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

2. GS-US-292-0119 Study: switch to E/C/F/TAF + DRV
Design
Randomisation*
2: 1
Open-label
W24
W48
W144
≥ 18 years
≥ 4 months with HIV RNA < 50 c/mL on ART containing DRV/r
≥ 2 prior failures + ≥ 2 class resistance by historical genotype (≤ 3 TAMS + K65R)
No Q151M, T69ins, or DRV mutations
Historical genotype with no INSTI-R
INSTI-naïve or suppressed on INSTI
eGFR > 50 mL/min
E/C/F/TAF + DRV 800 mg QD
N = 89
Baseline regimen
E/C/F/TAF + DRV 800 mg QD
N = 46
Objective
Primary Endpoint: proportion with treatment success (HIV RNA < 50 c/mL) at W24, ITT, FDA snapshot: non-inferiority of E/C/F/TAF with a lower margin of 12%, by 2-sided 95% CI
GS-US
Huhn GD, JAIDS 2017; 74:

3. Baseline characteristics and disposition at W48
GS-US Study: switch to E/C/F/TAF + DRV
Baseline characteristics and disposition at W48
E/C/F/TAF + DRV, N = 89
Baseline regimen, N = 46
Median age, years 49 47
Female, % 18 39
CD4/mm3, median
519
518
eGFR (Cockroft-Gault), mL/min, median 99
100
Baseline regimen
Number of pills/day, median
≥ 6 pills/day, %
At least BID dosing, %
TDF / ABC / Other NRTIs, %
RAL
61 / 11 / 12 56
54 /11 / 13 50
Resistance
2-class / 3-class resistance, %
M184V/I
K65R
TAMs (≥ 3 TAMs)
NNRTI-R / PI-R
GSS at study entry, mean
70 / (16.8)
89 / 38
2.45
74 / 20 78 30
39.1 (17.4)
87 / 28
2.56
Discontinuation before W24, N (%)
Lack of efficacy / Adverse event
2 (2.2%)
0 / 0
5 (10.9%)
GS-US
Huhn GD, JAIDS 2017; 74:

4. Pharmacokinetic substudy Results (N = 15)
GS-US Study: switch to E/C/F/TAF + DRV
Pharmacokinetic substudy Results (N = 15)
Once-daily dosing of E/C/F/TAF (150/150/200/10 mg) + DRV 800 mg
Mean (% CV)
ASC
(ng*h/mL)
Cmax
(ng/mL)
Cthough
EVG
(44)
2 180 (35)
464 (79)
DRV
(43)
6 670 (25)
1 250 (99)
TAF
89,9 (45)
98,1 (58) NA
COBI
7 900 (43)
997 (30)
36 (129)
EVG Ctrough >10-fold above IC95 (45 ng/mL)
DRV Ctrough >22-fold above EC50 (55 ng/mL)
TAF exposures in efficacious range demonstrated in pivotal Phase 3 studies
COBI exposure associated with robust boosting
TFV exposure (mean [%CV] AUC 367 [33] ng*h/mL) well below levels observed following TDF-containing regimens
GS-US
Huhn GD, JAIDS 2017; 74:

5. GS-US-292-0119 Study: switch to E/C/F/TAF + DRV
Efficacy and Safety Results
Virologic outcome at W48
HIV RNA < 50 c/mL (ITT, snapshot)
E/C/F/TAF + DRV
Baseline regimen
HIV RNA < 20 c/mL
90%
72% (p = 0.012)
Emergence of resistance mutations
M184V + K65R in 1 patient on RAL + ETR + DRV/r with BL PI-R and NRTI-R (3 TAMs) and history of TDF + FTC
E/C/F/TAF + DRV
Baseline regimen
≠ (95% IC)
5,3 (- 3.4 ; 17.4)
100 97 91 20 40 60 80 %
94 * 76
18,3 (3.5 ; 33.0)
p = 0.004
W24
W48
Safety, %
E/C/F/TAF + DRV
Baseline regimen
Study-drug related AE 15
AEs leading to discontinuation
Grade 3-4 adverse events
study-drug related 13 1
Serious adverse events 10 2
Grade 3-4 lab. abnormalities 11 9
* 91% if prior DRV/r dose 800 QD vs
100% if prior DRV/r dose 600/100 BID
GS-US
Huhn GD, JAIDS 2017; 74:

6. GS-US-292-0119 Study: switch to E/C/F/TAF + DRV
Conclusion
Simplifying therapy from ~5 pills/day to once-daily, 2-pill E/C/F/TAF + DRV
Provided efficacious plasma exposures of EVG, DRV, and TAF
Maintained virologic suppression through Week 24
Was superior to staying on baseline regimen at Week 48 at both < 50 and < 20 c/mL
Switch to TAF improved proximal tubular proteinuria without change in eGFR
E/C/F/TAF + DRV was safe, well tolerated, and associated with greater treatment satisfaction
For treatment-experienced individuals with ≥ 2 class resistance on complex, high-pill burden regimens, switching to E/C/F/TAF + DRV provides a simple, once-daily, two-pill option with superior efficacy and comparable tolerability
GS-US
Huhn GD, JAIDS 2017; 74: