Which mutations will darunavir select?
Classic resistance selection experiments performed by Tibotec’s Sandra De Meyer [7] showed that: – Mutations arose much more slowly against darunavir than against ritonavir, nelfinavir, saquinavir, amprenavir, lopinavir, atazanavir, or tipranavir. – The mutations eventually evoked by increasing concentrations of darunavirR41T and K70E in proteasehave not been linked to resistance to other PIs. – Viral strains constructed to carry these two mutations alone or together remained susceptible to darunavir and to the other PIs studied. – Several substitutions also arose in the gag gene in these experiments. Recombinant viruses engineered to carry both gag and protease mutations remained largely susceptible to darunavir at susceptibility fold changes ranging from 2 to 8.8. These experiments suggest darunavir selects mutant virus along a novel pathway not shared by other PIs. But what this may mean clinically will remain obscure for some time, since darunavir is licensed for PI-experienced peo
