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印度北部地区一线抗反转录病毒治疗失败的 HIV-1 感染者体内逆转录酶基因耐药突变的检测:一项随访队列研究。

Detection of Drug Resistance Mutations in the Reverse Transcriptase Gene of HIV-1-Infected North Indian Population Failing First-Line Antiretroviral Therapy "A Follow-Up Cohort Study".

机构信息

National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Agra, India.

National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, India.

出版信息

AIDS Res Hum Retroviruses. 2021 Oct;37(10):796-805. doi: 10.1089/AID.2020.0132. Epub 2021 Feb 24.

Abstract

We aim to characterize the drug resistance mutations in reverse transcriptase gene of HIV-1 subtype C-infected North Indian population in those who are failing first-line antiretroviral therapy (ART) and if these mutations are associated with mortality. We also attempted the assessment of switch over to second-line antiretroviral therapy in these patients. Based on the immunological marker CD4 count (<350 cubic/mm), 192 HIV/AIDS patients were selected and viral load was estimated in those who were enrolled from December 2009 to November 2016. Based on viral load, genotyping was carried out in 57 HIV-1 isolates (VL ≥1,000 copies/mL) by sequencing and drug resistance mutations were examined through the Stanford HIV Drug Resistance Database, USA. Among them, 21 (36.84%) first-line ART failure patients were shifted to second-line ART. These patients were followed for a period wide ranging from 10 months to 11 years. Drug resistance mutation M184V (ATG to GTA) (63.15%) associated with lamivudine and abacavir and K103N (AAG or AAA to AAU) (36.84%) associated with efavirenz and nevirapine were predominantly identified in first-line ART failure patients. During follow-up, it was observed that 3 out of 21 who were in second-line ART died, whereas 9 out of 36 died who were in the first-line ART. No mutation could be associated with mortality although TAM-2 mutations were absent in patients who died. This study indorses the need for a facility for viral load estimation and resistance monitoring in each treatment failure patient and availability of appropriate antiretroviral therapies.

摘要

我们旨在描述在一线抗逆转录病毒治疗(ART)失败的印度北部 HIV-1 型 C 感染人群的 HIV-1 逆转录酶基因中的耐药突变,如果这些突变与死亡率相关。我们还尝试评估这些患者转换为二线抗逆转录病毒治疗。根据免疫标志物 CD4 计数(<350 立方毫米),选择了 192 名 HIV/AIDS 患者,并且在 2009 年 12 月至 2016 年 11 月期间招募的患者中估计了病毒载量。根据病毒载量,对 57 个 HIV-1 分离物(VL≥1,000 拷贝/mL)进行了测序的基因分型,并通过美国斯坦福 HIV 耐药性数据库检查了耐药突变。其中,21 名(36.84%)一线 ART 失败患者转为二线 ART。这些患者的随访时间从 10 个月到 11 年不等。耐药突变 M184V(ATG 至 GTA)(63.15%)与拉米夫定和阿巴卡韦相关,K103N(AAG 或 AAA 至 AAU)(36.84%)与依非韦伦和奈韦拉平相关,主要在一线 ART 失败患者中发现。在随访期间,观察到在 21 名接受二线 ART 的患者中有 3 人死亡,而在 36 名接受一线 ART 的患者中有 9 人死亡。尽管在死亡患者中未发现 TAM-2 突变,但没有突变与死亡率相关。这项研究证明,每个治疗失败的患者都需要进行病毒载量评估和耐药监测的设施,以及提供适当的抗逆转录病毒治疗。

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