Zhao Ying, Holtman Melanie, Mudaly Vanessa, van Zyl Gert, Maartens Gary, Meintjes Graeme
Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Western Cape Government Department of Health and Wellness, Cape Town, South Africa.
J Acquir Immune Defic Syndr. 2025 Mar 3. doi: 10.1097/QAI.0000000000003657.
Dolutegravir resistance has been reported more frequently in patients with prior treatment experience compared to those on dolutegravir in first-line antiretroviral therapy (ART). The widespread use of dolutegravir in resource-limited programmatic settings might facilitate the emergence of resistance. Data on the prevalence of dolutegravir resistance from programmatic settings in Africa are scarce.
This retrospective observational cohort study assessed dolutegravir resistance in routine care settings of the Western Cape provincial public healthcare sector program between February 2021 and June 2024. Treatment-experienced adults who developed virologic failure (two HIV-1 RNA ≥1000 copies/mL), who had received dolutegravir-based ART for >24 months, were eligible for genotypic antiretroviral resistance testing (GART). Drug resistance mutations (DRMs) and resistance levels were classified using the Stanford database.
Among 99 eligible patients, 76 had GART performed, and 68 had successful sequences. Among these 68, 43 (63%) had dolutegravir DRMs with: 1 potential low, 1 low, 15 intermediate, and 26 high resistance levels. The median time on dolutegravir-based ART was 24 months (IQR, 23-31). Of the 43 patients with dolutegravir DRMs, 21 (49%) were receiving zidovudine-lamivudine-dolutegravir and 19 (44%) were receiving tenofovir-lamivudine-dolutegravir; 42/43 had prior ART experience.
Over 60% of patients with prior treatment experience who had been on dolutegravir-based ART for over two years and experienced virologic failure had intermediate or high level dolutegravir resistance. This suggests that criteria for GART used are too stringent, which has resource implications in programmatic settings where access to resistance testing for individual management is limited.
与一线抗逆转录病毒治疗（ART）中使用多替拉韦的患者相比，有过治疗经验的患者中多替拉韦耐药的报告更为频繁。在资源有限的项目环境中广泛使用多替拉韦可能会促使耐药性的出现。来自非洲项目环境中多替拉韦耐药流行率的数据很少。
这项回顾性观察队列研究评估了2021年2月至2024年6月期间西开普省公共卫生部门项目常规护理环境中的多替拉韦耐药情况。有治疗经验且出现病毒学失败（两次HIV-１RNA≥1000拷贝/mL）、接受基于多替拉韦的ART超过24个月的成年患者有资格进行基因型抗逆转录病毒耐药性检测（GART）。使用斯坦福数据库对耐药突变（DRM）和耐药水平进行分类。
在99名符合条件的患者中，76名进行了GART检测，68名获得了成功的序列。在这68名患者中，43名（63%）有多替拉韦DRM，其中：1名潜在低耐药、1名低耐药、15名中度耐药和26名高耐药水平。基于多替拉韦的ART的中位治疗时间为24个月（IQR，23 - 31）。在43名有多替拉韦DRM的患者中，21名（49%）接受齐多夫定-拉米夫定-多替拉韦治疗，19名（44%）接受替诺福韦-拉米夫定-多替拉韦治疗；42/43名患者有过ART治疗经验。
超过60%有过治疗经验且接受基于多替拉韦的ART超过两年并出现病毒学失败的患者有多替拉韦中度或高度耐药。这表明所使用的GART标准过于严格，这在个体管理的耐药性检测机会有限的项目环境中对资源有影响。
