Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance

Sung Yong Park; Gina Faraci; Gary Murphy; Christopher Pilcher; Michael P. Busch; Ha Youn Lee

doi:10.1093/infdis/jiab060

Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance

Sung Yong Park, Gina Faraci, Gary Murphy, Christopher Pilcher, Michael P. Busch, Ha Youn Lee^*

^*Corresponding author for this work

Clinical Services Unit

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Background: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all"target.

Methods: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences.

Results: We achieved greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and a 262-day mean duration of recent infection (average time span of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked DRMs. By screening all 93 World Health Organization surveillance DRMs, we detected 6 pretreatment drug resistance mutations with 2.6%-13.2% prevalence and cross-linked mutations.

Conclusions: HIDA with microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for surveillance of other pathogens.

Original language	English
Pages (from-to)	1048-1059
Number of pages	12
Journal	Journal of Infectious Diseases
Volume	224
Issue number	6
Early online date	31 Jan 2021
DOIs	https://doi.org/10.1093/infdis/jiab060
Publication status	Published - 15 Sept 2021

Bibliographical note

Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant R01-AI095066) and the Bill & Melinda Gates Foundation (grants OPP1017716, OPP1062806, and OPP1115799 to CEPHIA).

Open Access: No Open Access licence.

Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Citation: Sung Yong Park, Gina Faraci, Gary Murphy, Christopher Pilcher, Michael P Busch, Ha Youn Lee, Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance, The Journal of Infectious Diseases, Volume 224, Issue 6, 15 September 2021, Pages 1048–1059,

DOI: https://doi.org/10.1093/infdis/jiab060

Keywords

Drug resistance mutations
Genomic surveillance
HIV
Incidence

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/infdis/jiab060

Cite this

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title = "Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance",

abstract = "Background: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 {"}treatment for all{"}target. Methods: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences. Results: We achieved greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and a 262-day mean duration of recent infection (average time span of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked DRMs. By screening all 93 World Health Organization surveillance DRMs, we detected 6 pretreatment drug resistance mutations with 2.6%-13.2% prevalence and cross-linked mutations. Conclusions: HIDA with microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for surveillance of other pathogens.",

keywords = "Drug resistance mutations, Genomic surveillance, HIV, Incidence",

author = "Park, {Sung Yong} and Gina Faraci and Gary Murphy and Christopher Pilcher and Busch, {Michael P.} and Lee, {Ha Youn}",

note = "Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant R01-AI095066) and the Bill & Melinda Gates Foundation (grants OPP1017716, OPP1062806, and OPP1115799 to CEPHIA). Open Access: No Open Access licence. Publisher Copyright: {\textcopyright} 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Citation: Sung Yong Park, Gina Faraci, Gary Murphy, Christopher Pilcher, Michael P Busch, Ha Youn Lee, Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance, The Journal of Infectious Diseases, Volume 224, Issue 6, 15 September 2021, Pages 1048–1059, DOI: https://doi.org/10.1093/infdis/jiab060",

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AU - Park, Sung Yong

AU - Faraci, Gina

AU - Murphy, Gary

AU - Pilcher, Christopher

AU - Busch, Michael P.

AU - Lee, Ha Youn

N1 - Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant R01-AI095066) and the Bill & Melinda Gates Foundation (grants OPP1017716, OPP1062806, and OPP1115799 to CEPHIA). Open Access: No Open Access licence. Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Citation: Sung Yong Park, Gina Faraci, Gary Murphy, Christopher Pilcher, Michael P Busch, Ha Youn Lee, Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance, The Journal of Infectious Diseases, Volume 224, Issue 6, 15 September 2021, Pages 1048–1059, DOI: https://doi.org/10.1093/infdis/jiab060

PY - 2021/9/15

Y1 - 2021/9/15

N2 - Background: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all"target. Methods: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences. Results: We achieved greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and a 262-day mean duration of recent infection (average time span of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked DRMs. By screening all 93 World Health Organization surveillance DRMs, we detected 6 pretreatment drug resistance mutations with 2.6%-13.2% prevalence and cross-linked mutations. Conclusions: HIDA with microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for surveillance of other pathogens.

AB - Background: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all"target. Methods: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences. Results: We achieved greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and a 262-day mean duration of recent infection (average time span of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked DRMs. By screening all 93 World Health Organization surveillance DRMs, we detected 6 pretreatment drug resistance mutations with 2.6%-13.2% prevalence and cross-linked mutations. Conclusions: HIDA with microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for surveillance of other pathogens.

KW - Drug resistance mutations

KW - Genomic surveillance

KW - HIV

KW - Incidence

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SN - 0022-1899

VL - 224

SP - 1048

EP - 1059

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 6

ER -

Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance

Abstract

Bibliographical note

Keywords

UN SDGs

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