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12th Conference on Retroviruses and Opportunistic InfectionsBoston, Massachusetts - February 22-25, 2005 |
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Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 160
Frank Goebel1, A Yakovlev2, A Pozniak3, E Vinogradova4, P Lewi5, G Boogaerts6, R Hoetelmans6, M P De Béthune6, M Peeters
6, and B Woodfall6
1Ludwig Maximilians Univ, Munich, Germany; 2Hosp Botkin St Petersburg, Russia; 3Chelsea and Westminster Hosp, London, UK; 4Ctr for AIDS & Infectious Diseases, St Petersburg, Russia; 5Janssen Pharma, Vosselaar, Belgium; and 6Tibotec, Mechelen, Belgium
BACKGROUND: TMC278 is a new diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI), highly active against wild type and drug-resistant HIV-1 in vitro.
METHODS: TMC125-C201 was a randomized, double-blind, placebo-controlled phase IIa study to evaluate the antiviral activity of TMC278 daily as monotherapy for 7 days in ARV-naïve HIV-1-infected patients. After the TMC278 treatment, patients were switched to standard of care treatment.
RESULTS: We randomized 47 males to TMC278 twice daily to either placebo, 25, 50, 100, or 150 mg. Baseline median CD4 cell count was 255 cells/µL; median log10 HIV-1 RNA was 4.5 copies/mL. All patients completed the treatment period. Viral load response are shown in the table below. TMC278 produced a decrease in viral load that was statistically significant vs placebo for all doses studied (p < 0.001); 4 patients achieved a viral load of < 400 copies/mL during the treatment period. No viral rebounds were observed. Overall increase in CD4 cell count in the TMC278 groups was +55. No severe adverse effects were reported. The most common adverse effect was headache (placebo 18%; TMC278 14%). No genotypic changes associated with ARV resistance were observed between baseline and end of treatment.
| Viral load (log10 copies/mL) |
Placebo | 25 mg daily |
50 mg daily |
100 mg daily |
150 mg daily |
| Baseline | 4.3 | 4.6 | 4.5 | 4.5 | 4.6 |
| Day 8 | 0.002 | –1.3 | –1.2 | –1.1 | –1.2 |
| Range | –0.97 / 0.3 | –1.9 / –0.9 | –1.6 / –0.8 | –1.5 / –0.9 | –1.5 / –0.7 |
CONCLUSIONS: TMC278 was highly active as monotherapy for 7 days at all doses studied. TMC278 was safe and well tolerated. A further proof-of-principle study of TMC278 is being carried out in treatment-experienced HIV-1 patients.
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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.
