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高耐药水平危及赤道几内亚巴塔地区儿科和成年人群中 HIV 感染的控制。

High Drug Resistance Levels Compromise the Control of HIV Infection in Pediatric and Adult Populations in Bata, Equatorial Guinea.

机构信息

HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Ramón y Cajal-IRYCIS and CIBEREsp-RITIP-CoRISpe, 20834 Madrid, Spain.

Fundación Estatal, Salud, Infancia y Bienestar Social (CSAI), 28029 Madrid, Spain.

出版信息

Viruses. 2022 Dec 21;15(1):27. doi: 10.3390/v15010027.


DOI:10.3390/v15010027
PMID:36680067
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9864178/
Abstract

A lack of HIV viral load (VL) and HIV drug resistance (HIVDR) monitoring in sub-Saharan Africa has led to an uncontrolled circulation of HIV-strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART). This study updates HIVDR data and HIV-1 variants in Equatorial Guinea (EG), providing the first data on children/adolescents in the country. From 2019−2020, 269 dried blood samples (DBS) were collected in Bata Regional Hospital (EG) from 187 adults (73 ART-naïve/114 ART-treated) and 82 children/adolescents (25 HIV-exposed-ART-naïve/57 ART-treated). HIV-1 infection was confirmed in Madrid by molecular/serological confirmatory tests and ART-failure by VL quantification. HIV-1 pol region was identified as transmitted/acquired DRM, predicted antiretroviral susceptibility (Stanfordv9.0) and HIV-1 variants (phylogeny). HIV infection was confirmed in 88.1% of the individuals and virological failure (VL > 1000 HIV-1-RNA copies/mL) in 84.2/88.9/61.9% of 169 ART-treated children/adolescents/adults. Among the 167 subjects with available data, 24.6% suffered a diagnostic delay. All 125 treated had experienced nucleoside retrotranscriptase inhibitors (NRTI); 95.2% were non-NRTI (NNRTI); 22.4% had experienced integrase inhibitors (INSTI); and 16% had experienced protease inhibitors (PI). At sampling, they had received 1 (37.6%), 2 (32%), 3 (24.8%) or 4 (5.6%) different ART-regimens. Among the 43 treated children−adolescents/37 adults with sequence, 62.8/64.9% carried viruses with major-DRM. Most harbored DRM to NNRTI (68.4/66.7%), NRTI (55.3/43.3%) or NRTI+NNRTI (50/33.3%). One adult and one child carried major-DRM to PI and none carried major-DRM to INSTI. Most participants were susceptible to INI and PI. DRM was absent in 36.2% of treated patients with VL > 1000 cp/mL, suggesting adherence failure. TDR prevalence in 59 ART-naïve adults was high (20.3%). One-half (53.9%) of the 141 subjects with pol sequence carried CRF02_AG. The observed high rate of ART-failure and transmitted/acquired HIVDR could compromise the 95-95-95-UNAIDS targets in EG. Routine VL and resistance monitoring implementation are mandatory for early detection of ART-failure and optimal rescue therapy selection ART regimens based on PI, and INSTI can improve HIV control in EG.

摘要

在撒哈拉以南非洲地区,由于缺乏 HIV 病毒载量 (VL) 和 HIV 耐药性 (HIVDR) 监测,导致具有耐药突变 (DRM) 的 HIV 株不受控制地传播,从而影响了抗逆转录病毒治疗 (ART)。本研究更新了赤道几内亚 (EG) 的 HIVDR 数据和 HIV-1 变异情况,提供了该国儿童/青少年的首个数据。2019-2020 年,从巴塔地区医院 (EG) 采集了 187 名成人 (73 名未经 ART 治疗/114 名经 ART 治疗) 和 82 名儿童/青少年 (25 名 HIV 暴露但未经 ART 治疗/57 名经 ART 治疗) 的 269 份干血斑 (DBS)。马德里通过分子/血清学确认性检测和通过 VL 定量检测到的 ART 失败来确认 HIV-1 感染。鉴定了 HIV-1 pol 区的传播/获得性 DRM、预测的抗逆转录病毒药物敏感性 (斯坦福 v9.0) 和 HIV-1 变异体 (系统发育)。在 88.1%的个体中确认了 HIV 感染,在 88.9%/61.9%的 169 名接受 ART 治疗的儿童/青少年/成人中出现了病毒学失败 (VL > 1000 HIV-1-RNA 拷贝/ml)。在有可用数据的 167 名受试者中,24.6%的人存在诊断延迟。所有 125 名接受治疗的患者均经历过核苷逆转录酶抑制剂 (NRTI);95.2%是非核苷逆转录酶抑制剂 (NNRTI);22.4%经历过整合酶抑制剂 (INSTI);16%经历过蛋白酶抑制剂 (PI)。在采样时,他们接受了 1 (37.6%)、2 (32%)、3 (24.8%)或 4 (5.6%)种不同的 ART 方案。在 43 名接受治疗的儿童/青少年/37 名成人中有序列的患者中,62.8%/64.9%的患者携带主要 DRM 病毒。大多数患者携带对 NNRTI (68.4%/66.7%)、NRTI (55.3%/43.3%)或 NRTI+NNRTI (50%/33.3%)的 DRM。一名成人和一名儿童携带对 PI 的主要 DRM,没有人携带对 INSTI 的主要 DRM。大多数患者对 INI 和 PI 敏感。在 VL > 1000 cp/ml 的接受治疗的患者中,36.2%的患者不存在 DRM,这表明存在药物依从性失败。在 59 名未经 ART 治疗的成年人中,TDR 患病率很高 (20.3%)。在 141 名携带 pol 序列的受试者中,有一半 (53.9%)携带 CRF02_AG。观察到的高 ART 失败率和传播/获得性 HIVDR 可能会影响 EG 中 95-95-95-UNAIDS 目标的实现。为了早期发现 ART 失败和基于 PI 和 INSTI 选择最佳的挽救治疗方案,有必要实施常规的 VL 和耐药性监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/29906820f310/viruses-15-00027-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/99298ad91835/viruses-15-00027-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/8f75e25e57d2/viruses-15-00027-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/5ea45457c662/viruses-15-00027-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/5befa82fea21/viruses-15-00027-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/98e020e9918a/viruses-15-00027-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/7ca43504c70b/viruses-15-00027-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/29906820f310/viruses-15-00027-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/99298ad91835/viruses-15-00027-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/8f75e25e57d2/viruses-15-00027-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/5ea45457c662/viruses-15-00027-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/5befa82fea21/viruses-15-00027-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/98e020e9918a/viruses-15-00027-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/7ca43504c70b/viruses-15-00027-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5717/9864178/29906820f310/viruses-15-00027-g007.jpg

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本文引用的文献

[1]
Genetic Diversity and Low Therapeutic Impact of Variant-Specific Markers in HIV-1 Pol Proteins.

Front Microbiol. 2022-7-14

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Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.

N Engl J Med. 2021-12-30

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High drug resistance levels could compromise the control of HIV infection in paediatric and adolescent population in Kinshasa, the Democratic Republic of Congo.

PLoS One. 2021

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Sci Rep. 2020-10-28

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Antimicrob Agents Chemother. 2019-7-25

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Curr Opin Pharmacol. 2019-4-28

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Sci Rep. 2019-4-5

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