Estimating the individualized HIV-1 genetic barrier to resistance using a nelfinavir fitness landscape

BMC Bioinformatics

Research Article

Eric Van Wijngaerden¹  Yves Moreau²  Ricardo J Camacho³  Soo-Yon Rhee⁴  Robert W Shafer⁴  Koen Deforche⁵  Gertjan Beheydt⁵  Philippe Lemey⁵  Kristof Theys⁵  Kristel van Laethem⁵  Anne-Mieke Vandamme⁶ 

[1] Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA;ESAT, Katholieke Universiteit Leuven, Leuven, Belgium;Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal;Internal Medicine, University Hospitals Leuven, Leuven, Belgium;Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium;Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium;Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal;

关键词: Nelfinavir;    Virological Failure;    Fitness Landscape;    Genetic Barrier;    Viral Fitness;   

DOI  :  10.1186/1471-2105-11-409

 received in 2009-12-15, accepted in 2010-08-03,  发布年份 2010

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Theys et al; licensee BioMed Central Ltd. 2010