Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015:2015:938628.
doi: 10.1155/2015/938628. Epub 2015 Jan 15.

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

Catherine Orrell  1 , Franco Felizarta  2 , André Nell  3 , Thomas N Kakuda  4 , Ludo Lavreys  5 , Steven Nijs  5 , Lotke Tambuyzer  5 , Rodica Van Solingen-Ristea  4 , Frank L Tomaka  4
Affiliations

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

Catherine Orrell et al. AIDS Res Treat. 2015.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
TEACH study design. TEACH was an open-label, randomized, exploratory Phase II trial. A two-week pretreatment period was followed by 48 weeks of treatment. 3TC: lamivudine; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; ETR: etravirine; FTC: emtricitabine; NRTI: nucleoside reverse transcriptase inhibitor; PI: protease inhibitor; TDF: tenofovir disoproxil fumarate.
Figure 2
Figure 2
Patient disposition. AE: adverse event; ATV/r: atazanavir/ritonavir; ETR: etravirine; NRTI: nucleoside reverse transcriptase inhibitor.
Figure 3
Figure 3
Mean ± standard deviation atazanavir plasma concentration-time curves after administration of atazanavir/ritonavir 300/100 mg qd for two weeks in combination with two NRTIs (Day −1), followed by administration of etravirine 200 mg bid for two weeks in combination with one NRTI and (a) atazanavir/ritonavir 300/100 mg qd or (b) atazanavir/ritonavir 400/100 mg qd (Week 2). ATV/r: atazanavir/ritonavir; bid: twice daily; ETR: etravirine; NRTI: nucleoside reverse transcriptase inhibitor; qd: once daily.
Figure 4
Figure 4
Mean ± standard deviation etravirine plasma concentration-time curves after administration of etravirine 200 mg bid for two weeks in combination with atazanavir/ritonavir 300/100 mg qd or 400/100 mg qd and one NRTI. ATV/r: atazanavir/ritonavir; bid: twice daily; ETR: etravirine; NRTI: nucleoside reverse transcriptase inhibitor; qd: once daily.
Figure 5
Figure 5
Virologic response (viral load (VL) < 50 copies/mL) over time to Week 48 (intent-to-treat noncompleter equals failure: NC = F). NC = F missing values after discontinuation imputed with change = 0. Last observation was carried forward otherwise. ATV/r: atazanavir/ritonavir; CI: confidence interval; VL: viral load.
See this image and copyright information in PMC

References

    1. DHHS guidelines, Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, 2014, http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf.
    1. Günthard H. F., Aberg J. A., Eron J. J., et al. International Antiviral Society-USA Panel. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. The Journal of the American Medical Association. 2014;312(4):410–425. - PubMed
    1. BHIVA. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012 (Updated November 2013. All changed text is cast in yellow highlight.) HIV Medicine. 2014;15(supplement 1):1–85. doi: 10.1111/hiv.12119. - DOI - PubMed
    1. EACS. European Guidelines for treatment of HIV infected adults in Europe. Version 7.1, 2014, http://www.eacsociety.org/Portals/0/140601 EACS%20EN7.02.pdf.
    1. Schöller-Gyüre M., Woodfall B., De Marez T., et al. Pharmacokinetics of TMC125 with atazanavir and atazanavir/ritonavir. Proceedings of the 8th International Congress on Drug Therapy in HIV Infection; November 2006; Glasgow, UK.

LinkOut - more resources