艾滋病患者更换二线抗病毒药物的治疗效果

Treatment outcomes of HIV-infected patients switched to second-line therapy

目的分析艾滋病患者更换二线抗病毒药物后的病毒学、免疫学效果和耐药情况及病毒抑制失败的相关因素。方法将175名一线抗病毒药物治疗失败且更换二线抗病毒药物治疗的艾滋病患者纳入研究,比较其换药前后病毒抑制率、CD4细胞数及耐药情况。结果换二线药物12、24及36个月的病毒抑制率(VL<1 000 copies/m L)分别为73.4%、79.3%及92.8%(趋势检验,P=0.04),CD4细胞中位数由换二线药物前的193 cells/μL上升到318、371及378 cells/μL(P<0.01)。患者在更换二线药物前及换药后3个时间点的耐药率分别为81.1%、17.3%、14.0%和9.6%(趋势检验,P<0.01)。更换二线药物前核苷类反转录酶抑制剂(nucleoside reverse transcriptase inhibitor,NRTI)类耐药率为70.9%,出现频率较高的NRTIs类耐药突变为T215CFYI(45.7%)、M184V(42.3%)及M41L(40.0%);非核苷类反转录酶抑制剂(non-nucleoside reverse transcriptase inhibitor,NNRTI)类耐药率为81.1%,其中频率较高的NNRTIs类耐药突变包括K103NST(47.4%)、Y181C(40.0%)及G190AS(28.0%)。在更换二线药物前后未发现蛋白酶抑制剂(protease inhibitors,PIs)相关的耐药突变位点。更换二线药物后有漏服情况的患者更易在36个月发生病毒抑制失败。结论艾滋病患者更换二线药物后的治疗效果较好,提高服药依从性可进一步提高病毒抑制效果。

Objective To analyze the virological, immunological responses and drug resistance （DR） and influencing factors of virological failure among patients switched to second-line therapy. Methods A total of 175 patients who were switched to second-line ART after first-line failure were enrolled in the study. The rates of viral suppression, CD4 cell count and drug resistance before and after the regimen switching were analyzed. Results The rates of viral suppression （VL〈1000 copies/mL） in 12 months, 24 months and 36 months after switching were 73.4%, 79.3% and 92.8%, respectively （trend test, P= 0.04）. The median count of CD4 cells was increased from 193 cells/μL at baseline to 318, 371 and 378 cells/μL （P〈0.01） respectively. The rates of drug resistance at these four time points were 81.1%, 17.3%, 14.0% and 9.6%, respectively （trend test, P〈0.01）. The rates of NRTI-related and NNRTI-related resistance were 70.9% and 81.1% before switching, and the most frequent NRTI-related resistance mutations were T215CFYI （45.7%）, M184V（42.3%） and M41L（40.0%）, and the most common NNRTI-related resistance mutations were K103NST （47.4%）, Y181C（40.0%） and G190AS （28.0%）. No PI-related resistance was found. Having self-reported missing doses after switching was independently associated with the virological failure in 36 months of switching. Conclusions HIV-infected patients experiencing the first-line failure and then switched to second-line regimens have good virological and immunological responses. However, it is necessary to further study the drug resistance and adherence among the patients.