Sensitive HIV-1 DNA Pol Next-Generation Sequencing for the Characterisation of Archived Antiretroviral Drug Resistance

Author:

Botha Johannes C.12ORCID,Byott Matthew12,Spyer Moira J.12,Grant Paul R.3,Gärtner Kathleen1,Chen Wilson X.4,Burton James5,Bamford Alasdair156,Waters Laura J.7,Giaquinto Carlo89,Turkova Anna56ORCID,Vavro Cindy L.4,Nastouli Eleni12

Affiliation:

1. Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK

2. Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Trust, London NW1 2PG, UK

3. Health Services Laboratories, London WC1H 9AX, UK

4. ViiV Healthcare, Durham, NC 27709, USA

5. Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK

6. Medical Research Council Clinical Trials Unit, University College London, London WC1E 6BT, UK

7. Central and North West London NHS Foundation Trust, Mortimer Market, London WC1E 6JB, UK

8. Department of Women and Child Health, University of Padova, 35122 Padova, Italy

9. Fondazione Penta ETS, 35127 Padova, Italy

Abstract

Modern HIV-1 treatment effectively suppresses viral amplification in people living with HIV. However, the persistence of HIV-1 DNA as proviruses integrated into the human genome remains the main barrier to achieving a cure. Next-generation sequencing (NGS) offers increased sensitivity for characterising archived drug resistance mutations (DRMs) in HIV-1 DNA for improved treatment options. In this study, we present an ultra-sensitive targeted PCR assay coupled with NGS and a robust pipeline to characterise HIV-1 DNA DRMs from buffy coat samples. Our evaluation supports the use of this assay for Pan-HIV-1 analyses with reliable detection of DRMs across the HIV-1 Pol region. We propose this assay as a new valuable tool for monitoring archived HIV-1 drug resistance in virologically suppressed individuals, especially in clinical trials investigating novel therapeutic approaches.

Funder

D3/Penta 21 trial

ViiV Healthcare

UCLH APDU

UK Medical Research Council core funding

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

Reference32 articles.

1. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents (2023, May 19). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, Available online: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf.

2. European AIDS Clinical Society (2023, May 19). Guidelines Version 11.0 October 2021. Available online: https://www.eacsociety.org/media/final2021eacsguidelinesv11.0_oct2021.pdf.

3. Presence of an Inducible HIV-1 Latent Reservoir during Highly Active Antiretroviral Therapy;Chun;Proc. Natl. Acad. Sci. USA,1997

4. Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy;Finzi;Science,1997

5. Genetic Characterization of HIV-1 from Semen and Blood from Clade C-Infected Subjects from India and Effect of Therapy in These Body Compartments;Shen;Virology,2010

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3