1. Switch to D/C/F/TAF
EMERALD Study

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 ≥ 6 months
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 by 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 adjusted difference = - 4%, 89% power
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
Orkin C. Lancet HIV. 2018; 5 :e23-34.; Eron J, IDWeek 2018, Abs. 1768

3. EMERALD Study: Switch to D/C/F/TAF
Baseline characteristics and patient disposition
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 exposure to ≥ 5 ARV, % 59 57
Prior virologic failure, %
15.2
14.1
eGR (Cockroft-Gault), mL/min, median
104.2
103.3
Boosted PI at screening, %
DRV / ATV / LPV COBI
70.8 / 21.5 /
70.4 / 21.7 /
Discontinuation by W48, N (%)
For adverse event, N
Withdrew consent, N
Lost to follow-up, N
Non-compliant, N
Other reasons, N
34 (4.5) 11 10 5 2 6
20 (5.3) 8 3
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34.

4. EMERALD Study: Switch to D/C/F/TAF
Cumulative confirmed virologic rebound (HIV RNA ≥ 50 c/mL) through W48
Virologic response at W48
(HIV RNA < 50 c/mL), ITT snapshot
Difference : 0.4%
(95% CI : to 2.2)
2.5
2.1 20 40 60 80
100 %
D/C/F/TAF (N = 763)
Continuation PI (N = 378)
94.9
0.8
4.3
93.7
0.5
5.8
HIV RNA < 50 c/mL
HIV RNA ≥ 50 c/mL
No virologic data 20 40 60 80
100
Difference : 1.2%
(95 % CI : to 4.1) %
4 patients with virologic rebound genotyped: 1 in D/C/F/TAF (presence of D67D/N) and 3 in continuation group (E138E/G NNRTI mutation in 1)
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34

5. No previous ARV failure
EMERALD Study: Switch to D/C/F/TAF
Virologic rebound rate through W48 according to previous antiretroviral failure
Difference: 0%
(95% CI: to 2.0)
2.5 20 40 60 80
100 %
D/C/F/TAF (N = 647)
Continuation PI (N = 325)
No previous ARV failure
≥ 1 previous ARV failure
Difference: 2.6%
(95% CI: to 7.5)
2.6 20 40 60 80
100 %
D/C/F/TAF (N = 116)
Continuation PI (N = 53)
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34.

6. Confirmed virologic rebound (HIV RNA ≥ 50 c/mL)
EMERALD Study: Switch to D/C/F/TAF
Confirmed virologic rebound (HIV RNA ≥ 50 c/mL)
HIV RNA < 50 c/mL at W96,
ITT snapshot
D/C/F/TAF immediate switch D0-W48 (N = 763)
D/C/F/TAF immediate switch D0-W96 (N = 763)
3.1
2.5 20 40 60 80
100 %
90.7
94.9 20 40 60 80
100 %
Most rebounders (14/24 D/C/F/TAF immediate switch and 2/8 deferrred switch) resuppressed to HIV RNA < 50 c/mL by W96, without treatment change
Genotype performed if virologic rebound ≥ 400 c/mL (4 D/C/F/TAF immediate switch and 5 deferred switch): no emergence resistance to NRTI or PI
Eron J, IDWeek 2018, Abs. 1768

7. Mean (SE) % change from baseline in bone mineral density (g/cm2)
EMERALD Study: Switch to D/C/F/TAF
Mean (SE) % change from baseline in bone mineral density (g/cm2)
D/C/F/TAF
Continuation PI
Hip
Lumbar spine 24 48 -1 1 2
204
104
184
193
188 97
Weeks
D/C/F/TAF
Continuation PI
p <
No of participants
1.43 (2.34)
(2.00) 24 48 -1 1 2
206
107
192 97
101
Weeks
D/C/F/TAF
Continuation PI
p <
No of participants
1.49 (3.34)
(2.86)
Hip BMD change at W48
D/C/F/TAF
Continuation PI
 ≥ 3%
20.2
4.1
 ≥ 5%
4.8
1.0
 ≥ 3%
2.1
8.2
 ≥ 5%
Lumbar BMD change at W48
D/C/F/TAF
Continuation PI
 ≥ 3%
31.8
8.9
 ≥ 5%
15.1
1.0
 ≥ 3%
7.8
19.8
 ≥ 5%
1.6
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34

8. Mean (SE) % change from baseline in bone biomarkers
EMERALD Study: Switch to D/C/F/TAF
Mean (SE) % change from baseline in bone biomarkers
-20
Weeks 2 4 12 24 48
-10 5
p <
-30
N = 191
N = 98
Procollagen type N-terminal
propeptide
-20
Weeks 2 4 12 24 48
-15
-10 -5 5
p <
N = 193
N = 103
Alkaline phosphatase
-20
Weeks 2 4 12 24 48
-10
p <
p = 10 20
N = 185
N = 98
C-type collagen sequence
Parathyroid hormone
Weeks 24 48
-10 -5 5
p =
p = 10 15 20
N = 186
N = 96
25-hydroxy vitamin D
Weeks 24 48
-10 -5
p = 0.074
p = 0.495 10 20 30
N = 154
N = 76
D/C/F/TAF
Continuation PI
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34.

