云南省576例齐多夫定或替诺福韦方案治疗失败的HIV/AIDS患者基因型耐药差异性分析

Differential analysis of genotype drug resistance in 576 HIV/AIDS patients who failed treatment with a zidovudine-containing or tenofovir-containing regimen in Yunnan Province

目的比较抗病毒治疗药物齐多夫定(zidovudine,AZT)与替诺福韦(tenofovir,TDF)治疗失败后HIV/AIDS患者基因型耐药突变差异性并探讨相关影响因素。方法收集经一线治疗方案治疗半年以上且基因型耐药检测结果为耐药的患者信息,通过单因素检验确定与AZT或TDF耐药相关变量,再通过多重对应分析获得变量的相互关系。结果使用含AZT或TDF治疗方案患者576例,常见的耐药突变有M184V/I、D67N、K70R/E/Q、K65R及T69N,单因素分析显示接受含此两种药物方案治疗情况下患者年龄(χ^2=3.503,P=0.320)及感染途径(χ^2=3.122,P=0.210)无相关性,突变位点(χ^2=104.438,P=0.000)、病毒载量(χ^2=17.284,P=0.000)、CD4^+T淋巴细胞(χ^2=33.338,P=0.000)、性别(χ^2=8.904,P=0.003)及治疗时长(χ^2=40.081,P=0.000)相关;感染多重对应分析显示突变方式为AZT与患者治疗时长大于2年(>25月)、病毒载量<10 000 copies/ml、CD4^+T淋巴细胞计数≥200 cells/mm^3有关,TDF治疗方案则与患者在治疗时长为2年(0~24月)、病毒载量≥10 000 copies/ml、CD4^+T淋巴细胞计数<200 cells/mm^3以及K65R表现出聚集性。结论多重对应分析极其适用于HIV耐药人口学及突变的研究;M184V/I与D67N及K70R/E/Q出现相关性,与含TDF方案相比,NRTIs常见突变多以含AZT方案引起,T69N与AZT耐药出现低病毒载量有关,长期使用含AZT方案过程中需密切监测基因型耐药,含TDF治疗方案中早期应积极监测病毒载量与CD4^+T淋巴细胞数。

Objective To compare the differences in genotype drug resistance mutations in patients who failed treatment with a zidovudine(AZT)-containing or tenofovir(TDF)-containing regimen, and to explore the related influencing factors. Methods We collected the information about patients with first-line antiretroviral regimens for more than six months as well as positive results in genotypic antiretroviral drug resistance testing. Univariate testing was used to determine the variables associated with AZT or TDF resistance, and multiple correspondence analysis was performed to obtain the correlation of variables. Results Among 576 patients treated with an AZT-containing regimen or a TDF-containing regimen, the common drug-resistant mutations were M184 V/I, D67 N, K70 R/E/Q, K65 R and T69 N. Univariate analysis showed that drug-resistant mutations in the patients receiving the above-mentioned two drugs were not correlated with the patients’ age(χ^2=3.503, P=0.320) and pathways of infection(χ^2=3.122, P=0.210), but correlated with mutation sites(χ^2=104.438, P=0.000), virus load(χ^2=17.284, P=0.000), CD4^+ T lymphocytes(χ^2=33.338, P=0.000), gender(χ^2=8.904, P=0.003) and duration of treatment(χ^2=40.081, P=0.000). Multiple correspondence analysis showed that drug-resistant mutation induced by receiving an AZT-containing regimen was correlated with treatment duration more than 2 years(25 months), virus load < 10,000 copies/ml and CD4^+ T lymphocyte count ≥200 cells/mm^3, while drug-resistant mutation induced by receiving a TDF-containing regimen showed aggregation with treatment duration within 2 years(0-24 months), virus load ≥ 10,000 copies/ml, CD4^+ T lymphocyte count <200 cells/mm^3 and K65 R. Conclusions Multiple correspondence analysis is extremely suitable for studying HIV-resistant demographics and mutations. M184 V/I drug-resistant mutation is correlated with D67 N and K70 R/E/Q. As compared with the TDF-containing regimen, common mutations in NRTIs are mainly induced by the AZT-containing regimen. T69 N and AZT resistance is associated with low virus load. As for long-term use of an AZT-containing regimen, genotypic drug resistance should be closely monitored. With regard to receiving a TDF-containing regimen, virus load and CD4^+ T lymphocyte count should be actively monitored in the early stage.