Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects.
OBJECTIVE
To evaluate antiviral activity, pharmacokinetics, tolerability and safety of TMC278, a non-nucleoside reverse transcriptase inhibitor (NNRTI), when given as a 25, 50, 100 or 150 mg once-daily dose for 7 days to antiretroviral-naive HIV-infected subjects.


METHODS
Randomized, double-blind, placebo-controlled, phase IIa clinical trial.


METHODS
Participants were 47 antiretroviral naive HIV-infected subjects. Primary outcome was the change in plasma HIV-1 RNA viral load from baseline to day 8. Secondary outcomes were evaluation of pharmacokinetics of TMC278, immunologic changes, safety and tolerability, and evolution of viral genotypic and phenotypic patterns.


RESULTS
Patients treated with TMC278 achieved a median decrease in plasma viral load from baseline of 1.199 log10 copies/ml compared with a 0.002 log10 copies/ml gain in the placebo group (P < 0.01). A significantly higher proportion of subjects in the TMC278 groups obtained a viral load decrease of > 1.0 log10 compared with the placebo group (25/36 versus 0/11) (P < 0.01). No significant dose differences were noted in either antiviral effect or safety. No genotypic changes associated with antiretroviral resistance were detected between baseline and the end of the trial. Plasma concentrations of TMC278 were above the target concentration (13.5 ng/ml) at all time points for all TMC278-treated subjects. The most common reported adverse event was headache (TMC278 14%; placebo 18%).


CONCLUSIONS
TMC278 showed antiviral activity when given as monotherapy for 7 days at all doses studied and the drug was safe and well tolerated. 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.
Goebel
Frank
F
Ludwig-Maximilians University, Munich, Germany.
Yakovlev
Alexy
A
Pozniak
Anton L
AL
Vinogradova
Elena
E
Boogaerts
Griet
G
Hoetelmans
Richard
R
de Béthune
Marie-Pierre P
MP
Peeters
Monika
M
Woodfall
Brian
B
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016516:CD4-CD8 Ratio; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000068696:Rilpivirine; D019562:Viral Load
D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D000068696:Rilpivirine