Changing Trends in International Versus Domestic HCV Transmission in HIV-Positive Men Who Have Sex With Men: A Perspective for the Direct-Acting Antiviral Scale-Up Era

Abstract

Background: Scale-up of direct-acting antiviral therapy is expected to abate hepatitis C virus (HCV) incidence among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). International transmission could influence this process. We classified HCV infections in HIV-positive MSM as either domestically or internationally acquired, and estimated how this classification changed over time.

Methods: HCV subtype 1a (the most frequent subtype among MSM) genomes from 99 persons enrolled in the Swiss HIV Cohort Study and diagnosed with replicating HCV infections, were sequenced. Sixty-six of these sequences were from MSM. We inferred maximum-likelihood phylogenetic trees and time trees containing a fragment of the NS5B region of these and 374 circulating strains. We inferred transmission clusters from these trees and used the country composition of such clusters to attribute infections to domestic or international transmission.

Results: Of HCV transmissions, 50% to 80% were classified as domestic depending on the classification criterion. Between 2000 and 2007, the fraction attributable to domestic transmission was 54% (range 0-75%). It increased to 85% (range 67%-100%) between 2008 and 2016.

Conclusions: International and domestic transmission have played major roles in this epidemic. While international transmission persists, local transmission has established as the main source of infections.

Keywords: HIV; direct-acting antivirals; hepatitis C virus; men who have sex with men; transmission.

Figure 1.

Phylogenetic tree showing clusters that contained the study sequences (Swiss men who have sex with men [MSM] sequences). Clusters were defined as monophyletic trees with ≥70% bootstrap support value. The full tree (from which this one is derived, Supplementary Figure 1) was computed using RAxML with 100 replicates and a general time reversible model with invariant sites and gamma-distributed substitution rates.

Figure 2.

Likely geographic origin of infection (A) and international linkages of the Swiss men who have sex with men (MSM) sequences (B). This classification was derived from the clusters identified in the maximum likelihood phylogenetic tree. Swiss dominance criteria was defined as minimum percentage of sequences in the clusters that are Swiss necessary to classify a cluster as Swiss. Abbreviation: HCV, hepatitis C virus.

Figure 3.

Time trends in the fraction of hepatitis C virus (HCV) infections attributable to domestic and international transmission. This classification assumed an 80% dominance criterion and was derived from the time tree inferred using BEAST 2.0. Branching times involving our study sequences (Swiss men who have sex with men [MSM] sequences) served as proxy for transmission times.