Background Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (DTG) as HIV treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents. Methods A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm. Results 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL. Conclusions These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.

中文翻译：

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多哥接受基于 DTG 的治疗方案的儿童和青少年的药物病毒学结果和基因型耐药情况

背景 关于接受替诺福韦-拉米夫定-多替拉韦 (DTG) 作为艾滋病毒治疗的实际疗效的数据很少，特别是在西非的年轻人中。在这里，我们评估了多哥儿童和青少年的药物病毒学结果和耐药情况。方法 在多哥洛美进行了一项横断面研究，招募了年龄在 18 个月至 24 岁之间、接受过抗逆转录病毒治疗的艾滋病毒感染者。测量血浆 HIV-1 病毒载量和抗逆转录病毒浓度。对病毒载量＞200c/mL的所有样品进行蛋白酶、逆转录酶(RT)和整合酶的下一代测序(NGS)。使用 ANRS-MIE 算法识别和解释耐药突变 (DRM)。结果 共有 264 名参与者入组（中位年龄 = 17 岁），其中 226 名参与者接受了基于 DTG 的治疗方案，中位时间为 20.5 个月。其中，80.0%的参与者的病毒学抑制在200c/mL阈值。分别有74.1％、6.7％和19.2％的接受DTG的参与者的血浆DTG浓度是足够的(即，＞640ng/mL)、次优和低于定量限。总体而言，分别有 52%、66% 和 1.6% 的参与者发现病毒对任何核苷 RT 抑制剂、非 NRTI 和蛋白酶抑制剂具有抗药性。在病毒载量＞200c/mL的9.4％(n＝3/32、R263K、E138A-G140A-Q148R和N155H)参与者中观察到主要整合酶抑制剂DRM。结论 在低收入国家如此大量的青少年中进行的这些初步研究结果显示，80% 的病毒学反应良好，并且 9.4% 的病毒学失败中存在整合酶 DRM，这支持了监测 DTG 耐药性的必要性。降低获得耐药性的风险。