Blood safety markers in Dutch donors after relaxation of deferral for men who have sex with men: re-emergence of syphilis and HIV pre-exposure prophylaxis use.

BACKGROUND: Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion-transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre-exposure prophylaxis (PrEP). STUDY DESIGN AND METHODS: TTI trends in Dutch donors were studied over a 13-year period (2011-2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI-positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis. RESULTS: HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM-related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis. DISCUSSION: To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors.

Rapid, Sensitive, and Specific Severe Acute Respiratory Syndrome Coronavirus 2 Detection: A Multicenter Comparison Between Standard Quantitative Reverse-Transcriptase Polymerase Chain Reaction and CRISPR-Based DETECTR.

BACKGROUND: Recent advances in CRISPR-based diagnostics suggest that DETECTR, a combination of reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) and subsequent Cas12 bystander nuclease activation by amplicon-targeting ribonucleoprotein complexes, could be a faster and cheaper alternative to quantitative reverse-transcription polymerase chain reaction (qRT-PCR) without sacrificing sensitivity and/or specificity. METHODS: In this study, we compare DETECTR with qRT-PCR to diagnose coronavirus disease 2019 on 378 patient samples. Patient sample dilution assays suggest a higher analytical sensitivity of DETECTR compared with qRT-PCR; however, this was not confirmed in this large patient cohort, where we report 95% reproducibility between the 2 tests. RESULTS: These data showed that both techniques are equally sensitive in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) providing additional value of DETECTR to the currently used qRT-PCR platforms. For DETECTR, different guide ribonucleic acids can be used simultaneously to obviate negative results due to mutations in N-gene. Lateral flow strips, suitable as a point-of-care test, showed a 100% correlation to the high-throughput DETECTR assay. More importantly, DETECTR was 100% specific for SARS-CoV-2 relative to other human coronaviruses. CONCLUSIONS: Because there is no need for specialized equipment, DETECTR could be rapidly implemented as a complementary technically independent approach to qRT-PCR thereby increasing the testing capacity of medical microbiological laboratories and relieving the existent PCR platforms for routine non-SARS-CoV-2 diagnostic testing.

Incidence of HCV Reinfection Among HIV-Positive MSM and Its Association With Sexual Risk Behavior: A Longitudinal Analysis.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been comprehensively assessed. METHODS: Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection. RESULTS: In total, 122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range [IQR] 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (IQR 0.6-2.7). HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count <200 cells/mm3, and recent CD4 cell count <500 cells/mm3. CONCLUSIONS: Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM.

An international comparison of HIV prevalence and incidence in blood donors and general population: a BEST Collaborative study.

BACKGROUND AND OBJECTIVES: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. MATERIALS AND METHODS: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. RESULTS: There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. CONCLUSION: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.

High incidence of HCV in HIV-negative men who have sex with men using pre-exposure prophylaxis.

BACKGROUND & AIMS: HCV has emerged as a sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). We evaluated HCV incidence and its risk factors among HIV-negative MSM using HIV pre-exposure prophylaxis (PrEP). METHODS: Participants of the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. Participants used daily or event-driven PrEP and could switch regimens during follow-up. We calculated incidence rates (IRs) for overall HCV infection and separately for primary and re-infection. A univariable Bayesian exponential survival model was used to identify risk factors associated with incident HCV infection. The HCV NS5B gene fragment (709 bp) was sequenced and compared to HCV isolates from HIV-positive MSM and other risk groups (n = 419) using phylogenetic analysis. RESULTS: Among 350 participants contributing 653.6 person-years (PYs), we detected 15 HCV infections in 14 participants (IR = 2.30/100PY). There were 8 primary infections (IR = 1.27/100PY) and 7 re-infections (IR = 27.8/100PY). IR was 2.71/100PY in daily and 1.15/100PY in event-driven PrEP users. Factors associated with incident HCV infection were higher number of receptive condomless anal sex acts with casual partners (posterior hazard ratio [HR] 1.57 per ln increase; 95% credibility interval [CrI] 1.09-2.20), anal STI (posterior HR 2.93; 95% CrI 1.24-7.13), injecting drug use (posterior HR 4.69; 95% CrI 1.61-12.09) and sharing straws when snorting drugs (posterior HR 2.62; 95% CrI 1.09-6.02). We identified robust MSM-specific HCV clusters of subtypes 1a, 4d, 2b and 3a, which included MSM with and without HIV. CONCLUSIONS: HIV-negative MSM using PrEP are at risk of incident HCV infection, while identified risk factors are similar to those in HIV-positive MSM. Regular HCV testing is needed, especially for those with a previous HCV infection and those reporting risk factors. LAY SUMMARY: We report that hepatitis C virus infections are frequently acquired among HIV-negative men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV infection. New infections occurred more frequently in those reporting receptive anal sex without using condoms, having an anal sexually transmitted infection, injecting drugs, and sharing straws when snorting drugs. The viruses found in HIV-negative men using pre-exposure prophylaxis are genetically similar to those in HIV-positive men, but not in other hepatitis C risk groups, suggesting that (sexual) transmission is occurring between HIV-positive MSM and HIV-negative MSM using pre-exposure prophylaxis. CLINICAL TRIAL NUMBER: Dutch trial registration number NTR5411.

