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Mathematical simulation models to test the impact and cost-effectiveness of health interventions - applications in HIV, tuberculosis, cancer and hepatitis C

English title Mathematical simulation models to test the impact and cost-effectiveness of health interventions - applications in HIV, tuberculosis, cancer and hepatitis C
Applicant Keiser Olivia
Number 150934
Funding scheme Ambizione
Research institution Abteilung für Gesundheitsforschung Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Infectious Diseases
Start/End 01.01.2014 - 31.12.2015
Approved amount 419'862.00
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Keywords (8)

Africa; Switzerland; Cost-effectiveness; HIV; Mathematical model; Hepatitis C; Tuberculosis; Cancer

Lay Summary (German)

Lead
Das Ziel des Projektes ist es, mittels mathematischen Modellen kosteneffiziente Strategien zu entwickeln, welche die Behandlung von HIV-infizierten Patienten verbessern sollen.
Lay summary

In den letzten Jahren sind immer mehr HIV+ Patienten mit einer antiretroviralen Therapie behandelt worden und die Lebenserwartung ist gestiegen. Durch die Therapie ist auch die Ansteckungsgefahr und die Anzahl Neuinfektionen gesunken. Trotz diesem Fortschritt bleiben jedoch auch Probleme bestehen: Personen werden zu spät diagnostiziert, und starten die Therapie erst wenn die Gefahr von anderen Erkrankungen sehr hoch ist. Da HIV zunehmend zu einer chronischen Erkrankung wird, das Immunsystem jedoch beeinträchtigt bleibt, werden Koinfektionen (z.B. Tuberkulose und Krebs) häufiger. Patienten, die ein besonders hohes Risiko haben zu erkranken, spät diagnostiziert zu werden, oder einen schnellen Krankheitsverlauf haben, würden besonders von gezielten Interventionen profitieren.
So haben zum Beispiel HIV-infizierte homosexuelle Männer ein erhöhtes Risiko an Analkrebs oder Hepatitis C zu erkranken. Während bei uns neue Therapien gegen Hepatitis C seit kurzem auf dem Markt sind, ist jegliche Therapie in Entwicklungsländern meist zu teuer.

Wir werden ein mathematisches Simulationsmodell, das in unserer Gruppe entwickelt wurde, anwenden um folgende Fragen zu beantworten: 
• Was ist die (kosten-) effizienteste Art um die Mutter-Kind Übertragung von HIV in Afrika zu minimieren?
• Lohnt es sich HIV-infizierte homosexuelle Männer mit fortgeschrittener Immunschwäche zu screenen um das Risiko von Analkarzinom zu verkleinern?
• Wie stark kann man die Häufigkeit von Tuberkulose in Südafrika eindämmen indem man mehr Leute gegen HIV behandelt?
• Was ist die (kosten-)effizienteste Methode um Neuinfektionen von Hepatitis C in der Schweiz zu verhindern?
Wir werden grosse Patientendatenbanken analysieren und Literatursuchen machen um die Modelle möglichst realitätsgetreu zu entwickeln. Ziel ist es, eine Modellingplatform zu entwickeln, die von Akademikern und anderen Partnerorganisationen genutzt werden kann um Behandlungen zu optimieren.

