NNRTI Rilpivirine (TMC278) Shows Efficacy Comparable
to Efavirenz (Sustiva) at 96 Weeks, but with Fewer Side
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
(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.
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.
rilpivirine dose-response relationship for efficacy
or safety was observed.
demonstrated potent antiviral efficacy similar
to efavirenz over 48 weeks (76.9%-80.0% of rilpivirine
recipients with confirmed viral load < 50 copies/mL).
antiviral responses were sustained through week
96 (71.4%-76.3% of rilpivirine-treated patients
with < 50 copies/mL).
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.
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.
of serious adverse events, grade 3 or 4 adverse
events, and drug discontinuations due to adverse
events were similar across groups.
conclusion, the study authors wrote, "All TMC278
doses demonstrated potent and sustained efficacy comparable
with efavirenz in treatment-naive patients over 96
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
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.
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.