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

被引：1
|
作者：
Botha, Johannes C. [1 ,2 ]
Byott, Matthew [1 ,2 ]
Spyer, Moira J. [1 ,2 ]
Grant, Paul R. [3 ]
Gaertner, Kathleen [1 ]
Chen, Wilson X. [4 ]
Burton, James [5 ]
Bamford, Alasdair [1 ,5 ,6 ]
Waters, Laura J. [7 ]
Giaquinto, Carlo [8 ,9 ]
Turkova, Anna [5 ,6 ]
Vavro, Cindy L. [4 ]
Nastouli, Eleni [1 ,2 ]
机构：
[1] UCL, Great Ormond St Inst Child Hlth, London WC1N 1EH, England
[2] Univ Coll London Hosp NHS Trust, Adv Pathogen Diagnost Unit, London NW1 2PG, England
[3] Hlth Serv Labs, London WC1H 9AX, England
[4] ViiV Healthcare, Durham, NC 27709 USA
[5] Great Ormond St Hosp Children NHS Fdn Trust, London WC1N 3JH, England
[6] UCL, Med Res Council, Clin Trials Unit, London WC1E 6BT, England
[7] Cent & North West London NHS Fdn Trust, Mortimer Market, London WC1E 6JB, England
[8] Univ Padua, Dept Women & Child Hlth, I-35122 Padua, Italy
[9] Fdn Penta ETS, I-35127 Padua, Italy
来源：
VIRUSES-BASEL | 2023年 / 15卷 / 09期
基金：
英国医学研究理事会; 芬兰科学院;
关键词：
HIV-1; DNA; drug resistance; provirus; NGS; sanger; BLOOD; DIVERSITY; RESERVOIR; THERAPY; ASSAY;
D O I：
10.3390/v15091811
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
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.
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页数：12
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