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Long-term antiretroviral therapy of HIV-infected patients in sub-Saharan Africa - insights from causal and mathematical modelling

English title Long-term antiretroviral therapy of HIV-infected patients in sub-Saharan Africa - insights from causal and mathematical modelling
Applicant Keiser Olivia
Number 131629
Funding scheme Ambizione
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Infectious Diseases
Start/End 01.01.2011 - 31.12.2013
Approved amount 561'821.00
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All Disciplines (2)

Discipline
Infectious Diseases
Methods of Epidemiology and Preventive Medicine

Keywords (9)

HIV; Second-line therapy; Sub-Saharan Africa; Modelling; resource-limited; antiretroviral therapy; mathematical modelling; Large nested project; Swiss HIV Cohort Study

Lay Summary (English)

Lead
Lay summary
Background: With the introduction of combination Highly Active Antiretroviral Therapy (HAART) in 1996, mortality and morbidity associated with HIV infection have declined dramatically among those who have access to HAART. In resource-limited settings, where 90% of people with HIV/AIDS live, HAART became more widely available only in recent years. Both in adults and children a major challenge is treatment failure, and long-term outcomes of HAART are not well defined. Evidence-based strategies to optimize outcomes in these settings are urgently needed.Aims and objectives: The aim of this project is to conduct clinical and epidemiological research to inform the development and parameterisation of a mathematical model of long-term HAART in Southern Africa. We will analyze data from 20 treatment programmes including > 200,000 HIV positive patients in Botswana, Malawi, Mozambique, South Africa, Zambia and Zimbabwe and perform systematic reviews to obtain estimates of key parameters for inclusion in mathematical models. Several nested projects will be performed to parametrize the mathematical model: We will for example develop prognostic models of mortality and loss to follow-up, determine the effectiveness of switching to second-line HAART after failure and investigate whether growth can be used as a predictor of treatment failure in sites with no or limited laboratory capacities.Relevance of study: With the rapid scale-up of antiretroviral treatment delivery in sub-Saharan there is an urgent need to answer key questions about service design and delivery, as well as the effectiveness of HAART in individual patients. The mathematical model will allow estimation of life-years saved, according to different strategies for long-term HAART, such as switching all failing patients to second-line HAART, switching adherent patients only, not switching patients but using resources to initiate additional patients on first-line HAART etc. The findings will provide guidance about how HAART programmes should be implemented in resource-limited countries to maximise their benefit.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
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, Ministry of Health in Malawi and IeDEA Southern Africa (2014), Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi., in AIDS (London, England), 28(4), 589-98.
Are they really lost? "true" status and reasons for treatment discontinuation among HIV infected patients on antiretroviral therapy considered lost to follow up in Urban Malawi.
Tweya Hannock, Feldacker Caryl, Estill Janne, Jahn Andreas, Ng'ambi Wingston, Ben-Smith Anne, Keiser Olivia, Bokosi Mphatso, Egger Matthias, Speight Colin, Gumulira Joe, Phiri Sam (2013), Are they really lost? "true" status and reasons for treatment discontinuation among HIV infected patients on antiretroviral therapy considered lost to follow up in Urban Malawi., in PloS one, 8(9), 75761-75761.
Comparison of treatment outcomes of new smear-positive pulmonary tuberculosis patients by HIV and antiretroviral status in a TB/HIV clinic, Malawi.
Tweya Hannock, Feldacker Caryl, Phiri Sam, Ben-Smith Anne, Fenner Lukas, Jahn Andreas, Kalulu Mike, Weigel Ralf, Kamba Chancy, Banda Rabecca, Egger Matthias, Keiser Olivia (2013), Comparison of treatment outcomes of new smear-positive pulmonary tuberculosis patients by HIV and antiretroviral status in a TB/HIV clinic, Malawi., in PloS one, 8(2), 56248-56248.
Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study.
Estill Janne, Egger Matthias, Blaser Nello, Vizcaya Luisa Salazar, Garone Daniela, Wood Robin, Campbell Jennifer, Hallett Timothy B, Keiser Olivia, IeDEA Southern Africa (2013), Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study., in AIDS (London, England), 27(9), 1483-92.
Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies.
Johnson Leigh F, Mossong Joel, Dorrington Rob E, Schomaker Michael, Hoffmann Christopher J, Keiser Olivia, Fox Matthew P, Wood Robin, Prozesky Hans, Giddy Janet, Garone Daniela Belen, Cornell Morna, Egger Matthias, Boulle Andrew, International Epidemiologic Databases to Evaluate AIDS Southern Africa Collaboration (2013), Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies., in PLoS medicine, 10(4), 1001418-1001418.
Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis
Mugglin C., Estill J., Wandeler G., Bender N., Egger M., Gsponer T., Keiser O., for IeDEA Southern Africa (2013), Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis, in Trop Med Int Health, 1-1.
Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study.
Estill Janne, Egger Matthias, Johnson Leigh F, Gsponer Thomas, Wandeler Gilles, Davies Mary-Ann, Boulle Andrew, Wood Robin, Garone Daniela, Stringer Jeffrey S A, Hallett Timothy B, Keiser Olivia, IeDEA Southern Africa Collaboration (2013), Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study., in PloS one, 8(2), 57611-57611.
Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared.
Labhardt Niklaus Daniel, Keiser Olivia, Sello Motlalepula, Lejone Thabo Ishmael, Pfeiffer Karolin, Davies Mary-Ann, Egger Matthias, Ehmer Jochen, Wandeler Gilles, SolidarMed ART Program and IeDEA-Southern Africa (2013), Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared., in Journal of the International AIDS Society, 16, 18616-18616.
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, Wood Robin, Boulle Andrew, Egger Matthias, Keiser Olivia, for the IeDEA Southern Africa (IeDEA-SA) Collaboration (2013), Prognosis of Children with HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa: A Collaborative Analysis of Treatment Programs., in The Pediatric infectious disease journal, Epub ahead.
Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review.
Mugglin Catrina, Wandeler Gilles, Estill Janne, Egger Matthias, Bender Nicole, Davies Mary-Ann, Keiser Olivia (2013), Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review., in PloS one, 8(2), 56446-56446.
Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study.
Bertisch Barbara, Franceschi Silvia, Lise Mauro, Vernazza Pietro, Keiser Olivia, Schöni-Affolter Franziska, Bouchardy Christine, Dehler Silvia, Levi Fabio, Jundt Gernot, Ess Silvia, Pawlita Michael, Kovari Helen, Wandeler Gilles, Calmy Alexandra, Cavassini Matthias, Stöckle Marcel, Clifford Gary, Swiss HIV Cohort Study Investigators (2013), Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study., in American journal of epidemiology, 178(6), 877-84.
Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration.
Davies Mary-Ann, Phiri Sam, Wood Robin, Wellington Maureen, Cox Vivian, Bolton-Moore Carolyn, Timmerman Venessa, Moultrie Harry, Ndirangu James, Rabie Helena, Technau Karl, Giddy Janet, Maxwell Nicola, Boulle Andrew, Keiser Olivia, Egger Matthias, Eley Brian (2013), Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration., in PloS one, 8(12), 81037-81037.
The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure
Davies M. A., Boulle A., Technau K., Eley B., Moultrie H., Rabie H., Garone D., Giddy J., Wood R., Egger M., Keiser O., for the IeDEA Southern Africa Collaboration (2013), The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure, in Trop Med Int Health, 1-1.
Tracing of patients lost to follow-up and HIV transmission: Mathematical modelling study based on two large ART programmes in Malawi.
Estill Janne, Tweya Hannock, Egger Matthias, Wandeler Gilles, Feldacker Caryl, Johnson Leigh F, Blaser Nello, Vizcaya Luisa Salazar, Phiri Sam, Keiser Olivia (2013), Tracing of patients lost to follow-up and HIV transmission: Mathematical modelling study based on two large ART programmes in Malawi., in Journal of acquired immune deficiency syndromes (1999), Epub ahead.
Variability of growth in children starting antiretroviral treatment in southern Africa
