[Study on the relationship between HIV drug resistance and CD4(+)T cell counts among antiretroviral therapy patients with low viral load].

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4(+)T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4(+)T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4(+)T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4(+)T cell counts <200 cells/μl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95%CI) of CD4 <200 cells/μl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion: Decreased CD4(+)T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.目的： 分析中国2003—2015年HIV抗病毒治疗者中不同病毒载量下耐药情况，及其与CD4(+)T淋巴细胞计数的相关性。 方法： 在中国HIV耐药监测网络数据库中，选取2003—2015年接受HIV抗病毒治疗时间≥12个月且年龄≥18岁者的社会人口学特征、抗病毒治疗情况、CD4(+)T淋巴细胞计数、病毒载量及基因型耐药检测结果等信息，最终共纳入研究对象8 362例。采用多因素非条件logistic回归模型分析不同病毒载量下耐药情况与CD4(+)T淋巴细胞计数的相关性。 结果： 研究对象的年龄为（41.8±10.5）岁，男性占59.9%（5 009例），CD4(+)T淋巴细胞计数<200个/μl者占17.9%（1 496例）；病毒载量≥1 000拷贝/ml且耐药组中CD4(+)T淋巴细胞计数<200个/μl者比例最高，为43.0%（397/923），其次为病毒载量为50~999拷贝/ml且耐药组（31.1%，69/222），最低为病毒载量为50~999拷贝/ml且不耐药组（13.2%，273/2 068）。与病毒载量为50~999拷贝/ml且不耐药者相比，病毒载量<50拷贝/ml且耐药者、病毒载量为50~999拷贝/ml且耐药者、病毒载量≥1 000拷贝/ml且不耐药者、病毒载量≥1 000拷贝/ml且耐药者出现CD4(+)T淋巴细胞计数<200个/μl的OR（95%CI）值分别为0.9（0.7~1.0）、3.2（2.3~4.4）、2.6（2.1~3.2）、4.9（4.0~5.9）。222例病毒载量为50~999拷贝/ml且耐药的患者中，较常见的耐药药物为依非韦伦（EFV）和奈韦拉平（NVP），检出率均为94.1%（209例）。核苷类反转录酶抑制剂(NRTI)类耐药突变位点M184V/I为最主要突变位点，检出率为26.1%（58例），其次为NNRTI类耐药突变位点K103N，检出率为22.5%（50例），蛋白酶抑制剂（PI）类耐药突变位点V32L/E和V82A的检出率较低，分别为0.9%（2例）和0.5%（1例）。 结论： HIV抗病毒治疗者CD4(+)T淋巴细胞计数低与低病毒载量时耐药相关。低病毒载量时，易出现耐药的是EFV和NVP等NNRTI类抗病毒药物。.