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HIV and viral hepatitis co-infection: informing management strategies through dedicated cohort studies in sub-Saharan Africa and Switzerland

Applicant Wandeler Gilles Olivier
Number 154730
Funding scheme Ambizione
Research institution Klinik und Poliklinik für Infektiologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Internal Medicine
Start/End 01.09.2014 - 31.08.2017
Approved amount 603'960.00
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All Disciplines (2)

Discipline
Internal Medicine
Infectious Diseases

Keywords (3)

Viral hepatitis; HIV; sub-Saharan Africa

Lay Summary (French)

Lead
Les hépatites virales comptent parmi les causes les plus importantes de mortalité au sein de la population infectée par le VIH en Afrique sub-Saharienne. Malgré cela, peu d’étude ont évalué l’impact du VIH sur les complications liées aux infections par les virus de l’hépatite B (VHB) et C (VHC). Ce projet vise à mieux comprendre l’épidémiologie, la virologie ainsi que les conséquences cliniques des hépatites virales en Afrique.
Lay summary

Contenu et objectifs du travail de recherche

L’objectif principal du projet est d’analyser la prévalence des hépatites virales dans différentes régions d’Afrique sub-Saharienne, ainsi que de déterminer leurs principales caractéristiques épidémiologiques, cliniques et virologiques. L’évaluation de la réponse au traitement de l’hépatite B durant plusieurs années de suivi constituera également un des éléments majeurs de cette étude.

Le projet s’appuie sur le réseau de cohortes IeDEA, une collaboration dans le domaine du VIH établie depuis plusieurs années en Afrique sub-Saharienne. Dans ce contexte, nous avons mis en place plusieurs cohortes dédiées à l’étude des hépatites virales B et C en Zambie, au Mozambique, ainsi que dans plusieurs pays d’Afrique de l’Ouest. Des analyses virologiques détaillées ainsi que l’évaluation de la fibrose hépatique seront effectuées en plus des analyses de routine. Les résultats obtenus seront comparés avec ceux de la cohorte VIH Suisse, ce qui nous permettre de mettre en évidence les différences épidémiologiques fondamentales entre ces deux régions.

Contexte scientifique et social du projet de recherche

Les hépatites virales sont un problème de santé publique majeur en Afrique sub-Saharienne. Ce projet permettra de répondre aux questions les plus importantes liées à ce sujet et d’aider à la mise en place de stratégies de prévention et de traitement dans cette région. Le transfert de connaissances  prendra une part importante de ce projet, en incluant des médecins et virologues locaux dans la collecte et l’analyse des données.