Gsponer T., Weigel R., Davies M. A., Bolton C., Moultrie H., Vaz P., Rabie H., Technau K., Ndirangu J., Eley B., Garone D., Wellington M., Giddy J., Ehmer J., Egger M., Keiser O., Ie D. E. A. Southern Africa (2013), Variability of growth in children starting antiretroviral treatment in southern Africa, in Pediatrics, 130, 966-77.
When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa.
Schomaker Michael, Egger Matthias, Ndirangu James, Phiri Sam, Moultrie Harry, Technau Karl, Cox Vivian, Giddy Janet, Chimbetete Cleophas, Wood Robin, Gsponer Thomas, Bolton Moore Carolyn, Rabie Helena, Eley Brian, Muhe Lulu, Penazzato Martina, Essajee Shaffiq, Keiser Olivia, Davies Mary-Ann, International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) Collaboration (2013), When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa., in PLoS medicine, 10(11), 1001555-1001555.
Zidovudine impairs immunological recovery on first-line antiretroviral therapy: collaborative analysis of cohort studies in southern Africa.
Wandeler Gilles, Gsponer Thomas, Mulenga Lloyd, Garone Daniela, Wood Robin, Maskew Mhairi, Prozesky Hans, Hoffmann Christopher, Ehmer Jochen, Dickinson Diana, Davies Mary-Ann, Egger Matthias, Keiser Olivia, IeDEA Southern Africa Collaboration (2013), Zidovudine impairs immunological recovery on first-line antiretroviral therapy: collaborative analysis of cohort studies in southern Africa., in AIDS (London, England), 27(14), 2225-32.
Characteristics of adults and children diagnosed with tuberculosis in Lilongwe, Malawi: findings from an integrated HIV/TB clinic.
Feldacker C, Tweya H, Keiser O, Weigel R, Kalulu M, Fenner L, Egger M, Manda E, Mwafilaso J B, Kamba C, Phiri S (2012), Characteristics of adults and children diagnosed with tuberculosis in Lilongwe, Malawi: findings from an integrated HIV/TB clinic., in Tropical medicine & international health : TM & IH, 17(9), 1108-16.
Missed Opportunities to Prevent Mother-to-Child-Transmission in sub-Saharan Africa: Systematic Review and Meta-Analysis.
Wettstein Celina, Mugglin Catrina, Egger Matthias, Blaser Nello, Salazar Luisa, Estill Janne, Bender Nicole, Davies Mary-Ann, Wandeler Gilles, Keiser Olivia (2012), Missed Opportunities to Prevent Mother-to-Child-Transmission in sub-Saharan Africa: Systematic Review and Meta-Analysis., in AIDS (London, England), 1-1.
Mortality and loss to follow-up in the first year of ART: Malawi national ART programme.
Weigel Ralf, Estill Janne, Egger Matthias, Harries Anthony D, Makombe Simon, Tweya Hannock, Jahn Andreas, Keiser Olivia (2012), Mortality and loss to follow-up in the first year of ART: Malawi national ART programme., in AIDS (London, England), 26(3), 365-373.
Outcomes of Antiretroviral Treatment Programs in Rural Southern Africa.
Wandeler Gilles, Keiser Olivia, Pfeiffer Karolin, Pestilli Sabrina, Fritz Christiane, Labhardt Niklaus D, Mbofana Franzisco, Mudyiradima Robert, Emmel Jan, Egger Matthias, Ehmer Jochen, For the SolidarMed ART program and IeDEA-Southern Africa (2012), Outcomes of Antiretroviral Treatment Programs in Rural Southern Africa., in Journal of acquired immune deficiency syndromes (1999), 59(2), 9-16.
Rates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in South Africa.
Fox Matthew P, Cutsem Gilles Van, Giddy Janet, Maskew Mhairi, Keiser Olivia, Prozesky Hans, Wood Robin, Hernán Miguel A, Sterne Jonathan A C, Egger Matthias, Boulle Andrew, IeDEA-SA collaboration (2012), Rates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in South Africa., in Journal of acquired immune deficiency syndromes (1999), 60(4), 428-37.
Tenofovir in Second-Line ART in Zambia and South Africa: Collaborative Analysis of Cohort Studies.
Wandeler Gilles, Keiser Olivia, Mulenga Lloyd, Hoffmann Christopher J, Wood Robin, Chaweza Thom, Brennan Alana, Prozesky Hans, Garone Daniela, Giddy Janet, Chimbetete Cleophas, Boulle Andrew, Egger Matthias, for the IeDEA Southern Africa Collaboration (2012), Tenofovir in Second-Line ART in Zambia and South Africa: Collaborative Analysis of Cohort Studies., in Journal of acquired immune deficiency syndromes (1999), 61(1), 41-48.
The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring.
Gsponer Thomas, Petersen Maya, Egger Matthias, Phiri Sam, Maathuis Marloes H, Boulle Andrew, Musondad Patrick, Tweya Hannock, Peter Karin, Chi Benjamin H, Keiser Olivia, IeDEA Southern Africa (2012), The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring., in AIDS (London, England), 26(1), 57-65.
Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa: a mathematical modelling analysis.
Estill Janne, Aubrière Cindy, Egger Matthias, Johnson Leigh, Wood Robin, Garone Daniela, Gsponer Thomas, Wandeler Gilles, Boulle Andrew, Davies Mary-Ann, Hallett Timothy B, Keiser Olivia, IeDEA Southern Africa (2012), Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa: a mathematical modelling analysis., in AIDS (London, England), 26(11), 1403-13.
A Comparison of Initial Antiretroviral Therapy in the Swiss HIV Cohort Study and the Recommendations of the International AIDS Society-USA.
Wandeler Gilles, Keiser Olivia, Hirschel Bernard, Günthard Huldrych F, Bernasconi Enos, Battegay Manuel, Clerc Olivier, Vernazza Pietro L, Furrer Hansjakob, the Swiss HIV Cohort Study (2011), A Comparison of Initial Antiretroviral Therapy in the Swiss HIV Cohort Study and the Recommendations of the International AIDS Society-USA., in PloS one, 6(12), 27903-27903.
Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data.
Rudin C, Spaenhauer A, Keiser O, Rickenbach M, Kind C, Aebi-Popp K, Brinkhof M W G, Swiss HIV Cohort Study (SHCS), Swiss Mother & Child HIV Cohort Study (MoCHiV) (2011), Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data., in HIV medicine, 12(4), 228-35.
Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland.
Schöni-Affolter Franziska, Keiser Olivia, Mwango Albert, Stringer Jeffrey, Ledergerber Bruno, Mulenga Lloyd, Bucher Heiner C, Westfall Andrew O, Calmy Alexandra, Boulle Andrew, Chintu Namwinga, Egger Matthias, Chi Benjamin H (2011), Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland., in PloS one, 6(12), 27919-27919.
Longer term clinical and virological outcome of sub-Saharan African participants on antiretroviral treatment in the Swiss HIV Cohort Study.
Staehelin Cornelia, Keiser Olivia, Calmy Alexandra, Weber Rainer, Elzi Luigia, Cavassini Matthias, Schmid Patrick, Bernasconi Enos, Furrer Hansjakob, Swiss HIV Cohort Study (2011), Longer term clinical and virological outcome of sub-Saharan African participants on antiretroviral treatment in the Swiss HIV Cohort Study., in Journal of acquired immune deficiency syndromes (1999), 59(1), 79-85.
Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa.
Keiser Olivia, Chi Benjamin H, Gsponer Thomas, Boulle Andrew, Orrell Catherine, Phiri Sam, Maxwell Nicola, Maskew Mhairi, Prozesky Hans, Fox Matthew P, Westfall Andrew, Egger Matthias, IeDEA Southern Africa Collaboration (2011), Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa., in AIDS (London, England), 25(14), 1761-9.
Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration.
Davies Mary-Ann, Moultrie Harry, Eley Brian, Rabie Helena, Van Cutsem Gilles, Giddy Janet, Wood Robin, Technau Karl, Keiser Olivia, Egger Matthias, Boulle Andrew, International Epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) Collaboration (2011), Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration., in Journal of acquired immune deficiency syndromes (1999), 56(3), 270-8.
Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - The IeDEA Southern Africa Collaboration.
Davies Mary-Ann, Boulle Andrew, Eley Brian, Moultrie Harry, Technau Karl, Rabie Helena, van Cutsem Gilles, Giddy Janet, Wood Robin, Egger Matthias, Keiser Olivia, for the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) Collaborat, Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - The IeDEA Southern Africa Collaboration., in Tropical medicine & international health : TM & IH.
Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection.
Clifford G M, Lise M, Franceschi S, Egger M, Bouchardy C, Korol D, Levi F, Ess S, Jundt G, Wandeler G, Fehr J, Schmid P, Battegay M, Bernasconi E, Cavassini M, Calmy A, Keiser O, Schöni-Affolter F, the Swiss HIV Cohort Study, Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection., in British journal of cancer.
Outcomes of Antiretroviral Therapy in the Swiss HIV Cohort Study: Latent Class Analysis.
Keiser Olivia, Spycher Ben, Rauch Andri, Calmy Alexandra, Cavassini Matthias, Glass Tracy R, Nicca Dunja, Ledergerber Bruno, Egger Matthias, The Swiss HIV Cohort Study, Outcomes of Antiretroviral Therapy in the Swiss HIV Cohort Study: Latent Class Analysis., in AIDS and behavior.

