Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/96297
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dc.contributor.authorProsperi, Mattia C. F.en
dc.contributor.authorSloot, Peter M. A.en
dc.contributor.authorvan de Vijver, David A. M. C.en
dc.contributor.authorRosen-Zvi, Michalen
dc.contributor.authorAltmann, Andréen
dc.contributor.authorZazzi, Maurizioen
dc.contributor.authorSchülter, Eugenen
dc.contributor.authorStruck, Danielen
dc.contributor.authorDi Giambenedetto, Simonaen
dc.contributor.authorKaiser, Rolfen
dc.contributor.authorVandamme, Anne-Miekeen
dc.contributor.authorSönnerborg, Andersen
dc.date.accessioned2013-04-29T07:03:42Zen
dc.date.accessioned2019-12-06T19:28:22Z-
dc.date.available2013-04-29T07:03:42Zen
dc.date.available2019-12-06T19:28:22Z-
dc.date.copyright2010en
dc.date.issued2010en
dc.identifier.citationProsperi, M. C. F., Rosen-Zvi, M., Altmann, A., Zazzi, M., Di Giambenedetto, S., Kaiser, R., et al. (2010). Antiretroviral Therapy Optimisation without Genotype Resistance Testing: A Perspective on Treatment History Based Models. PLoS ONE, 5(10), e13753.en
dc.identifier.issn1932-6203en
dc.identifier.urihttps://hdl.handle.net/10356/96297-
dc.identifier.urihttp://hdl.handle.net/10220/9870en
dc.description.abstractAlthough genotypic resistance testing (GRT) is recommended to guide combination antiretroviral therapy (cART), funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH) impacts response to subsequent therapy, we investigated a set of statistical learning models to optimise cART in the absence of GRT information. Methods and Findings The EuResist database was used to extract 8-week and 24-week treatment change episodes (TCE) with GRT and additional clinical, demographic and TH information. Random Forest (RF) classification was used to predict 8- and 24-week success, defined as undetectable HIV-1 RNA, comparing nested models including (i) GRT+TH and (ii) TH without GRT, using multiple cross-validation and area under the receiver operating characteristic curve (AUC). Virological success was achieved in 68.2% and 68.0% of TCE at 8- and 24-weeks (n = 2,831 and 2,579), respectively. RF (i) and (ii) showed comparable performances, with an average (st.dev.) AUC 0.77 (0.031) vs. 0.757 (0.035) at 8-weeks, 0.834 (0.027) vs. 0.821 (0.025) at 24-weeks. Sensitivity analyses, carried out on a data subset that included antiretroviral regimens commonly used in low to middle income countries, confirmed our findings. Training on subtype B and validation on non-B isolates resulted in a decline of performance for models (i) and (ii). Conclusions Treatment history-based RF prediction models are comparable to GRT-based for classification of virological outcome. These results may be relevant for therapy optimisation in areas where availability of GRT is limited. Further investigations are required in order to account for different demographics, subtypes and different therapy switching strategiesen
dc.language.isoenen
dc.relation.ispartofseriesPLoS ONEen
dc.rights© 2010 Prosperi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectDRNTU::Engineering::Computer science and engineering::Computer applications::Life and medical sciencesen
dc.titleAntiretroviral therapy optimisation without genotype resistance testing : a perspective on treatment history based modelsen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Computer Engineeringen
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0013753en
dc.description.versionPublished versionen
item.grantfulltextopen-
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