TY - JOUR
T1 - Hepatitis C virus transmission between eight high-income countries among men who have sex with men
T2 - a whole-genome analysis
AU - Koopsen, Jelle
AU - REACT study group
AU - Matthews, Gail
AU - Rockstroh, Juergen
AU - Applegate, Tanya L.
AU - Bhagani, Sanjay
AU - Rauch, Andri
AU - Grebely, Jason
AU - Sacks-Davis, Rachel
AU - Ingiliz, Patrick
AU - Boesecke, Christoph
AU - Rebers, Sjoerd
AU - Feld, Jordan
AU - Bruneau, Julie
AU - Martinello, Marianne
AU - Hellard, Margaret
AU - Dore, Gregory J.
AU - Schinkel, Janke
AU - van der Valk, Marc
AU - Adams, Tanya
AU - Amjad, Sophia
AU - Appelhans, Christina
AU - Applegate, Tanya
AU - Becker, Brigitta
AU - Bouchard, Rachel
AU - Braun, Dominique
AU - Bruelisauer, Christine
AU - Calcagnile, Selma
AU - Carroll, Anne
AU - Cerocchi, Orlando
AU - Chronister, Karen
AU - Cordes, Christiane
AU - Dore, Greg
AU - Evans, Fiona
AU - Fedele, Serge
AU - Ferguson, Catherine
AU - Fraser, Chris
AU - Ganase, Bruce
AU - Gane, Ed
AU - George, Valerie
AU - Gerlach, Christoph
AU - Gilleece, Yvonne
AU - Gilliver, Rosie
AU - Grube, Christina
AU - Gustafson, Jenna
AU - Haas, Annette
AU - Hagenauer, Michelle
AU - Harris, Marianne
AU - Helder, Jeltje
AU - Hirter, Daniela
AU - Peters, Martine
AU - Hull, Mark
N1 - Funding Information: We thank the study participants for their contribution to the research. We also acknowledge the work undertaken by collaborators at all study sites. The REACT trial was funded by the National Institutes of Health (National Institute on Drug Abuse division, grant number R01DA040506). Sequencing of Dutch viral isolates was partially funded by Dr. C.J. Vaillant Fonds. Study medication was provided by Gilead Sciences. The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Funding Information: We thank the study participants for their contribution to the research. We also acknowledge the work undertaken by collaborators at all study sites. The REACT trial was funded by the National Institutes of Health (National Institute on Drug Abuse division, grant number R01DA040506). Sequencing of Dutch viral isolates was partially funded by Dr. C.J. Vaillant Fonds. Study medication was provided by Gilead Sciences. The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Publisher Copyright: © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4·0 license
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Background: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. Methods: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. Findings: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6–43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. Interpretation: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. Funding: National Institutes of Health and Dr. C.J. Vaillant Fonds.
AB - Background: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. Methods: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. Findings: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6–43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. Interpretation: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. Funding: National Institutes of Health and Dr. C.J. Vaillant Fonds.
UR - http://www.scopus.com/inward/record.url?scp=85166302857&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S2666-5247(23)00108-8
DO - https://doi.org/10.1016/S2666-5247(23)00108-8
M3 - Article
C2 - 37336226
SN - 2666-5247
VL - 4
SP - e622-e631
JO - The Lancet Microbe
JF - The Lancet Microbe
IS - 8
ER -