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

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 ...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Kristof Theys, Koen Deforche, Gertjan Beheydt, Yves Moreau, Kristel Van Laethem, Philippe Lemey, Ricardo Camacho, Soo-Yon Rhee, Robert W. Shafer, Eric Van Wijngaerden, Anne-Mieke Vandamme
• Keywords: BMCBI 2010, Estimated Genetic Barrier, Genetic Barrier, Individualized Genetic Barrier