Direct link to Lay Summary Last update: 22.08.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique.
Wandeler Gilles, Mulenga Lloyd, Hobbins Michael, Joao Candido, Sinkala Edford, Hector Jonas, Aly Musa, Chi Benjamin H, Egger Matthias, Vinikoor Michael J (2016), Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique., in Open forum infectious diseases, 3(2), 049-049.
Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia.
Wandeler Gilles, Musukuma Kalo, Zürcher Samuel, Vinikoor Michael J, Llenas-García Jara, Aly Mussa M, Mulenga Lloyd, Chi Benjamin H, Ehmer Jochen, Hobbins Michael A, Bolton-Moore Carolyn, Hoffmann Christopher J, Egger Matthias, Egger Matthias (2016), Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia., in PloS one, 11(3), 0152043-0152043.
Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa.
Azevedo Tiago Castro Lopes, Zwahlen Marcel, Rauch Andri, Egger Matthias, Wandeler Gilles (2016), Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa., in Journal of the International AIDS Society, 19(1), 20711-20711.
HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa.
Jaquet Antoine, Wandeler Gilles, Tine Judicaël, Dagnra Claver A, Attia Alain, Patassi Akouda, Ndiaye Abdoulaye, de Ledinghen Victor, Ekouevi Didier K, Seydi Moussa, Dabis François (2016), HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa., in BMC infectious diseases, 16, 249-249.
Liver fibrosis in treatment-naïve HIV-infected and HIV/HBV co-infected patients: Zambia and Switzerland compared.
Wandeler Gilles, Mulenga Lloyd, Vinikoor Michael J, Kovari Helen, Battegay Manuel, Calmy Alexandra, Cavassini Matthias, Bernasconi Enos, Schmid Patrick, Bolton-Moore Carolyn, Sinkala Edford, Chi Benjamin H, Egger Matthias, Rauch Andri, Rauch Andri (2016), Liver fibrosis in treatment-naïve HIV-infected and HIV/HBV co-infected patients: Zambia and Switzerland compared., in International journal of infectious diseases : IJID : official publication of the International Soci, 51, 97-102.
Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia.
Vinikoor Michael J, Sinkala Edford, Mweemba Aggrey, Zanolini Arianna, Mulenga Lloyd, Sikazwe Izukanji, Fried Michael W, Eron Joseph J, Wandeler Gilles, Chi Benjamin H (2015), Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia., in Liver international : official journal of the International Association for the Study of the Liver, 35(7), 1886-92.
Implementation of routine screening for chronic hepatitis B virus co-infection by HIV clinics in Lusaka, Zambia.
Vinikoor M J, Musukuma K, Munamunungu V, Masaninga M, Sikazwe I, Chi B H, Wandeler G (2015), Implementation of routine screening for chronic hepatitis B virus co-infection by HIV clinics in Lusaka, Zambia., in Journal of viral hepatitis, 22(10), 858-60.
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, Swiss HIV Cohort Study (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.
Molecular epidemiology of hepatitis B virus infection in Switzerland: a retrospective cohort study.
Hirzel Cédric, Wandeler Gilles, Owczarek Marta, Gorgievski-Hrisoho Meri, Dufour Jean-Francois, Semmo Nasser, Zürcher Samuel (2015), Molecular epidemiology of hepatitis B virus infection in Switzerland: a retrospective cohort study., in BMC infectious diseases, 15, 483-483.
Performance of HBsAg point-of-care tests for detection of diagnostic escape-variants in clinical samples.
Hirzel Cédric, Pfister Stefan, Gorgievski-Hrisoho Meri, Wandeler Gilles, Zuercher Samuel (2015), Performance of HBsAg point-of-care tests for detection of diagnostic escape-variants in clinical samples., in Journal of clinical virology : the official publication of the Pan American Society for Clinical Vir, 69, 33-5.
Response to 'Is AST-to-platelet ratio index a reliable tool in HIV patients in Africa?'
Vinikoor Michael J., Sinkala Edford, Wandeler Gilles, Chi Benjamin H. (2014), Response to 'Is AST-to-platelet ratio index a reliable tool in HIV patients in Africa?', in Liver International, 35(8), 2060-2060.
Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia.
Vinikoor Michael J, Mulenga Lloyd, Siyunda Alice, Musukuma Kalo, Chilengi Roma, Moore Carolyn Bolton, Chi Benjamin H, Davies Mary-Ann, Egger Matthias, Wandeler Gilles, Wandeler Gilles, Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia., in Tropical medicine & international health : TM & IH.
Hepatitis B viral load in dried blood spots: A validation study in Zambia
Vinikoor Michael, Zürcher Samuel, Musukuma Kalo, Kachuwaire Obert, Rauch Andri, Chi Benjamin, Gorgievski Meri, Zwahlen Marcel, Wandeler Gilles, Hepatitis B viral load in dried blood spots: A validation study in Zambia, in Journal of clinical virology : the official publication of the Pan American Society for Clinical Vir.
Hepatitis C virus transmission among HIV-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 Ana, Bernasconi Enos, Calmy Alexandra, Vernazza Pietro, Furrer Hansjakob, Egger Matthias, Keiser Olivia, Rauch Andri, Rauch Andri, Hepatitis C virus transmission among HIV-infected men who have sex with men: Modeling the effect of behavioral and treatment interventions., in Hepatology (Baltimore, Md.).