Infection Pressure in Men Who Have Sex With Men and Their Suitability to Donate Blood.

BACKGROUND: Deferral of men who have sex with men (MSM) from blood donation is highly debated. We therefore investigated their suitability to donate blood. METHODS: We compared the antibody prevalence of 10 sexually and transfusion-transmissible infections (TTIs) among 583 MSM and 583 age-matched repeat male blood donors. MSM were classified as low risk (lr) or medium-to-high risk (hr) based on self-reported sexual behavior and as qualified or unqualified using Dutch donor deferral criteria. Infection pressure (IP) was defined as the number of antibody-reactive infections, with class A infections (human immunodeficiency virus-1/2, hepatitis B virus, hepatitis C virus, human T-cell lymphotropic virus-1/2, syphilis) given double weight compared to class B infections (cytomegalovirus, herpes simplex virus-1/2, human herpesvirus 8, hepatitis E virus, parvovirus B19). RESULTS: Donors had a lower median IP than qualified lr-MSM and qualified hr-MSM (2 [interquartile range {IQR}, 1-2] vs 3 [IQR, 2-4]; P < .001). Low IP was found in 76% of donors, 39% of qualified lr-MSM, and 27% of qualified hr-MSM. The prevalence of class A infections did not differ between donors and qualified lr-MSM but was significantly higher in qualified hr-MSM and unqualified MSM. Recently acquired class A infections were detected in hr-MSM only. Compared to blood donors, human herpesviruses were more prevalent in all MSM groups (P < .001). CONCLUSIONS: IP correlates with self-reported risk behavior among MSM. Although lr-MSM might form a low threat for blood safety with regard to class A infections, the high seroprevalence of human herpesviruses in lr-MSM warrants further investigation.

Predonation screening of candidate donors and prevention of window period donations.

BACKGROUND: Infectious window period donations slip through routine donor screening procedures. To explore the potential value of predonation screening of candidate donors, we compared the proportion of incident transfusion-transmissible infections in candidate donors, in first-time donors, and in repeat donors. STUDY DESIGN AND METHODS: A retrospective analysis was performed of all incident hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in candidate, first-time, and repeat donors in the Netherlands during the period 2009 to 2013. RESULTS: In total, 176,716 candidate donors, 144,226 first-time donations, and 4,143,455 repeat donations were screened for HBV, HCV, and HIV infection. Acute HBV infection was identified in the predonation sample of six candidate donors. One first-time donor, testing HIV-negative at predonation screening, tested positive for anti-HIV and HIV RNA in the first donation 29 days later. Among repeat donations we identified 15, one, and six incident HBV, HCV and HIV infections, respectively. The proportion of incident infections among candidate donors/first-time donations/repeat donations was for HBV, 3.40/0/0.36; for HCV, 0/0/0.02; and for HIV 0/0.69/0.14 per 100,000, respectively. CONCLUSION: Predonation screening of candidate donors very likely causes a loss of donations, but it might prevent undetected window period donations. Further studies are necessary to determine the value of predonation screening as an additional safety measure.

