Resistant minority species are rarely observed in patients on darunavir/ritonavir monotherapy.

OBJECTIVES: To analyse the emergence of resistant viruses in patients failing darunavir monotherapy, including minority species, and to investigate the impact of baseline reverse transcriptase (RT), protease (PR) and gag resistance mutations on virological failure (VF) occurrence.
METHODS: Nine of the 225 HIV-1-infected patients enrolled in the MONOI trial (darunavir/ritonavir monotherapy or darunavir/ritonavir + two nucleoside reverse transcriptase inhibitors in a switch strategy) experienced VF, defined as two plasma HIV-1 viral loads >400 copies/mL at least 2 weeks apart. Among these nine patients with VF, five were in the darunavir/ritonavir monotherapy arm and four were in the darunavir/ritonavir triple therapy arm. Bulk sequences of the PR, RT and gag genes at baseline (on DNA) and at the time of VF (on RNA) were determined for all patients with two viral loads >50 copies/mL at least 2 weeks apart (n = 47). PR and gag gene clonal analysis was performed on plasma samples of the nine patients with VF.
RESULTS: There was no association between mutations in RT, PR and gag genes in DNA and VF occurrence. None of the patients demonstrated selection of darunavir resistance mutations among the 47 patients with a viral load >50 copies/mL at least 2 weeks apart. The virus of one of the nine patients with VF presented minority variants with darunavir resistance mutations at positions 32, 47 and 50. Clonal analysis of the gag region for the nine patients with VF did not show any selection of minority variants.
CONCLUSIONS: In patients with failure on darunavir/ritonavir monotherapy we did not find any selection of darunavir resistance mutations using standard genotype testing. However, the virus of one patient among nine failures presented minority variants plus darunavir resistance mutations.