1. Switch from TDF to TAF GS-US-292-0109 Study GS-US-311-1089 Study
ARV-trial.com
Switch from TDF to TAF
GS-US Study
GS-US Study 1

2. GS-US-311-1089 Study: Switch TDF to TAF
Design
Randomisation
1 : 1
Double blind
W48
W96
N = 333
F/TAF * + F/TDF placebo + 3rd agent unchanged
HIV+ ≥ 18 years
On F/TDF + 3rd agent
HIV RNA < 50 c/ml > 6 months
eGFR (Cockroft-Gault) > 50 mL/min
F/TDF + F/TAF * placebo + 3rd agent unchanged
N = 330
Randomisation stratified on 3rd agent (boosted PI or other)
* F/TAF: 200/10 mg if boosted PI, 200/25 mg if other
Endpoints
Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (ITT, snapshot) ; non-inferiority if lower margin of a two-sided 95% CI for the difference = -10%, > 95% power
Secondary with multiple adjustments: percentage change in hip and spine bone mineral density
GS-US
Gallant J. Lancet HIV. 2016;3:e158-65, Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31

3. Baseline characteristics and outcome
ARV-trial.com
GS-US Study: Switch TDF to TAF
Baseline characteristics and outcome
F/TAF
N = 333
F/TDF
N = 330
Median age, years 48 49
Female
14%
16%
Race: white / black / other
73% / 21% / 6%
77% / 20% / 3%
CD4/mm3, median
663
624
eGR (Cockroft-Gault), mL/min, median
99.4
100.2
3rd agent: PI/r / other
DRV/r / ATV/r / LPV/r
NVP/ RAL / DTG / other
47% / 53%
25% / 16% / 5%
22% / 20% / 8% / 4%
45% / 55%
25% / 15% / 5%
20% / 22% / 7% / 5%
Discontinuation by W48, N (%)
Adverse event
Investigator decision
Consent withdrawal
Lost to follow-up / Non compliance
Pregnancy / Protocol violation
Discontinuation by W96, N (%)
21 (6%) 7 1 10
1 / 1
1 / 0
36 (11%) 3
1 / 2
0 / 4
39 (12%)
GS-US
Gallant J. Lancet HIV. 2016;3:e158-65, Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31 3

4. Virologic outcome (ITT, snapshot)
GS-US Study: Switch TDF to TAF
Virologic outcome (ITT, snapshot)
W48
W48
F/TAF + 3rd agent (N = 333)
F/TDF + 3rd agent (N = 330)
Difference (95% CI) W48 = 1.3% (-2.5 to 5.1)
W96 = -0.5% (- 5.3 to 4.4)
Success
HIV RNA< 50 c/mL
Virologic failure
No virologic data
W96 %
94.3
0.3
5.4 93
1.5
5.5 20 40 60 80
100
88.6
89.1
2.4
0.6
9.0
10.3
W96
Resistance data
F/TAF (N = 333)
F/TDF
(N = 330)
N tested for resistance *
- D0 to W48
- W48 to W96 2 1
Emergence of resistance
1 (M184V (isolated at W36)
* Confirmed HIV-1 RNA ≥ 50 c/mL at any visit or unconfirmed > 400 c/mL at endpoint or discontinuation
GS-US
Gallant J. Lancet HIV. 2016;3:e158-65, Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31

5. HIV-1 RNA < 50 c/mL at W48 according to 3rd agent, %
GS-US Study: Switch TDF to TAF
HIV-1 RNA < 50 c/mL at W48 according to 3rd agent, %
All
Boosted PI
Other 3rd agent 20 40 60 80
100 94 93 92 97
333
330
155
151
178
179 %
N =
F/TDF
F/TAF
Virologic success was similar between treatment groups for the subgroups of age, sex, race, and study drug adherence
Mean changes in CD4 at W48
+ 20/mm3 F/TAF
+ 21/mm3 F/TDF
GS-US
Gallant J, CROI 2016, Abs. 29, Gallant J. Lancet HIV. 2016;3:e158-65

6. GS-US-311-1089 Study: Switch TDF to TAF
Adverse events, N (%)
F/TAF
N = 333
F/TDF
N = 330
Adverse events related to study drug (D0 to W48)
Leading to discontinuation
Adverse events leading to study discontinuation by W96 9%
N = 2 (0.6%)
N = 8 (2%)
12%
N = 3 (0.9%)
N = 4 (1%)
Serious adverse event (D0 to W48)
18 (5%)
14 (4%)
Serious adverse event related to study drug at W48
1 (< 1%)
Most common adverse events (D0 to W48)
Upper respiratory tract infection
Diarrhea
Headache
Nasopharyngitis
Cough
Bronchitis
Back pain
Arthralgia
Fatigue
Sinusitis
9% 8% 8% 6% 6% 6% 6% 5% 4%
14% 10% 4.5% 6% 5% 5% 5%
3% 4% 7%
Gallant J, CROI 2016, Abs. 29, Gallant J. Lancet HIV. 2016;3:e158-65, Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31
GS-US

7. GS-US-311-1089 Study: Switch TDF to TAF
Discontinuation for adverse event, laboratory abnormalities grade 3-4 (D0-W96)
F/TAF (N = 333)
F/TDF (N = 330)
Discontinuation for adverse event
Insomnia / Mood altered
Dysphagia
Atrial fibrillation
Diarrhea
Peripheral edema
Overdose
Lymphoma
Acquired lipodystrophy/affective disorder
Increased serum creatinine
Rectal tenesmus
Feeling abnormal / Headache
Renal tubular disorder
8 (2.4%) 1
4 (1.2%)
Laboratory abnormalities grade 3-4 ≥ 2 % (no treatment discontinuation), %
LDL
Total bilirubin CK
Total cholesterol
Gamma GT
Glycosuria
Hematuria
AST / ALT
Amylase
Lipase 10 7 5 4 2 3
2 / 2 6
< 1
< 1 / < 1
Gallant J, CROI 2016, Abs. 29, Gallant J. Lancet HIV. 2016;3:e158-65, Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31
GS-US

