Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals

Abstract

Background: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium.

Methods: We included 89 MSM that were recently infected with HCV genotype 1a in ten Dutch and one Belgian HIV treatment centers. Sequences were generated using next gene sequencing and Sanger sequencing. Maximum likelihood phylogenetic analysis (general time reversible model) was performed on concatenated NS5A and NS5B sequences and a reference set of 389 highly similar control sequences selected from GenBank. A cluster was based on a minimum bootstrap support of 90% and a 3% genetic distance threshold.

Results: We found that 78 (88%) of individuals were part of seven major clusters. All clusters included individuals from across the study region, however, different cities were part of different clusters. In three clusters, HIV-negative MSM clustered with sequences from HIV-positive MSM. All clusters that were observed before the introduction of DAAs persisted after unrestricted access to DAAs became available.

Conclusion: Recently acquired HCV infections among MSM in the Netherlands and Belgium are strongly clustered and therefore highly suitable for targeted prevention strategies, such as contact tracing and partner notification. Importantly, despite an HCV incidence reduction after high DAA uptake and continuously monitoring, HCV transmission persisted in the same clusters.

Trial registration: ClinicalTrials.gov NCT01912495 NCT02600325.

Keywords: HIV-infected Men-who-have-sex-with-men; hepatitis C elimination; hepatitis c; phylogenetic analysis; transmission dynamics.

Conflict of interest statement

S.P.: nothing to disclose; L.C.: has nothing to disclose; M.A.A.C.: Dr. Claassen has nothing to disclose; G.E.v.d.B.: no disclosures; A.d.W.: Dr. De Weggheleire has nothing to disclose; J.E.A.: Dr. Arends reports other from Gilead, other from Janssen, other from ViiV, other from MSD, outside the submitted work; A.B.: has no conflict of interest; R.M.: Dr. Molenkamp has nothing to disclose; M.P.G.K.: Dr. Koopmans has nothing to disclose; A.V.: has nothing to disclose; C.B.: received honaria from ViiV outside of the submitted work; B.R.: reports research grants from Gilead, research grants from Merck Sharp and Dohme and honoraria from Jansen-Cilag, BMS, Pfizer and Viiv; D.v.d.V.: Gilead Sciences, MSD, ViiV, and Jansen & Jansen.

Figures

Figure 1

An overview of the clusters and transmission pairs (I–VIII) with a genetic distance threshold <3%. The circles represent HCV infections included prior to the widespread use of DAA therapy (all in HIV-positive MSM). The triangles represent HCV infections among HIV-positive and star among HIV-negative MSM after DAA introduction. The size of the nodes represents the number of sequences to which that particular node was phylogenetically linked. The colours represent the centres where patients were diagnosed with HCV (dark blue = Haarlem, dark green = The Hague, grey = Arnhem, light blue = Amsterdam, light green = Antwerp (Belgium), pink = Maastricht, orange = Utrecht, and red = Rotterdam) The clusters consisted only of study samples and did not include any of the control samples, which mostly originated from other European countries and the United States. The figure is established using Microbe Trace [20].