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)
** Patients were switched to open-label D/C/F/TAF after unblinding that occurred at various time after W4
Median duration of exposure (weeks) : D/C/F/TAF = 96.1 ; D/C + F/TDF = 73.1 ; D/C/F/TAF deferred switch = 22.3
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
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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
Genotype at screening, %
≥ 1 NNRTI RAM
≥ 1 NRTI RAM ≥ 1 primary PI RAM
15 5 2
17 4 2
Discontinuation by W48, N (%)
For adverse event, N
Lost to follow-up / Withdrew consent, N
Physician decision, N
Non-compliance, N
Death, N
Other reasons, N
27 (7%)
8 / 4
3 2
42 (12%) 16
9 / 9 4 1 3
AMBER
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4. 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 66
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. AIDS 2018 ;32:

5. 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 66
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
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6. 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 66
Virologic outcome at W96 (ITT, snapshot) 85 6 9 84 4 12 20 40 60 80
100
HIV RNA < 50 c/mL
HIV RNA ≥ 50 c/mL
No data %
D/C/F/TAF (N = 362)
D/C + F/TDF D0-W48 then switch
to D/C/F/TDF * (N = 363)
* 295 switched to D/C/F/TAF by W96
Resistance analysis
Virologic failures with paired genotypes (baseline and failure with HIV RNA ≥ 400 c/mL), N = 9/15 [D/C/F/TAF] + 8/19 [Control arm]
1 patient with emergence of M184I/V (D/C/F/TAF) at W36; at baseline: K103N on plasma genotype and minority variant M184V (9%) by ultradeep sequencing
1 patient from control arm, with emergence of M184V after switch to D/C/F/TAF, at W84
AMBER
Eron J. AIDS 2018 ;32:

7. 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
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)
** p = -4 -8
-12 4 8 12 16 20 24 28 32 36 40 44 48
Weeks
* p < * **
Median change from baseline in eGFR (ml/min/1,73 m2), CKD-EPI formula, in the D/C/F/TAF arm
W48
W96
eGFR based on serum creatinine
- 5.5
- 5.6
eGFR base on serum cystatin C
+ 4.0
+ 3.2
AMBER
Eron J. AIDS 2018 ;32:

8. 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
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
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9. 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
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. AIDS 2018 ;32:

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
Median lipid values (mg/dL)
TC:HDL-C
ratio 4 3 2 1 50
100
150
200
250
Total cholesterol
LDL-C
HDL-C
Triglycerides
TC:HDL-C ratio
D/C/F/TAF baseline
D/C + F/TDF baseline
D/C/F/TAF W48
D/C + F/TDF W48
163
196
162
172 96
116 97
101 42 48 44
123 95
112
3.8
4.0
3.9
AMBER
Eron J. AIDS 2018 ;32:

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
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 through W96
AMBER
Eron J. AIDS 2018 ;32:

12. 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 at 96
D/C/F/TAF resulted in high virologic suppression in treatment-naïve patients
At W48: 91.4% (FDA Snapshot) that was non-inferior to DRV/C + F/TDF (88.4%)
At W96: 85% vs 84%
No development of DRV, primary PI or TDF/TAF RAMs
Two patients developed M184I/V (D/C/F/TAF arm)
Few serious adverse events, grade 3/4 adverse events, or adverse events- related discontinuations
Discontinuation for adverse events in D/C/F/TAF arm: 2.5% at W48, 2.8% at W96
No discontinuations due to bone, renal, or CNS adverse events
Stability of eGFR, proteinuria and bone mineral density changes between W48 and W96 in the D/C/F/TAF arm
Grade 3-4 LDL-cholesterol increase in D/C/F/TAF arm: 4.9% at W48, 8.7% at W96
Bone, renal and lipid safety consistent with known profiles of TAF and cobicistat
AMBER
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