Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: Primary 24-week analysis

Jeffrey P. Nadler, Daniel S. Berger, Gary Blick, Paul J. Cimoch, Calvin J. Cohen, Richard N. Greenberg, Charles B. Hicks, Richard M W Hoetelmans, Kathy J. Iveson, Dushyantha T Jayaweera, Anthony M. Mills, Monika P. Peeters, Peter J. Ruane, Peter Shalit, Shannon R. Schrader, Stephen M. Smith, Corklin R. Steinhart, Melanie Thompson, Johan H. Vingerhoets, Ellen VoorspoelsDouglas Ward, Brian Woodfall

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1. DESIGN: A total of 199 patients were randomly assigned 2:2:1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population. METHODS: Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide). RESULTS: The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity. CONCLUSION: Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control.

Original languageEnglish
JournalAIDS
Volume21
Issue number6
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

etravirine
HIV-1
Reverse Transcriptase Inhibitors
Safety
Anti-Retroviral Agents
Protease Inhibitors
Control Groups
RNA
Lopinavir
Ritonavir
Exanthema
Viral Load
Nucleosides

Keywords

  • 24-week primary analysis
  • Etravirine
  • Non-nucleoside reverse transcriptase inhibitor
  • Randomized trial
  • Resistant HIV-1
  • TMC125

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Nadler, J. P., Berger, D. S., Blick, G., Cimoch, P. J., Cohen, C. J., Greenberg, R. N., ... Woodfall, B. (2007). Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: Primary 24-week analysis. AIDS, 21(6). https://doi.org/10.1097/QAD.0b013e32805e8776

Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1 : Primary 24-week analysis. / Nadler, Jeffrey P.; Berger, Daniel S.; Blick, Gary; Cimoch, Paul J.; Cohen, Calvin J.; Greenberg, Richard N.; Hicks, Charles B.; Hoetelmans, Richard M W; Iveson, Kathy J.; Jayaweera, Dushyantha T; Mills, Anthony M.; Peeters, Monika P.; Ruane, Peter J.; Shalit, Peter; Schrader, Shannon R.; Smith, Stephen M.; Steinhart, Corklin R.; Thompson, Melanie; Vingerhoets, Johan H.; Voorspoels, Ellen; Ward, Douglas; Woodfall, Brian.

In: AIDS, Vol. 21, No. 6, 01.03.2007.

Research output: Contribution to journalArticle

Nadler, JP, Berger, DS, Blick, G, Cimoch, PJ, Cohen, CJ, Greenberg, RN, Hicks, CB, Hoetelmans, RMW, Iveson, KJ, Jayaweera, DT, Mills, AM, Peeters, MP, Ruane, PJ, Shalit, P, Schrader, SR, Smith, SM, Steinhart, CR, Thompson, M, Vingerhoets, JH, Voorspoels, E, Ward, D & Woodfall, B 2007, 'Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: Primary 24-week analysis', AIDS, vol. 21, no. 6. https://doi.org/10.1097/QAD.0b013e32805e8776
Nadler, Jeffrey P. ; Berger, Daniel S. ; Blick, Gary ; Cimoch, Paul J. ; Cohen, Calvin J. ; Greenberg, Richard N. ; Hicks, Charles B. ; Hoetelmans, Richard M W ; Iveson, Kathy J. ; Jayaweera, Dushyantha T ; Mills, Anthony M. ; Peeters, Monika P. ; Ruane, Peter J. ; Shalit, Peter ; Schrader, Shannon R. ; Smith, Stephen M. ; Steinhart, Corklin R. ; Thompson, Melanie ; Vingerhoets, Johan H. ; Voorspoels, Ellen ; Ward, Douglas ; Woodfall, Brian. / Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1 : Primary 24-week analysis. In: AIDS. 2007 ; Vol. 21, No. 6.
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T2 - Primary 24-week analysis

AU - Nadler, Jeffrey P.

AU - Berger, Daniel S.

AU - Blick, Gary

AU - Cimoch, Paul J.

AU - Cohen, Calvin J.

AU - Greenberg, Richard N.

AU - Hicks, Charles B.

AU - Hoetelmans, Richard M W

AU - Iveson, Kathy J.

AU - Jayaweera, Dushyantha T

AU - Mills, Anthony M.

AU - Peeters, Monika P.

AU - Ruane, Peter J.

AU - Shalit, Peter

AU - Schrader, Shannon R.

AU - Smith, Stephen M.

AU - Steinhart, Corklin R.

AU - Thompson, Melanie

AU - Vingerhoets, Johan H.

AU - Voorspoels, Ellen

AU - Ward, Douglas

AU - Woodfall, Brian

PY - 2007/3/1

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N2 - OBJECTIVE: TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1. DESIGN: A total of 199 patients were randomly assigned 2:2:1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population. METHODS: Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide). RESULTS: The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity. CONCLUSION: Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control.

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KW - 24-week primary analysis

KW - Etravirine

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KW - Randomized trial

KW - Resistant HIV-1

KW - TMC125

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