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多哥接受基于多替拉韦方案治疗的儿童和青少年的药物病毒学结果及基因型耐药谱

Pharmaco-virological Outcomes and Genotypic Resistance Profiles Among Children and Adolescents Receiving a Dolutegravir-Based Regimen in Togo.

作者信息

Konu Yao Rodion, Takassi Elom, Peytavin Gilles, Dapam Nina, Damond Florence, Oumarou Wone Adama, Zaidi Meryem, Franco-Yusti Anna-Maria, Dagnra Claver A, Le Hingrat Quentin, Coppée Romain, Descamps Diane, Diallo Fatoumata Binta Tidiane, Ekouevi Didier K, Charpentier Charlotte

机构信息

Faculté des Sciences de la Santé, Département de Santé Publique, Université de Lomé, Lomé, Togo.

Centre Africain de Recherche en Epidémiologie et en Santé Publique (CARESP), Lomé, Togo.

出版信息

Clin Infect Dis. 2025 Feb 5;80(1):144-152. doi: 10.1093/cid/ciae278.

DOI:10.1093/cid/ciae278
PMID:38748464
Abstract

BACKGROUND

Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (-DTG) as human immunodeficiencyvirus (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 of protease, reverse transcriptase (RT), and integrase was performed on all samples with viral loads >200 copies/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, there was virological suppression at the 200-copies/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (ie, >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 copies/mL.

CONCLUSIONS

These first findings in 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 virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.

摘要

背景

关于接受替诺福韦-拉米夫定-多替拉韦(-DTG)作为人类免疫缺陷病毒(HIV)治疗的真实疗效的数据很少,尤其是在西非的年轻人中。在此,我们评估了多哥儿童和青少年的药物病毒学结果和耐药谱。

方法

在多哥洛美进行了一项横断面研究,纳入年龄在18个月至24岁之间接受抗逆转录病毒治疗的HIV感染者。测量血浆HIV-1病毒载量和抗逆转录病毒药物浓度。对所有病毒载量>200拷贝/mL的样本进行蛋白酶、逆转录酶(RT)和整合酶的下一代测序。使用ANRS-MIE算法鉴定和解释耐药突变(DRM)。

结果

共纳入264名参与者(中位年龄17岁);226人接受了以DTG为基础的治疗方案,中位治疗时间为20.5个月。其中,80.0%的参与者在200拷贝/mL阈值时实现了病毒学抑制。接受DTG治疗的参与者中,血浆DTG浓度充足(即>640 ng/mL)、次优和低于定量下限的比例分别为74.1%、6.7%和19.2%。总体而言,分别在52%、66%和1.6%的参与者中发现了对任何核苷类RT抑制剂、非核苷类RT抑制剂和蛋白酶抑制剂耐药的病毒。在病毒载量>200拷贝/mL的参与者中,9.4%(n = 3/32;R263K、E138A-G140A-Q148R和N155H)观察到主要的整合酶抑制剂DRM。

结论

在低收入国家的一大群青少年中的这些初步发现显示,病毒学应答良好率为80%,在9.4%的病毒学失败中存在整合酶DRM,支持监测DTG耐药性以降低耐药风险的必要性。

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