SUMMARY: According to results of a dose-ranging study published in the January 2, 2010 issue of the journal AIDS, the experimental non-nucleotide reverse transcriptase inhibitor rilpivirine (aka TMC278) demonstrated potent and sustained antiviral efficacy at all doses, comparable to that of efavirenz (Sustiva) in treatment-naive HIV patients over 96 weeks. In addition, rilpivirine was associated with fewer neurological and psychiatric side effects, less skin rash, and lower lipid elevations.

Rilpivirine is a next-generation NNRTI that has been shown to be highly active against wild-type and NNRTI-resistant HIV in vitro. In the current study, researchers with the TMC278-C204 study group evaluated different doses of rilpivirine in previously untreated HIV patients.

A total of 368 study participants were randomized and treated with 3 blinded once-daily doses of rilpivirine (25, 75, or 150 mg) or with open-label 600 mg once-daily efavirenz (Sustiva). All patients also received 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). The primary analysis was at week 48.

Results

	No rilpivirine dose-response relationship for efficacy or safety was observed.
	Rilpivirine demonstrated potent antiviral efficacy similar to efavirenz over 48 weeks (76.9%-80.0% of rilpivirine recipients with confirmed viral load < 50 copies/mL).
	Comparable antiviral responses were sustained through week 96 (71.4%-76.3% of rilpivirine-treated patients with < 50 copies/mL).
	Median increases from baseline in CD4 cell count among rilpivirine recipients were 108.0-123.0 cells/mm3 at week 48, increasing to 138.0-149.0 cells/mm3 by week 96.
	The most commonly reported grade 2-4 (moderate to severe) adverse events at least possibly related to study medication -- including nausea, dizziness, abnormal dreams, dyspepsia, asthenia, rash, somnolence and vertigo -- occurred less frequently with rilpivirine than with efavirenz.
	Frequencies of serious adverse events, grade 3 or 4 adverse events, and drug discontinuations due to adverse events were similar across groups.

In conclusion, the study authors wrote, "All TMC278 doses demonstrated potent and sustained efficacy comparable with efavirenz in treatment-naive patients over 96 weeks."

In addition, the researchers noted that rilpivirine was well tolerated at all doses, "with lower incidences of neurological and psychiatric adverse events, rash, and lower lipid elevations than those with efavirenz."

Based on these findings, they noted, the 25 mg dose of TMC278 has been selected for further clinical development.

Chelsea and Westminster NHS Foundation Trust and PKR/SSR, London, UK; Clinical Research Puerto Rico, Inc, San Juan, Puerto Rico; Uganda Makerere University, Kampala, Uganda; University of the Free State, Bloemfontein, South Africa; Universidad Nacional de Rosario, Santa Fe, Argentina; Hospital Carlos Mac Gregor IMSS, Mexico City, Mexico; Instituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil; HIV-NAT, Thai Red Cross AIDS Research Centre and Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc., Yardley, PA.

12/08/09

Reference
AL Pozniak, J Morales-Ramirez, E Katabira, and others (on behalf of the TMC278-C204 study group). Efficacy and safety of TMC278 (rilpivirine) in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial. AIDS 24(1): 55-65 (Abstract). January 2, 2009.