Antiretroviral therapy optimisation without genotype resistance testing: a perspective on treatment history based models

Mattia C F Prosperi, Michal Rosen-Zvi, EuResist study group, Virolab study group, André Altmann, Maurizio Zazzi, Simona Di Giambenedetto, Rolf Kaiser, Eugen Schülter, Daniel Struck, Peter Sloot, David A van de Vijver, Anne-Mieke Vandamme, Anders Sönnerborg

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)

Abstract

BACKGROUND: 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.

Original languageEnglish
Article numbere13753
Number of pages8
JournalPLoS One (print)
Volume5
Issue number10
DOIs
Publication statusPublished - 29 Oct 2010

Bibliographical note

Funding: The EuResist Foundation: www.euresist.org/(former EU grant IST-2004-027173). The Virolab project: www.virolab.org/(EU grant #027446).

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