International Clustering Found for HCV Patients From Europe

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Men who have sex with men in Europe were more likely to be in a cluster compared to non-European men who have sex with men.

Despite goals to eliminate hepatitis C virus (HCV) infections in the next decade, there remains a need to better stop the transmission of the virus in certain target populations, including men who have sex with men.1

A team, led by Jelle Koopsen, PhD, Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, University of Amsterdam, analyzed whole-genome HCV sequences from men who have sex with men with a recently acquired infection to identify international clustering and the prevalence and transmission of resistance-associated substitutions (RAS).

“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 harboring clinically significant resistance-associated substitutions,” the authors wrote.


In recent years, international stakeholders have set a goal of eliminating HCV worldwide by 2030. Crucial to that goal is identifying subgroups more vulnerable to HCV transmission, including people who are incarcerated, people who inject drugs, and men who have sex with men with HIV.

In the large, international HCV treatment REACT trial the investigators obtained HCV sequences from 128 participants who had acquired HCV within the previous 12 months from 24 sites in 8 countries.

The investigators inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately and constructed time-scaled phylogenies to estimate cluster introduction dates.

Finally, they used a Bayesian Skygrid approach to estimate the effective population size over the previous 50 years and calculated the prevalence of RAS and the extent of RAS transmission within the patient population.


The results show most of the recent infections were part of international networks from the late 1990s and early 2000s.

The investigators also found that sequences from the same country clustered frequently and 36% of subclusters since 2015 had evidence of international transmission.

Men who have sex with men in Europe were more likely to be in a cluster compared to non-European men who have sex with men (odds ratio [OR], 11.9; 95% confidence interval [CI], 3.6-43.4; P <0.0001).

The effective population size in Europe ultimately decreased rapidly since 2015 and RAS associated with substantially diminished cure rates were infrequently identified and transmission of highly resistant viruses were not detected.

“Despite antiviral treatment becoming widely available, international transmission of HCV among [men who have sex with men] has still occurred over the past 8 years, which could complicate microelimination of the virus in this population,” the authors wrote. “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 [men who have sex with men].”


Koopsen, J., Matthews, G., Rockstroh, J., Applegate, T. L., Bhagani, S., Rauch, A., Grebely, J., Sacks-Davis, R., Ingiliz, P., Boesecke, C., Rebers, S., Feld, J., Bruneau, J., Martinello, M., Hellard, M., Dore, G. J., Schinkel, J., van der Valk, M., Adams, T., … Witele, E. (2023). Hepatitis C virus transmission between eight high-income countries among men who have sex with men: A whole-genome analysis. The Lancet Microbe.