Direct link to Lay Summary Last update: 30.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries
Yotebieng Marcel, Meyers Tammy, Behets Frieda, Davies Mary-Ann, Keiser Olivia, Ngonyani Kapella Zacharia, Lyamuya Rita E., Kariminia Azar, Hansudewechakul Rawiwan, Leroy Valeriane, Koumakpai Sikiratou, Newman Jamie, Van Rie Annelies (2015), Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries, in AIDS, 29(1), 101-109.
Brief Report: HIV Testing Among Pregnant Women Who Attend Antenatal Care in Malawi
Tenthani Lyson, Haas Andreas D., Egger Matthias, Van Oosterhout Joep J., Jahn Andreas, Chimbwandira Frank, Tal Kali, Myer Landon, Estill Janne, Keiser Olivia (2015), Brief Report: HIV Testing Among Pregnant Women Who Attend Antenatal Care in Malawi, in JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 69(5), 610-614.
gems: An R Package for Simulating from Disease Progression Models
Blaser Nello, Vizcaya Luisa Salazar, Estill Janne, Zahnd Cindy, Kalesan Bindu, Egger Matthias, Gsponer Thomas, Keiser Olivia (2015), gems: An R Package for Simulating from Disease Progression Models, in JOURNAL OF STATISTICAL SOFTWARE, 64(10), 1-22.
Growth in virologically suppressed children on antiretroviral therapy: individual and population-level references
Keiser O, Blaser N, Davies MA, Wessa P, Eley B, Moultrie H, Rabie H, Technau K, Ndirangu J, Garone D, Giddy J, Grimwood A, Gsponer T, Egger M (2015), Growth in virologically suppressed children on antiretroviral therapy: individual and population-level references, in Pediatr Infect Dis J, 34(10), e254-e259.
Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in treatment uptake and outcomes between 1991 and 2013
Wandeler G, Schlauri M, Jaquier ME, Rohrbach J, Metzner KJ, Fehr J, Ambrosioni J, Cavassini M, Stöckle M, Schmid P, Bernasconi E, Keiser O, Salazar-Vizcaya L, Furrer H, Rauch A (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 Infect Dis , 2(1), ofv026.
Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis
Haas Andreas D., Keiser Olivia, Balestre Eric, Brown Steve, Bissagnene Emmanuel, Chimbetete Cleophas, Dabis Francois, Davies Mary-Ann, Hoffmann Christopher J., Oyaro Patrick, Parkes-Ratanshi Rosalind, Reynolds Steven J., Sikazwe Izukanji, Wools-Kaloustian Kara, Zannou D. Marcel, Wandeler Gilles, Egger Matthias (2015), Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis, in LANCET HIV, 2(7), 271-278.
Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings
Koller Manuel, Fatti Geoffrey, Chi Benjamin H., Keiser Olivia, Hoffmann Christopher J., Wood Robin, Prozesky Hans, Stinson Kathryn, Giddy Janet, Mutevedzi Portia, Fox Matthew P., Law Matthew, Boulle Andrew, Egger Matthias (2015), Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings, in JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 70(3), 110-119.
The Cost-Effectiveness of Monitoring Strategies for Antiretroviral Therapy of HIV Infected Patients in Resource-Limited Settings: Software Tool
Estill Janne, Salazar-Vizcaya Luisa, Blaser Nello, Egger Matthias, Keiser Olivia (2015), The Cost-Effectiveness of Monitoring Strategies for Antiretroviral Therapy of HIV Infected Patients in Resource-Limited Settings: Software Tool, in PLOS ONE, 10(3), NA.
Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents
Rothenbuehler Martina, O'Sullivan Crochan J., Stortecky Stefan, Stefanini Giulio G., Spitzer Ernest, Estill Janne, Shrestha Nikesh R., Keiser Olivia, Jueni Peter, Pilgrim Thomas (2014), Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents, in LANCET GLOBAL HEALTH, 2(12), 717-726.
Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models
Keebler Daniel, Revill Paul, Braithwaite Scott, Phillips Andrew, Blaser Nello, Borquez Annick, Cambiano Valentina, Ciaranello Andrea, Estill Janne, Gray Richard, Hill Andrew, Keiser Olivia, Kessler Jason, Menzies Nicolas A., Nucifora Kimberly A., Vizcaya Luisa Salazar, Walker Simon, Welte Alex, Easterbrook Philippa, Doherty Meg, Hirnschall Gottfried, Hallett Timothy B. (2014), Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models, in LANCET GLOBAL HEALTH, 2(1), 35-43.
Do Increasing Rates of Loss to Follow-up in Antiretroviral Treatment Programs Imply Deteriorating Patient Retention?
Johnson Leigh F., Estill Janne, Keiser Olivia, Cornell Morna, Moolla Haroon, Schomaker Michael, Grimsrud Anna, Davies Mary-Ann, Boulle Andrew (2014), Do Increasing Rates of Loss to Follow-up in Antiretroviral Treatment Programs Imply Deteriorating Patient Retention?, in AMERICAN JOURNAL OF EPIDEMIOLOGY, 180(12), 1208-1212.
Effect of Baseline Renal Function on Tenofovir-Containing Antiretroviral Therapy Outcomes in Zambia
Mulenga Lloyd, Musonda Patrick, Mwango Albert, Vinikoor Michael J., Davies Mary-Ann, Mweemba Aggrey, Calmy Alexandra, Stringer Jeffrey S., Keiser Olivia, Chi Benjamin H., Wandeler Gilles (2014), Effect of Baseline Renal Function on Tenofovir-Containing Antiretroviral Therapy Outcomes in Zambia, in CLINICAL INFECTIOUS DISEASES, 58(10), 1473-1480.
Immunodeficiency at the Start of Combination Antiretroviral Therapy in Low-, Middle-, and High-Income Countries
