1. ARV-trial.com
Switch to D/C/F/TAF
EMERALD Study 1

2. EMERALD Study: Switch to D/C/F/TAF
Design
Randomisation *
2 : 1
Open label
W48
W96
HIV+ ≥ 18 years
On F/TDF + PI/r or/c
Absence of history of virologic failure
on DRV (previous VF allowed)
Absence of DRV RAM (if historical
genotype available)
HIV RNA < 50 c/mL ≥ 2 months
(1 blip c/mL within
past 12 months allowed)
eGFR (Cockroft-Gault) ≥ 50 mL/min
N = 763
D/C/F/TAF QD
D/C/F/TAF
Continuation
PI/r or /C + F/TDF
D/C/F/TAF
N = 378
* Randomisation stratified on boosted PI
Primary endpoint
Proportion of patients with virologic rebound at W48 ; non-inferiority if lower margin of a two-sided 95% CI for the difference = - 4%
Virologic rebound: confirmed HIV RNA ≥ 50 c/mL (or single HIV RNA > 50 c/mL at W48), or premature discontinuation, irrespective of reason, with last HIV RNA ≥ 50 c/mL through W48
EMERALD
Molina JM. IAS 2017, Abs. TUAB0101

3. Baseline characteristics Continuation PI/r or/C + F/TDF
ARV-trial.com
EMERALD Study: Switch to D/C/F/TAF
Baseline characteristics
D/C/F/TAF
N = 763
Continuation PI/r or/C + F/TDF
N = 378
Median age, years 46 45
Female, %
18.3
17.2
Race: white / black / other, %
75 / 20 / 5
75 / 22 / 4
CD4/mm3, median
630
624
On first ARV regimen, %
41.6
42.6
Prior virologic failure, %
15.2
14.1
eGR (Cockroft-Gault), mL/min, mean
107.5
107.0
Boosted PI at screening, %
DRV ATV
LPV COBI
EMERALD
Molina JM. IAS 2017, Abs. TUAB0101 3

4. EMERALD Study: Switch to D/C/F/TAF
Cumulative confirmed virologic rebound (HIV RNA ≥ 50 c/mL) through W24
Virologic response at W24
(HIV RNA < 50 c/mL), ITT snapshot
Difference : - 0.3%
(95% CI : to 1.5)
1.8
2.1 20 40 60 80
100 %
D/C/F/TAF (N = 763)
Continuation PI (N = 378)
96.3
0.5
3.1
95.5
0.8
3.7
Success
Virologic
failure
No virologic
data 20 40 60 80
100
Difference : 0.8%
(95 % CI : to 3.3) %
Most rebounders (10/14 D/C/F/TAF and 5/8 continuation PI) resuppressed (HIV RNA < 50 c/mL) at W24 without change in therapy
No confirmed rebound ≥ 200 c/ml, no resistance mutation emergence (2 patients genotyped in each group)
EMERALD
Molina JM. IAS 2017, Abs. TUAB0101

5. Mean (SE) % change in bone mineral density at W24
EMERALD Study: Switch to D/C/F/TAF
Mean (SE) % change in bone mineral density at W24
D/C/F/TAF (N = 209)
Continuation PI (N = 108)
p < 0.001
0.6
0.3 -1 1 2
1.1
Hip
Spine
p-values for the difference between the groups in changes from baseline, controlling for bPI at screening
EMERALD
Molina JM. IAS 2017, Abs. TUAB0101

6. Adverse events between D0 and W24, %
EMERALD Study: Switch to D/C/F/TAF
Essai EMERALD : switch pour D/C/F/TAF Résultats à S24 (5)
Adverse events between D0 and W24, %
D/C/F/TAF
(N = 763)
PI/r or PI/C + F/TDF
(N = 378)
Grade 3-4 adverse event
1.2
0.5
Serious adverse event
2.5
3.2
Discontinuation for adverse event
Due to renal event
1.3% (N = 10)
0.1% (N = 1 *)
1.1% (N = 4)
0.5% (N = 2 **)
Adverse event in ≥ 5% of both arms
Naso-pharyngitis
Upper respiratory tract infection
Vitamin D deficiency
7.6
6.3
5.5
6,6
6,3
5,0
Grade 3-4 laboratory abnormalities
Creatinine clearance < 60 mL/min
LDL-cholesterol ≥ 4,9 mmol/L
Phosphate < 0,65 mmol/L
Creatine kinase ≥ 10 x ULN
Total bilirubin ≥ 2,6 x ULN
2.0
1.3
0.1
4.0
2.1
4.3
* Worsening of pre-existing renal insufficiency
** Toxic nephropathy, N = 1 ; tubulopathy, N = 1
EMERALD
Molina JM. IAS 2017, Abs. TUAB0101

7. EMERALD Study: Switch to D/C/F/TAF
ARV-trial.com
EMERALD Study: Switch to D/C/F/TAF
Conclusion
Through Week 24, switching from boosted PI + FTC/TDF to D/C/F/TAF resulted in:
Low virologic rebound rate cumulative (1.8%)
High virologic suppression rate (96.3%)
No discontinuations for VF
No resistance to any study drug
Few serious adverse events and discontinuations due to adverse events
D/C/F/TAF bone, renal and lipid safety vs control were consistent with known profiles of TAF and cobicistat
EMERALD
Molina JM. IAS 2017, Abs. TUAB0101 7