Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.
Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.
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DOI：
10.1093/jac/dkad195
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发表时间：
2023-08-02
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影响因子：
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自2018年以来，由于对基于非核苷类逆转录酶抑制剂（NNRTI）的抗逆转录病毒疗法（ART）的耐药性高发，世界卫生组织（WHO）的综合建议已表明多替拉韦是全球艾滋病治疗的首选药物。来自西非流行的HIV - 1非B亚型的耐药结果数据匮乏。
我们对尼日利亚东北部一个横断面队列中基于多替拉韦的抗逆转录病毒疗法方案失败的艾滋病病毒感染者的突变谱进行了特征分析。
使用Illumina平台对61名基于多替拉韦的抗逆转录病毒疗法出现病毒学失败的HIV - 1感染者的血浆样本进行全基因组测序（WGS）。55名参与者的样本测序成功完成。经过质量控制，对年龄中位数为40岁、接受抗逆转录病毒疗法时间中位数为9年的参与者的33个全基因组进行了分析。使用SNAPPy进行HIV - 1亚型分型。
大多数参与者的突变谱反映出曾接触过由核苷类逆转录酶抑制剂（NRTIs）和非核苷类逆转录酶抑制剂组成的既往一线和二线抗逆转录病毒疗法方案。超过一半的参与者具有一种或多种影响对核苷类逆转录酶抑制剂（17/33；52%）和非核苷类逆转录酶抑制剂（24/33；73%）敏感性的耐药相关突变（DRMs）。近四分之一的参与者（8/33；24.4%）具有一种或多种影响替诺福韦敏感性的耐药相关突变。只有一名感染HIV - 1 G亚型的参与者有影响多替拉韦敏感性的耐药相关突变的证据——其特征为T66A、G118R、E138K和R263K突变。
这项研究发现对多替拉韦的耐药率较低；因此，这些数据支持将多替拉韦作为未接受过抗逆转录病毒疗法的参与者的主要一线方案继续推广，并支持在该地区将其作为转换为二线抗逆转录病毒疗法的首选药物。然而，需要收集关于多替拉韦治疗结果的人群层面的长期数据，以进一步指导该地区的实施和政策行动。
Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa. We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen. WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy. Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility—this was characterized by the T66A, G118R, E138K and R263K mutations. This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.
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DOI：
10.1097/qai.0000000000002918
发表时间：
2022-05-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
El Bouzidi K;Murtala-Ibrahim F;Kwaghe V;Datir RP;Ogbanufe O;Crowell TA;Charurat M;Dakum P;Gupta RK;Ndembi N;Sabin CA
通讯作者：
Sabin CA
影响因子：
6.4
作者：
Datir R;Kemp S;El Bouzidi K;Mlchocova P;Goldstein R;Breuer J;Towers GJ;Jolly C;Quiñones-Mateu ME;Dakum PS;Ndembi N;Gupta RK
通讯作者：
Gupta RK
影响因子：
1.5
作者：
Chaplin, B.;Eisen, G.;Kanki, P.
通讯作者：
Kanki, P.
影响因子：
15.1
作者：
Chimukangara, Benjamin;Lessells, Richard J.;de Oliveira, Tulio
通讯作者：
de Oliveira, Tulio
影响因子：
3.8
作者：
Aliyu, Gambo G.;Lawton, Jonathan G.;Stafford, Kristen A.
通讯作者：
Stafford, Kristen A.