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Background Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recrui

INTRODUCTION: Affordable and sensitive screening methods for acute hepatitis C (HCV) are necessary to successfully intervene in the current HCV epidemic among HIV-positive men having sex with men. HCV core antigen (Ag) testing has been proven effective in diagnosing chronic HCV-infected patients at low costs. We studied the characteristics of HCV Ag testing in acute HCV-infected HIV-positive patients. Methods Plasma samples were selected from acutely HCV genotype 1-infected patients treated with peginterferon, ribavirin and boceprevir in the Dutch Acute HCV in HIV Study. The control group consisted of HIV-positive patients with a newly raised alanine aminotransferase (ALT) (>41 U/L) in whom HCV RNA was undetectable and who were tested for HCV Ag. Spearman correlation coefficient between HCV RNA and HCV Ag was calculated together with the sensitivity and specificity of HCV Ag testing at acute HCV diagnosis.RESULTS AND DISCUSSION: Upon acute HCV diagnosis, HCV Ag was identified in 39 out of 44 patients with detectable HCV RNA levels. In all 23 control patients without detectable HCV RNA in plasma, HCV Ag was undetectable as well. This resulted in a sensitivity and specificity of HCV Ag of respectively 89% (95% CI 75-96) and 100% (95% CI 82-100). The correlation between HCV Ag and HCV RNA was 0.97 (p < 0.001) upon diagnosis.CONCLUSION: The data presented in this study suggest that HCV Ag testing is a sensitive and specifi

Item does not contain fulltext, Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.

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Item does not contain fulltext, BACKGROUND & AIMS: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24weeks. The addition of a protease inhibitor could shorten therapy without loss of efficacy. METHODS: We performed an open-label, single arm study to investigate the efficacy and safety of a 12-week course of boceprevir, PegIFN and RBV for AHCV genotype 1 infections in 10 Dutch HIV treatment centers. The primary endpoint of the study was achievement of sustained virological response rate at week 12 (SVR12) in patients reaching a rapid viral response at week 4 (RVR4) and SVR12 in the intent to treat (ITT) entire study population was the most relevant secondary endpoint. RESULTS: One hundred twenty-seven AHCV patients were screened in 16months, of which 65 AHCV genotype 1 patients were included. After spontaneous clearance in six patients and withdrawal before treatment initiation in two, 57 started therapy within 26weeks after infection. RVR4 rate was 72%. SVR12 rate was 100% in the RVR4 group. SVR12 rate in the ITT group was 86% and comparable to the SVR12 rate of 84% in 73 historical controls treated for 24weeks with PegIFN and RBV in the same study centers. CONCLUSION: With the addition of boceprevir to PegIFN and RBV, treatment duration of AHCV genotype 1 can be reduced to 12weeks without loss of efficacy. Given the high drug costs and limited availability of interferon-free regimens, boceprevir PegIFN and RBV can be a considered a valid treatment option for AHCV. ClinicalTrials.gov, number NCT01912495.

The general aim of this thesis is to study different aspects of an acute HCV infection in HIV positive MSM. The primary aim is to study the effectivity and safety of boceprevir in addition to pegIFN and RBV for the treatment of acute HCV infections within the Dutch Acute HCV in HIV study (DAHHS). Subsequently, the DAHH-Study provided an unique opportunity to study the epidemiologic, clinical, immunologic and virologic characteristics of acute HCV infections among HIV positive MSM in the Netherlands

Objective Mucosal-associated invariant T (MAIT) cells comprise a subpopulation of T cells that can be activated by bacterial products and cytokines to produce IFN-γ. Since little is known on MAIT cells during HCV infection, we compared their phenotype and function in comparison to HIV and HCV/HIV co-infected patients, and determined the effect of IFN-α-based and direct-acting antiviral therapy on MAIT cells of HCV patients. Methods Blood samples from patients with chronic HCV (CHCV), virologically suppressed HIV, acute HCV/HIV co-infection (AHCV/HIV) and healthy individuals were examined by flowcytometry for phenotype and function of MAIT and NK cells. Results and Conclusions Compared to healthy individuals, the frequency of CD161+ Vα7.2+ MAIT cells was significantly decreased in patients with CHCV, HIV and AHCV/HIV co-infection. CD38 expression on MAIT cells was increased in AHCV/HIV patients. MAIT cells were responsive to IFN-α in vitro as evidenced by enhanced frequencies of IFN-γ producing cells. IFN-α-based therapy for CHCV decreased the frequency of IFN-γ+ MAIT cells, which was still observed 24 weeks after successful therapy. Importantly, even after successful IFN-α-based as well as IFN-αfree therapy for CHCV, decreased frequencies of MAIT cells persisted. We show that the frequencies of MAIT cells are reduced in blood of patients with CHCV, HIV and in AHCV/ HIV co-infection compared to healthy individuals. Successful therapy for CHCV did not normalize MAIT cell frequencies at 24 weeks follow up. The impact of HIV and HCV infection on the numbers and function of MAIT cells warrant further studies on the impact of viral i