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高水平的耐药性可能会影响刚果民主共和国金沙萨儿科和青少年人群中 HIV 感染的控制。

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

机构信息

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

Microbiology Department, Clínica Universidad de Navarra, Navarra Institute for Health Research, Institute of Tropical Health, Universidad de Navarra, Pamplona, Spain.

出版信息

PLoS One. 2021 Apr 15;16(4):e0248835. doi: 10.1371/journal.pone.0248835. eCollection 2021.

Abstract

BACKGROUND

The inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC).

METHODS

From 2016-2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization.

RESULTS

HIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants.

CONCLUSION

The high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.

摘要

背景

非洲的 HIV 病毒血症和耐药监测不足导致具有耐药突变(DRM)的 HIV 毒株不受控制地传播,从而影响抗逆转录病毒治疗(ART)的效果。本研究描述了金沙萨(刚果民主共和国)两所医院接受 ART 治疗的 71 名 HIV 感染儿科患者的 DRM 流行情况及其治疗影响。

方法

2016 年至 2018 年,从金沙萨的两家医院中收集了 71 名接受 ART 治疗的 HIV 感染儿童和青少年的干血样,用于 HIV-1 DRM pol 分析,通过斯坦福大学和系统发育特征预测 ARV 敏感性。

结果

从 55 名中位年龄为 14 岁的儿童/青少年中恢复了 HIV-1 序列。所有患者均接受了核苷和非核苷逆转录酶抑制剂(NRTI、NNRTI)、9.1%蛋白酶抑制剂(PI)和仅一种整合酶抑制剂(INI)治疗。尽管接受了 ART,但 89.1%的患者出现病毒学失败,67.3%的患者携带一种(12.7%)、两种(47.3%)或三种(5.5%)抗逆转录病毒药物家族的主要 DRM。大多数儿童/青少年携带 NNRTI(73.5%)或 NRTI(61.2%)耐药突变。8.3%的患者存在主要 PI 耐药突变,15%的患者存在次要 INI 耐药突变。双重 NRTI+NNRTI 耐药出现在 53.1%的患者中。病毒对奈韦拉平(72.9%的患者)、依非韦伦(70.9%)、恩曲他滨/替诺福韦(47.9%)、利匹韦林(41.7%)、依曲韦林(39.6%)、多拉韦林(33.3%)、齐多夫定(22.9%)等药物具有高度/中度耐药性。大多数参与者对 INI 和 PI 敏感。发现了大量的变异体,其中 40%的变异体是独特的重组体。

结论

在金沙萨接受治疗的 HIV 感染儿童和青少年中观察到的高 DRM 流行率可能会影响刚果民主共和国 95-95-95-UNAIDS 目标的实现。这也再次强调了在这一弱势群体中需要常规进行耐药监测,以选择最佳的挽救治疗方案,从而控制该国耐药 HIV 的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d4d/8049233/535630b31846/pone.0248835.g001.jpg

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