台州市2020—2022年新报告HIV感染者治疗失败及耐药情况分析

李艳; 吴烜赫; 时路; 李桂霞; 汪剡灵; 王雅婷; 陈泰霖; 王婷婷; 谢亚莉; 沈伟伟; 林海江; 陈潇潇; 何纳

doi:10.19428/j.cnki.sjpm.2024.23877

台州市2020—2022年新报告HIV感染者治疗失败及耐药情况分析

Treatment failure and drug resistance among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022

摘要

摘要:
目的分析台州市2020—2022年新报告HIV感染者抗逆转录病毒治疗（ART）失败及耐药情况。
方法研究对象为2020—2022年台州市接受ART时间≥6个月的新报告HIV感染者，收集其血液样本、社会人口学特征和ART信息等，进行新发感染和HIV‑1基因型耐药检测。采用多因素logistic回归分析治疗失败的影响因素，将接受ART失败患者的基因序列提交至美国斯坦福大学HIV耐药数据库，分析耐药突变位点和药物耐药情况。
结果 1 023例新报告接受ART的患者，年龄M（P₂₅，P₇₅）为47（33，58）岁，男性占81.4%，传播途径以异性性传播为主，占66.4%（679/1 023），WHO临床分期为Ⅰ/Ⅱ的占74.7%，首次CD4计数>200个·μL^-1的占62.2%，治疗策略以立即接受ART为主，占94.4%（966/1 023），长期感染者占78.7%。治疗失败66例（6.5%），同性性传播（OR=0.39，95%CI：0.17~0.84）和无性病史者（OR=0.45，95%CI：0.24~0.92）治疗失败的可能性较低。首次CD4计数≤200个·μL^-1更容易发生治疗失败，延迟启动ART（OR=3.19，95%CI：1.24~7.52）和原发性耐药患者（OR=4.69，95%CI：1.68~11.89）治疗失败的可能性较高。36例病毒学治疗失败的HIV感染者中，样本成功扩增率为75.0%（27/36），总耐药率为55.6%（15/27），其中核苷类反转录酶抑制剂（NRTIs）、非核苷类反转录酶抑制剂（NNRTIs）和蛋白酶抑制剂（PIs）的耐药率分别为37.0%（10/27）、51.9%（14/27）和3.7%（1/27）。在NNRTIs中，依非韦伦和奈韦拉平耐药程度一致，以高度耐药为主，耐药率为51.9%（14/27）。K103N和M184V是最常见的突变位点，PIs突变发生较少。共检出8个基因亚型，以CRF01_AE亚型为主［37.0%（10/27）］，其次是CRF07_BC［14.8%（4/27）］、CRF08_BC［14.8%（4/27）］和C亚型［14.8% （4/27）］。
结论 2020—2022年台州市新报告HIV感染者中长期感染者居多，立即启动ART策略可以降低HIV感染者治疗失败的风险，病毒学治疗失败者以NRTIs、NNRTIs耐药为主。建议强化主动检测发现，尽快启动ART，减少治疗失败的发生。同时，加强针对治疗失败患者的耐药检测，科学指导药物更换。

Abstract:
Objective To analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022.
Methods Blood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics.
Results Among the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC 14.8% (4/27), CRF08_BC 14.8% (4/27) and subtype C 14.8% (4/27).
Conclusion During the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

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