Avila Dorita, Althoff Keri N., Mugglin Catrina, Wools-Kaloustian Kara, Koller Manuel, Dabis Franois, Nash Denis, Gsponer Thomas, Sungkanuparph Somnuek, McGowan Catherine, May Margaret, Cooper David, Chimbetete Cleophas, Wolff Marcelo, Collier Ann, McManus Hamish, Davies Mary-Ann, Costagliola Dominique, Crabtree-Ramirez Brenda, Chaiwarith Romanee, Cescon Angela, Cornell Morna, Diero Lameck, Phanuphak Praphan, Sawadogo Adrien (2014), Immunodeficiency at the Start of Combination Antiretroviral Therapy in Low-, Middle-, and High-Income Countries, in JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 65(1), 8-16.
Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis
Blaser Nello, Wettstein Celina, Estill Janne, Vizcaya Luisa Salazar, Wandeler Gilles, Egger Matthias, Keiser Olivia (2014), Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis, in AIDS, 28(7), 1021-1029.
Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies
Boulle Andrew, Schomaker Michael, May Margaret T., Hogg Robert S., Shepherd Bryan E., Monge Susana, Keiser Olivia, Lampe Fiona C., Giddy Janet, Ndirangu James, Garone Daniela, Fox Matthew, Ingle Suzanne M., Reiss Peter, Dabis Francois, Costagliola Dominique, Castagna Antonella, Ehren Kathrin, Campbell Colin, Gill M. John, Saag Michael, Justice Amy C., Guest Jodie, Crane Heidi M., Egger Matthias (2014), Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies, in PLOS MEDICINE, 11(9), NA.
Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa A Collaborative Analysis of Treatment Programs
Davies Mary-Ann, May Margaret, Bolton-Moore Carolyn, Chimbetete Cleophas, Eley Brian, Garone Daniela, Giddy Janet, Moultrie Harry, Ndirangu James, Phiri Sam, Rabie Helena, Technau Karl-Guenter, Wood Robin, Boulle Andrew, Egger Matthias, Keiser Olivia (2014), Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa A Collaborative Analysis of Treatment Programs, in PEDIATRIC INFECTIOUS DISEASE JOURNAL, 33(6), 608-616.
Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi
Tenthani Lyson, Haas Andreas D., Tweya Hannock, Jahn Andreas, van Oosterhout Joep J., Chimbwandira Frank, Chirwa Zengani, Ng'ambi Wingston, Bakali Alan, Phiri Sam, Myer Landon, Valeri Fabio, Zwahlen Marcel, Wandeler Gilles, Keiser Olivia (2014), Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi, in AIDS, 28(4), 589-598.
Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland
Avila Dorita, Keiser Olivia, Egger Matthias, Kouyos Roger, Boeni Juerg, Yerly Sabine, Klimkait Thomas, Vernazza Pietro L., Aubert Vincent, Rauch Andri, Bonhoeffer Sebastian, Guenthard Huldrych F., Stadler Tanja, Spycher Ben D. (2014), Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland, in AMERICAN JOURNAL OF EPIDEMIOLOGY, 179(12), 1514-1525.
Tracing of Patients Lost to Follow-up and HIV Transmission: Mathematical Modeling Study Based on 2 Large ART Programs in Malawi
Estill Janne, Tweya Hannock, Egger Matthias, Wandeler Gilles, Feldacker Caryl, Johnson Leigh F., Blaser Nello, Vizcaya Luisa Salazar, Phiri Sam, Keiser Olivia (2014), Tracing of Patients Lost to Follow-up and HIV Transmission: Mathematical Modeling Study Based on 2 Large ART Programs in Malawi, in JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 65(5), 179-186.
Viral load versus CD4(+) monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: a cohort-based modelling study
Salazar-Vizcaya Luisa, Keiser Olivia, Technau Karl, Davies Mary-Ann, Haas Andreas D., Blaser Nello, Cox Vivian, Eley Brian, Rabie Helena, Moultrie Harry, Giddy Janet, Wood Robin, Egger Matthias, Estill Janne (2014), Viral load versus CD4(+) monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: a cohort-based modelling study, in AIDS, 28(16), 2451-2460.
Firearm legislation and firearm mortality in the United States
Kalesan B, Mobily M, Keiser O, Fagan J, Galea S, Firearm legislation and firearm mortality in the United States, in The Lancet.
Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study
Clifford G, Franceschi S, Keiser O, Schöni-Affolter F, Lise M, Dehler S, Levi F, Mousavi M, Bouchardy C, Wolfensberger A, Darling K, Staehelin C, Bertisch B, Kuenzli E, Bernasconi E, Pawlita M, Egger M, Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study, in Int J Cancer.
In utero exposure to antiretroviral drugs: effect on birth weight and growth among HIV-exposed uninfected children in Brazil
Barroso Hofer C, Keiser O, Zwahlen M, Sepulveda Lustosa C, CisneFrota AC, de Oliveira RH, Abreu TF, Weber Carvalho, Evangelista Araujo L, Egger M, In utero exposure to antiretroviral drugs: effect on birth weight and growth among HIV-exposed uninfected children in Brazil, in Pediatr Infect Dis J.
Reducing CD4 Monitoring in Children on Antiretroviral Therapy with Virologic Suppression
Davies MA, Ford N, Rabie H, Fatti G, Stinson K, Giddy J, Tanser F, Technau K, Sawry S, Eley B, Wood R, Mofenson L, Keiser O, Boulle A, Reducing CD4 Monitoring in Children on Antiretroviral Therapy with Virologic Suppression, in Pediatr Infect Dis J.
Tuberculosis in Cape Town: an age-structured transmission model
Blaser N, Zahnd C, Hermans S, Salazar-Vizcaya L, Estill J, Morrow C, Egger M, Keiser O, Wood R, Tuberculosis in Cape Town: an age-structured transmission model, in Epidemics.

