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Retroviral recombination is a potential mechanism for the development of multiply drug resistant viral strains but the impact on the clinical outcomes of antiretroviral therapy in HIV-infected patients is unclear. Recombination can favour resistance by combining single-point mutations into a multiply resistant genome but can also hinder resistance by breaking up associations between mutations. Previous analyses, based on population genetic models, have suggested that whether recombination is favoured or hindered depends on the fitness interactions between loci, or epistasis. In this paper, a mathematical model is developed that includes viral dynamics during therapy and shows that population dynamics interact non-trivially with population genetics. The outcome of therapy depends critically on the changes to the frequency of cell co-infection and I review the evidence available. Where recombination does have an effect on therapy, it is always to slow or even halt the emergence of multiply resistant strains. I also find that for patients newly infected with multiply resistant strains, recombination can act to prevent reversion to wild-type virus. The analysis suggests that treatment targeted at multiple parts of the viral life-cycle may be less prone to drug resistance due to the genetic barrier caused by recombination but that, once selected, mutants resistant to such regimens may be better able to persist in the population.

Original publication

DOI

10.1098/rsif.2005.0064

Type

Journal article

Journal

Journal of the Royal Society, Interface

Publication Date

12/2005

Volume

2

Pages

489 - 503

Addresses

Faculty of Medicine, Imperial College London, Department of Infectious Disease Epidemiology, St Mary's Campus, Norfolk Place, London W2 1PG, UK. c.fraser@imperial.ac.uk

Keywords

HIV, HIV Infections, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Genetics, Population, Drug Resistance, Viral, Virus Replication, Recombination, Genetic, Models, Genetic, Computer Simulation