Thijs J.W. van de Laar

Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission

We retrospectively screened 1836 men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (1984-2003) for hepatitis C virus (HCV) antibodies. HCV incidence was 0.18/100 person-years (PY) in human immunodeficiency virus (HIV)-positive MSM (8/4408 PY [95% confidence interval {CI}, 0.08-0.36]) but was 0/100 PY in MSM without HIV (0/7807 PY [95% CI, 0.00-0.05]). After 2000, HCV incidence among HIV-positive men increased 10-fold to 0.87/100 PY (5/572 PY [95% CI, 0.28-2.03]). Additional hospital cases (n=34) showed that MSM in Amsterdam who acquired HCV infection after 2000 reported high rates of ulcerative sexually transmitted infections (59%) and rough sexual techniques (56%), denied injection drug use, and were infected mainly with the difficult-to-treat HCV genotypes 1 (56%) and 4 (36%). Phylogenetic analysis showed 3 monophyletic clusters of MSM-specific HCV strains. The emergence of an MSM-specific transmission network suggests that HIV-positive MSM with high-risk sexual behaviors are at risk for sexually acquired HCV. Targeted prevention and routine HCV screening among HIV-positive MSM is needed to deter the spread of HCV.

Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic.

Background:Since 2000 outbreaks of sexually transmitted hepatitis C Virus (HCV) infections have been reported among HIV-infected men who have sex with men (MSM). We studied the prevalence and determinants of HCV-infection among MSM attending a large sexually transmitted infection (STI) clinic in the Netherlands. Methods:In 2007–2008, 3125 attendees of the STI clinic Amsterdam, including 689 MSM, participated in an anonymous biannual crosssectional survey. Participants were interviewed and screened for HIV and HCV antibodies. Additionally, all anti-HCV positive and HIV-infected individuals were tested for HCV RNA. Using phylogenetic analysis, HCV strains of the STI clinic attendees were compared with those isolated from MSM with acute HCV in 2000–2007. Determinants of HCV-infection were analysed using logistic regression. Results:Two of 532 (0.4%) HIV-negative MSM and 28 of 157 (17.8%) HIV-positive MSM were infected with HCV. Over the study period, HCV prevalence among HIV-infected MSM increased (14.6%–20.9%). Seven of 28 (25.0%) HIV/HCV coinfected MSM had acute HCV infection. Only five of 28 (17.9%) HIV/HCV coinfected MSM ever injected drugs (IDU). HIV-infection, IDU, fisting and gamma hydroxy butyrate (GHB)-use were significantly associated with HCV-infection. Phylogenetic analyses revealed a high degree of MSM-specific clustering. Conclusion:We found a high and increasing HCV prevalence in HIV-infected MSM. Though not statistically significant, this trend, and the relatively large proportion of acute infections suggest ongoing transmission of HCV in HIV-positive MSM. Regardless of IDU, rough sexual techniques and use of recreational drugs were associated with HCV-infection; phylogenetic analysis supported sexual transmission. Targeted prevention, like raising awareness and routine testing, is needed to stop the further spread among HIV-infected MSM, and to prevent possible spillover to HIV-negative MSM.

Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection.

Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.

Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam

BACKGROUND/AIMS This study investigates the occurrence of HCV reinfection and superinfection among HCV seroconverters participating in the Amsterdam Cohort Studies among drug users from 1985 through 2005. METHODS HCV seroconverters (n=59) were tested for HCV RNA at five different time points: the last visit before seroconversion (t=-1), the first visit after seroconversion (t=1), six months after (t=2) and one year after (t=3) seroconversion, and the last visit prior to November 2005 (t=4). If HCV RNA was present, part of the NS5B region was amplified and sequenced. Additional phylogenetic analysis and cloning was performed to establish HCV reinfection and superinfection. RESULTS Multiple HCV infections were detected in 23/59 (39%) seroconverters; 7 had HCV reinfections, 14 were superinfected, and 2 had reinfection followed by superinfection. At the moment of HCV reinfection, 7/9 seroconverters were HIV-negative: persistent HCV reinfection developed in both HIV-positive cases but also in 4/7 HIV-negative cases. In total, we identified 93 different HCV infections, varying from 1 to 4 infections per seroconverter. Multiple HCV infections were observed in 10/24 seroconverters with spontaneous HCV clearance (11 reinfections, 3 superinfections) and in 13/35 seroconverters without viral clearance (20 superinfections). CONCLUSIONS HCV reinfection and superinfection are common among actively injecting drug users. This might further complicate the development of an effective HCV vaccine.

Incidence and duration of hepatitis E virus infection in Dutch blood donors.

The incidence of hepatitis E virus (HEV) infection in the Netherlands is high. Blood donors are not routinely screened for HEV infection, but since January 2013, donations used for the production of solvent/detergent (S/D)‐treated plasma have been screened for HEV RNA.

Trends in hepatitis C virus infections among MSM attending a sexually transmitted infection clinic; 1995-2010.

Background:Since 2000, there is growing evidence that hepatitis C virus (HCV) infection has emerged as a sexually transmitted infection (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 biannual cross-sectional anonymous surveys (1995–2010), participants were interviewed and tested for HIV and HCV-antibodies. Additional HCV RNA tests were performed in all HIV-positives. Determinants of HCV infection were analysed using logistic regression. 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%). Prevalent HCV infection was more strongly associated with fisting in 2007–2008 [adjusted odds ratio (aOR) 2.85, 95% confidence interval (CI) 1.19–6.82] than in 2009–2010 (aOR 0.92, 95% CI0.42–2.02). 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. Identification of a new MSM-specific HCV lineage and the finding of recent HCV infections (0–4%) in established HCV clusters during recent years argue for ongoing transmission of HCV among HIV-positive MSM. HCV prevalence among HIV-negative MSM remained low (2007–2010: 0.5%). Conclusion: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 for HCV infection remains needed to guide prevention efforts.

Sexual transmission of hepatitis C virus in human immunodeficiency virus-negative men who have sex with men: a series of case reports.

Hepatitis C Virus (HCV) has recently emerged as sexual transmitted infection among (human immunodeficiency virus) HIV-positive but not HIV-negative men who have sex with men (MSM). We present 4 case reports showing that HIV-infection is not an absolute prerequisite for sexual HCV transmission in MSM. HIV-negative MSM with ulcerative sexual transmitted infection, those who engage in rough sexual practices or report a HCV-positive sexual partner, should be regularly screened for HCV.

Stabilizing incidence of hepatitis C virus infection among men who have sex with men in Amsterdam.

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Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study

Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0–52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63–15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04–12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02–6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27–192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39–8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19–2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60–14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.

MSM starting preexposure prophylaxis are at risk of hepatitis C virus infection

OBJECTIVES AND DESIGN Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM. METHODS At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis. RESULTS Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV. CONCLUSION HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.Objectives and design: Hepatitis C virus (HCV) has been recognized as an emerging sexually transmitted infection (STI) among HIV-positive MSM. However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start preexposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM. Methods: At enrolment in the Amsterdam PrEP demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis. Results: Of 375 HIV-negative MSM enrolled in Amsterdam PrEP, 18 (4.8%, 95% confidence interval 2.9–7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15 of 18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%), and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV. Conclusion: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.