1. Switch ABC/3TC to TAF/FTC
ARV-trial.com
Switch ABC/3TC to TAF/FTC
GS-US-1717 Study 1

2. GS-US-1717 Study: Switch ABC/3TC to TAF/FTC
Randomisation
1 : 1
Double-blind
Design
W48
W96
TAF/FTC * + continuation 3rd agent
+ ABC/3TC placebo
HIV+ adults
On ABC/3TC + 3rd agent ≥ 6 months
HIV-1 RNA < 50 c/mL ≥ 6 months
Any CD4 Creatinine clearance ≥ 50 mL/min
N = 280
ABC/3TC + continuation 3rd agent
+ TAF/FTC placebo
N = 276
* TAF/FTC : 100/200 mg when coadministered with ATV boosted, DRV boosted or LPV/r ; 25/200 mg when co-administered with NNRTI, RAL, DTG or MVC
Objective
Primary endpoint: non-inferiority of TAF/FTC at W48: % HIV-1 RNA < 50 c/mL by ITT, snapshot analysis ; lower limit of the 95% CI for the difference = - 10%, 90% power
GS-US-1717
Winston A, Lancet HIV.2018 ; 5:e162-71

3. GS-US-1717 Study: Switch ABC/3TC to TAF/FTC
Baseline characteristics and patient disposition
TAF/FTC
N = 280
ABC/3TC
N = 276
Median age, years 52
Female, % 14 22
Race : white / black, %
73 / 23
72 / 24
CD4/mm3, median
654
700
Median duration on ABC/3TC, years 8
Third agent, %
NNRTI
Boosted PI
INI 51 30 19
53 30 16
Discontinuation by W48, N (%)
For lack of efficacy, N
For adverse event, N
Withdrew consent / Lost to follow-up, N
Investigator decision, N
Non compliance / Protocol violation, N
Death, N
31 (11) 1 12
10 / 3 3
1 / 0
18 (7) 9
6 / 0
0 / 2
GS-US-1717
Winston A, Lancet HIV.2018 ; 5:e162-71

4. GS-US-1717 Study: Switch ABC/3TC to TAF/FTC88
Efficacy at W48 (ITT, snapshot)
Per protocol analysis
TAF/FTC (N = 253)
ABC/3TC (N = 248)
HIV RNA < 50 c/mL at W48
TAF/FTC : 99.1%
ABC/3TC : 99.1%
Difference : 0.0% (95% CI: -2.5 to 2.3)
Difference (95% CI) :
0.8% (- 1.5 to 3.3)
HIV RNA
< 50 c/mL
> 50 c/mL
No virologic data 2 1 9 6 93 90 20 40 60 80
100
Difference : - 3.0%
(95%CI : to 2.0) %
Emergence of resistance, N
TAF/FTC
ABC/3TC
Genotype at virologic failure * 4 1
Emergence of resistance
NRTI : K65K/R
PI : M46I + I50L + N88S
1 0
* Confirmed HIV RNA > 50 c/mL or unconfirmed > 400 c/mL at last visit
GS-US-1717
Winston A, Lancet HIV.2018 ; 5:e162-71

5. GS-US-1717 Study: Switch ABC/3TC to TAF/FTC
ARV-trial.com
GS-US-1717 Study: Switch ABC/3TC to TAF/FTC
Adverse events
TAF/FTC
ABC/3TC
Adverse events ≥ 5% in either arm, %
Nasopharyngitis
Upper respiratory tract infection
Diarrhea
Headache
Arthralgia
Cough
Fatigue
Back pain
Urinary tract infection
Adverse events leading to drug discontinuation, N (%)
12 (4) *
9 (3) **
Grade 3-4 laboratory abnormalities ≥ 2% in either arm, %
LDL-cholesterol
Hyperbilirubinemia
Creakine kinase
Amylase
Hypercholesterolemia 22 18
* Considered related to study drug (n = 8) : abdominal distension + myalgia, nausea + vomiting + dehydration, nausea + feeling jittery + decrease appetite, anxiety, Brugada syndrome, increased creatinine, burning sensation + headache + paresthesia, vision blurred + visual field defect + eye pain ; not related to study drug : cough, tuberculosis, sudden cardiac death, neutropenia
** Considered related to study drug (n = 8) : affective disorder, panic attack, depression + bone pain + arthralgia, dermatitis + pruritus, rash + pruritus, diarrhea, myalgia + dysesthesia, tinnitus + dry mouth + dyspnea ; not related to study drug : depression + suicide attempt
GS-US-1717
Winston A, Lancet HIV.2018 ; 5:e162-71 5

6. GS-US-1717 Study: Switch ABC/3TC to TAF/FTC89
Median changes in creatinine clearance (Q1, Q3), mL/min
TAF/FTC
ABC/3TC 12 24 36 48
-10 10
1.3 mL/min
- 1.1 mL/min
p = 0.05
Weeks
No difference between groups in changes at W48:
in renal biomarkers (urine RBP:creatinine and B2M:creatinine ratios)
in bone mineral density
(hip and lumbar spine)
Median changes in fasting lipids at W48, mg/dL
TAF/FTC
ABC/3TC -1 3 2 4 -2
-10 10
Total
cholesterol
LDL- cholesterol
HDL- cholesterol
Triglycerides
p = 0.18
p = 0.54
p = 0.48
p < 0.001
GS-US-1717
Winston A, Lancet HIV.2018 ; 5:e162-71

7. GS-US-1717 Study: Switch ABC/3TC to TAF/FTC
ARV-trial.com
GS-US-1717 Study: Switch ABC/3TC to TAF/FTC
Conclusion
Switch from ABC/3TC to TAF/FTC was non inferior to ABC/3TC in maintaining virologic suppression in combination with a variety of third agents
No differences of TAF/FTC vs ABC/3TC in
Renal biomarkers
Bone mineral density
Fasting lipids
In virologically suppressed patients with creatinine clearance > 50 mL/min, TAF/FTC provides an alternative backbone to ABC/3TC with similar effects on kidney and bone
GS-US-1717
Winston A, Lancet HIV.2018 ; 5:e162-71 7