1. ARV-trial.com
Switch to E/C/F/TAF
GS-US Study 1

2. GS-US-292-0112 Study: Switch to E/C/F/TAF in patients with renal impairment
Design
Open-label
W24
W96
HIV+ ≥ 18 years
Undetectable HIV-1 RNA ≥ 6 months
HIV-1 RNA < 50 c/mL at screening
Estimated creatinine clearance
(Cockroft-Gault) mL/min,
stable in past 3 months
CD4 ≥ 50/mm3
No resistance to EVG, TDF or FTC
No HBV or HCV co-infection
N = 242
Switch to E/C/F/TAF
Co-formulated EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg (E/C/F/TAF) qd with food
Endpoints
Primary: change from baseline at W24 in estimated glomerular filtration rate by various formulas: Cockroft-Gault, CKD-EPI-cystatin C, CKD-EPI-creatinine
Secondary: eGFR at W48 and W96, measured GFR, renal and bone biomarkers, hip and spine BMD (DXA), adverse events, virologic control
GS-US
Pozniak A. JAIDS 2016;71:530-7

3. Baseline characteristics
ARV-trial.com
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Baseline characteristics
Baseline eGFR
< 50 mL/min
N = 80
≥ 50 mL/min
N = 162
Median age, years 59 58
Female
26%
18%
Race : black
19%
HIV-1 RNA < 50 c/mL
98%
CD4 cell count (/mm3), median
622
635
eGFR, median
Cockroft-Gault, mL/min
CKD-EPI, creatinine, mL/min/1.73 m2
CKD-EPI, cystatin C, mL/min/1.73 m2 43 45 57 60 77
Dipstick proteinuria : grade 1 or 2
44%
27%
Urine protein:creatinine (UPCR) ≥ 200 mg/g
56%
35%
Urine albumin:creatinine (UACR) ≥ 30 mg/g
64%
42%
Pre-switch TDF use
58%
69%
Hypertension
50%
34%
Diabetes
15%
13%
GS-US
Pozniak A. JAIDS 2016;71:530-7 3

4. Estimated GFR (mL/min): Median change from Baseline to Week 24
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Estimated GFR (mL/min): Median change from Baseline to Week 24
eGFRCG mL/min
eGFRCKD-EPI Cr mL/min/1.73m2
eGFRCKD-EPI cys C mL/min/1.73m2
< 50 mL/min
≥ 50 mL/min
Total
-0.4
+1.2
- 0.9
-1.8
+ 0.3
-2.2
+3.8 - 5
No clinically appreciable change in estimated creatinine clearance
In 32 patients, GFR was measured by iohexol clearance: actual GFR was not affected over 24 weeks of treatment for the whole group, subgroups with baseline eGFRCG < 50 vs ≥ 50, or with or without TDF prior to switch
GS-US
Pozniak A. JAIDS 2016;71:530-7

5. Proteinuria: median value (mg/g) at baseline and W48
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Proteinuria: median value (mg/g) at baseline and W48
Total*
TDF*
Non-TDF†
Baseline
Week 48
3 477
1 563
200
189
1 600
1 525
161
160
1 200
109
120
801
800
105 80 85 78
399 41
400 40 29
228 18
197
214
207
221 10 10 14
166
151
UPCR
UACR
RBP:Cr
b-2-m:Cr
Tubular Proteins
*All Total and TDF changes statistically significant; †all non-TDF changes not statistically significant.
GS-US
Pozniak A. JAIDS 2016;71:530-7

6. Clinically significant proteinuria and albuminuria: baseline and W48
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Clinically significant proteinuria and albuminuria: baseline and W48
Proteinuria (UPCR)
Albuminuria (UACR) BL
W48 BL
W48 BL
W48 BL
W48 BL
W48 BL
W48
Total
eGFR
< 50 mL/min
eGFR
≥ 50 mL/min
Total
eGFR
< 50 mL/min
eGFR
≥ 50 mL/min
GS-US
Pozniak A. JAIDS 2016;71:530-7

7. BMD: mean change (%, SD) from baseline to W48
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
BMD: mean change (%, SD) from baseline to W48
TDF
Non-TDF
Total
Spine
Hip 4 4
2.95*
2.29* 2 2
1.85*
1.47*
0.99
0.70 -2 -2
Baseline N = 236
W24 N = 226
W48 N = 214
Baseline N = 236
W24 N = 225
W48 N = 216
Spine
Hip
*p < 0.05 by two-sided
Wilcoxon signed-rank test
6 %
4 %
BMD change at week 48
37 %
> 3 % gain
37 %
Gain or loss < 3 %
59 %
> 3 % loss
72 %
GS-US
Pozniak A. JAIDS 2016;71:530-7

8. ARV-trial.com
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Adverse events
Most common adverse events
Diarrhea 11%
Upper respiratory tract infection 9%
Arthralgia 9%
Bronchitis 8%
Osteopenia 8%
Nausea 8%
Headache 7%
Pain in extremity 7%
Back pain 7%
Dizziness 6%
Fatigue 6%
Renal cyst 6%
Cough 6%
Adverse events leading to study drug discontinuation, N = 8 (3%), 2/8 for decreased GFR (both patients with hypertension)
Fractures, N = 6, all related to mechanical trauma
GS-US
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9. ARV-trial.com
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Fasting lipid changes
Decrease in patients who used non-TDF-containing regimens prior to switching to E/C/F/TAF
Increase in those using TDF-containing regimens prior to E/C/F/TAF
Pharmacokinetics
EVG and COBI: in the range of historical data in patients without renal impairment
FTC: higher than historical data in patients without renal impairment, higher in patients with eGFR < 50 mL/min vs ≥ 50 mL/min
TAF: consistent with historical data in patients without renal impairment
TFV: higher than historical data in patients without renal impairment, but well below the TFV exposures from TDF-containing regimens
Efficacy at W48
HIV-1 RNA < 50 c/mL: 92%
Virologic failure: 1% (N = 3)
GS-US
Pozniak A. JAIDS 2016;71:530-7 9

10. ARV-trial.com
GS-US Study: Switch to E/C/F/TAF in patients with renal impairment
Conclusion
In virologically suppressed HIV-infected subjects with renal impairment, switch to E/C/F/TAF was associated with minimal change in eGFR
Proteinuria and albuminuria significantly improved
Bone mineral density significantly improved in patients receiving TDF-containing regimens prior to switching to E/C/F/TAF
Virologic success was maintained in 92% of patients
These data support the efficacy and safety of once daily E/C/F/TAF in HIV-1 infected patients with mild (eGFR mL/min) or moderate (eGFR mL/min) renal impairment without dose adjustment
GS-US
Pozniak A. JAIDS 2016;71:530-7 10