant to NNRTIs,the resistance rate of NVP and EFV has increased dramatically.The risk factors for PDR are related to subtype B,subtype CRF55_01B,subtype.Others,year,and low CD4 cell counts were risk factors for PDR.Therefore,we need to strengthen the monitoring of PDR.Drug resistance testing should be implemented before treatment when conditions permit the clinical selection of the best antiretroviral therapy to avoid virological failure and reduce the spread of resistant strains.