1. Switch from TDF to TAF GS-US-292-0109 Study GS-US-311-1089 Study
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Switch from TDF to TAF
GS-US Study
GS-US Study
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2. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
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GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Design
Randomisation
1 : 1
Double blind
W48
W96
HIV+ ≥ 18 years
On RPV/FTC/TDF > 6 months
HIV RNA < 50 c/mL ≥ 6 months
eGFR (Cockroft-Gault) > 50 mL/min
No resistance to RPV, FTC or TDF
N = 316
RPV/FTC/TAF 25/200/25 mg QD
+ RPV/FTC/TDF placebo
RPV/FTC/TDF 25/200/300 mg QD
+ RPV/FTC/TAF placebo
N = 316
Endpoints
Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (ITT, snapshot) ; non-inferiority if lower margin of a two-sided % CI for the difference = - 8%, 85% power
Secondary: percentage change for hip and spine bone mineral density between treatment groups ; 90% power to detect a 1.38% difference (non- inferiority margin) ; multiple adjustments to test for superiority
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

3. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
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GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Baseline characteristics and outcome
RPV/FTC/TAF
N = 316
RPV/FTC/TDF
N = 314
Median age, years 46 44
Female, % 13 8
Race: white / black / other, %
75 / 21 / 4
75 / 17 / 8
CD4/mm3, median
673
668
HIV RNA < 50 c/mL, % 97 99
eGR (Cockroft-Gault), mL/min, median
103.5
99.7
Proteinuria: grade 1 / grade 2, %
10 / 0
9 / < 1
Discontinuation by W48, N (%)
Adverse event
Death
Pregnancy
Investigator decision
Consent withdrawal
Lost to follow-up
Protocol violation
18 (5.7%) 4 1 2 6
18 (5.8%) 3
GS-US
Orkin C. Lancet HIV 2017 ; 4:e 3

4. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
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GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Virologic outcome at W48 (ITT, snapshot)
Difference (95% CI) = - 0.3% (- 4.2 to 3.7)
93.7
0.6
5.7
93.9
6.1 20 40 60 80
100
Success
HIV RNA< 50 c/mL
Virologic failure
No virologic data %
313 *
316
RPV/FTC/TAF
RPV/FTC/TDF
Other efficacy results at W48
Per protocol analysis (HIV RNA < 50 c/mL)
99.3% RPV/FTC/TAF
100% RPV/FTC/TDF
Virologic success was similar between treatment groups for the subgroups of age, sex, race, geographic region, and study drug adherence
Mean changes in CD4/mm3
+ 9 RPV/FTC/TAF
- 1 RPV/FTC/TDF
* 1 patient excluded from full-analysis set (was taking EFV/FTC/TDF)
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

5. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Resistance analysis
Genotype and Phenotype testing if confirmed HIV RNA ≥ 50 c/mL and confirmatory sample ≥ 400 c/mL, or HIV RNA ≥ 400 c/mL at W48 or at the last visit on study drug
1 patient in the RPV/FTC/TAF group: re-emergence of archived mutations M41K, E44D, D67N, V118I, L210W, T215Y; no new mutations (did not re- suppress)
1 patient in the RPV/FTC/TDF group: no resistance detected, was re- suppressed on continued therapy
Historical genotypes: resistance mutations to study drug in 3 participants
3 patients in the TAF group: M184V (N = 2), E138A, K101E + E138K
1 discontinued at W4 with HIV RNA < 50 c/mL, 3 with HIV RNA < 50 c/mL at W48
3 patients in the TDF group: M184V, E138A (N = 2)
All 3 with HIV RNA < 50 c/mL at W48
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

6. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Adverse events, %
RPV/FTC/TAF
N = 316
RPV/FTC/TDF
N = 314
Adverse events related to study drug 6 12
Serious adverse event
related to study drug 4
Adverse event leading to discontinuation
1 *
1 **
Most common adverse events (≥ 5% of patients)
Upper respiratory tract infection
Diarrhea
Nasopharyngitis
Headache
Bronchitis
Sinusitis 9 7 5 8
* Gastroesophageal reflux disease (N = 1), hiatus hernia and ulcerative oesophagitis (N = 1), fatigue (N = 1), leading to discontinuation), suicidal depression (N = 1)
** Drug hypersensitivity (N = 1), leading to discontinuation), increased ALT and AST (N = 1), chronic myeloid leukaemia (N = 1)
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

7. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Change in renal biomarkers at W48
- 18.8
- 7.8
- 18.0
- 29.0
7.3
16.8
21.5
12.0 - 50 40 30 20 10
P/Cr
Alb/Cr
RBP/Cr
b2MG/Cr
Cr: creatininuria ;
P: proteinuria ; Alb: albuminuria ; RBP : retinol binding protein ; b2MG : béta-2 microglobinuria
Urine protein to creatinine ratio (% median change)
* p < 0.001 *
F/TAF
F/TDF
Median change in eGFR: mg/dL on RPV/FTC/TAF vs mg/dL on RPV/FTC/TDF (p = )
No discontinuation for study-drug renal adverse event in either group
No reported cases of proximal renal tubulopathy or Fanconi syndrome in either group
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

8. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Mean % change in bone mineral density through W48 (%, 95% CI)
Hip
Lumbar spine 3
1.61 2
1.04 1
p <
p <
0.08
RPV/FTC/TAF -1
- 0.25
RPV/FTC/TDF -2
Baseline
W24
W48
Baseline
W24
W48
Number assessed RPV/FTC/TAF
RPV/FTC/TDF
184
173
175
171
168
165
187
176
178
174
172
168
≥ 3 % BMD increase at W48
RPV/FTC/TAF
16%
EFV/FTC/TDF 4%
27%
11%
p < 0.001
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

9. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Fasting lipids changes at W48
Increases in total cholesterol, direct LDL, HDL and triglycerides in the RPV/FTC/TAF group
Stable in the RPV/FTC/TDF group
Change in total cholesterol:HDL-cholesterol ratio: similar in both groups
Introduction of lipid-lowering agent between baseline and W48: 4% in the RPV/FTC/TAF group vs 1% in the RPV/FTC/TDF group (p = 0.067)
GS-US
Orkin C. Lancet HIV 2017 ; 4:e

10. GS-US-366-1216 Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch RPV/FTC/TDF to RPV/FTC/TAF
Conclusion
Overall, virally suppressed, HIV-1 infected participants who switched to rilpivirine, emtricitabine, and tenofovir alafenamide maintained viral suppression at 48 weeks with low rates of virological failure, good tolerability, and improvements in measures of bone and renal safety compared with rilpivirine, emtricitabine, and tenofovir disoproxil fumarate
GS-US
Orkin C. Lancet HIV 2017 ; 4:e