Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China

BackgroundChina’s National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.MethodA cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous blood was sampled for CD4 cell counts, measurement of the HIV viral load (VL), and HIV drug resistance (HIVDR) genotyping. Possible risk factors for HIVDR were analyzed by the logistic regression model.ResultsThe study included 765 patients. Among them, 65 patients (8.5%) had virological failure (VLF) defined as ≥1,000 copies/ml. Among the individuals with VLF, 64 were successful genotyped, and of these, 33 had one or more HIVDR mutations. The prevalence of HIVDR mutations among patients receiving first-line ART was 4.3% (33/765). All of the patients with HIVDR mutations were resistant to non-nucleoside transcriptase inhibitors, 81.8% were resistant to nucleoside reverse transcriptase inhibitors, and only 3% had mutations that caused resistance to protease inhibitors. Having lower ratios of drug intake in the past month and dwelling in two southwestern provinces were factors independently associated with the emergence of HIVDR.ConclusionMost patients receiving first-line ART treatment achieved sound virological and immunological outcomes. However, poor adherence is still a key problem, which has led to the high rate of HIVDR. It was notable that the proportion of drug resistance widely varied among the provinces. More studies are needed to focus on adherence.研究背景 中国国家免费抗反转录病毒治疗项目（National Free Antiretroviral Treatment Program, NFATP）自2002年实施以来，已大幅提升了患者生存率。然而，HIV耐药性（HIV drug resistance, HIVDR）的出现限制了抗反转录病毒治疗（antiretroviral treatment, ART）在高危患者中的持久性与有效性。 研究方法 本研究在中国8个省份开展横断面调查，纳入的患者接受抗反转录病毒治疗的中位时长为13.9个月。研究人员收集了患者的人口学与临床信息，并采集静脉血样以检测CD4细胞计数、HIV病毒载量（viral load, VL）以及进行HIV耐药基因分型。通过logistic回归模型分析HIVDR的潜在危险因素。 研究结果 本研究共纳入765例患者。其中，65例（8.5%）符合病毒学失败（virological failure, VLF）判定标准，即病毒载量≥1000拷贝/毫升。在发生病毒学失败的患者中，64例成功完成基因分型，其中33例存在1种及以上HIV耐药突变。一线抗反转录病毒治疗患者的HIV耐药突变流行率为4.3%（33/765）。所有携带HIV耐药突变的患者均对非核苷类反转录酶抑制剂耐药，81.8%的患者对核苷类反转录酶抑制剂耐药，仅3%的患者存在对蛋白酶抑制剂耐药的突变。近1个月服药依从性较低以及居住在西南两省，是与HIVDR发生独立相关的危险因素。 研究结论 多数接受一线抗反转录病毒治疗的患者取得了良好的病毒学与免疫学结局。然而，服药依从性不佳仍是核心问题，这导致了较高的HIV耐药发生率。值得注意的是，各省的耐药比例存在显著差异。未来需开展更多聚焦于服药依从性的相关研究。