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

• Published in: AIDS Research and Treatment Vol. 2015; no. 2015; pp. 129 - 139
• Main Authors: Orrell, Catherine, Felizarta, Franco, Nell, André, Kakuda, Thomas N., Lavreys, Ludo, Nijs, Steven, Tambuyzer, Lotke, Van Solingen-Ristea, Rodica, Tomaka, Frank L.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01-01-2015; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Antiretroviral drugs; Atazanavir; Clinical Study; Dosage and administration; Drug dosages; Drug resistance; Etravirine; Health aspects; Highly active antiretroviral therapy; HIV; HIV (Viruses); Human immunodeficiency virus; Patients; Pharmacokinetics; Studies
• ISSN: 2090-1240; 2090-1259
• DOI: 10.1155/2015/938628

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 Cmin⁡ by 18% and 9%, respectively, with no change in AUC24 h or Cmax⁡ 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.