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Understanding and Predicting the Hepatitis C Epidemic in HIV-infected Patients

English title Understanding and Predicting the Hepatitis C Epidemic in HIV-infected Patients
Applicant Rauch Andri
Number 146143
Funding scheme Project funding (special)
Research institution Klinik und Poliklinik für Infektiologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Infectious Diseases
Start/End 01.05.2013 - 30.04.2017
Approved amount 343'360.00
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All Disciplines (2)

Discipline
Infectious Diseases
Methods of Epidemiology and Preventive Medicine

Keywords (5)

Epidemic; HCV; Prevention; Transmission model; HIV

Lay Summary (German)

Lead
Infektionen mit Hepatitis C Viren (HCV) sind eine der häufigsten Krankheits- und Todesursachen bei HIV-infizierten Patienten in der Schweiz. Seit dem Jahre 2000 beobachten wir ausgeprägte Veränderungen der Übertragungswege und eine massive Zunahme von HCV Infektionen in gewissen Risikogruppen. Ein besseres Verständnis von Übertragungswegen und Verlauf von HCV Infektionen ist dringend, damit die Prävention und Behandlung dieser Infektion verbessert werden kann.
Lay summary

Inhalt und Ziel des Forschungsprojektes:

Wir werden den natürlichen Verlauf und das Therapieansprechen bei akuten HCV Infektionen in der Schweizerischen HIV Kohortenstudie untersuchen. In einem zweiten Schritt werden wir die genetischen Eigenschaften der Hepatitis C Viren bestimmen, da dies wichtige Rückschlüsse sowohl auf die Übertragungsfrequenz als auch auf die Übertragungswege erlaubt.  Diese klinischen und virologischen Daten sind die Basis für ein mathematisches Modell der Hepatitis C Epidemie. Mit Hilfe dieses Modells werden wir schliesslich untersuchen, welche präventiven und therapeutischen Massnahmen zur Eindämmung der HCV Epidemie bei HIV-infizierten Patienten ergriffen werden müssen.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts:

Diese Untersuchungen werden neue Erkenntnisse liefern über Übertragungswege und Verlauf der HCV Infektion bei HIV-infizierten Patienten. Das mathematische Modell wird ein wichtiges Instrument sein, um verschiedene Interventionen bei der Hepatitis C und anderen Infektionskrankheiten testen zu können. Diese Informationen werden dazu dienen, Patienten besser beraten und behandeln zu können. Zudem werden die Erkenntnisse dieser Studie von Ärzten und Gesundheitsbehörden genutzt werden können, um die optimalen Massnahmen zur Eindämmung der Hepatitis C Epidemie in der Bevölkerung treffen zu können.

Direct link to Lay Summary Last update: 04.06.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Hepatitis C virus transmission among human immunodeficiency virus-infected men who have sex with men: Modeling the effect of behavioral and treatment interventions.
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 Hepatology (Baltimore, Md.), 64(6), 1856-1869.
Modelling the impact of deferring HCV treatment on liver-related complications in HIV coinfected men who have sex with men.
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 Journal of hepatology, 65(1), 26-32.
Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013.
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.

Collaboration

Group / person Country
Types of collaboration
Gilles Wandeler, MD, MPH, ISPM Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Professors Gail Matthews and Gregory; Dr. David Boettiger; The Kirby Institute, UNSW Australia Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Dr Roger Kouyos, University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr Gail Matthews and Dr Silvana Gaudieri, University of New South Wales; Murdoch University, Perth Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Dr Christian Althaus, ISPM Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
International Workshop on HIV and Hepatitis Observational Databases (IWHOD) Poster WHERE DO SWISS HIV-POSITIVE MEN WHO HAVE SEX WITH MEN ACQUIRE HEPATITIS C VIRUS? A MOLECULAR EPIDEMIOLOGY STUDY 30.03.2017 Lisbon, Portugal Metzner Karin; Salazar Vizcaya Luisa; Keiser Olivia; Rauch Andri;
International Workshop on HIV and Hepatitis Observational Databases (IWHOD) Talk given at a conference A transmission model for predicting the effect of treatment and risk counselling in “The Swiss HCVree-Trial”: validating a mathematical model with trial data 07.04.2016 Budapest, Hungary Salazar Vizcaya Luisa; Keiser Olivia; Rauch Andri;
Conference on Retroviruses and Opportunistic Infections (CROI) Poster Behavioural and Treatment Interventions to Reduce HCV Transmissions in HIV+ MSM 23.02.2015 Seattle, United States of America Keiser Olivia; Salazar Vizcaya Luisa; Rauch Andri; Zahnd Cindy;
Conference on Retroviruses and Opportunistic Infections (CROI) Talk given at a conference Impact of Deferring HCV Treatment on Liver-Related Events in HIV+ Patients 23.02.2015 Seattle, United States of America Zahnd Cindy; Rauch Andri; Keiser Olivia; Salazar Vizcaya Luisa;
Conference on Retroviruses and Opportunistic Infections (CROI) Poster Incident HCV Infections in the Swiss HIV Cohort Study: Natural History and Treatment Outcomes 03.03.2014 Boston, United States of America Rauch Andri; Metzner Karin; Keiser Olivia;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Swiss HCV Strategy (several meetings) Workshop 27.03.2015 Bern, Switzerland Rauch Andri; Zahnd Cindy; Keiser Olivia;
HCV Workshop with FOPH Workshop 23.03.2015 Bern, Switzerland Rauch Andri;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Der Preis der Rationierung Tagesanzeiger, Der Bund German-speaking Switzerland 2015

Associated projects

Number Title Start Funding scheme
150934 Mathematical simulation models to test the impact and cost-effectiveness of health interventions - applications in HIV, tuberculosis, cancer and hepatitis C 01.01.2014 Ambizione
148522 Swiss HIV Cohort Study (SHCS) 01.01.2014 Cohort Studies Large
127017 HIV-1 whole-genome quasispecies analysis by ultra-deep sequencing and computational haplotype inference to determine the mechanisms of drug resistance development 01.01.2010 Interdisciplinary projects
179567 The role of sexual behaviour dynamics and treatment-as-prevention in the spread of HIV, Hepatitis C and syphilis: Predicting the conditions for control and elimination 01.07.2018 Project funding (special)
137106 Scale up of antiretroviral therapy and transmission of HIV in Southern Africa: Mathematical model 01.10.2011 ProDoc
141234 Pharmacologie clinique et pharmacogénétique de la prise en charge complexe des sujets infectés par HIV ou co-infectés par HIV et HCV 01.04.2012 Project funding (special)
131629 Long-term antiretroviral therapy of HIV-infected patients in sub-Saharan Africa - insights from causal and mathematical modelling 01.01.2011 Ambizione
116862 Impact of HIV and antiretroviral therapy on Hepatitis C virus (HCV) evolution and on HCV-specific cellular immunity 01.06.2007 Project funding (special)
177521 The Swiss Hepatitis C Cohort Study 01.01.2018 Cohort Studies Large

Abstract

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.
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