Changing trends in international versus domestic HCV transmission in HIV-positive MSM: A perspective for the DAA scale-up era.

Background: Scale-up of direct-acting antiviral(DAA) therapy is expected to abate HCV incidence among HIV-positive men-who-have-sex-with-men(MSM). Treatment programs in neighbouring countries may influence each other's outcomes through international transmission. We aimed at classifying HCV infections in HIV-positive MSM as either domestically or internationally acquired, and at estimating 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(SHCS) and diagnosed with replicating HCV infections between 1999 and 2016, 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 other 374 circulating strains retrieved from national and international databases. We inferred transmission clusters from these trees and used the country composition of such clusters to attribute infections to domestic or international transmission.

Results: Fifty to 80% of HCV transmissions 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 the epidemic. While international transmission persists, local transmission has established as the main source of infections.