Collaboration

Group / person Country
Types of collaboration
Prof Matthias Egger, ISPM, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof Bindu Kalesan, Boston University United States of America (North America)
- Publication
Dr Mary-Ann Davies, University of Cape Town South Africa (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr Frank Chimbwandira, Ministry of Health Malawi Malawi (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof David Wilson, Burnet Institute Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
Prof Robin Wood, University of Cape Town South Africa (Africa)
- Publication
Dr Andri Rauch, Inselspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof Francesco Negro, University of Geneva 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
IAS Conference on HIV Pathogenesis, Treatment and Prevention; Talk given at a conference Post prevention of mother-to-child-transmission: 30-months outcomes in the Malawian "Option B+ programme 19.07.2015 Vancouver, United States of America Keiser Olivia;
International Workshop on HIV Observational Databases (IWHOD) Poster Projecting future second-line needs in Malawi 26.03.2015 Catania, Italy Estill Janne Anton Markus; Keiser Olivia;
Conference on Retroviruses and Opportunistic Infections (CROI) Poster Behavioural and treatment interventions to reduce Hepatitis C virus transmission among HIV-infected men who have sex with men: a cohort based modelling study 23.02.2015 Seattle, United States of America Keiser Olivia;
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 Estill Janne Anton Markus; Bertisch Barbara; Keiser Olivia;
Implementing HIV and TB Diagnostics Workshop Talk given at a conference Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings 22.09.2014 Cape Town, South Africa Keiser Olivia; Estill Janne Anton Markus;
International AIDS Conference Poster The cost-effectiveness of ART monitoring strategies in African settings: Software tool 20.07.2014 Melbourne, Australia Estill Janne Anton Markus; Keiser Olivia;
International AIDS Conference Poster The impact of viral load monitoring and tracing of patients lost to follow-up on HIV epidemic in Malawi: Mathematical model 20.07.2014 Melbourne, Australia Estill Janne Anton Markus; Keiser Olivia;
International Workshop on HIV Observational Databases (IWHOD) Poster The impact of viral load monitoring and tracing patients lost to follow-up on the HIV epidemic 27.03.2014 Sitges, Spain Estill Janne Anton Markus; Keiser Olivia;
International Workshop on HIV Observational Databases (IWHOD) Poster Age-structure in the TB-HIV co-epidemic in Cape Town: a mathematical modeling study 27.03.2014 Sitges, Spain Keiser Olivia;
International Workshop on HIV Observational Databases (IWHOD) Talk given at a conference Age-structure in the TB-HIV co-epidemic in Cape Town: a mathematical modeling study 27.03.2014 Sitges, Spain Estill Janne Anton Markus; Keiser Olivia;


