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.
journal_name
BMC Bioinformaticsjournal_title
BMC bioinformaticsauthors
Theys K,Deforche K,Beheydt G,Moreau Y,van Laethem K,Lemey P,Camacho RJ,Rhee SY,Shafer RW,Van Wijngaerden E,Vandamme AMdoi
10.1186/1471-2105-11-409subject
Has Abstractpub_date
2010-08-03 00:00:00pages
409issn
1471-2105pii
1471-2105-11-409journal_volume
11pub_type
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