Open AccessDarunavir/cobicistat showing similar effectiveness as darunavir/ritonavir monotherapy despite lower trough concentrations
Author(s) -
GutierrezValencia Alicia,
TrujilloRodriguez Maria,
FernandezMagdaleno Tamara,
Espinosa Nuria,
Viciana Pompeyo,
LópezCortés Luis F
Publication year - 2018
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.1002/jia2.25072
Subject(s) - darunavir , medicine , ritonavir , cobicistat , trough concentration , gastroenterology , trough level , trough (economics) , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , virology , pharmacokinetics , transplantation , tacrolimus , economics , macroeconomics
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 (mt DRV cobi ). Methods Prospective observational study on virologically suppressed HIV ‐infected subjects who switched to mt DRV 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 mt DRV 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.