9. EMERALD Study: Switch to D/C/F/TAF
Median lipid values
TC:HDL-C
ratio
D/C/F/TAF baseline
Continuation PI baseline
D/C/F/TAF W48
Continuation PI W48
mg/dL
mmol/L 50
100
150
200
1.3
2.6
3.9
5.2
184
205 *
181
186
107
123 *
103
106 47
50 * 48
123
129
128
3.8
4 **
3.9 ** 1 2 3 4
* p < W48 vs baseline ; **p < D/C/F/TAF vs continuation PI
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34

10. Mean Changes in eGFR (mL/min/1.73 m2) at W48 Between-group comparison
EMERALD Study: Switch to D/C/F/TAF
Mean Changes in eGFR (mL/min/1.73 m2) at W48
D/C/F/TAF
Continuation PI
Between-group comparison p
eGFRcyst
- 0.4 ± 9.6
- 1.9 ± 10.7
0.034
eGFR cr
- 1.9
- 0.9
0.092
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34

11. Adverse events between D0 and W48, %
EMERALD Study: Switch to D/C/F/TAF
Adverse events between D0 and W48, %
D/C/F/TAF
(N = 763)
PI/r or PI/C + F/TDF
(N = 378)
Grade 3-4 adverse event 7 8
Serious adverse event 5
Discontinuation for adverse event
Due to renal event
1.4% (N = 11)
0.1% (N = 1 *)
1.3% (N = 5)
0.5% (N = 2 **)
Adverse event in ≥ 5% of either group
Naso-pharyngitis
Upper respiratory tract infection
Diarrhea
Headache
Back pain
Vitamin D deficiency
Osteopenia 11
Grade 3-4 laboratory abnormalities
LDL-cholesterol ≥ 4,9 mmol/L
Total-cholesterol ≥ 7.77 mmol/L
Phosphate < 0,65 mmol/L
Total bilirubin ≥ 2,6 x ULN
7 4 3 < 1
* Worsening of pre-existing renal insufficiency ; ** Toxic nephropathy, N = 1 ; tubulopathy, N = 1
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34

12. EMERALD Study: Switch to D/C/F/TAF
Adverse events, D0-W96(%)
D/C/F/TAF
(N = 763)
PI/b + F/TDF
(N = 378)
(N = 352)
D0-W48
D0-W96
D0-W52
W52-W96
Grade 3-4 adverse events
7.1
12.8
8.2
7.4
Serious adverse events
4.6
8.7
4.8
6.0
Discontinuation for adverse event
1.6
2.2
1.3
2.0
Deaths
0.4 *
* 1 metastatic pancreas cancer and 2 myocardial infarction
Eron J, IDWeek 2018, Abs. 1768

13. Changes in renal, lipid and bone parameters at W96 (%)
EMERALD Study: Switch to D/C/F/TAF
Changes in renal, lipid and bone parameters at W96 (%)
D/C/F/TAF
(N = 763)
PI/b + F/TDF
(N = 378)
(N = 352)
D0-W96
D0-W52
W52-W96
Median change in eGDRCKD-EPI, mL/min/1,73 m2
UPCR
UACR
RBP:CR
B2M:CR
- 1.3
- 0.63
- 0.6
- 7.37
0.40
- 0.7
- 0.93
Median change in lipids, mg/dL
Total cholesterol
LDL-cholesterol
HDL-cholesterol
Triglycerides
Total cholesterol/HDL-cholesterol ratio
+ 22.0
+ 7.0
+ 0.2
+ 1.3
+ 1.9
+ 4.9
+ 0.1
+ 8.0
Mean % change in BMD
Lumbar spine
Total hip
Femoral neck
+ 1.99
+ 1.86
+ 1.40
- 0.27
- 0.51
+ 2.91
+ 1.22
+ 0.98
Eron J, IDWeek 2018, Abs. 1768

14. EMERALD Study: Switch to D/C/F/TAF
Conclusion
Through Week 96, switching from boosted PI + FTC/TDF to D/C/F/TAF resulted in:
Low virologic rebound rate cumulative (2.5% at W48, 3.1 % at W96)
High virologic suppression rate (94.9% at W48, 91% at W96)
Virologic non-response rate of 1%
No resistance to any study drug
Few serious adverse events and discontinuations due to adverse events (2%)
D/C/F/TAF bone, renal and lipid safety were consistent with known profiles of TAF and cobicistat
EMERALD
Orkin C. Lancet HIV. 2018; 5 :e23-34; Eron J, IDWeek 2018, Abs. 1768