WELBB01 - Oral Abstract
A daily dose of 400mg efavirenz (EFV) is non-inferior to the standard 600mg dose: week 48 data from the ENCORE1 study, a randomised, double-blind, placebo controlled, non-inferiority trial
Presented by Rebekah Puls (Australia).
R. Puls, Encore1 Study Group
University of New South Wales, The Kirby Institute, Sydney, Australia
Background: ENCORE1 compares the efficacy and safety of reduced dose with standard dose EFV with tenofovir/emtricitabine (TDF/FTC) as first-line therapy for HIV. An effective and safe reduced dose could yield meaningful cost savings.
Methods: ENCORE1 is an ongoing study in HIV-1 infected adults (plasma HIV-RNA (pVL) >1,000 log10copies/mL, CD4+ Tcells/µL 50-500) randomised to TDF/FTC with reduced daily dose (400mg, EFV400) or standard dose (600mg, EFV600) EFV. The primary endpoint is the difference in proportions of participants with pVL< 200 log10copies/mL at 48 weeks. Treatment arms are non-inferior if the lower limit of the 95% confidence interval for the difference in pVL between arms < -10% in the modified intention-to-treat (mITT) population. Non-inferiority was also examined in per protocol (PP) and non-completer=failure (NC=F) populations. Time to pVL< 200 copies/mL, loss of virological response (pVL>200 copies/mL; TLOVR) and EFV-cessation were compared using Kaplan Meier plots and log-rank tests. Adverse events (AEs) and serious adverse events (SAEs) were summarised by treatment.
Results: The mITT population comprised 630 patients (EFV400=321; EFV600=310). 32% were female; 37%, 33% and 30% were African, Asian and Caucasian respectively. The mean(SD) baseline CD4+ Tcell count was 273(99) cells/µL and median(IQR) pVL was 4.75(0.88) log10 copies/mL.
[Non-inferiority: pVL<200copies/mL at 48 weeks]
| ||Proportion patients <200 copies/mL (%)|| || |
| ||EFV400||EFV600||Difference (95%CI)||p|
|mITT||94.1||92.2||1.85 (-2.10, 5.79)||0.36|
|NC=F||90.0||85.8||4.27 (-0.82, 9.36)||0.10|
|PP||98.3||97.4||0.88 (-1.52, 3.28)||0.47|
There was no difference in time to pVL< 200 copies/mL, TLOVR or EFV-cessation. Mean CD4+ Tcell counts at week 48 were significantly higher for EFV400 versus EFV600 (difference=25, 95%CI 6, 44; p=0.01). There was no difference in frequency of AEs (EFV400=89.1%, EFV600=88.4%; difference=0.75%, 95%CI -4.19, 5.69; p=0.77) or grade. SAEs did not differ in frequency (EFV400=7.17%, EFV600=7.12%; difference=0.05%, 95%CI -3.98, 4.07; p=0.98).
Conclusion: Reduced dose EFV (400mg) demonstrated non-inferior suppression of HIV replication compared to standard dose EFV (600mg), over 48 weeks. EFV400 was not associated with significant differences in AEs/SAEs compared to EFV600. 400mg EFV can be recommended as part of routine care.
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