Hepatitis C virus infection : Spread and impact in the Netherlands

Background: Since 2000 there is growing evidence that HCV infection has emerged as an STI among HIV-positive MSM. Here we present a 15-year overview of the HCV epidemic among MSM visiting a large STI-clinic in the Netherlands. Methods: During bi-annual cross-sectional anonymous surveys (1995-2010), participants were interviewed and tested for HIVand HCV-antibodies. Additional HCV RNA tests were performed in all HIV-positives. Determinants of HCV infection were analyzed using logistic regression. HCV incidence was estimated using the window period from HCV RNA detection to HCV-antibody development. Phylogenetic analysis provided evidence for sexual transmission. Results: HCV prevalence among HIV-positive MSM increased from 1995 onwards (5.6%) and peaked in 2008 (20.9%). Estimated HCV incidence peaked in 2006 (14.0/100 PY; 95%CI: 5.0237.69) and thereafter decreased, although not significantly. Prevalent HCV infection was more strongly associated with fisting in 2007/2008 (aOR 2.85, 95%CI: 1.19-6.82) than in 2009/2010 (aOR 0.92, 95%CI:0.42-2.02). In addition, HCV infection was independently associated with Chlamydia, injecting drug use, unprotected anal intercourse, and older age. Phylogenetic analysis revealed a high degree of MSM-specific clustering from 2000 onwards. HCV prevalence among HIV-negative MSM remained low (0.5%). Conclusions: HCV prevalence among HIV-positive MSM significantly increased over calendar time but appears to level off in recent years, possibly due to increased awareness, saturation in the population, decreased risk behaviour, and earlier HCV screening and treatment. The association with fisting became less strong over time, but our analyses continue to support sexual transmission. Monitoring HIV-positive and HIV-negative MSM remains needed to guide prevention efforts. HCV epidemiology among subpopulations in the general Dutch population 79 3 Introduction Infection with hepatitis C virus (HCV) is transmitted primarily by blood and occurs frequently in injecting drug users (IDU) (1). Since 2000, acute HCV infections have increasingly been reported internationally among HIV-positive men who have sex with men (MSM) (2-9). Phylogenetic analysis confirms the existence of MSM-specific HCV transmission networks. The absence of reported parenteral routes of transmission suggests that most of these infections were acquired sexually. (2;5;6;9-11). HCV incidence data from HIV-seroconverter cohorts (CASCADE) and molecular-clock calculations based on circulating MSM-specific HCV strains, indicate that the HCV-epidemic among HIVpositive MSM in Europe arose with the introduction of combination antiretroviral therapy (cART) for HIV in 1996, with a substantial increase after 2002 (11-13). In the Netherlands, an alarming HCV prevalence of 17% among HIV-infected MSM was found in a biannual cross-sectional survey conducted in 2007/2008 at a large city STI outpatient clinic in Amsterdam (14). Multiple MSM-specific HCV clusters of genotypes 1a and 4d were revealed by phylogenetic analysis. HCV infection was independently associated with HIV infection, IDU, fisting and noninjecting recreational drug use (14). Adequate longitudinal data on acute and chronic HCV infections among HIV-positive and HIVnegative MSM is needed to determine the past and current state of this epidemic, reveal possible causes, and assist prevention and case-finding strategies. In the Netherlands, our first report on HCV spread in HIV-infected MSM (14) led to prevention measures focused on the sexual transmission of HCV. Even before publication, our finding of a high HCV prevalence spurred the Amsterdam STI clinic to start routine HCV-antibody testing for all MSM clients with positive or unknown HIV status. To put our earlier results on the HCV epidemic among HIV-positive MSM (2007-2008) (14) in a larger timeframe, we retrospectively tested stored serum samples of HIV-infected MSM participating in the same biannual cross-sectional survey at the Amsterdam STI clinic during the period 1995-2004, and complemented the dataset with newly recruited HIV-positive and HIVnegative MSM participating in the period 2008-2010. Combined HCV RNA and HCV-antibody testing allowed us to estimate HCV incidence over time. Phylogenetic analysis was used to gain insight into transmission networks and the emergence of MSM-specific HCV clusters. Methods Subjects Since 1991, biannual cross-sectional and anonymous HIV surveys have been performed at the STI outpatient clinic in Amsterdam (15). Each spring and autumn, consecutive clinic visitors are asked to participate until one thousand are included. Upon informed consent, their blood is drawn, tested, and stored. As participation is anonymous, multiple visits of one visitor cannot be linked and therefore the number of possible duplicate visits during the surveys is unknown. Participants are interviewed about risk factors for blood-borne and sexually transmitted infections (STI), using a standardized questionnaire. Since 2007, the interview has addressed traditional HCV-related risk behaviour (e.g. blood transfusion prior to 1992) and HCV status. Over the years, the participation rate of the clinic population has varied between 65% to 95%, depending on changes in screening procedures. Looking at 2007-2010, characteristics of survey participants and non-participants were comparable; participation was refused more often by HIV-positive MSM than by HIV-negative MSM (overall P=0.005). The present study includes selected HIV-infected MSM who took part in the biannual surveys of 1995-1996, 1999-2000, 2003-2004, and 2007-2010. A total of 831 HIV-positive MSM participated