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Abstract
Neuropsychiatric events with TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI)
Pozniak A.1, Steyn D.2, Grinsztejn B.3, Vinogradova E.4, Lupo S.5, Techasathit W.6, Vanveggel S.7, Peeters M.7, Goilav C.7, Williams P.7, Woodfall B.7, Boven K.8
Objectives: TMC278 is a next-generation NNRTI with potent and sustained efficacy in ARV-naïve patients. Efavirenz (EFV) is a commonly used NNRTI associated with neuropsychiatric events in more than 50% of patients. The neuropsychiatric adverse event profile of TMC278 was evaluated in a PhIIb study and compared with EFV.
Methods: TMC278-C204 is an ongoing randomized, active controlled, partially blinded dose-finding study to evaluate efficacy, safety and tolerability of three doses of TMC278 (25mg, 75mg, 150mg q.d.) in ARV-naïve HIV-1 infected patients. The active control is EFV 600mg q.d.; all treatments include 2 NRTIs.
Results: 368 patients were enrolled in the study; 33% were female. Combivir was used by 76% and Truvada by 24%. The median age was 35 years. Median treatment duration was 52 weeks (0-70). The incidence of nervous system (NS) events was similar for all TMC278 doses (combined 33%) and lower than for EFV (53%) (p=0.002). The most frequent NS events were headache (18% TMC278 vs 16% EFV, p=0.6), dizziness (9% vs 30%, p<0.001) and somnolence (4% vs 11%, p=0.01). 0.4% of TMC278- vs 1% of EFV-treated patients reported a grade 3 or 4 NS event. None of these led to treatment discontinuation. The incidence of psychiatric disorders was similar for all TMC278 doses (combined: 13%) and EFV (16%) (p=0.6). The most frequent were insomnia (6% TMC278 vs 5% EFV, p=0.8), depression (5% vs 2%, p=0.5) and abnormal dreams/nightmares (3% vs 10%, p=0.005). Grade 3 or 4 psychiatric events were reported in 2% of TMC278- and 1% of EFV-treated patients. Psychiatric disorders resulted in discontinuations in 0.4% of TMC278- and 1% of EFV-patients.
Conclusions: In the open label comparison between EFV and TMC278, TMC278-treated patients reported less dizziness, somnolence and abnormal dreams/nightmares than EFV-treated patients. The incidence of neuropsychiatric events with TMC278 was not related to dose.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
Abstract no.
WEPEA105
Suggested Citation
"PozniakA., et al.
Neuropsychiatric events with TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI).
Poster exhibition:
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention:
Abstract no.
WEPEA105"
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