Collaboration

Group / person Country
Types of collaboration
Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Colloque Méditerranée, l’AFRAMED VIH / Hépatites Talk given at a conference Hépatites virales B et C : tendances épidémiologiques 28.09.2017 Hammamet, Tunisia Wandeler Gilles Olivier;
International Workshop on HIV Observational Databases 2017 Poster Diagnostic performance of serological tests to predict liver fibrosis in African HIV/HBV-coinfected patients 30.03.2017 Lisbon, Portugal Wandeler Gilles Olivier;
Conference on Retroviruses and Opportunistic Infections (CROI) 2017 Poster MORTALITY OF HIV/HBV COINFECTED PATIENTS ON ART IN URBAN AND RURAL SOUTHERN AFRICA 13.02.2017 Seattle, United States of America Wandeler Gilles Olivier;
Journées de la Société Sénégalaise de Gastroentérologie et d'Hépatologie Talk given at a conference Coinfections VIH/VHB et VIH/VHC 29.07.2016 Dakar, Senegal Wandeler Gilles Olivier;
Conference on Retroviruses and Opportunistic Infections (CROI) 2016 Poster Changes in Viral Hepatitis Screening Practices Over Time in African HIV Clinics 22.02.2016 Boston, United States of America Wandeler Gilles Olivier;
UVP Workshop on HIV, Nutrition and NCDs: Talk given at a conference Implementing NCD-related research projects within HIV cohort collaborations in southern Africa: the example of IeDEA: Southern Africa 19.01.2016 Lusaka, Zambia Wandeler Gilles Olivier;
10èmes Rencontres Nord/Sud: VIH en Afrique, Co-infection VHB, Co-infection VHC Talk given at a conference Epidémiologie des hépatites virales B en Afrique au cours de l’infection VIH 16.12.2015 Paris, France Wandeler Gilles Olivier;
Gemeinsame Jahrestagung SGI/SGInf/SGNOR/SGHS Talk given at a conference HCV treatment in 2015: The global perspective 02.09.2015 Interlaken, Switzerland Wandeler Gilles Olivier;
IAS Conference on HIV Pathogenesis, Treatment and Prevention 2015 Poster Retention in care of HIV-infected pregnant and lactating women starting option B+ ART in rural Mozambique 19.07.2015 Vancouver, Canada Wandeler Gilles Olivier;
The international Liver Congress (EASL) 2015 Poster Liver fibrosis in treatment-naïve HIV-infected and HIV/HBV-coinfected patients: Zambia and Switzerland compared 22.04.2015 Vienna, Austria Wandeler Gilles Olivier;
Conference on Retroviruses and Opportunistic Infections (CROI) 2015 Poster Clinical correlates of alcohol use disorders among HIV‐infected adults in Zambia 23.02.2015 Seattles, WA, United States of America Wandeler Gilles Olivier;


Associated projects

Number Title Start Funding scheme
177118 HIV and viral hepatitis co-infection: informing management strategies through dedicated cohort studies in sub-Saharan Africa and Switzerland 01.09.2017 Ambizione
176944 Towards the functional cure of hepatitis B virus infection: longitudinal studies to assess long-term outcomes in Switzerland and sub-Saharan Africa 01.09.2018 SNSF Professorships
177118 HIV and viral hepatitis co-infection: informing management strategies through dedicated cohort studies in sub-Saharan Africa and Switzerland 01.09.2017 Ambizione

