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Title: Estimating the individualized HIV-1 genetic barrier to resistance using a nelfinavir fitness landscape
Authors: Theys, Kristof ×
Deforche, Koen
Beheydt, Gertjan
Moreau, Yves
Van Laethem, Kristel
Lemey, Philippe
Camacho, Ricardo Jorge
Rhee, Soo-Yon
Shafer, Robert W
Van Wijngaerden, Eric
Vandamme, Anne-Mieke #
Issue Date: Aug-2010
Publisher: BioMed Central
Series Title: BMC Bioinformatics vol:11 pages:409
Abstract: ABSTRACT: BACKGROUND: Failure on Highly Active Anti-Retroviral Treatment is often accompanied with development of antiviral resistance to one or more drugs included in the treatment. In general, the virus is more likely to develop resistance to drugs with a lower genetic barrier. Previously, we developed a method to reverse engineer, from clinical sequence data, a fitness landscape experienced by HIV-1 under nelfinavir (NFV) treatment. By simulation of evolution over this landscape, the individualized genetic barrier to NFV resistance may be estimated for an isolate. RESULTS: We investigated the association of estimated genetic barrier with risk of development of NFV resistance at virological failure, in 201 patients that were predicted fully susceptible to NFV at baseline, and found that a higher estimated genetic barrier was indeed associated with lower odds for development of resistance at failure (OR 0.62 (0.45 - 0.94), per additional mutation needed, p = .02). CONCLUSIONS: Thus, variation in individualized genetic barrier to NFV resistance may impact effective treatment options available after treatment failure. If similar results apply for other drugs, then estimated genetic barrier may be a new clinical tool for choice of treatment regimen, which allows consideration of available treatment options after virological failure.
URI: 
ISSN: 1471-2105
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
Department of Microbiology & Immunology - miscellaneous
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Laboratory for Clinical Infectious and Inflammatory Disorders
× corresponding author
# (joint) last author

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