8. Mean change in bone mineral density through W96 (%, 95% CI)
GS-US Study: Switch TDF to TAF
Mean change in bone mineral density through W96 (%, 95% CI)
Spine
Hip -1 1 2 3 24 48 72 96
Week
2.2
-0.2
p < 0.001
1.7
-0.1 -1 1 2 3 24 48 72 96
Week
1.9
-0.3
p < 0.001
1.2
-0.1
FTC/TAF, N
321
310
300
294
287
321
309
300
293
288
FTC/TDF, N
320
310
306
297
292
317
305
303
296
289
Gallant J, CROI 2016, Abs. 29, Gallant J. Lancet HIV. 2016;3:e158-65, Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31
GS-US

9. Bone mineral density status changes through W48
GS-US Study: Switch TDF to TAF
Bone mineral density status changes through W48
The distribution of the bone mineral density status (normal, osteopenia, osteoporosis) adjusted for baseline status was significantly different between treatment groups at W48
at the hip (p = 0.012)
and at the spine (p = 0.037)
Driven by a higher percentage of subjects in the F/TAF group with an improvement in BMD status (i.e. osteopenia to normal, osteoporosis to normal or osteopenia), and correspondingly, a lower percentage of subjects in the F/TAF with worsening BMD status (i.e. normal to osteopenia or osteoporosis, or osteopenia to osteoporosis) 20 40 60 80
100
Normal
Osteopenia
Osteoporosis
6.2
4.0
5.6
0.9
0.7
1.3
39.5
38.7
34.0
35.0
33.0
30.3
33.8
35.3
54.2
57.3
60.3
59.5
66.0
69.0
65.3
63.4 BL
W48
F/TAF N = 321
F/TDF N = 320
F/TDF N = 317
Patients (%)
Spine
Hip
GS-US
Gallant J. Lancet HIV. 2016;3:e158-65

10. Change in renal biomarkers at W96 Median Change (mL/min)
GS-US Study: Switch TDF to TAF
Change in renal biomarkers at W96
eGFR
Median Change (mL/min)
Urine protein to creatinine ratio (% median change)
* p < 0.001
- 26.0
3.4
- 4.1
- 29.7
2.7
27.0
42.6
46.8
-30
-20
-10 10 20 30
P/Cr
Alb/Cr
RBP/Cr
b2MG/Cr
Cr: creatininuria * 40 50
F/TAF
F/TDF *
10.0
4.0
Discontinuation for renal adverse event
F/TAF = 0
F/TDF = 2 (creatinine increase = 1, renal tubular disorder = 1)
GS-US
Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31

11. GS-US-311-1089 Study: Switch TDF to TAF
Safety by 3rd Agent
Boosted PI
Other 3rd Agent
FTC/TAF
N = 155
FTC/TDF
N = 151
N = 178
N = 179
Renal safety (Changes at W96)
eGFR (mL/min)
+ 9.3
+ 4.2
+ 10.6
+ 3.3
Urine protein/Cr (%)
- 27.2
- 1.8
-25.6
+ 7.8
Urine albumin/Cr (%)
- 1.3
+ 21.7
+ 5.0
+ 29.2
Urine RBP/Cr (%)
- 5.5
+ 36.5
- 2.0
+ 49.9
Urine β2MG/Cr (%)
- 28.2
+ 41.8
- 31.9
+ 51.5
Bone safety (Changes at W96)
Spine BMD (%)
+ 2.03
- 0.49
+ 2.26
+ 0.10
Hip BMD (%)
+ 1.82
- 0.28
+ 1.88
- 0.38
GS-US
Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31

12. Median fasting lipids W48 versus baseline (mg/dL)
GS-US Study: Switch TDF to TAF
Median fasting lipids W48 versus baseline (mg/dL)
F/TAF
F/TDF
Week 48
Baseline
TC: HDL Ratio
p = 0.094
3.7
3.6 1 2 3 4
Total Cholesterol
LDL
HDL
Triglycerides
p = 0.073
128
118
112
110
p = 0.02 51 49 50
p < 0.001
125
114
201
187
183
182
100
150
200
250
F/TAF
F/TDF
Patients initiating lipid-lowering agents 4%
GS-US
Gallant J. Lancet HIV. 2016;3:e158-65

13. GS-US-311-1089 Study: Switch TDF to TAF
ARV-trial.com
GS-US Study: Switch TDF to TAF
Conclusion
In this randomised double-blind study, switch of patients on F/TDF + 3rd agent with suppressed viral load for F/TAF + continuation of 3rd agent
Is non-inferior at W48 and W96 for maintaining virologic suppression (HIV-1 RNA < 50 c/mL)
in rare cases of virologic failure, the risk of resistance emergence is low (1 case of M184V on F/TAF), none after W48
Is associated with a similar clinical and biological tolerance
Leads to improvement of renal parameters: increase in eGFR and decrease in proteinuria, no renal discontinuations or renal tubulopathy in F/TAF group
Improves bone mineral density: increase on F/TAF with significant difference of changes at W48 vs F/TDF and continuing increase in hip and spine BMD after W48
Increases lipid parameters, with no change in the total cholesterol total: HDL-cholesterol ratio
Similar safety findings by 3rd agent
GS-US
Gallant J. Lancet HIV. 2016;3:e158-65; Raffi F. J Acquir Immune Defic Syndr. 2017;75:226-31 13