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在葡萄牙语非洲国家(PALOP)减少 HIV-1 耐药性的出现和传播的 MARVEL 研究:用于非洲 HIV-1 监测的低成本便携式 NGS 平台。

MARVEL-minimising the emergence and dissemination of HIV-1 drug resistance in Portuguese-speaking African Countries (PALOP): low-cost portable NGS platform for HIV-1 surveillance in Africa.

机构信息

Global Health and Tropical Medicine, Associate Laboratory in Translation and Innovation Towards Global Health, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, Lisboa, 1349-008, Portugal.

Centro de Investigação em Saúde de Angola (CISA), Caxito, Angola.

出版信息

BMC Infect Dis. 2024 Aug 29;24(1):884. doi: 10.1186/s12879-024-09803-1.

Abstract

BACKGROUND

HIV-1 infections remain a global public health concern. Scaled-up antiretroviral treatment (ART) is crucial for reducing morbidity and mortality related to HIV/AIDS. The emergence of drug-resistance mutations (DRMs) compromises viral suppression and contributes to the continued HIV-1 transmission. Several reports indicate a recent increase in acquired (ADR) and transmitted (TDR) drug resistance in Africa, probably linked to the lack of implementation of HIV drug resistance (HIVDR) testing and suboptimal treatment adherence. Herein, we will develop a low-cost protocol using third-generation sequencing (Oxford Nanopore Technology) for HIV-1 surveillance in Portuguese-speaking African Countries - PALOP [Angola (AO), Cape Verde (CV), Mozambique (MZ), and Sao Tome & Principe (STP)].

METHODS

This is a multicentric cross-sectional study that includes around 600 adult patients newly diagnosed with HIV-1 in the PALOP. An epidemiological questionnaire previously validated by our research team will be used to collect sociodemographic and clinical data. Also, whole blood samples will be collected and the plasma samples will be subjected to drug resistance testing using an in-house low-cost NGS protocol. Data analysis will involve bioinformatics, biostatistics and machine learning techniques to generate accurate and up-to-date information about HIV-1 genetic diversity, ADR and TDR.

DISCUSSION

The implementation of this low-cost NGS platform for HIV-1 surveillance in the PALOP will allow: (i) to increase DRM surveillance capacity in resource-limited settings; (ii) to understand the pattern and determinants of dissemination of resistant HIV-1 strains; and (iii) to promote the development of technical and scientific skills of African researchers for genomic surveillance of viral pathogens and bioinformatics analysis. These objectives will contribute to reinforcing the capacity to combat HIV infection in Africa by optimizing the selection of ART regimens, improving viral suppression, and reducing ADR or TDR prevalence in PALOPs, with relevant implications for public health.

摘要

背景

HIV-1 感染仍然是全球公共卫生关注的问题。扩大抗逆转录病毒治疗(ART)对于降低与 HIV/AIDS 相关的发病率和死亡率至关重要。耐药突变(DRMs)的出现会影响病毒抑制,并导致 HIV-1 的持续传播。有几项报告表明,非洲获得性(ADR)和传播性(TDR)耐药性最近有所增加,这可能与缺乏 HIV 耐药性(HIVDR)检测和治疗依从性不佳有关。在此,我们将开发一种使用第三代测序(Oxford Nanopore Technology)的低成本方案,用于监测葡萄牙语非洲国家 - PALOP[安哥拉(AO)、佛得角(CV)、莫桑比克(MZ)和圣多美和普林西比(STP)]的 HIV-1。

方法

这是一项多中心横断面研究,包括 PALOP 中大约 600 名新诊断为 HIV-1 的成年患者。我们的研究团队之前已经验证了一份流行病学问卷,将用于收集社会人口统计学和临床数据。还将采集全血样本,并使用内部低成本 NGS 方案对血浆样本进行耐药性检测。数据分析将涉及生物信息学、生物统计学和机器学习技术,以生成有关 HIV-1 遗传多样性、ADR 和 TDR 的准确和最新信息。

讨论

在 PALOP 中实施这种低成本 NGS 平台进行 HIV-1 监测将允许:(i)提高资源有限环境下 DRM 监测能力;(ii)了解耐药性 HIV-1 株传播的模式和决定因素;(iii)促进非洲研究人员在病毒病原体基因组监测和生物信息学分析方面的技术和科学技能发展。这些目标将有助于通过优化 ART 方案的选择、提高病毒抑制率以及降低 PALOPs 中的 ADR 或 TDR 患病率,加强非洲对抗 HIV 感染的能力,从而对公共卫生产生重要影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a89/11360575/7f2233aa3757/12879_2024_9803_Fig1_HTML.jpg

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