OBJECTIVE: To investigate the feasibility of ritonavir-boosted atazanavir monotherapy in HIV-1-infected patients with stable antiretroviral therapy (ART). DESIGN: Single-armed single-center pilot trial. METHODS:Adult HIV-1-infected patients, without protease inhibitor (PI) experience, were eligible if they had maintained a viral load <20 copies/mL for a minimum of 12 months on conventional ART. The trial regimen was atazanavir/ritonavir at a dose of 300/100 mg once daily. The atazanavir dose could be adjusted if plasma concentrations showed a low exposure. The study was intended to recruit 30 patients to be followed over 72 weeks. If 5 cases of virologic failure occurred during this period, the study was to be terminated. RESULTS: The study was terminated according to protocol when 15 of the planned 30 patients had been recruited, because 5 cases of virologic failure had occurred. In patients failing therapy, viral rebound was seen at weeks 12 through 16. Plasma atazanavir concentrations were not associated with the outcome. The median serum bilirubin concentration was significantly lower in the patients failing therapy, however. No PI resistance was found in samples from patients failing therapy. CONCLUSIONS:Ritonavir-boosted atazanavir as maintenance monotherapy in HIV-1 infection might not be as potent as conventional ART. Serum bilirubin should be further studied as a biomarker of adequate atazanavir exposure.
RCT Entities:
OBJECTIVE: To investigate the feasibility of ritonavir-boosted atazanavir monotherapy in HIV-1-infectedpatients with stable antiretroviral therapy (ART). DESIGN: Single-armed single-center pilot trial. METHODS: Adult HIV-1-infectedpatients, without protease inhibitor (PI) experience, were eligible if they had maintained a viral load <20 copies/mL for a minimum of 12 months on conventional ART. The trial regimen was atazanavir/ritonavir at a dose of 300/100 mg once daily. The atazanavir dose could be adjusted if plasma concentrations showed a low exposure. The study was intended to recruit 30 patients to be followed over 72 weeks. If 5 cases of virologic failure occurred during this period, the study was to be terminated. RESULTS: The study was terminated according to protocol when 15 of the planned 30 patients had been recruited, because 5 cases of virologic failure had occurred. In patients failing therapy, viral rebound was seen at weeks 12 through 16. Plasma atazanavir concentrations were not associated with the outcome. The median serum bilirubin concentration was significantly lower in the patients failing therapy, however. No PI resistance was found in samples from patients failing therapy. CONCLUSIONS:Ritonavir-boosted atazanavir as maintenance monotherapy in HIV-1 infection might not be as potent as conventional ART. Serum bilirubin should be further studied as a biomarker of adequate atazanavir exposure.
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Authors: Bruce R Schackman; Callie A Scott; Paul E Sax; Elena Losina; Timothy J Wilkin; John E McKinnon; Susan Swindells; Milton C Weinstein; Kenneth A Freedberg Journal: Clin Infect Dis Date: 2007-09-04 Impact factor: 9.079
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Authors: Filip Josephson; Maria C H Andersson; Leo Flamholc; Magnus Gisslén; Lars Hagberg; Vidar Ormaasen; Anders Sönnerborg; Jan Vesterbacka; Ylva Böttiger Journal: Eur J Clin Pharmacol Date: 2009-12-05 Impact factor: 2.953
Authors: Timothy J Wilkin; John E McKinnon; A Gregory DiRienzo; Katie Mollan; Courtney V Fletcher; David M Margolis; Barbara Bastow; Gary Thal; William Woodward; Catherine Godfrey; Ann Wiegand; Frank Maldarelli; Sarah Palmer; John M Coffin; John W Mellors; Susan Swindells Journal: J Infect Dis Date: 2009-03-15 Impact factor: 5.226