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Background: The investigational reformulated RAL 600mg tablet for QD use at 1200mg dose could provide a more convenient option for treatment of HIV-1 infection.
Methods: ONCEMRK is a phase 3, multicenter, double-blind, randomized, controlled trial to evaluate if reformulated RAL 1200mg QD is non-inferior to RAL 400mg BID. Treatment-naïve HIV-1-infected subjects were assigned (2:1) to reformulated RAL 2x600mg QD or RAL 400mg BID, both with tenofovir/emtricitabine, for up to 96 weeks. Randomization was stratified by screening HIV-1 RNA (vRNA) and chronic hepatitis B/C status. The primary efficacy endpoint was the proportion of subjects with vRNA < 40 copies/mL at Week 48 (Non-Completer=Failure).
Results: Of 802 subjects randomized, 797 received study therapy and were included in the analyses; 732 (92%) completed 48 weeks of treatment. The study population was 85% male, 59% white, mean age 35.9 years, mean CD4 count 415/mm3, mean plasma vRNA 4.6 log10 copies/mL, 28.4% had baseline vRNA >100,000 copies/mL, 2.9% had hepatitis B and/or C co-infection. Subjects in both groups achieved a rapid decline in vRNA (>50% reaching vRNA < 40 copies/mL by Week 4). At Week 48, RAL 1200mg QD was non-inferior to RAL 400mg BID (vRNA < 40 copies/mL in 88.9% and 88.3%, respectively, Δ(QD-BID)=0.5%, 95% CI [-4.2,5.2]). Study results did not differ significantly by baseline vRNA or hepatitis co-infection status. RAL 1200mg QD also had comparable immunologic efficacy, as measured by change from baseline in CD4 cell counts. Both treatment regimens were well-tolerated with comparable incidence of clinical adverse events (table) and laboratory values exceeding predefined limits of change (based on DAIDS toxicity criteria).
Conclusions: In HIV-1-infected treatment-naïve subjects receiving tenofovir/emtricitabine, reformulated RAL 1200mg QD demonstrated potent and non-inferior efficacy compared to RAL 400mg BID at Week 48. RAL 1200mg QD was safe and well tolerated with a safety profile similar to RAL 400mg BID.


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