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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.
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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 One subject was withdrawn on day 4 (placebo;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.
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