Cargando…

Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction

BACKGROUND: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, whi...

Descripción completa

Detalles Bibliográficos
Autores principales: Mbisa, Jean L, Kirwan, Peter, Tostevin, Anna, Ledesma, Juan, Bibby, David F, Brown, Alison, Myers, Richard, Hassan, Amin S, Murphy, Gary, Asboe, David, Pozniak, Anton, Kirk, Stuart, Gill, O Noel, Sabin, Caroline, Delpech, Valerie, Dunn, David T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743824/
https://www.ncbi.nlm.nih.gov/pubmed/30534981
http://dx.doi.org/10.1093/cid/ciy1048
_version_ 1783451336435564544
author Mbisa, Jean L
Kirwan, Peter
Tostevin, Anna
Ledesma, Juan
Bibby, David F
Brown, Alison
Myers, Richard
Hassan, Amin S
Murphy, Gary
Asboe, David
Pozniak, Anton
Kirk, Stuart
Gill, O Noel
Sabin, Caroline
Delpech, Valerie
Dunn, David T
author_facet Mbisa, Jean L
Kirwan, Peter
Tostevin, Anna
Ledesma, Juan
Bibby, David F
Brown, Alison
Myers, Richard
Hassan, Amin S
Murphy, Gary
Asboe, David
Pozniak, Anton
Kirk, Stuart
Gill, O Noel
Sabin, Caroline
Delpech, Valerie
Dunn, David T
author_sort Mbisa, Jean L
collection PubMed
description BACKGROUND: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient. METHODS: Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%. Sequence alignments including >110 000 HIV-1 partial pol consensus sequences from the UK HIV Drug Resistance Database (UK-HDRD), linked to epidemiological and clinical data from the HIV and AIDS Reporting System, were used for transmission cluster analysis. Transmission clusters were identified using Cluster Picker with a clade support of >90% and maximum genetic distances of 4.5% or 1.5%, the latter to limit detection to likely direct transmission events. RESULTS: Drug-resistant majority variants (DRMajVs) were detected in 66 (7.9%) and DRMinVs in 84 (10.1%) of the recently infected individuals. High levels of clustering to sequences in UK-HDRD were observed for both DRMajV (n = 48; 72.7%) and DRMinV (n = 63; 75.0%) sequences. Of these, 43 (65.2%) with DRMajVs were in a transmission cluster with sequences that harbored the same DR mutation compared to only 3 (3.6%) sequences with DRMinVs (P < .00001, Fisher exact test). Evidence of likely direct transmission of DRMajVs was observed for 25/66 (37.9%), whereas none were observed for the DRMinVs (P < .00001). CONCLUSIONS: Using a densely sampled HIV-infected population, we show no evidence of DRMinV transmission among recently infected individuals.
format Online
Article
Text
id pubmed-6743824
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-67438242019-12-11 Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction Mbisa, Jean L Kirwan, Peter Tostevin, Anna Ledesma, Juan Bibby, David F Brown, Alison Myers, Richard Hassan, Amin S Murphy, Gary Asboe, David Pozniak, Anton Kirk, Stuart Gill, O Noel Sabin, Caroline Delpech, Valerie Dunn, David T Clin Infect Dis Articles and Commentaries BACKGROUND: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient. METHODS: Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%. Sequence alignments including >110 000 HIV-1 partial pol consensus sequences from the UK HIV Drug Resistance Database (UK-HDRD), linked to epidemiological and clinical data from the HIV and AIDS Reporting System, were used for transmission cluster analysis. Transmission clusters were identified using Cluster Picker with a clade support of >90% and maximum genetic distances of 4.5% or 1.5%, the latter to limit detection to likely direct transmission events. RESULTS: Drug-resistant majority variants (DRMajVs) were detected in 66 (7.9%) and DRMinVs in 84 (10.1%) of the recently infected individuals. High levels of clustering to sequences in UK-HDRD were observed for both DRMajV (n = 48; 72.7%) and DRMinV (n = 63; 75.0%) sequences. Of these, 43 (65.2%) with DRMajVs were in a transmission cluster with sequences that harbored the same DR mutation compared to only 3 (3.6%) sequences with DRMinVs (P < .00001, Fisher exact test). Evidence of likely direct transmission of DRMajVs was observed for 25/66 (37.9%), whereas none were observed for the DRMinVs (P < .00001). CONCLUSIONS: Using a densely sampled HIV-infected population, we show no evidence of DRMinV transmission among recently infected individuals. Oxford University Press 2019-10-01 2018-12-11 /pmc/articles/PMC6743824/ /pubmed/30534981 http://dx.doi.org/10.1093/cid/ciy1048 Text en © Crown copyright 2018. http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/This article contains public sector information licensed under the Open Government Licence v3.0 (http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/).
spellingShingle Articles and Commentaries
Mbisa, Jean L
Kirwan, Peter
Tostevin, Anna
Ledesma, Juan
Bibby, David F
Brown, Alison
Myers, Richard
Hassan, Amin S
Murphy, Gary
Asboe, David
Pozniak, Anton
Kirk, Stuart
Gill, O Noel
Sabin, Caroline
Delpech, Valerie
Dunn, David T
Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction
title Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction
title_full Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction
title_fullStr Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction
title_full_unstemmed Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction
title_short Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction
title_sort determining the origins of human immunodeficiency virus type 1 drug-resistant minority variants in people who are recently infected using phylogenetic reconstruction
topic Articles and Commentaries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743824/
https://www.ncbi.nlm.nih.gov/pubmed/30534981
http://dx.doi.org/10.1093/cid/ciy1048
work_keys_str_mv AT mbisajeanl determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT kirwanpeter determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT tostevinanna determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT ledesmajuan determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT bibbydavidf determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT brownalison determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT myersrichard determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT hassanamins determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT murphygary determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT asboedavid determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT pozniakanton determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT kirkstuart determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT gillonoel determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT sabincaroline determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT delpechvalerie determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT dunndavidt determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction
AT determiningtheoriginsofhumanimmunodeficiencyvirustype1drugresistantminorityvariantsinpeoplewhoarerecentlyinfectedusingphylogeneticreconstruction