AMBER and EMERALD Trial: 96-week Resistance Analysis of Once-daily Single Tablet Regimen of D/C/F/TAF in HIV-1 Adults Patients

16 Jun, 21

Introduction

AMBER and EMERALD are two Phase 3, multicentre, randomized, active-controlled non-inferiority trials

Aim

To analyse the baseline resistance and post-baseline resistance data in all patients with week 96 protocol-defined virologic failure (PDVF) and PDVR in AMBER and EMERALD study respectively.

Patient Profile

AMBER Study: ART-naïve adults with screening plasma VL ≥1000 copies/mL, CD4+ count >50 cells/mm³ and HIV-1 with genotypic sensitivity to darunavir, emtricitabine and tenofovir.

EMERALD Study: ART-experienced adults who were virologically suppressed (VL 50 copies/ml for ≥2 months before screening) while on a stable bPI plus F/TDF regimen for ≥6 months

Methods

bPI=boosted protease inhibitor

· Protocol-defined virologic failure (PDVF): PDVF was defined as:

o virologic nonresponse (VL <1 log₁₀ reduction from baseline and ≥50 copies/mL at week 8, confirmed at next visit) or

o virologic rebound (confirmed VL ≥50 copies/mL after confirmed, consecutive VL <50 copies/mL or confirmed VL >1 log₁₀ increase from the nadir) and/or viremia at the final time point (VL ≥400 copies/mL at study endpoint or study discontinuation after week 8)

· Protocol-defined virologic rebound (PDFVR) defined as cumulative confirmed VL ≥50 copies/mL or premature discontinuation with last VL ≥50 copies/mL) and VL ≥400 copies/mL at failure (confirmed or unconfirmed), or at later time points, including patients who discontinued with a last single VL ≥400 copies/mL

Results

· No resistance mutations related to the study drugs were observed

· No darunavir, primary protease inhibitor or tenofovir resistance-associated-mutations (RAMs) occurred post-baseline in 1,125 patients continuing the once-daily, STR (D/C/F/TAF) or in 715 patients switching to D/C/F/TAF

Figure 1: AMBER Study: Post-baseline resistance through week 96 evaluated in patients with PDVF

· The emtricitabine RAM, M184I/V, was detected in only one patient in each arm of AMBER.

Figure 2: EMRALD Study: Post-baseline resistance through week 96 evaluated in patients with PDVF

· PDVR mainly consisted of low-level and transient viremia

o four patients in the D/C/F/TAF arm and two in the control arm with confirmed rebound ≥200 copies/mL through 96 weeks

· Patients with prior virologic failure and baseline genoarchive data who received D/C/F/TAF, baseline archived darunavir, emtricitabine and tenofovir RAMs, including those with predicted antiretroviral resistance, did not preclude virologic response.

Conclusion

· High virologic response and low virologic failure rates were observed with the D/C/F/TAF once-daily STR through Week 96

· D/C/F/TAF provides a convenient treatment option by combining the efficacy and high barrier to resistance of darunavir with the safety advantages of TAF, all in a single-tablet regimen for ART-naïve and -experienced adults living with HIV-1, even in those with virus harbouring archived resistance to study drugs at baseline.

Reference

J Med Virol.2021;93;6:3985-3990