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AIDS Res Ther. 2012; 9: 13.
Published online 2012 May 3. doi:  10.1186/1742-6405-9-13
PMCID: PMC3439255
Standardized representation, visualization and searchable repository of antiretroviral treatment-change episodes
Soo-Yon Rhee,corresponding author1,10 Jose Luis Blanco,2 Tommy F Liu,1 Iñaki Pere,2 Rolf Kaiser,3 Maurizio Zazzi,4 Francesca Incardona,5 William Towner,6 Josep Maria Gatell,2 Andrea De Luca,7,8 W Jeffrey Fessel,9 and Robert W Shafer1
1Department of Medicine, Stanford University, Stanford, CA, USA
2Hospital Clinic Universitari-IDIBAPS, University of Barcelona, Barcelona, Spain
3Institute of Virology, EuResist Network GEIE, University of Cologne, Cologne, Germany
4Department of Medical Biotechnologies, EuResist Network GEIE, University of Siena, Siena, Italy
5Informasrl, EuResist Network GEIE, Rome, Italy
6Department of Infectious Disease, Kaiser Permanente, Los Angeles, CA, USA
7Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy
8Unit of Infectious Diseases 2, University Hospital of Siena, Siena, Italy
9Kaiser Permanente Medical Care Program, South San Francisco, CA, USA
10Division of Infectious Diseases, Room S-169, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA, 94305, USA
corresponding authorCorresponding author.
Soo-Yon Rhee: syrhee/at/stanford.edu; Jose Luis Blanco: jlblanco/at/clinic.ub.es; Tommy F Liu: tliu/at/stanford.edu; Iñaki Pere: iperez1/at/clinic.ub.es; Rolf Kaiser: rolf.kaiser/at/uk-koeln.de; Maurizio Zazzi: zazzi/at/unisi.it; Francesca Incardona: f.incardona/at/informacro.info; William Towner: william.j.towner/at/kp.org; Josep Maria Gatell: gatell0/at/attglobal.net; Andrea De Luca: andrea.deluca/at/rm.unicatt.it; W Jeffrey Fessel: jeffrey.fessel/at/kp.org; Robert W Shafer: rshafer/at/stanford.edu
Received October 19, 2011; Accepted March 16, 2012.
Abstract
Background
To identify the determinants of successful antiretroviral (ARV) therapy, researchers study the virological responses to treatment-change episodes (TCEs) accompanied by baseline plasma HIV-1 RNA levels, CD4+ T lymphocyte counts, and genotypic resistance data. Such studies, however, often differ in their inclusion and virological response criteria making direct comparisons of study results problematic. Moreover, the absence of a standard method for representing the data comprising a TCE makes it difficult to apply uniform criteria in the analysis of published studies of TCEs.
Results
To facilitate data sharing for TCE analyses, we developed an XML (Extensible Markup Language) Schema that represents the temporal relationship between plasma HIV-1 RNA levels, CD4 counts and genotypic drug resistance data surrounding an ARV treatment change. To demonstrate the adaptability of the TCE XML Schema to different clinical environments, we collaborate with four clinics to create a public repository of about 1,500 TCEs. Despite the nascent state of this TCE XML Repository, we were able to perform an analysis that generated a novel hypothesis pertaining to the optimal use of second-line therapies in resource-limited settings. We also developed an online program (TCE Finder) for searching the TCE XML Repository and another program (TCE Viewer) for generating a graphical depiction of a TCE from a TCE XML Schema document.
Conclusions
The TCE Suite of applications – the XML Schema, Viewer, Finder, and Repository – addresses several major needs in the analysis of the predictors of virological response to ARV therapy. The TCE XML Schema and Viewer facilitate sharing data comprising a TCE. The TCE Repository, the only publicly available collection of TCEs, and the TCE Finder can be used for testing the predictive value of genotypic resistance interpretation systems and potentially for generating and testing novel hypotheses pertaining to the optimal use of salvage ARV therapy.
Keywords: Human immunodeficiency virus, Antiretroviral treatment, Drug resistance, Clinical outcomes, XML schema, Database
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