Abstract

Background: Hepatitis B Virus (HBV) and hepatitis C virus (HCV) infections are major causes of morbidity and mortality in HIV infected patients in industrialized countries and resource-limited settings (RLS). Worldwide, 5-15% of HIV-infected individuals have chronic HBV infection and up to 30% in high-income countries and 10% in RLS have chronic HCV infection. HIV infection has a profound impact on the natural history of viral hepatitis including the acceleration of the progression to end-stage liver disease. Furthermore, hepatotoxicity of antiretroviral therapy (ART) is more likely and immunological recovery on ART seems to be impaired in HIV/HBV and HIV/HCV-coinfected individuals. Due to the short follow-up periods in most studies evaluating HBV-related treatment outcomes, the long-term virological efficacy of HBV treatments, and the time needed to fully suppress viral replication remains largely unknown. Similarly, little is known about the impact of HBV genotypes on virological outcomes. Furthermore, data on the prevalence of significant liver fibrosis in HIV/HBV-coinfected patients are scarce and the possibility of a reversal of fibrosis during ART needs to be explored. Whereas the HCV epidemic has been shown to rapidly evolve in high-income countries, epidemiological data on HIV/HCV-coinfection in Sub-Saharan Africa (SSA) are limited and studies have often been based on serological testing with poor specificity. In light of the advent of interferon-free HCV treatment, it is of great importance to describe the clinical epidemiology of HCV infections in order to assess treatment eligibility and optimal antiviral therapy strategies. Objectives: The overarching aim of my Ambizione/PROSPER fellowship proposal is to define the epidemiological, clinical and virological characteristics of HBV and HCV infections in HIV-infected people, and to evaluate the impact of these coinfections on clinical outcomes with a focus on Southern and West Africa. My main objectives are:1.To determine the prevalence and incidence of HBV and HCV infections in West African and Southern African HIV cohorts and to assess the impact of viral hepatitis infections on the development of liver fibrosis and end-stage liver disease, as well as on HIV-related outcomes and mortality. 2.To describe the HBV genotype distribution and compare long-term virological outcomes of HBV therapy in HIV/HBV-coinfected patients between African countries and Switzerland, and between genotypes and treatment regimens, and to assess HBV resistance patterns and changes in liver fibrosis stage.3.To describe the HCV genotype distribution across the regions and assess the demographic and clinical characteristics of HIV/HCV-coinfected individuals as well as potential HCV treatment eligibility criteria in these patients.Methods: The study will be based on data from the International epidemiological Databases to Evaluate AIDS (IeDEA) and the Swiss HIV Cohort Study (SHCS), and on the sub-cohorts and projects on viral hepatitis coinfections I established within these cohorts. In IeDEA, I will perform dedicated studies in HIV cohorts in Zambia, Mozambique, Senegal, Ivory Coast, Togo, Burkina Faso and Benin and use data from the SHCS where liver-related events and antiviral treatment are recorded systematically. Clinical and virological outcomes in HIV/hepatitis-coinfected patients from SSA will be compared with data from the SHCS. The virological analyses will be performed in dedicated laboratories in SSA. Liver fibrosis assessment will be based on non-invasive serological scores and transient elastography (Fibroscan®). Data from individual-based questionnaires will be used to assess risk factors for viral hepatitis coinfection in SSA. I will use standard methods for the analysis of longitudinal data, but also advanced methods, including causal modeling to control for time-dependent confounding, time to event analyses taking into account competing risks and linear missed-effect for the longitudinal assessment of biological markers of liver disease and CD4 recovery. Incidence rates of HBV and HCV infections will be assessed using Bayesian Poisson regression models.Significance: A better understanding of the burden and determinants of HBV and HCV coinfections in HIV-infected individuals will improve the detection, treatment and monitoring of these coinfections, as well as their complications. This project builds on existing, well established cohorts in Southern Africa, West Africa and Switzerland and will inform the optimization of treatment programs for viral hepatitis in SSA. The frameworks of the IeDEA collaboration and the SHCS provide optimal platforms to study and compare HBV and HCV epidemiology and treatment outcomes as these two study populations are complementary in many ways, including differences in transmission mode, treatment regimens and access to monitoring and treatment.
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