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 (Ctrough) 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-transcript...
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/25242 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/25242 |
| Access Level: | acceso abierto |
| Palabra clave: | Ctrough Darunavir Cobicistat Monotherapy Pharmacokinetic Ritonavir Adult Anti-HIV Agents Drug Therapy, Combination Female HIV Infections Humans Male Middle Aged Prospective Studies Reverse Transcriptase Inhibitors Viral Load |
| Sumario: | Introduction: When darunavir (DRV) 800 mg is boosted with 150 mg cobicistat (DRVcobi), DRV trough concentration (Ctrough) 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 Ctrough would undermine the effectiveness of DRVcobi when given as monotherapy (mtDRVcobi). Methods: Prospective observational study on virologically suppressed HIV-infected subjects who switched to mtDRVcobi . 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 mtDRVrtv conducted at our centre. Plasma DRV Ctrough 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 Ctrough 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 Ctrough 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. |
|---|