Background:  TMC278 is a new diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI), highly active against wild type and drug-resistant HIV-1 in vitro.

Methods:  TMC125-C201 was a randomized, double-blind, placebo-controlled phase IIa study to evaluate the antiviral activity of TMC278 daily as monotherapy for 7 days in ARV-naïve HIV-1-infected patients. After the TMC278 treatment, patients were switched to standard of care treatment.

Results:  We randomized 47 males to TMC278 twice daily to either placebo, 25, 50, 100, or 150 mg. Baseline median CD4 cell count was 255 cells/μL; median log₁₀ HIV-1 RNA was 4.5 copies/mL. All patients completed the treatment period. Viral load response are shown in the table below. TMC278 produced a decrease in viral load that was statistically significant vs placebo for all doses studied (p < 0.001); 4 patients achieved a viral load of < 400 copies/mL during the treatment period. No viral rebounds were observed. Overall increase in CD4 cell count in the TMC278 groups was +55. No severe adverse effects were reported. The most common adverse effect was headache (placebo 18%; TMC278 14%). No genotypic changes associated with ARV resistance were observed between baseline and end of treatment.

Conclusions: TMC278 was highly active as monotherapy for 7 days at all doses studied. TMC278 was safe and well tolerated. A further proof-of-principle study of TMC278 is being carried out in treatment-experienced HIV-1 patients.

Keywords: TMC278; NNRTI; treatment-naive