Efficient SARS-CoV-2 Surveillance during the Pandemic-Endemic Transition Using PCR-Based Genotyping Assays.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOC) pose an increased risk to public health due to higher transmissibility and/or immune escape. In this study, we assessed the performance of a custom TaqMan SARS-CoV-2 mutation panel consisting of 10 selected real-time PCR (RT-PCR) genotyping assays compared to whole-genome sequencing (WGS) for identification of 5 VOC circulating in The Netherlands. SARS-CoV-2 positive samples (N = 664), collected during routine PCR screening (15 ≤ CT ≤ 32) between May-July 2021 and December 2021-January 2022, were selected and analyzed using the RT-PCR genotyping assays. VOC lineage was determined based on the detected mutation profile. In parallel, all samples underwent WGS with the Ion AmpliSeq SARS-CoV-2 research panel. Among 664 SARS-CoV-2 positive samples, the RT-PCR genotyping assays classified 31.2% as Alpha (N = 207); 48.9% as Delta (N = 325); 19.4% as Omicron (N = 129), 0.3% as Beta (N = 2), and 1 sample as a non-VOC. Matching results were obtained using WGS in 100% of the samples. RT-PCR genotyping assays enable accurate detection of SARS-CoV-2 VOC. Furthermore, they are easily implementable, and the costs and turnaround time are significantly reduced compared to WGS. For this reason, a higher proportion of SARS-CoV-2 positive cases in the VOC surveillance testing can be included, while reserving valuable WGS resources for identification of new variants. Therefore, RT-PCR genotyping assays would be a powerful method to include in SARS-CoV-2 surveillance testing. IMPORTANCE The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genome changes constantly. It is estimated that there are thousands of variants of SARS-CoV-2 by now. Some of those variants, variants of concern (VOC), pose an increased risk to public health due to higher transmissibility and/or immune escape. Pathogen surveillance helps researchers, epidemiologists, and public health officials to monitor the evolution of infectious diseases agents, alert on the spread of pathogens, and develop counter measures like vaccines. The technique used for the pathogen surveillance is called sequence analysis which makes it possible to examine the building blocks of SARS-CoV-2. In this study, a new PCR method based on the detection of specific changes of those building blocks is presented. This method enables a fast, accurate and cheap determination of different SARS-CoV-2 VOC. Therefore, it would be a powerful method to include in SARS-CoV-2 surveillance testing.

Hepatitis C virus seroprevalence in the Netherlands.

A population-based anti-hepatitis C virus (HCV) prevalence is important for surveillance purposes and it provides an insight into the burden of disease. In The Netherlands, a recent HCV seroprevalence estimate is not available. This national population-based cross-sectional serosurvey (PIENTER-2) resulted in a weighted national HCV seroprevalence of 0.30% (95% confidence interval 0.05-0.55%). About 70% of the HCV positive individuals found were born in an HCV-endemic country.

Hepatitis C in the general population of various ethnic origins living in the Netherlands: should non-Western migrants be screened?

BACKGROUND & AIMS: Little is known about the HCV prevalence in non-Western migrant populations. To determine whether targeted HCV screening and prevention programs for migrants are needed, we examined HCV prevalence and determinants among non-Western, Western migrants, and the native Dutch population in the Netherlands. METHODS: Data were obtained from four surveys: (1) 3895 heterosexual visitors recruited during biannual surveys at the STI-clinic Amsterdam, 2007-2009; (2) random sample of 4563 pregnant women in Amsterdam, 2003; (3) population-based random sample of 1309 inhabitants of Amsterdam, 2004; (4) population-based random sample of 4428 people living in the Netherlands, 2006-2007. Characteristics associated with HCV-positivity were examined and phylogenetic analysis was used to obtain insight in the geographical origin of HCV strains. RESULTS: HCV seroprevalence in the four surveys was low (0.3-0.6%). In total 4860/14,195 (34%) were non-Western and 9329/14,195 (66%) Western participants (including Dutch). First-generation non-Western migrants were more likely to be HCV-positive (0.7-2.3%) than Western participants (0.1-0.4%). Except for survey 3, second-generation non-Western migrants had a lower HCV prevalence than first-generation migrants, comparable to Western migrants and the Dutch population. Phylogenetic analysis showed that the majority of the HCV-positive, first-generation non-Western non-European migrants were infected with endemic strains which are rarely observed in Europe. CONCLUSIONS: First-generation non-Western migrants are at increased risk for HCV. Phylogenetic analysis suggests that transmission likely took place in the country of origin, causing introduction but no further transmission of endemic HCV strains in the Netherlands. HCV screening and prevention programs should target first-generation, but not second-generation, non-Western migrants.

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.

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study.

BACKGROUND: The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands. METHODS: We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation. RESULTS: We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3-infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS. CONCLUSIONS: The DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.

Erratum to: Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study.

[This corrects the article DOI: 10.1093/ofid/ofab006.].

Monitoring Recently Acquired HIV Infections in Amsterdam, The Netherlands: The Attribution of Test Locations.

