8th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 4 - 8, 2001



TMC120, a new non-nucleoside reverse transcriptase inhibitor, is a potent antiretroviral in treatment naïve, HIV-1 infected subjects

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:46 (abstract no. 13)

B. Gruzdev1, A. Horban2, A. Boron-Kaczmarska3, D. Gille4, G. Van't Klooster4, and R. Pauwels4
1Infectious. Disease Hosp., Moscow, Russia; 2Hosp. for Infectious Diseases, Warsaw, Poland; 3Pomeranian Med. Acad., Scezcin, Poland; and 4Tibotec, Mechelen, Belgium.

BACKGROUND: TMC120 (R147681), a dianilinopyrimidine (DAPY) derivative, is a novel, non- nucleoside reverse transcriptase inhibitor (NNRTI) with equipotent in vitro activity (IC50 = 1-10 nM) against wild-type HIV-1 and NNRTI-resistant variants encoding K103N, Y181C or G190A/S mutations.

METHODS: Randomized, double-blind, phase I/II study comparing two doses of TMC120 to placebo in treatment-native HIV-1 infected patients (HIV RNA: 5,000-125,000 cps/ml). Patients received placebo or TMC120 monotherapy (50 or 100 mg po BID) for 7 days. Triple therapy with new antiretrovirals was offered thereafter.

RESULTS: 34 men and 9 women were enrolled. Median baseline (BL) characteristics were: age 24 years; CD4 cell count 571 cells/mL; and HIV-1 RNA 40,258 copies/ml. Decay rates were -0.02 for the placebo, -0.213 for the 50 mg (p<0.001 vs placebo) and -0.237 for the 100 mg (p<0.001 vs placebo) group (p<0.001 vs placebo, ITT). Changes in HIV-1 RNA (log10 copies/ml) by treatment group (placebo or TMC120 po BID) are shown below:

TMC120 treatment placebo (n=15) 50 mg (n=13) 100 mg (n=15)
BL HIV-1 RNA 4.48 4.60 4.52
Day 8, morning 4.31 3.10 3.01
Mean decrease day 8 -0.17 -1.44*** -1.51***
Decrease range +0.20/-0.72 -0.89/-1.97 -1.23/-1.96

TMC120 was safe and well tolerated. Three patients reported possible drug-related mild adverse events (somnolence, insomnia). One subject (50 mg BID) was withdrawn after day 4 because of acute HIV infection.

CONCLUSIONS: These results indicate that TMC120 administered twice daily at doses of 50 and 100 mg for 7 days is a safe and potent antiretroviral agent.

2001-02-04
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Copyright © 2001 - 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.