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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
An update to the HIV-TRePS system: The development of new computational models that do not require a genotype to predict HIV treatment outcomes
Journal of Antimicrobial Chemotherapy, Volume 69, No. 4, Article dkt447, Year 2014
Notification
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Description
Objectives: The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings. Methods: Random forest models were trained to predict the probability of a virological response to therapy (<50 copies HIV RNA/mL) following virological failure using the following data from 22 567 treatment-change episodes including 1090 from southern Africa: baseline viral load and CD4 cell count, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. The models were assessed during cross-validation and with an independent global test set of 1000 cases including 100 from southern Africa. The models' accuracy [area under the receiver-operating characteristic curve (AUC)] was evaluated and compared with genotyping using rules-based interpretation systems for those cases with genotypes available. Results: The models achieved AUCs of 0.79-0.84 (mean 0.82) during cross-validation, 0.80 with the global test set and 0.78 with the southern African subset. The AUCs were significantly lower (0.56-0.57) for genotyping. Conclusions: The models predicted virological response to HIV therapy without a genotype as accurately as previous models that included a genotype. They were accurate for cases from southern Africa and significantly more accurate than genotyping. These models will be accessible via the online treatment support tool HIV-TRePS and have the potential to help optimize antiretroviral therapy in resource-limited settings where genotyping is not generally available. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Revell, Andrew D.
United Kingdom, London
Hiv Resistance Response Database Initiative Rdi
Wang, Dechao
United Kingdom, London
Hiv Resistance Response Database Initiative Rdi
Wood, Robin Y.
South Africa, Cape Town
University of Cape Town
Morrow, Carl D.
South Africa, Cape Town
University of Cape Town
Tempelman, Hugo A.
South Africa, Globlersdal
Ndlovu Care Group
Hamers, Raph L.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Alvarez-Uria, G.
India, Anantapur
Rural Development Trust Rdt Hospital
Streinu-Cercel, Adrian
Romania, Bucharest
National Institute of Infectious Diseases Prof. Dr. Matei Bals
Ene, Luminiţa
Romania, Bucharest
Victor Babes National Institute
Wensing, Annemarie Marie J.
Netherlands, Utrecht
University Medical Center Utrecht
Reiss, Peter
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Netherlands, Amsterdam
Stichting Hiv Monitoring
van Sighem, Ard I.
Netherlands, Amsterdam
Stichting Hiv Monitoring
Nelson, Mark Richard
United Kingdom, London
Chelsea and Westminster Hospital
Emery, Sean
Australia, Kensington
The Kirby Institute
Montaner, Julio S.G.
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Lane, Henry Clifford
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Larder, Brendan A.
United Kingdom, London
Hiv Resistance Response Database Initiative Rdi
van Sighem, Ard I.
Netherlands
Athena
Harrigan, P. Richard
Canada
Bc Center for Excellence in Hiv and Aids
Rinke de Wit, Tobias Floris
Unknown Affiliation
Sigaloff, Kim Catherina Eve
Unknown Affiliation
Agan, Brian K.
United States, Arlington
United States Department of Defense
Marconi, Vincent Charles
United States, Arlington
United States Department of Defense
Wegner, Scott A.
United States, Arlington
United States Department of Defense
Sugiura, Wataru
United States, Bethesda
National Institutes of Health Nih
Zazzi, Maurizio
Unknown Affiliation
Gatell, José Mariá A.
Spain, Barcelona
University Hospital
de Làzzari, Elisa
Spain, Barcelona
University Hospital
Gazzard, Brian George L.
United Kingdom, London
Chelsea and Westminster Hospital
Pozniak, Anton Louis
United Kingdom, London
Chelsea and Westminster Hospital
Mandalia, Sundhiya
United Kingdom, London
Chelsea and Westminster Hospital
Ruíz, Lídia
Spain, Barcelona Province
Fundacion Irsicaixa
Clotet, Bonaventura
Spain, Barcelona Province
Fundacion Irsicaixa
Staszewski, Schlomo
Germany, Frankfurt am Main
Universitätsklinikum Frankfurt
Torti, Carlo
Italy, Brescia
Università Degli Studi Di Brescia
Metcalf, Julia A.
United States, Bethesda
National Institutes of Health Nih
Pérez-Elías, Mariá Jésus
Spain, Madrid
Instituto Ramón y Cajal de Investigación Sanitaria
Carr, Andrew D.
Australia, Sydney
St. Vincent's Hospital Sydney
Norris, Richard
Australia, Sydney
St. Vincent's Hospital Sydney
Hesse, Karl
Australia, Sydney
St. Vincent's Hospital Sydney
Vlahakis, Emanuel
Unknown Affiliation
Barth, Roos E.
South Africa, Globlersdal
Ndlovu Care Group
Dragovic-Lukic, Gordana
Serbia, Belgrade
University of Belgrade
Statistics
Citations: 43
Authors: 43
Affiliations: 24
Identifiers
Doi:
10.1093/jac/dkt447
ISSN:
03057453
e-ISSN:
14602091
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study