Darunavir/cobicistat showing similar effectiveness as darunavir/ritonavir monotherapy despite lower trough concentrations

Introduction: When darunavir (DRV) 800 mg is boosted with 150 mg cobicistat (DRVcobi), DRV trough concentration (C-trough) is about 30% lower as compared to 100 mg ritonavir (DRVrtv). DRVcobi shows similar virological efficacy as DRVrtv when combined with two nucleos(t) ide analogue reverse-transcriptase inhibitors, but it is unknown whether a lower DRV C-trough would undermine the effectiveness of DRVcobi when given as monotherapy (mtDRV(cobi)).Methods: Prospective observational study on virologically suppressed HIV-infected subjects who switched to mtDRV(cobi). Virological failure was defined as two consecutive HIV-RNA > 200 copies/mL. Efficacy was evaluated by intention-to-treat (ITT) and on-treatment (OT) analyses, and compared with data from a previous cohort of subjects on mtDRV(rtv) conducted at our centre. Plasma DRV C-trough was measured using LC-MS/MS.Results: A total of 234 subjects were enrolled. At week 96, the efficacy rates were 67.8% (CI95, 61.8 to 73.7) by ITT and 86.9% (CI95, 78.0 to 87.7) by OT analyses. The corresponding rates in our historical DRVrtv controls were 67.6% (CI95, 60.0 to 75.2) and 83.6% (CI95: 77.2 to 90.0). A total of 135 DRV determinations were performed in 83 subjects throughout the follow- up period, with a median plasma DRV C-trough of 1305 ng/mL (range, 150 to 5895) compared with 1710 ng/mL (range, 200 to 3838) in subjects on monotherapy with DRVrtv (p = 0.05).Conclusions: DRV C-trough was lower in HIV-infected subjects receiving DRVcobi than with DRVrtv. However, this did not appear to influence the efficacy of DRVcobi, when administered as monotherapy