抗病毒治疗后低病毒血症患者HIV-1基因型耐药特征分析

Features analysis of HIV-1 genotype resistance in patients with low-level viremia after antiretroviral therapy

目的 分析北京佑安医院ART后发生低病毒血症(LLV)的HIV/AIDS患者病毒亚型及耐药特征。方法收集2020年1月至2021年6月期间在北京佑安医院性病艾滋病门诊常规接受ART≥6个月且发生LLV的HIV/AIDS患者随访3个月后的外周静脉血,通过对分离的血浆进行超速离心后提取HIV RNA,利用反转录-巢式荧光定量聚合酶链反应(RT-PCR)技术扩增pol基因区,测序成功后进行基因亚型和耐药突变分析。结果 共筛查了10 693例患者,LLV患者225例,LLV发生率2.1%。纳入研究期间成功留血液样本的患者134例,成功收集73份VL在50~999拷贝/mL的血浆样本。扩增得到51条序列,扩增成功率69.9%。51条序列来自41例患者,CRF01_AE亚型最常见(43.9%,18/41),其次为CRF07_BC亚型(19.5%,8/41),B亚型(19.5%,8/41)和C亚型(7.3%,3/41)。19例患者发现了耐药突变,整体耐药突变率为46.3%(19/41)。其中,以NNRTIs相关耐药突变为主,占36.6%(15/41),最常见的耐药突变位点为V106I/M和V179D/E;其次为NRTIs和PIs相关突变,分别占34.1%(14/41)和19.5%(8/41),最常见的突变位点M184V/I和M46I。结论 ART后LLV患者耐药突变较常见。VL较低的情况下也可以检测到耐药突变。对出现LLV的患者进行耐药检测将有助于优化治疗方案、改善临床结果。

Objective To analyze the viral subtypes and drug resistance characteristics of HIV/AIDS patients with low viremia(LLV) after ART in Beijing Youan Hospital. Methods Peripheral venous blood was collected from HIV/AIDS patients who routinely received ART for ≥ 6 months after 3 months of follow-up and developed LLV in the STD and AIDS clinic of Beijing Youan Hospital from January 2020 to June 2021. HIV RNA was extracted from the isolated plasma after ultracentrifugation. The pol gene region was amplified by reverse transcription-nested polymerase chain reaction(RTPCR) technique. The gene subtypes and drug resistance mutations were analyzed after successful sequencing. Results A total of 10 693 patients were screened. 225 patients with LLV, and the incidence of LLV was 2.1%. 134 patients who successfully retained blood samples during the study period were included, and 73 plasma samples with VL between 50and 999 copies/mL were successfully collected. Fifty-one sequences were amplified, and the amplification success rate was 69.9%. Fifty-one sequences came from 41 patients, with CRF01AE being the most common(43.9%, 18/41) subtype,followed by CRF07BC subtype(19.5%, 8/41), B subtype(19.5%, 8/41) and C subtype(7.3%, 3/41). Resistance mutations were identified in 19 patients, and the overall resistance mutation rate was 46.3%(19/41). Among them, NNRTIs-related drug resistance mutations were predominant, accounting for 36.6%(15/41), and the most common drug resistance mutation sites were V106I/M and V179D/E, followed by NRTIs and PIs-related mutations, accounting for 34.1%(14/41)and 19.5%(8/41), respectively. The most common mutation sites were M184V/I and M46I. Conclusion Drug resistance mutations are common in patients with LLV after ART.Resistance mutations can also be detected at lower VL.Resistance testing in patients who develop LLV will help to optimize treatment regimens and improve clinical outcomes.