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 (DRV_cobi ), DRV trough concentration (C_trough ) is about 30% lower as compared to 100 mg ritonavir (DRV_rtv ). DRV_cobi shows similar virological efficacy as DRV_rtv 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 DRV_cobi 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 DRV_rtv 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 DRV_rtv (p = 0.05).

Conclusions: DRV C_trough was lower in HIV-infected subjects receiving DRV_cobi than with DRV_rtv . However, this did not appear to influence the efficacy of DRV_cobi , when administered as monotherapy.