13   TMC120, a New Non- Nucleoside Reverse Transcriptase Inhibitor, Is a Potent Antiretroviral in Treatment Naive, HIV-1 Infected Subjects.

B. Gruzdev¹, A. Horban², A. Boron-Kaczmarska³, D. Gille⁴, G. Van't Klooster⁴, and R. Pauwels*⁴.
¹Infectious. Disease Hosp., Moscow, Russia;²Hosp. for Infectious Diseases, Warsaw, Poland;³Pomeranian Med. Acad., Scezcin, Poland; and⁴Tibotec, 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 (log₁₀copies/ml) by treatment group (placebo or TMC120 po BID) are shown below:

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 One subject (50 mg BID) was withdrawn after day 4 because of acute HIV infection.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.