Background: Surveillance of recent HIV infections (RHI) using an avidity assay has been implemented at Dutch sexual health centres (SHC) since 2014, but data on RHI diagnosed at other test locations is lacking. Setting: Implementation of the avidity assay in HIV treatment clinics for the purpose of studying RHI among HIV patients tested at different test locations. Methods: We retrospectively tested leftover specimens from newly diagnosed HIV patients in care in 2013-2015 in Amsterdam. Avidity Index (AI) values ≤0.80 indicated recent infection (acquired ≤6 months prior to diagnosis), and AI > 0.80 indicated established infection (acquired >6 months prior to diagnosis). An algorithm for RHI was applied to correct for false recency. Recency based on this algorithm was compared with recency based on epidemiological data only. Multivariable logistic regression analysis was used to identify factors associated with RHI among men who have sex with men (MSM). Results: We tested 447 specimens with avidity; 72% from MSM. Proportions of RHI were 20% among MSM and 10% among heterosexuals. SHC showed highest proportions of RHI (27%), followed by GPs (15%), hospitals (5%), and other/unknown locations (11%) (p < 0.001). Test location was the only factor associated with RHI among MSM. A higher proportion of RHI was found based on epidemiological data compared to avidity testing combined with the RHI algorithm. Conclusion: SHC identify more RHI infections compared to other test locations, as they serve high-risk populations and offer frequent HIV testing. Using avidity-testing for surveillance purposes may help targeting prevention programs, but the assay lacks robustness and its added value may decline with improved, repeat HIV testing and data collection.

HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study.

BACKGROUND: In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015. METHODS: In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years. FINDINGS: Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5·2 per 1000 person-years [95% CI 5·0-5·5]). The highest incidence was observed in men who have sex with men (MSM; 7·7 per 1000 person-years [7·3-8·2]) and was lower in people who inject drugs (PWID; 1·7 per 1000 person-years [0·7-4·1]) and other key populations (1·0 per 1000 person-years [0·8-1·2]). In MSM, incidence increased in 2007 to 14·3 per 1000 person-years and fluctuated between 8·7 and 13·0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6·1 cases per 1000 person-years and remained steady between 4·1 and 4·9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26·9 per 1000 person-years [95% CI 23·9-30·3]). The highest incidence rate was observed in MSM (38·5 per 1000 person-years [33·9-43·7]) and was lower in PWID (10·9 per 1000 person-years [3·5-33·8]) and other key populations (8·9 per 1000 person-years [6·3-12·5]). In MSM, reinfection incidence fluctuated between 38·0 and 88·9 per 1000 person-years from 2006 to 2015, reaching 55·6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41·4 per 1000 person-years, followed by further decreases to 24·4 per 1000 person-years in 2017 and 11·4 per 1000 person-years in 2019. INTERPRETATION: The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. FUNDING: Dutch Ministry of Health, Welfare, and Sport.

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.

Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles.

Hepatitis C virus (HCV) genotype 4 (HCV-4) infection is considered to be difficult to treat and has become increasingly prevalent in European countries, including The Netherlands. Using a molecular epidemiological approach, the present study investigates the genetic diversity and evolutionary origin of HCV-4 in Amsterdam, The Netherlands. Phylogenetic analysis of the NS5B sequences (668 bp) obtained from 133 patients newly diagnosed with HCV-4 infection over the period from 1999 to 2008 revealed eight distinct HCV-4 subtypes; the majority of HCV-4 isolates were of subtypes 4d (57%) and 4a (37%). Three distinct monophyletic clusters were identified, with each one having a specific epidemiological profile: (i) Egyptian immigrants infected with HCV-4a (n = 46), (ii) Dutch patients with a history of injecting drug use infected with HCV-4d (n = 44), and (iii) Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) infected with HCV-4d (n = 26). Subsequent molecular clock analyses confirmed that the emergence of HCV-4 within these three risk groups coincided with (i) the parenteral antischistosomal therapy campaigns in Egypt (1920 to 1960), (ii) the popularity of injecting drug use in The Netherlands (1960 to 1990), and (iii) the rise in high-risk sexual behavior among MSM after the introduction of highly active antiretroviral therapy (1996 onwards). Our data show that in addition to the influx of HCV-4 strains from countries where HCV-4 is endemic, the local spread of HCV-4d affecting injecting drug users and, in recent years, especially HIV-positive MSM will further increase the relative proportion of HCV-4-infected patients in The Netherlands. HCV-4-specific agents are drastically needed to improve treatment response rates and decrease the future burden of HCV-4-related disease.

Spontaneous Clearance of Hepatitis C Virus Infection Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men.

We assessed spontaneous clearance in 27 human immunodeficiency virus-infected men who have sex with men (MSM) who seroconverted for hepatitis C virus (HCV). In contrast with a recent estimate of 45.8%, we found a spontaneous clearance rate of 11.1% (95% confidence interval = 2.4-29.2). This finding suggests that treatment deferral to await spontaneous clearance might not be justified for MSM with sexually acquired HCV.

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

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.