Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors

Background: To estimate to what extent darunavir might be effective in patients failing distinct protease inhibitors (PIs), the genotypic resistance scores recently reported for the drug were examined in a large clinical HIV-1 drug resistance database. Methods: All clinical specimens from HIV-infected patients failing PI-based regimens referred for drug resistance testing between 1999 and 2007 to a reference centre in Madrid were analysed. Darunavir-specific resistance mutations listed by the September 2006 IAS-USA panel update were considered. Results: A total of 1021 genotypes from patients failing lopinavir (39.2%), nelfinavir (28.1%), saquinavir (14.5%), indinavir (13.7%), atazanavir (6.6%), fosamprenavir (5.3%) and tipranavir (1.1%) were identified. The prevalence of major darunavir resistance mutations was I50V 2.1%, I54M 1.3%, L76V 2.7 % and I84V 14.5%. For minor darunavir resistance mutations, the rates were V11I 3.3%, V32I 3.9%, L33F 11%, I47V 2.1%, I54L 2.3%, G73S 12.8 % and L89V 2.4%. Overall, 6.7 % (n5 68) of the genotypes had three or more darunavir resistance mutations, which corresponded to a mean total number of PI resistance mutations of 12.3+ 1.9. In the multivariate analysis, prior fosamprenavir failure, prior saquinavir failure, the total number of PI resistance mutations and the number of prior PIs used were all independently associated with having more darunavir resistance mutations. Conclusions: The prevalence of darunavir resistance mutations is low in patients failing other PI-based regimens, although prior failure to amprenavir and saquinavir might produce more cross-resistance to darunavir. Thus, darunavir may be a good option for patients who have failed other PI-based regimens