Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/96297
Title: Antiretroviral therapy optimisation without genotype resistance testing : a perspective on treatment history based models
Authors: Prosperi, Mattia C. F.
Sloot, Peter M. A.
van de Vijver, David A. M. C.
Rosen-Zvi, Michal
Altmann, André
Zazzi, Maurizio
Schülter, Eugen
Struck, Daniel
Di Giambenedetto, Simona
Kaiser, Rolf
Vandamme, Anne-Mieke
Sönnerborg, Anders
Keywords: DRNTU::Engineering::Computer science and engineering::Computer applications::Life and medical sciences
Issue Date: 2010
Source: Prosperi, 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.
Series/Report no.: PLoS ONE
Abstract: Although 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 strategies
URI: https://hdl.handle.net/10356/96297
http://hdl.handle.net/10220/9870
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0013753
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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCSE Journal Articles

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