Salazar-Vizcaya Luisa, Kouyos Roger D, Zahnd Cindy, Wandeler Gilles, Battegay Manuel, Darling Katharine Elizabeth Anna, Bernasconi Enos, Calmy Alexandra, Vernazza Pietro, Furrer Hansjakob, Egger Matthias, Keiser Olivia, Rauch Andri (2016), Hepatitis C virus transmission among human immunodeficiency virus-infected men who have sex with men: Modeling the effect of behavioral and treatment interventions., in
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Zahnd Cindy, Salazar-Vizcaya Luisa, Dufour Jean-François, Müllhaupt Beat, Wandeler Gilles, Kouyos Roger, Estill Janne, Bertisch Barbara, Rauch Andri, Keiser Olivia (2016), Modelling the impact of deferring HCV treatment on liver-related complications in HIV coinfected men who have sex with men., in
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Wandeler Gilles, Schlauri Marion, Jaquier Marie-Eve, Rohrbach Janine, Metzner Karin J, Fehr Jan, Ambrosioni Juan, Cavassini Matthias, Stöckle Marcel, Schmid Patrick, Bernasconi Enos, Keiser Olivia, Salazar-Vizcaya Luisa, Furrer Hansjakob, Rauch Andri, Aubert V, Battegay M, Bernasconi E, Böni J, Bucher H C, Burton-Jeangros C, Calmy A, Cavassini M, Dollenmaier G (2015), Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013., in
Open forum infectious diseases, 2(1), 026-026.
Background: Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in HIV-infected patients. While AIDS-related mortality substantially decreased since the introduction of antiretroviral therapy, there is an increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. For many years, HCV infections occurred almost exclusively in injection drug users (IDU) or haemophiliacs. However, during the last 10 years, we and others have observed dramatic changes in the Hepatitis C epidemic. We reported recently an alarming 18-fold increase in the HCV incidence among HIV-infected men who have sex with men (MSM), reaching 4.1 cases per 100 person-years in 2011 in the Swiss HIV Cohort Study (SHCS, www.shcs.ch). In contrast, the HCV infection incidence decreased in injection drug users (IDU) and remained stable in heterosexuals. The SHCS provides an optimal framework for a thorough study of the HCV epidemic with a comprehensive clinical and laboratory database including data on risk behaviour, results from routine serial HCV screening and HCV treatment history, as well as stored plasma samples for HCV sequencing. Aims: The first aim is to assess risk factors, natural history and treatment responses in all incident HCV infections in the SHCS. The second aim is to assess HCV transmission patterns by comparing HCV phylogenies of incident infections with published sequences from national and international HCV epidemics, and to determine the reproductive number R0 using molecular epidemiology methods. The third aim is to develop an individual-based mathematical model of the HCV epidemic based on parameter estimates from aims 1 and 2, and to use this model to test the impact of different screening, treatment and counselling interventions on HCV transmissions.Methods: Study population: The SHCS is a nationwide prospective cohort study of more than 17’000 HIV-infected patients. Since 1991, there were 238 incident HCV infections: 121 in MSM, 72 in IDU, 36 in heterosexuals and 9 in other HIV-transmission risk groups. Risk factors and course of incident HCV infections will be assessed using descriptive analyses and multivariate Cox regression models. Phylogenetic analyses: The non-structural proteins NS3 and NS5B will be sequenced using Illumina shotgun sequencing technology which provides information on both major and minor HCV variants in the virus population. Transmission history, cluster analyses and molecular clock analyses will be performed using the Bayesian tree-inference software BEAST. Cluster analyses will include HCV sequences data from this study, as well as sequences from our previous research in chronic HCV infected patients (n=168), from the Swiss Hepatitis C Cohort Study (n=325), and from the international HCV database (www.hcv.lanl.gov). Transmission rates and the basic reproductive number R0 will be determined using phylogenetic methods combined with birth-death processes, as described before. Modelling the HCV epidemic: The parameter estimates generated in aims 1 and 2 will be used to model the disease-treatment process by simulating the trajectories of individual patients through different stages including natural history and treatment associated events, similar to a model of HIV-infection recently developed by our group. This cohort model will inform the transmission model, which will examine HCV transmissions, incidence and prevalence in HIV-infected patients. The model will be validated using data from international cohorts. Different intervention strategies will then be tested using the final HCV transmission model. Significance: The alarming increase in HCV infections among HIV-infected MSM is a clear indication that we urgently need improved preventive and therapeutic strategies to control this worrisome epidemic. By combining the unique advantages of the SHCS with HCV phylogenies, we will be able to provide a complete and representative picture of the HCV epidemic in HIV-infected patients. This will allow to optimally parametrize an individual-based model of the rapidly evolving HCV epidemic, and to identify which screening and treatment interventions will be most effective. Furthermore, our study will inform which patients would benefit most from HCV-vaccines, and which HCV-genotypes and subtypes should be included in a vaccine with optimal coverage of the circulating strains.