Background: The aim of this analysis was to characterize viral resistance in the Phase III, randomized ODIN trial, which demonstrated non-inferiority of once-daily darunavir/ritonavir (DRV/r) 800/100 mg to DRV/r 600/100 mg twice daily, each combined with an optimized background regimen in treatment-experienced patients with no DRV resistance-associated mutations (RAMs) at screening.
Methods: Virological failure (VF) was defined as never achieving or losing confirmed virological suppression after week 12, with patients being classed as 'never suppressed' (never achieved HIV-1 RNA<50 copies/ml) or 'rebounders' (achieved two consecutive HIV-1 RNA<50 copies/ml but then ≥ 50 copies/ml). Phenotypes and genotypes of plasma HIV-1 viruses, using population-based sequencing and Antivirogram(®), were determined at screening/baseline and on samples from VFs with HIV-1 RNA ≥ 50 copies/ml.
Results: Mean baseline HIV-1 RNA was 4.16 log10 copies/ml and 53.9% of patients were protease inhibitor (PI)-experienced at enrolment. VF rate was similar in both arms. A similar proportion of virologically failing patients in both arms developed PI RAMs (11.7% versus 9.5%, respectively) or nucleoside reverse transcriptase inhibitor RAMs (6.7% versus 7.1%). One patient with VF (once-daily arm) developed four primary PI mutations, three of which were also DRV RAMs. This patient was also the only VF to lose susceptibility to DRV. Loss of susceptibility to other PIs (once daily 3.4%; twice daily 0%) and nucleoside reverse transcriptase inhibitors (once daily 13.6%; twice daily 9.8%) in VF patients was infrequent and comparable between treatment arms.
Conclusions: These analyses showed once-daily DRV/r 800/100 mg was associated with similar rates of VF and emergence of resistance as DRV/r 600/100 mg twice daily in treatment-experienced patients with no DRV RAMs.
Trial registration: ClinicalTrials.gov NCT00524368.