抗病毒治疗失败的HIV感染/AIDS老年患者基因型耐药特点分析

Profiling of genotypic drug resistance in the elderly HIV/AIDS patients for whom antiviral therapy failed

目的 分析抗病毒治疗失败的HIV感染/AIDS老年患者的耐药特点。方法 回顾性分析2020年1月—2021年12月在四川省某地抗反转录病毒治疗(ART)失败并判定为耐药的HIV感染/AIDS老年患者,分析其基因型耐药特点。结果354例研究对象中,男性为主(74.3%);年龄中位数为66.6岁;基线CD4+T细胞<350个/μL为主(79.2%);ART中位时长26.6个月;初始ART方案与ART时长差异存在统计学意义(P<0.05)。各类药物耐药突变位点多样;亚型以CRF08_BC为主(40.7%);非核苷类反转录酶抑制剂(NNRTI)耐药率最高,其次为核苷类反转录酶抑制剂(NRTI),蛋白酶抑制剂(PI)耐药率最低;NRTI中,恩曲他滨(FTC)和拉米夫定(3TC)耐药率偏高,均为29.7%;NNRTI中,奈韦拉平(NVP)和依非韦伦(EFV)耐药率高,分别为92.4%和91.5%。Fisher确切概率法显示年龄与ART药物耐药模式差异存在统计学意义(P<0.05)。结论 ART失败的HIV感染/AIDS老年患者耐药情况复杂,需要加强ART管理,基线耐药检测可以为ART方案的选择提供依据,应该加强对HIV-1 RNA、CD4+T细胞等指标的基线及治疗过程中的监测,加强老年HIV感染/AIDS患者的随访管理,及时进行耐药检测。

Objective To profile the genotypic drug resistance in the elderly HIV/AIDS patients who failed to respond to antiviral therapy(ART).Methods The elderly HIV/AIDS patients for whom ART failed due to drug resistance in Sichuan Province from January 2020 to December 2021 were investigated retrospectively for their drug resistance profiles.Results Most(74.3%)of the 354 patients were males.The median age of the patients was 66.6 years.Baseline CD4+T cells<350/μL were identified in 79.2%of the patients.The median time on ART was 26.6 months.The prevalence of drug resistance was significantly different between initial ART regimens and ART duration(P<0.05).Resistance mutation sites were diverse across drug classes.CRF08_BC was the predominant subtype(40.7%).The highest resistance rate was found for non-nucleoside reverse transcriptase inhibitors(NNRTIs),followed by nucleoside reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs).Among the NRTIs,emtricitabine and lamivudine were associated with a resistance rate of 29.7%.Among NNRTIs,nevirapine and efavirenz were associated with a high resistance rate(92.4%and 91.5%,respectively).Fisher Exact Probability test showed a statistically significant difference between age and ART drug resistance pattern(P<0.05).Conclusions The drug resistance in the elderly HIV/AIDS patients who failed to respond to ART is complex.The ART in the elderly HIV/AIDS patients should be managed carefully.Baseline drug resistance testing can inform the selection of ART regimens.HIV-1 RNA,CD4+T cells,and other biomarkers should be monitored at baseline and during treatment to improve treatment compliance and success.