icon_folder.gif   Conference Reports for NATAP  
 
  ICAAC 41st Interscience Conference on Antimicrobial Agents and Chemotherapy
 
Chicago, Illinois, December 16-19
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Abstract: I-668. TMC125 is a Highly Potent Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) in Antiretroviral Therapy (ART)-Naive, HIV-1 Infected Subjects.
 
 
  B. GRUZDEV1, A. RAKHMANOVA2, K. DE DIER3, S. COMHAIRE4, P. BAEDE-VAN DIJK5, G. VAN T KLOOSTER3
 
1 Inf. Dis. Hosp, Moscow, Russian Federation; 2 Med. Acad. Postgraduate Studies, St. Petersburg, Russian Federation; 3 Tibotec-Virco, Mechelen, Belgium; 4 MediSearch Int, Mechelen, Belgium; 5 Kinesis, Breda, The Netherlands
 
TMC125 (R165335) is a novel NNRTI with potent in vitro activity (EC50 = 1-10 nM) against wild-type HIV-1 and NNRTI-resistant variants with L100I, K103N, Y181C, Y188L or G190A/S mutations (40th ICAAC, 2000: abstracts 1840, 1841). It appears in this study to show potent HIV activity during this 7-day study.
 
The authors reported results from a 7-day phase 2A randomized, double-blind, placebo-controlled study conducted in Russia to evaluate the antiviral activity of 900mg TMC125 BID as monotherapy for 7 days in ART-naive HIV-1 infected patients. Standard of care ART was offered thereafter. The drug is being developed by Tibotec-Virco.
 
19 males enrolled (median age 23 years; CD4 cell count: 650 cd4 cells, HIV-1 RNA: 57,619 copies/ml). One subject was withdrawn on day 4 (placebo; heartburn). Patients received 900 mg twice daily (n=12) or placebo (n=7). After 7 days, 2 of 12 (17%) TMC125-treated patients (baseline plasma viral loads (VLs) of 61,551 cps/ml and 5,643 cps/ml) achieved VLs below 50 cps/ml; 8 of 12 (67%) had VLs below 400 cps/ml. Mean VL change was -1.99 log (range -1.13 to -3.39). The patients receiving placebo had virtually no viral load reduction P<.001 for the TMC-125 arm compared to placebo patients and baseline viral load. No viral rebounds were observed.
 
Mean TMC125 trough plasma level was 237 76 ng/ml. TMC125 was safe and well tolerated. Seven patients (3/placebo, 4/TMC125) reported adverse events. Mild somnolence was most common (n=4/12). The drug is formulated in 50mg capsules, so it will have to be reformulated.