1. Comparison of INSTI vs INSTI
ARV-trial.com
Comparison of INSTI vs INSTI
QDMRK
SPRING-2
ONCEMRK
GS-US
GS-US 1

2. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG + F/TAF QD
Design
Randomisation*
1 : 1
Double-blind
W48
W144
> 18 years
ARV-naïve
HIV RNA > 500 c/mL
Any CD4 cell count
eGFR ≥ 30 mL/min
No resistance to FTC or TDF
HBV or HCV co-infection allowed
N = 320
BIC/F/TAF QD
DTG + F/TAF placebo QD
N = 325
DTG + F/TAF QD
BIC/F/TAF placebo QD
* Randomisation was stratified by HIV RNA (< c/mL, c/mL or > c/mL), CD4 (< 50/mm3, /mm3 or ≥ 200/mm3) at screening and geographic region (USA vs non-USA)
BIC/F/TAF : 50/200/25 mg, as STR
Objective
Non inferiority of BIC/F/TAF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2-sided % CI for the difference= -12%, 95% power)
GS-US
Sax PE. Lancet 2017, Aug 31, ePub ahead of print 2

3. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG + F/TAF QD
Baseline characteristics and patient disposition
BIC/F/TAF
N = 320
DTG + F/TAF
N = 325
Median age, years 33 34
Female, % 12 11
HIV RNA (log10 c/mL), median
4.43
4.45
HIV RNA > c/mL, % 21 17
CD4 cell count (/mm3), median
440
441
CD4 < 200/mm3, % 14 10
HBV/HCV co-infection, %
3 / 2
2 /2
Discontinuation by W48, % 9 6
For lack of efficacy, N
For adverse event, N 5 1
Lost to follow-up, N 8
Non-compliance 2
Patient decision / investigator discretion
7 / 4
7 / 0
Other 4
GS-US
Sax PE. Lancet 2017, Aug 31, ePub ahead of print 3

4. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG + F/TAF QD
Virologic outcome at week 48
BIC/F/TAF
DTG + F/TAF
89.4 4 6
92.9 1 20 40 60 80
100
HIV RNA
< 50 c/mL
≥ 50 c/mL
No data %
DTG + F/TAF
BIC/F/TAF
‒ 12%
+ 12%
1.0
- 7.9
- 3.5
Difference (95 % CI)
Met criteria for resistance testing (HIV RNA ≥ 200 c/mL)
BIC/F/TAF: 7 vs DTG + F/TAF: 5
No resistance emergence
Mean CD4 increase at W48
BIC/F/TAF: + 180/mm3
DTG + F/TAF: + 201/mm3
HIV RNA < 50 c/mL (per-protocol)
BIC/F/TAF: 98.9%
DTG + F/TAF: 99.7%
GS-US
Sax PE. Lancet 2017, Aug 31, ePub ahead of print 4

5. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG + F/TAF QD
Adverse events
BIC/F/TAF
N = 320
DTG + F/TAF
N = 325
Adverse events leading to study drug discontinuation, N
5 *
1 **
Adverse event ≥ 5% in either group, %
Headache
Diarrhea
Nausea
Nasopharyngitis
Fatigue
Influenza
Lymphadenopathy
Arthralgia
Insomnia
Upper respiratory tract infection
Pyrexia
Back pain
Grade 3-4 laboratory abnormalities, %
CK elevation
LDL-cholesterol elevation
ALT / AST elevation
Hyperglycemia /
/ 2.5
2.2
* Abdominal distension ; Cardiac arrest (sepsis, appendicitis) ; Chest pain ; Paranoia, crystal metamphetamine use ; sleep disorders, insomnia, dyspepsia, tension headache, depressed mood
** Erythema, pruritus
GS-US
Sax PE. IAS 2017, Abs. TUPDB0201LB ; Sax PE. Lancet 2017, Aug 31, ePub ahead of print 5

6. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG + F/TAF QD
Change from baseline in eGFR and lipids at W48
BIC/F/TAF
N = 314
DTG + F/TAF
N = 315 p
Median change in eGFR (Cockroft-Gault), mL/min
- 7.3
- 10.8
0.0181
Mean changes in fasting lipids, mg/dL
Total cholesterol
LDL cholesterol
HDL cholesterol
Triglycerides ns
No discontinuations due to renal adverse events and no proximal tubulopathy in either arm
GS-US
Sax PE. Lancet 2017, Aug 31, ePub ahead of print 6

7. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
Steady-state pharmacokinetic parameters of BIC/F/TAF (N = 17)
Bictegravir
FTC
TAF
AUCtau (hr*ng/mL)
Mean (% CV ; min-max)
(43.8 ; )
(28.4 ; )
259.4
(59.9 ; )
Cmax (ng/mL)
(37.3 ; )
1 920
(20.7 ; )
309.4
(59.9 ; )
Ctau (ng/mL) * **
(52.0 ; )
97.7
(38.4 ; ) -
Tmax (h)
Median (Q1-Q3)
1.02 ( )
1.02 ( )
0.50 ( )
t1/2 (h)
18.56 ( )
7.05 ( )
0.43 ( )
* N = 15
** BIC mean Ctau about 16 times higher than the protein adjusted effective concentration (162 ng/mL) against wild type HIV-1 virus
Sax PE. Lancet 2017, Aug 31, ePub ahead of print

8. Study GS-US-380-1490: BIC/F/TAF QD vs DTG + F/TAF QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG + F/TAF QD
Summary of week 48 results
Virologic suppression at W48 was high in both arms, with BIC/F/TAF being non inferior to DTG + F/TAF in treatment-naïve adults
Sensitivity analyses confirmed BIC/F/TAF was non inferior to DTG + F/TAF
No patient discontinued either treatment arm due to lack of efficacy
No treatment-emergent resistance to any study medication was observed in either arm
BIC/F/TAF was safe and well tolerated
Less decrease in eGFRCG was observed with BIC/F/TAF vs DTG + F/TAF
There were no discontinuations due to renal adverse events and no cases of renal tubulopathy, including Fanconi syndrome, in either treatment group
Changes from baseline in lipid parameters were equivalent
GS-US
Sax PE. Lancet 2017, Aug 31, ePub ahead of print 8