Abstract
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.