TY - JOUR
T1 - A comprehensive genomics solution for HIV surveillance and clinical monitoring in low-income settings
AU - HPTN 071 (PopART) Team
AU - Bonsall, David
AU - Golubchik, Tanya
AU - de Cesare, Mariateresa
AU - Limbada, Mohammed
AU - Kosloff, Barry
AU - MacIntyre-Cockett, George
AU - Hall, Matthew
AU - Wymant, Chris
AU - Azim Ansari, M.
AU - Abeler-Dörner, Lucie
AU - Schaap, Ab
AU - Brown, Anthony
AU - Barnes, Eleanor
AU - Piwowar-Manning, Estelle
AU - Eshleman, Susan
AU - Wilson, Ethan
AU - Emel, Lynda
AU - Hayes, Richard
AU - Fidler, Sarah
AU - Ayles, Helen
AU - Bowden, Rory
AU - Fraser, Christophe
N1 - Funding Information:
This work was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) under cooperative agreement numbers UM1-AI068619, UM1-AI068617, and UM1-AI068613 and funded by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), the International Initiative for Impact Evaluation (with support from the Bill & Melinda Gates Foundation), NIAID, the National Institute of Mental Health (NIMH), and the National Institute on Drug Abuse (NIDA). E.B. was funded by the Medical Research
Funding Information:
This work was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) under cooperative agreement numbers UM1-AI068619, UM1-AI068617, and UM1-AI068613 and funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the International Initiative for Impact Evaluation (with support from the Bill & Melinda Gates Foundation), NIAID, the National Institute of Mental Health (NIMH), and the National Institute on Drug Abuse (NIDA). E.B. was funded by the Medical Research Council UK and the Oxford NIHR Biomedical Research Centre and is an NIHR Senior Investigator. We thank Monique Andersson and the John Radcliffe Hospital, Oxford, Clinical Microbiology Department for assistance with viral load testing. We acknowledge the support of the HPTN 071 (PopART) study team and Zambian Ministry for Health. Sequencing was supported by the Oxford Viromics initiative (Paul Klenerman, David Bonsall, and Rory Bowden) and the Oxford Genomics Centre (With thanks to John Broxholme, Lorne Lonie, Angie Green, Jerome Nicod, and David Buck). Sample and data collection have been supported by the PANGEA HIV consortium, funded by the Bill & Melinda Gates Foundation.
Funding Information:
Sequencing was supported by the Oxford Viromics initiative (Paul Klenerman, David Bonsall, and Rory Bowden) and the Oxford Genomics Centre (With thanks to John Broxholme, Lorne Lonie, Angie Green, Jerome Nicod, and David Buck). Sample and data collection have been supported by the PANGEA HIV consortium, funded by the Bill & Melinda Gates Foundation.
Publisher Copyright:
Copyright © 2020 Bonsall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2020/10
Y1 - 2020/10
N2 - Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, next-generation sequencing (NGS) is still prohibitively costly for routine use in generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method's performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.
AB - Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, next-generation sequencing (NGS) is still prohibitively costly for routine use in generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method's performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.
KW - Antiretroviral resistance
KW - Antiretroviral therapy
KW - Bait capture
KW - Drug resistance
KW - Drug resistance evolution
KW - Gene sequencing
KW - HIV
KW - HPTN
KW - HPTN 071
KW - Human immunodeficiency virus
KW - Illumina
KW - NGS
KW - Phylogenetic analysis
KW - Phylogenetics
KW - PopART
KW - Public health
KW - RNA virus
KW - SMARTer
KW - Short-read sequencing
KW - Sub-Saharan Africa
KW - Surveillance studies
KW - Viral evolution
KW - Viral genomics
KW - Viral sequencing
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U2 - 10.1128/JCM.00382-20
DO - 10.1128/JCM.00382-20
M3 - Article
C2 - 32669382
AN - SCOPUS:85091563596
VL - 58
JO - Journal of Clinical Microbiology
JF - Journal of Clinical Microbiology
SN - 0095-1137
IS - 10
M1 - e0038220
ER -