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.

引用

页数：12

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