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% (CI (95), 61.8 to 73.7) by ITT and 86.9% (CI (95), 78.0 to 87.7) by OT analyses. The corresponding rates in our historical DRV (rtv) controls were 67.6% (CI (95), 60.0 to 75.2) and 83.6% (CI (95): 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.