Collaboration

Group / person Country
Types of collaboration
Imperial College London, Tim Hallett Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
International Agency for Research on Cancer, Dr Gary Clifford, Dr Silvia Franceschi France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Swiss Federal Institute of Technology (ETH), Zürich, Dr Tanja Stadler Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
University of Cape Town, Dr Mary Ann Davies, Dr Leigh Johnson South Africa (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Lighthouse clinic Malawi Malawi (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Inselspital Bern, Dr Andri Rauch Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Ministry of Health, Malawi, Lyson Tenthani Malawi (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
University of California, Berkeley, Prof Maya Petersen United States of America (North America)
- 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
Hepatitis C Symposium Individual talk Hepatitis C Epidemiologie in der Schweiz 02.10.2013 Zürich, Switzerland Keiser Olivia;
17th International Workshop on HIV Observational Databases 2013 Talk given at a conference The importance of viral load and the duration of primary infection for HIV transmission: a systematic review 11.04.2013 Cavtat, Croatia Keiser Olivia;
EPICC HIV meeting 2012 Individual talk Immunodeficiency at the start of ART 17.12.2012 Paris, France Keiser Olivia;
Steering Group meeting IeDEA Southern Africa 2012 Individual talk Mathematical modelling in IeDEA-SA 26.11.2012 Cape Town, South Africa Keiser Olivia;
IAS Conference 2012 Talk given at a conference Viral load versus CD4 monitoring: impact on mortality, HIV transmission and cost-effectiveness 18.07.2012 Washington, United States of America Keiser Olivia;
Gates Foundation - meeting on linkage to care in HIV-infected patients 2012 Talk given at a conference Linkage to care between HIV diagnosis and start of antiretroviral therapy in resource limited settings – systematic reviews and meta-analyses 31.05.2012 London, Great Britain and Northern Ireland Keiser Olivia; Estill Janne Anton Markus;
16th International Workshop on HIV Observational Databases 2012 Talk given at a conference Defining optimal growth response in children on antiretroviral treatment in South Africa 19.03.2012 Athens, Greece Keiser Olivia;
AIDS Conference 2011 Talk given at a conference Variability of growth response in children on antiretroviral treatment: The IeDEA Southern Africa Collaboration 17.07.2011 Rome, Italy Keiser Olivia;
15th International Workshop on HIV Observational Databases 2011 Talk given at a conference Variability of growth response in children on antiretroviral treatment: The IeDEA Southern Africa collaboration. 24.03.2011 Prague, Czech Republic Keiser Olivia;
19th Conference on Retroviruses and Opportunistic Infections CROI 2012 Poster Tracing Patients Lost to Follow-up: The Effect on HIV Transmission. 05.03.2011 Seattle, United States of America Keiser Olivia; Estill Janne Anton Markus;
18th Conference on Retroviruses and Opportunistic Infections CROI 2011 Poster Immunological Response and Mortality in ART Programmes with and without Routine Viral Load Monitoring in Southern Africa 27.02.2011 Boston, United States of America Keiser Olivia;


