Background: Hepatitis C virus (HCV) prevalence was 4.8% among HIV-negative men who have sex with men (MSM) starting pre-exposure prophylaxis (PrEP) in the Netherlands. We studied the HCV incidence rate (IR), characteristics of newly infected individuals, HCV genotype distribution and phylogenetic clustering among MSM and transgender persons (TGP) who use PrEP in the Netherlands.
Methods: HIV-negative MSM (n=374) and TGP (n=2) participating in the Amsterdam PrEP project at the Public Health Service of Amsterdam were tested biannually for HCV antibodies, and subsequently for HCV RNA if antibodies were present. We analyzed data from study start (August 2015) through December 2017. We calculated the HCV IR, overall and separately for primary infection and re-infection, and described baseline characteristics of participants with incident HCV infection. HCV genotyping was performed by sequencing part of the HCV NS5B gene (420 bp). Phylogenetic trees were constructed to compare HCV strains from HIV-negative participants, HIV-positive MSM with acute or chronic HCV in Amsterdam and Dutch risk groups other than MSM.
Results: The median follow-up was 1.76 person years (py) (IQR 1.57-1.98). We diagnosed 12 incident HCV infections, all in MSM: 6 primary infections and 6 re-infections. The overall HCV IR was 1.9/100 py (95%CI 1.1-3.4). The IR of primary infection was 1.0/100 py (95%CI 0.5-2.2) and of re-infection 25.5/100 py (95%CI 11.5-56.8).
Incident HCV infections were of genotype 1a (n=9), 4d (n=1), 2b (n=1) and 3a (n=1). Phylogenetic analysis revealed that 8/9 HCV-1a infections were part of 4 large MSM-specific HCV-1a clusters containing MSM with and without HIV (Figure)

Hepatitis C virus (HCV) phylogenetic tree for subtype 1a, comparing HCV sequences from HIV negative MSM with HIV positive MSM and unrelated persons.
[Hepatitis C virus (HCV) phylogenetic tree for subtype 1a, comparing HCV sequences from HIV negative MSM with HIV positive MSM and unrelated persons.]

Median age of those with incident infection was 35 years (IQR 26-41), most were white (83%), chose for daily PrEP (92%) and reported chemsex (75%) before initiating PrEP (table).

Age in years, median (IQR)35 (26-41)
White ethnicity, no. (%)10 (83%)
Living in Amsterdam, no. (%)5 (42%)
Chose daily PrEP regimen, no. (%)11 (92%)
Reported chemsex*, no. (%)9 (75%)
Total number of anal sex partners in preceding 3 months, median (IQR)19 (14-34)
Number of receptive condomless anal sex acts with unknown partners in preceding 3 months, median (IQR)8 (3-22)
Chemsex is defined as use of gamma-hydroxybutyric-acid, mephedrone or crystal-methamphetamine around sex
[Characteristics of 12 MSM with incident HCV infection, the Netherlands, 2015-2017. All data were collected at the study inclusion visit.]

Conclusions: In the Netherlands, incidence of initial and re-HCV infection among HIV-negative MSM on PrEP was high and comparable to that observed in HIV-positive MSM. The high degree of phylogenetic clustering between HCV strains acquired by MSM with and without HIV suggests a shared transmission network. Regular HCV testing to provide prompt treatment as well interventions to lower HCV-related behavior should be offered to MSM on PrEP.