Awards

Title Year
Theodor Kocher prize 2014. Award for outstanding and innovative scientific achievements for young researchers of any faculty at the University of Bern. 2014

Associated projects

Number Title Start Funding scheme
146143 Understanding and Predicting the Hepatitis C Epidemic in HIV-infected Patients 01.05.2013 Project funding (special)
137106 Scale up of antiretroviral therapy and transmission of HIV in Southern Africa: Mathematical model 01.10.2011 ProDoc
131629 Long-term antiretroviral therapy of HIV-infected patients in sub-Saharan Africa - insights from causal and mathematical modelling 01.01.2011 Ambizione
163878 Understanding the HIV epidemic in Malawi: integrating quantitative and qualitative data in a mathematical model 01.03.2017 SNSF Professorships

Abstract

Background: In the first three years of my PROSPER fellowship, I achieved one of its main objectives by developing a simulation model for HIV-infected adults and children in sub-Saharan Africa. With the assistance of several PhD students, I built an individual-based simulation model to assess the effectiveness of different strategies for monitoring antiretroviral therapy (ART) and compared the effect of viral load, CD4 and clinical monitoring on morbidity, mortality and HIV transmission. I am applying for support of the second phase, in which I will extend this model to other research questions about HIV, and will focus on important co-infections and co-morbidities of HIV (tuberculosis, hepatitis C, cancer) in high and in low-income settings.Research questions: I aim to answer the following questions: 1. What is the most (cost-)effective strategy to prevent mother-to-child transmission of HIV in resource-limited settings?2. To what extent can viral load monitoring prevent HIV transmission?3. Is targeted screening in a subset of HIV-infected homosexual men with low CD4 cell counts a (cost-) effective strategy to decrease the incidence of anal cancer in homosexual men, and how does it compare to universal cytological screening? 4. To what extent can the incidence of tuberculosis in Cape Town be reduced by scaling-up antiretroviral therapy, isoniazide preventive therapy, and intensified case finding? 5. Which screening and treatment strategy most effectively reduces hepatitis C incidence in HIV-infected homosexual men in Switzerland?Methods:I and my team will analyse large longitudinal observational databases and perform systematic literature searches to parameterise our models. I will continue to use state of the art techniques to analyse data from the IeDEA Southern Africa database, the Swiss HIV Cohort and the Malawian national ART programme. We will build a separate model for each application and will therefore need to continuously expand and adapt previously developed models. For example we will simultaneously model continuous outcomes (such as CD4 cell counts which is an important marker for disease progression) and event data (such as mortality). We will determine cost-effectiveness of interventions by calculating incremental cost-effectiveness ratios. Our goal is to build a modelling platform for academic and non-academic partners across the world, and we will seek new collaborations to carry out our work.Relevance of study: Our work will serve the clinicians, patients and policy makers responsible for optimising treatment provision and for care of those with HIV and its co-infections. Our findings can guide them in making decisions about efficient use of limited resources, at both the individual and population levels.
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