Awards

Title Year
Young investigator award for my MD Student Catrina Mugglin for Conference Abstract (15.12.2011) 2011
Young investigator award for my PhD Student Janne Estill for Conference Abstract 2011

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
122116 Second-line regimens after treatment failure in HIV-infected patients in resource-constrained settings: a multicentre collaborative study 01.10.2008 Project funding (special)
137106 Scale up of antiretroviral therapy and transmission of HIV in Southern Africa: Mathematical model 01.10.2011 ProDoc
146143 Understanding and Predicting the Hepatitis C Epidemic in HIV-infected Patients 01.05.2013 Project funding (special)

Abstract

Background: With the introduction of combination Highly Active Antiretroviral Therapy (HAART) in 1996, mortality and morbidity associated with HIV infection have declined dramatically among those who have access to HAART. In resource-limited settings, where 90% of people with HIV/AIDS live, HAART became more widely available only in recent years. Both in adults and children a major challenge is treatment failure, and long-term outcomes of HAART are not well defined. Evidence-based strategies to optimize outcomes in these settings are urgently needed. I propose to address these issues for Southern Africa in a number of studies, which will lead to a mathematical model of long-term HAART in this region.Aims and objectives: The aim of this project is to conduct clinical and epidemiological research to inform the development and parameterisation of a mathematical model of long-term HAART in Southern Africa. Specifically, I intend: • To describe and compare rates of switching to second-line HAART regimens in adults and children in Southern Africa and to identify the main determinants of switching in different settings.• To analyze data from treatment cohorts in Southern Africa and perform systematic reviews to obtain estimates of key parameters for inclusion in mathematical models, including o To determine the effectiveness of switching to second-line HAART in adults and children; o To develop prognostic models of mortality and loss to follow-up for adults and children; o To investigate child growth patterns and to determine whether growth can be used as a predictor of treatment failure in sites with no or limited laboratory capacities.• To develop mathematical models of different strategies of switching to second-line HAART for children and adults, and for settings with and without access to routine viral load monitoring.Methods: Collaborative analysis of longitudinal data from HIV treatment programmes, with a focus on Southern Africa. I will have access to a database of over 120,000 adult patients and over 10,000 children on first-line HAART and over 3,000 patients on second-line HAART from 22 treatment programmes in Botswana, Malawi, Mozambique, South Africa, Zambia and Zimbabwe. I will use standard methods for the analysis of longitudinal data, but also more advanced methods, including causal modelling to control for time-dependent confounding, time to event analyses taking into account competing risks, prognostic modelling, latent class analysis, and hierarchical regression models. I will then develop a stochastic mathematical model, where I determine properties of individuals and timing of events probabilistically based on a number of rules and parametric distributions. Relevance of study: With the rapid scale-up of antiretroviral treatment delivery in sub-Saharan there is an urgent need to answer key questions about service design and delivery, as well as the effectiveness of HAART in individual patients. The mathematical model will allow estimation of life-years saved, according to different strategies for long-term HAART, such as switching all failing patients to second-line HAART, switching adherent patients only, not switching patients but using resources to initiate additional patients on first-line HAART etc. The findings will provide guidance about how HAART programmes should be implemented in resource-limited countries to maximise their benefit.
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