Antiviral Treatment Center, Butuo County People's Hospital, Sichuan, China.
Division of Tuberculosis and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Int J Antimicrob Agents. 2024 Aug;64(2):107215. doi: 10.1016/j.ijantimicag.2024.107215. Epub 2024 May 23.
To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes.
Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database.
Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine.
The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.
研究 CRF07_BC 和 CRF_08BC 亚型中耐药突变(DRMs)的特征及其对药物敏感性的影响。
对病毒学失败的患者进行基因分型,使用系统发生分析。使用斯坦福大学 HIV 耐药性数据库分析 DRMs 和抗逆转录病毒药物的敏感性。
在成功扩增的 1296 个序列中鉴定出 6 种 HIV 亚型,其中 CRF07_BC 亚型占主导地位,比例为 91.7%,其次是 CRF08_BC。总体而言,CRF07_BC 和 CRF08_BC 亚型在 DRMs 的分布和频率上相似,最常见的 DRMs 是 K103N 和 M184V。然而,在接受抗逆转录病毒治疗≥3 年发生耐药的患者中,CRF08_BC 在 184、138、221 和 188 位点的突变频率更高(卡方检验,P<0.05),与 CRF07_BC 相比,CRF08_BC 患者更易发生阿巴卡韦、恩曲他滨、拉米夫定、多替拉韦、依非韦伦和利匹韦林耐药。此外,CRF08_BC 患者中,新型 NNRTIs 与依非韦伦/奈韦拉平之间的交叉耐药率增加;多替拉韦(r=1.0)、利匹韦林(r=0.93)和依非韦伦(r=0.86)耐药与依非韦伦/奈韦拉平高度相关。
本研究提供了宝贵的信息,了解了在布拖发生治疗失败的 CRF07_BC 和 CRF08_BC 患者的 DRMs 特征和耐药模式。这些发现有助于制定未来的 HIV 控制和治疗策略。