多哥接受以 DTG 为基础的治疗方案的儿童和青少年的药物治疗结果和基因型耐药性概况。

IF 8.2 1区 医学 Q1 IMMUNOLOGY
Yao Rodion Konu, Elom Takassi, Gilles Peytavin, Nina Dapam, Florence Damond, Wone Adama Oumarou, Meryem Zaidi, Anna-Maria Franco-Yusti, Claver A Dagnra, Quentin Le Hingrat, Romain Coppée, Diane Descamps, Fatoumata Binta Tidiane Diallo, Didier K Ekouevi, Charlotte Charpentier
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引用次数: 0

摘要

背景:有关接受替诺福韦酯-拉米夫定-去替拉韦(DTG)作为艾滋病治疗药物的实际疗效的数据很少,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治疗结果和耐药性概况:方法:我们在多哥洛美开展了一项横断面研究,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 HIV 感染者。对血浆 HIV-1 病毒载量和抗逆转录病毒药物浓度进行了测量。对病毒载量大于 200 c/mL 的所有样本进行了蛋白酶、逆转录酶和整合酶的新一代测序 (NGS)。结果:264 名参与者(中位年龄=17 岁)中有 226 人接受了以 DTG 为基础的治疗,中位时间为 20.5 个月。其中,80.0%的参与者的病毒学抑制达到了 200 c/mL 的临界值。在接受 DTG 治疗的参与者中,分别有 74.1%、6.7% 和 19.2% 的人血浆中 DTG 浓度足够(即大于 640 纳克/毫升)、不达标和低于定量限。总体而言,在 52%、66% 和 1.6% 的参与者中分别发现了对任何核苷 RT 抑制剂、非 NRTI 和蛋白酶抑制剂耐药的病毒。在病毒载量大于 200 c/mL 的参与者中,9.4%(n=3/32,R263K、E138A-G140A-Q148R 和 N155H)的患者出现了主要整合酶抑制剂 DRM:这些首次在低收入国家青少年中进行的大规模研究结果表明,80%的青少年病毒学应答良好,9.4%的病毒学应答失败者体内存在整合酶DRM,这表明有必要监测DTG耐药性,以降低耐药性产生的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmaco-virological Outcomes and Genotypic Resistance Profiles Among Children and Adolescents Receiving a Dolutegravir-Based Regimen in Togo.

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.

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来源期刊
Clinical Infectious Diseases
Clinical Infectious Diseases 医学-传染病学
CiteScore
25.00
自引率
2.50%
发文量
900
审稿时长
3 months
期刊介绍: Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.
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