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BMC Bioinformatics

, 11:409

First Online: 03 August 2010Received: 15 December 2009Accepted: 03 August 2010

Abstract

BackgroundFailure 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.

ResultsWe 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.

ConclusionsThus, 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2105-11-409 contains supplementary material, which is available to authorized users.

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Autor: Kristof Theys - Koen Deforche - Gertjan Beheydt - Yves Moreau - Kristel van Laethem - Philippe Lemey - Ricardo J Camacho -

Fuente: https://link.springer.com/







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