Efficacy and safety of TMC278 in treatment-naïve, HIV-infected patients: week 96 data from TMC278-C204

Background

NNRTIs are very effective antiretrovirals, but new NNRTIs with improved tolerability are needed.

Methods

A randomised Phase IIb study assessed the investigational next-generation NNRTI, TMC278, 25, 75 and 150 mg QD blinded up to 96 weeks and an open-label control, efavirenz (EFV) 600 mg QD in 368 treatment-naïve patients (33% females). All patients received AZT/3TC (76%) or TDF/FTC (24%).

Summary of results

No differences in efficacy were observed across TMC278 arms or vs. EFV at week 96. The potent antiviral efficacy of TMC278 at week 48 was sustained to week 96. Mean increase from baseline in CD4 cell count was higher at week 96 vs. 48. (Table 1.)

Table 1

At week 96 vs. week 48, there were few TMC278 dose-related effects, and no change in types nor notable increase in incidence of AEs. All rashes were grade 1 or 2, except one case of grade 3 rash (TMC278 75 mg arm, dapsone-related). Rashes resolved with continued dosing (median duration: all TMC278 17 vs. EFV 15 days). Incidences of grade 3 or 4 nervous system AEs (no discontinuations; all TMC278: 0.7% vs. EFV: 1.1%) and psychiatric AEs (1.8% vs. 1.1%) were low. Psychiatric AEs led to discontinuation in 0.4% vs. 2.2% of patients.

Conclusion

Over 96 weeks, TMC278 demonstrated a high, sustained virological response rate and was generally well tolerated with lower incidences of rash, nervous system and psychiatric AEs, and less lipid increases than EFV.