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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.

In order to perform clinical investigations on integrated biomedical data sets and to predict virological and epidemiological outcome, medical experts require an IT-based collaborative environment that provides them a user-friendly space for building and executing their complex studies and workflows on largely available and high-quality data repositories. In this paper, the authors introduce such a novel collaborative working environment a so-called virtual laboratory for clinicians and medical researchers, which allows users to interactively access and browse several biomedical research databases and re-use relevant data sets within own designed experiments. Firstly, technical details on the integration of relevant data resources into the virtual laboratory infrastructure and specifically developed user interfaces are briefly explained. The second part describes research possibilities for medical scientists including potential application fields and benefits as using the virtual laboratory functionalities for a particular exemplary study.

The complete cascade from genome, proteome, metabolome, and physiome, to health forms multiscale, multiscience systems and crosses many orders of magnitude in temporal and spatial scales. The interactions between these systems create exquisite multitiered networks, with each component in nonlinear contact with many interaction partners. Understanding, quantifying, and handling this complexity is one of the biggest scientific challenges of our time. In this paper we argue that computer science in general, and Grid computing in particular, provide the language needed to study and understand these systems, and discuss a case study in decision support for HIV drug resistance treatment within the European ViroLab project.