1. Comparison of NRTI combinations
ARV-trial.com
Comparison of NRTI combinations
ZDV/3TC vs TDF + FTC
Study 934
ABC/3TC vs TDF/FTC
HEAT Study
ACTG A5202 Study
ASSERT Study
FTC/TDF vs FTC/TAF
Studies GS-US and GS-US
AMBER Study

2. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
ARV-trial.com
AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Design
Randomisation*
1:1
Double-blind
W48
W96
N = 362
D/C/F/TAF QD
D/C + F/TDF placebo
HIV+ Adults
ARV-naïve
HIV RNA > c/mL
CD4 cell count > 50/mm3
eGFR > 50 mL/min
D/C/F/TAF QD
N = 363
D/C + F/TDF QD
D/C/F/TAF placebo
D/C/F/TAF QD
* Randomisation was stratified by HIV RNA (< or ≥ c/mL) and CD4 cell count (< or ≥ 200/mm3)
Objective
Non inferiority of E/C/F/TAF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 95% CI for the difference = -10%)
AMBER
Eron J, EACS 2017, Abs. PS8/2

3. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
ARV-trial.com
AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Baseline characteristics and patient disposition
D/C/F/TAF
N = 362
D/C + F/TDF
N = 363
Median age, years 34
Female, %
12.2
11.3
HIV RNA (log10 c/mL), median
4.4
4.6
HIV RNA > c/mL, %
16.6
19.3
CD4 cell count (/mm3), median
461.5
440
CD4 < 200 per mm3, %
6.1 8
eGFR (Cockroft-Gault), mL/min, median
119
118
Discontinuation by W48, N (%)
23 (6.4)
28 (7.7)
For adverse event, N 15
Lost to follow-up / Withdrew consent, N
5 / 4
5 / 6
Physician decision 3
Non-compliance, N 1
Death, N
1 (follow-up phase)
Other reasons, N 2
AMBER
Eron J, EACS 2017, Abs. PS8/2

4. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD66
Virologic outcome at W48 (ITT, snapshot)
D/C/F/TAF (N = 362)
D/C + F/TDF (N = 363)
91.4
4.4
4.1
88.4
3.3
8.3 20 40 60 80
100
HIV RNA
< 50 c/mL
≥ 50 c/mL
No data %
- 1.6
Adjusted difference, % (95% CI)
Favours D/C/F/TAF
Favours D/C + F/TDF
Resistance analysis
Virologic failures with paired genotypes (baseline and failure with HIV RNA ≥ 400 c/mL), N = 9 [7 D/C/F/TAF + 2 D/C + F + TDF]: 1 patient with emergence of M184I/V (D/C/F/TAF)
AMBER
Eron J, EACS 2017, Abs. PS8/2

5. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD66
Virologic outcome at W48 by baseline strata (ITT, snapshot)
D/C/F/TAF (N = 362)
D/C + F/TDF (N = 363)
91.7
90.4 20 40 60 80
100
CD4 ≥ 200/mm3 %
92.6
88.6
72.7
86.2
CD4 < 200/mm3
HIV RNA
≤ c/mL
> c/mL
89.8
80.0 N
303
293
340 59 70
334 22 29
Difference (95% CI)
1.3 (-3.4 to 6.1)
9.8 (- 3.3 to 22.5)
4 (- 0.4 to 8.6)
( to 9.6)
AMBER
Eron J, EACS 2017, Abs. PS8/2

6. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Mean (SE) change from baseline in eGFR (mL/min/1.73m2)
based on serum creatinine and CKD-EPI formula
based on serum cystatin and CKD-EPI formula
D/C/F/TAF (N = 340)
D/C + F/TDF (N = 330)
D/C/F/TAF (N = 337)
D/C + F/TDF (N = 329) 4 8 12 16 20 24 28 32 36 40 44 48
Weeks ** -4 -8
-12 -4 -8
-12 4 8 12 16 20 24 28 32 36 40 44 48
Weeks
* p < *
** p =
AMBER
Eron J, EACS 2017, Abs. PS8/2

7. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Mean (SE) changes (mg/g) in proteinuria at W48
D/C/F/TAF
Urinary protein: creatinine
D/C + F/TDF
Urinary albumin: creatinine BL
66.23 (3.66)
77.67 (6.51) BL
11.38 (1.57)
17.92 (5.07) 10
p = 0.033
-22.42
-10.34
-40
-30
-20
-10
p = 0.003
-2.45
-0.58 5 -5
-10
-25
Retinol binding protein: creatinine
β-2-microglobulin: creatinine
p <
401.12
16.84
200
400
600
p <
837.63
1 500
500
-500 BL
(7.12)
(74.66) BL
(40.36)
(176.11)
AMBER
Eron J, EACS 2017, Abs. PS8/2

8. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Mean (SE) % changes in bone mineral density at W48
Spine
Hip
D/C/F/TAF (N = 96)
D/C + F/TDF (N = 85)
D/C/F/TAF (N = 96)
D/C + F/TDF (N = 85)
p <
p = 0.00* 1 2 -1 -2 -3 -4
-1.3
-3.4
Weeks 24 48
p <
0.3
-1.7
-2.7
0.2 1 2 -1 -2 -3 -4
Weeks 24 48
D/C/F/TAF
D/C + F/TDF
≥ 3% decrease
27.1%
41.2%
12.5%
44.7%
≥ 3% increase
4.7%
2.4%
AMBER
Eron J, EACS 2017, Abs. PS8/2

9. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Median lipid values (mg/dL)
TC:HDL-C
ratio
D/C/F/TAF baseline
D/C + F/TDF baseline
D/C/F/TAF W48
D/C + F/TDF W48
250
196
4.0
3.9
200
3.8
3.8 4
172
163
162
150 3
123
116
112 97
101 96 97 95
100 2 48 42 42 44 50 1
Total cholesterol
LDL-C
HDL-C
Triglycerides
TC:HDL-C ratio
AMBER
Eron J, EACS 2017, Abs. PS8/2

10. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
ARV-trial.com
AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Adverse events through W48, %
D/C/F/TAF
N = 362
D/C + F/TDF
N = 363
Grade 3-4 adverse event
5.2
6.1
Serious adverse event
4.7
5.8
Discontinuation due to adverse event
1.9 *
4.4 **
Death
Adverse event possibly related to study drug
Diarrhea
Rash
Nausea
34.8
41.6
Diarrhea, any grade
19.6
18.2
* rash (N = 6); diarrhea (N = 1)
** rash/erythema (N = 7), diarrhea (N = 1), toxic skin eruption (N = 2), Stevens Johnson syndrome (N = 1),
bone marrow oedema (N = 1), increased beta-2 macroglobulin (N = 1), arthralgia (N = 1), neoplasm (N = 2)
No grade 3 or 4 laboratory abnormalities in ≥ 5% of patients in either arm
No discontinuation of D/C/F/TAF for bone, renal or CNS adverse event
AMBER
Eron J, EACS 2017, Abs. PS8/2

11. AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
ARV-trial.com
AMBER Study: D/C/F/TAF QD vs D/C + F/TDF QD
Conclusion
Through Week 48, D/C/F/TAF resulted in high virologic suppression in treatment-naïve patients (91.4% ; FDA Snapshot) that was non-inferior to DRV/C + F/TDF (88.4%)
No development of DRV, primary PI or TDF/TAF RAMs
One patient developed M184I/V (D/C/F/TAF arm)
Few serious adverse events, grade 3/4 adverse events, or adverse events- related discontinuations
No discontinuations due to bone, renal, or CNS adverse events
Bone, renal and lipid safety consistent with known profiles of TAF and cobicistat
AMBER
Eron J, EACS 2017, Abs. PS8/2 11