Short-Term
Activity of Experimental NNRTI TMC278 in Treatment-naive Patients As
the new non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (aka
TMC125) becomes available through an expanded access program, manufacturer
Tibotec is also testing another experimental drug in the same class, TMC278. As
reported in the August 22, 2006 issue of AIDS, an international team of
researchers evaluated the antiviral activity, pharmacokinetics, tolerability,
and safety of TMC278. The randomized, double-blind Phase IIa trial included 47
antiretroviral-naive HIV positive participants who received TMC278 at doses of
25, 50, 100, or 150 mg, or else placebo, once daily for 7 days. Results 
At day 8, participants who received TMC278 experienced a median decrease in plasma
HIV RNA of 1.199 log10 copies/mL from baseline, compared with 0.002 log10 copies/mL
in the placebo group (P < 0.01).
A significantly higher proportion of subjects in the TMC278 groups experienced
a viral load decrease greater than 1.0 log10, compared with the placebo group
(25 out of 36 vs 0 out of 11; P < 0.01).
Plasma concentrations of TMC278 were above the target concentration (13.5 ng/mL)
at all time points for all subjects treated with active drug.
No significant dose differences were noted in either antiviral activity or safety.
The most common reported adverse event was headache (14% TMC278 vs 18% placebo).
No genotypic changes associated with antiretroviral resistance were observed between
baseline and the end of the trial.
Conclusion The
authors concluded that, "TMC278 showed antiviral activity when given as monotherapy
for 7 days at all doses studied and the drug was safe and well tolerated."
They added that, "Trials of longer treatment duration with TMC278, in combination
with other antiretroviral drugs, are underway to assess the long-term durability
of antiviral response, safety and tolerability." Ludwig-Maximilians
University, Munich, Germany; Hospital Botkin, St Petersburg, Russia; Chelsea and
Westminster Hospital, London, UK; Centre for AIDS & Infectious Diseases, St
Petersburg, Russia; Tibotec, Mechelen, Belgium. 09/22/06 Reference
F
Goebel, A Yakovlev, A L Pozniak AL, and others. Short-term antiviral activity
of TMC278 - a novel NNRTI - in treatment-naive HIV-1-infected subjects. AIDS
20(13): 1721-1726. August 22, 2006.
| 
