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
GS-US Study
GS-US Study

2. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
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GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Design
Randomisation
1 : 1
Double blind
W48
W96
HIV+ ≥ 18 years
On EFV/FTC/TDF > 6 months
HIV RNA < 50 c/mL ≥ 6 months
eGFR (Cockroft-Gault) > 50 mL/min
No resistance to
EFV, RPV, FTC or TDF
N = 438
RPV/FTC/TAF 25/200/25 mg QD *
+ EFV/FTC/TDF placebo
EFV/FTC/TDF 600/200/300 mg QD ** + RPV/FTC/TAF placebo
N = 437
* With food, AM
** Without food, PM
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%, 95% power
Secondary: percentage change for hip and spine bone mineral density between treatment groups ; 95% power to detect a 1.38% difference (non-inferiority margin) ; multiple adjustments to test for superiority
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

3. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Baseline characteristics and patient disposition
RPV/FTC/TAF
N = 438
EFV/FTC/TDF
N = 437
Median age, years 49 48
Female, % 15 11
Race: white / black / other, %
66 / 27 / 7
67 / 28 / 5
CD4/mm3, median
673
666
HIV RNA < 50 c/mL, % 98 99
eGR (Cockroft-Gault), mL/min, median
110.4
107.6
Proteinuria: grade 1 / grade 2, %
6 / < 1
8 / < 1
Discontinuation by W48, N (%)
Adverse event
Lack of efficacy
Death
Pregnancy
Investigator decision
Consent withdrawal
Lost to follow-up
Protocol violation
43 (9.8%) 3 1 2 17 5 4
35 (8.0%) 8 6
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

4. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Virologic outcome at W48 (ITT, snapshot)
Other efficacy results at W48
Difference (95% CI) = - 2.0% (- 5.9 to 1.8)
90.0
1.1
8.9
92.0
0.9
7.1 20 40 60 80
100
Success
HIV RNA< 50 c/mL
Virologic failure
No virologic data %
RPV/FTC/TAF
EFV/FTC/TDF
437
438
Per protocol analysis (HIV RNA < 50 c/mL)
99.1% RPV/FTC/TAF
99.3% EFV/FTC/TDF
Virologic success was similar between treatment groups for the subgroups of age, sex, race, and geographic region
Virologic success lower in RPV/FTC/TAF group if adherence ≥ 95%: 91% vs 95% for EFV/FTC/TDF
Mean changes in CD4/mm3
+ 23 RPV/FTC/TAF
+ 12 EFV/FTC/TDF
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

5. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/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
6 patients in the RPV/FTC/TAF group: no emergent resistance mutations ; 4 were re-suppressed without changing therapy
2 patients in the EFV/FTC/TDF group: emergence of resistance to FTC (M184V) and RPV (V106I/L + Y188L)
Historical genotypes : resistance mutations to study drug in 3 participants
2 patients in the RPV/FTC/TAF group (K103N ; E138A)
1 patient in the EFV/FTC/TDF group (K103N)
All 3 discontinued at W36 or W48 with HIV RNA < 50 c/mL
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

6. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Adverse events, %
RPV/FTC/TAF, n = 438
EFV/FTC/TDF, n = 437
Adverse events related to study drug 13 10
Serious adverse event
related to study drug 6
< 1
Adverse event leading to discontinuation
3 *
2 **
Most common adverse events (≥ 5% of patients)
Upper respiratory tract infection
Nasopharyngitis
Cough
Headache
Diarrhea
Arthralgia
* Anaemia (N = 1), diarrhea (N = 1), vomiting (N = 1), constipation (N = 1), fatigue (N = 2), ulcer haemorrhage (N = 1), localised infection (N = 1), multiple fractures (N = 1), road traffic accident (N = 1), dysgeusia (N = 1), headache (N = 1), somnolence (N = 1), anxiety (N = 1), cough (N = 1), decreased GFR (N = 1), generalised pruritus (N = 1)
** Atrial fibrillation (N = 1), diarrhea (N = 1), vomiting (N = 1), abdominal distension (N = 1), abdominal pain (N = 1), constipation (N = 1), dysphagia (N = 1), gastro-oesophageal reflux (N = 1), nausea (N = 1), hypersensitivity (N = 1), sinusitis (N = 1), arthralgia (N = 1), confusional state (N = 1), insomnia (N = 1), asthma (N = 1), rash (N = 1)
1 patient died from methamphetamine and cocaine overdose in the RPV/FTC/TAF group
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

7. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Change in renal biomarkers at W48
Urine protein to creatinine ratio (% median change)
- 30.0
- 13.5
- 41.0
-2.0
12.2
29.1
17.1 - 50 40 30 20 10
P/Cr
Alb/Cr
RBP/Cr
b2MG/Cr
Cr: creatininuria
* p < 0.001 *
RPV/FTC/TAF
EFV/FTC/TDF
Median change in eGFR: mg/dL on RPV/FTC/TAF vs – 0.6 mg/dL on EFV/FTC/TDF (p < )
1 patient discontinued for study-drug renal adverse event in RPV/FTC/TAF group (decrease in eGFR from 54.2 to 26.4 mL/min)
No reported cases of proximal renal tubulopathy or Fanconi syndrome in either group
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

8. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Mean % change in bone mineral density through W48 (%, 95% CI)
Hip
Lumbar spine 4
1.65 2
1,28
p <
p <
- 0.13
- 0.05 -2
RPV/FTC/TAF
EFV/FTC/TDF -4
Baseline
W24
W48
Baseline
W24
W48
Number assessed
RPV/FTC/TAF
EFV/FTC/TDF
388
399
369
382
347
367
394
400
373
382
351
369
Improvement of osteopenia or osteoporosis at W48
RPV/FTC/TAF
N = 15
EFV/FTC/TDF
N = 9
N = 27
N = 6
p =
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

9. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Fasting lipids changes at W48
Decreases in total cholesterol, direct LDL, HDL and triglycerides in the RPV/FTC/TAF group
Stable in the EFV/FTC/TDF group
Change in total cholesterol:HDL-cholesterol ratio was similar in both groups
Introduction of lipid-lowering agent between baseline and W48: 4% in both groups
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13

10. GS-US-366-1160 Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
ARV-trial.com
GS-US Study: Switch EFV/FTC/TDF to RPV/FTC/TAF
Conclusion
Overall, virally suppressed, HIV-infected individuals who switched to rilpivirine, emtricitabine, and tenofovir alafenamide maintained viral suppression at 48 weeks similarly to those who remained on efavirenz, emtricitabine, and tenofovir disoproxil fumarate
The rilpivirine, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and associated with significant improvements in measures of bone and renal safety
GS-US
De Jesus E. Lancet HIV 2017; 4:e205-13