Pharmacokinetics of Etravirine Combined with Atazanavir/Ritonavir and a Nucleoside Reverse Transcriptase Inhibitor in Antiretroviral Treatment-Experienced, HIV-1-Infected Patients.

ABSTRACT: Objectives. TEACH (NCT00896051) was a randomized, open-label, two-arm Phase II trial to investigate the pharmacokinetic interaction between etravirine and atazanavir/ritonavir and safety and efficacy in treatment-experienced, HIV-1-infected patients. Methods. After a two-week lead-in of two nucleoside reverse transcriptase inhibitors (NRTIs) and atazanavir/ritonavir 300/100?mg, 44 patients received etravirine 200?mg?bid with one NRTI, plus atazanavir/ritonavir 300/100?mg or 400/100?mg?qd (n = 22 each group) over 48 weeks. Results. At steady-state etravirine with atazanavir/ritonavir 300/100?mg?qd or 400/100?mg?qd decreased atazanavir C min? by 18% and 9%, respectively, with no change in AUC24?h or C max? versus atazanavir/ritonavir 300/100?mg?qd alone (Day -1). Etravirine AUC12?h was 24% higher and 16% lower with atazanavir/ritonavir 300/100 or 400/100?mg?qd, respectively, versus historical controls. At Week 48, no significant differences were seen between the atazanavir/ritonavir groups in discontinuations due to adverse events (9.1% each group) and other safety parameters, the proportion of patients with viral load <50 copies/mL (intent-to-treat population, noncompleter = failure) (50.0%, atazanavir/ritonavir 300/100?mg?qd versus 45.5%, 400/100?mg?qd), and virologic failures (31.8% versus 27.3%, resp.). Conclusions. Etravirine 200?mg?bid can be combined with atazanavir/ritonavir 300/100?mg?qd and an NRTI in HIV-1-infected, treatment-experienced patients without dose adjustment.

SUBMITTER: Orrell C 

PROVIDER: S-EPMC4312629 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature