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2022年乌干达接受基于多替拉韦的抗逆转录病毒治疗方案的HIV感染者中的HIV-1耐药性:一项基于全国实验室的利用残余病毒载量样本的调查

HIV-1 drug resistance among people living with HIV receiving dolutegravir-based anti-retroviral regimens in Uganda: a national laboratory-based survey using remnant viral load samples, 2022.

作者信息

Watera Christine, Da Silva Juliana de Fatima, Namayanja Grace, Asio Juliet Nkugwa, Ssemwanga Deogratius, Pals Sherri, Nabukenya Miriam, Raizes Elliot, Nanyonjo Maria, Elur Bill, Nazziwa Esther, Sanyu Grace, Ayitewala Alisen, Ssali Mina, Katureebe Cordelia, Balidawa Hudson, Zheng Du-Ping, Zeh Clement, Hackett Stephanie, Mwangi Christina, Naluguza Mary, Ntale Jonathan, Katongole Mbidde Edward, Kaleebu Pontiano

机构信息

Department of General Virololgy, Uganda Virus Research Institute (UVRI), Entebbe, Uganda.

Division of Global HIV & TB, U.S. Centers for Disease Control and Prevention, Atlanta, USA.

出版信息

J Antimicrob Chemother. 2025 Aug 1;80(8):2126-2134. doi: 10.1093/jac/dkaf180.

Abstract

BACKGROUND AND OBJECTIVES

Uganda adopted dolutegravir as its preferred HIV treatment regimen in the national guidelines for treatment of HIV and AIDS in 2018. We conducted a survey to estimate dolutegravir resistance 4 years post-dolutegravir introduction in routine clinical settings. This was a cross-sectional survey to estimate the prevalence of HIV drug resistance (HIVDR) to dolutegravir among children and adults with viral non-suppression (VNS; ≥1000 copies/mL) receiving dolutegravir-based antiretroviral therapy for at least 9 months.

METHODS

We used remnant specimens from routine viral load monitoring stored at Central Public Health Laboratories during February-April 2022. Genotyping of the protease, reverse transcriptase and integrase regions of the HIV-1 pol gene was done using Thermo Fisher® kits and analysed using the Stanford HIVDR database. Weighted prevalences of HIVDR with 95% confidence intervals (CI) were estimated for adults (≥15 years) and children (0-14 years).

RESULTS

We randomly selected 857 specimens including 457 from adults and 400 from children for HIVDR testing from 3578 eligible specimens collected during February-April 2022. Five hundred and eleven (59.6%) were successfully genotyped in the integrase region. Intermediate- to high-level dolutegravir HIVDR prevalence was 3.9% (CI: 0.7, 7.1) for adults and 6.6% (CI: 3.5, 9.6) for children.

CONCLUSION

HIVDR to dolutegravir was uncommon but present among both children and adults with VNS after 9 months or more of exposure to dolutegravir. Additional longitudinal outcomes data are needed to determine if adherence counselling for patients with VNS on dolutegravir regimens might improve outcomes.

摘要

背景与目的

乌干达在2018年的国家艾滋病毒和艾滋病治疗指南中采用多替拉韦作为首选的艾滋病毒治疗方案。我们开展了一项调查,以评估在常规临床环境中引入多替拉韦4年后的多替拉韦耐药情况。这是一项横断面调查,旨在估计接受基于多替拉韦的抗逆转录病毒治疗至少9个月且病毒未得到抑制(VNS;≥1000拷贝/mL)的儿童和成人中对多替拉韦的艾滋病毒耐药性(HIVDR)患病率。

方法

我们使用了2022年2月至4月期间保存在中央公共卫生实验室的常规病毒载量监测剩余样本。使用赛默飞世尔科技公司的试剂盒对HIV-1 pol基因的蛋白酶、逆转录酶和整合酶区域进行基因分型,并使用斯坦福HIVDR数据库进行分析。估计了成人(≥15岁)和儿童(0-14岁)HIVDR的加权患病率及95%置信区间(CI)。

结果

我们从2022年2月至4月收集的3578份合格样本中随机选取了857份样本进行HIVDR检测,其中457份来自成人,400份来自儿童。511份(59.6%)在整合酶区域成功进行了基因分型。成人中多替拉韦中至高水平HIVDR患病率为3.9%(CI:0.7,7.1),儿童为6.6%(CI:3.5,9.6)。

结论

在接触多替拉韦9个月或更长时间后,对多替拉韦的HIVDR在病毒未得到抑制的儿童和成人中并不常见,但存在。需要更多纵向结局数据来确定对接受多替拉韦治疗方案且病毒未得到抑制的患者进行依从性咨询是否可能改善结局。

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