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. 2023 Aug;4(8):e622-e631.
doi: 10.1016/S2666-5247(23)00108-8. Epub 2023 Jun 16.

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis

Jelle Koopsen  1 , Gail Matthews  2 , Juergen Rockstroh  3 , Tanya L Applegate  4 , Sanjay Bhagani  5 , Andri Rauch  6 , Jason Grebely  4 , Rachel Sacks-Davis  7 , Patrick Ingiliz  8 , Christoph Boesecke  3 , Sjoerd Rebers  9 , Jordan Feld  10 , Julie Bruneau  11 , Marianne Martinello  4 , Margaret Hellard  12 , Gregory J Dore  2 , Janke Schinkel  9 , Marc van der Valk  13 ; REACT Study Group
Collaborators, Affiliations
Free article

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis

Jelle Koopsen et al. Lancet Microbe. 2023 Aug.
Free article

Abstract

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.

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Conflict of interest statement

Declaration of interests GM reports grants from Gilead Sciences and AbbVie, outside of the submitted work. SB reports grants from Gilead Sciences and personal fees for advisory board membership, lectures, and presentations from Gilead Sciences, all outside the submitted work. MvdV reports grants and personal fees from AbbVie, Gilead Sciences, Johnson & Johnson, MSD, and ViiV, outside the submitted work. JR reports personal fees from Gilead Sciences, Janssen, Merck, Theratechnologies, and ViiV, outside the submitted work. JF reports grants and personal fees from Gilead Sciences, Enanta, and AbbVie; personal fees from GSK, Arubutus, and Roche; and grants from Janssen and Eiger, all outside the submitted work. AR is a member of advisory boards of MSD and Gilead Sciences; has received travel grants from Gilead Sciences, Pfizer, and AbbVie; and has received an investigator-initiated trial grant from Gilead Sciences; all remuneration was to his home institution (Bern University Hospital, Bern, Switzerland) and not to AR personally. JB reports grants from the National Institutes of Health during the conduct of the study; personal fees from AbbVie; grants and personal fees from Gilead Sciences; and grants from the Canadian Institutes of Health Research, Fonds de Recherche—Québec, Substance Use and Abuse program, and Health Canada, outside the submitted work. MH reports grants from Gilead Sciences and AbbVie, outside the submitted work. PI reports grants and personal fees from Gilead Sciences and personal fees from AbbVie and ViiV, outside the submitted work. JG reports grants and personal fees from AbbVie, Gilead Sciences, Merck, and Cepheid; grants from Hologic and Indivior; payment or honoraria and travel support from AbbVie, Gilead Sciences, and Cepheid; receipt of testing equipment and cartridges from Cepheid; and receipt of testing reagents from Hologic; outside the submitted work. GJD reports grants, personal fees, and non-financial support from Gilead Sciences, AbbVie, and Merck and grants from Bristol-Myers Squibb, outside the submitted work. JS's institution (Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands) has received research support and consultancy fees from Gilead Sciences (NoCO grant) and a speaker's fee from Janssen Pharmaceuticals, outside the submitted work. CB reports honoraria for lectures and/or consultancies from AbbVie, Gilead Sciences, Janssen, MSD, and ViiV and funding from Dt. Leberstiftung, DZIF, Hector Stiftung, and NEAT ID. JK, SR, RS-D, MM, and TLA declare no competing interests.

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