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-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Design
Randomisation*
1 : 1
Double-blind
W48
W144
> 18 years, ARV-naïve
HIV RNA > 500 c/mL
Any CD4 cell count
HLA B*5701 negative
eGFR ≥ 50 mL/min
HBs Ag negative
No resistance to
FTC/3TC, TDF or ABC
N = 314
BIC/F/TAF QD
DTG/ABC/3TC placebo QD
DTG/ABC/3TC QD
BIC/F/TAF placebo QD
N = 315
* 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
Gallant J. Lancet Nov 4;390(10107): ; Wohl DA Lancet HIV 2019 ; 6:e355-63 2

3. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Baseline characteristics and patient disposition
BIC/F/TAF
N = 314
DTG/ABC/3TC
N = 315
Median age, years 31 32
Female, % 9 10
HIV RNA (log10 c/mL), median
4.42
4.51
HIV RNA > c/mL, % 17 16
CD4 cell count (/mm3), median
443
450
CD4 < 200/mm3, % 11
Discontinuations
at W48
W48-W96
Total discontinuations, N (%)
19 (6%)
17 (5.8%)
16 (5%)
15 (5%)
For lack of efficacy, N
For adverse event, N 4 1
Lost to follow-up, N 8 6
Non-compliance / Other, N
1 / 9
1 / 8
1 / 5
2 / 6
GS-US
Gallant J. Lancet Nov 4;390(10107): ; Wohl DA Lancet HIV 2019 ; 6:e355-63 3

4. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Virologic outcome at week 48
BIC/F/TAF
DTG/ABC/3TC
92.4
1.0
6.7
93.0
2.5
4.4 20 40 60 80
100
HIV RNA
< 50 c/mL
≥ 50 c/mL
No data %
DTG/ABC/3TC
BIC/F/TAF
‒ 12%
+ 12%
3.6
- 4.8
- 0.6
Difference (95 % CI)
Met criteria for resistance testing (HIV RNA ≥ 200 c/mL)
BIC/F/TAF: 1 vs DTG/ABC/3TC: 4
No resistance emergence
Mean CD4 increase at W48
BIC/F/TAF: + 233/mm3
DTG/ABC/3TC: + 229/mm3
HIV RNA < 50 c/mL (per-protocol)
BIC/F/TAF: 99.3%
DTG/ABC/3TC: 98.6%
GS-US
Gallant J. Lancet Nov 4;390(10107): 4

5. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
HIV RNA < 50 c/mL at W48 according to baseline CD4 and HIV RNA, ITT-E snapshot
> ≤
> 200
≤ 200
HIV RNA, c/ml
CD4/mm3 20 40 60 80
100 93 94 87 90 83 81 % N=
261
265 53 50
278
283 36 32
BIC/F/TAF
DTG/ABC/3TC
GS-US
Gallant J. Lancet Nov 4;390(10107):

6. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Adverse events at W48
BIC/F/TAF
N = 314
DTG/ABC/3TC
N = 315
Adverse events leading to study drug discontinuation, N
4 *
Adverse event ≥ 5% in either group, %
Diarrhea
Headache
Nausea
Nasopharyngitis
Cough
Upper respiratory tract infection
Fatigue
Syphilis
Insomnia
Arthralgia
Vomiting
Bronchitis
Abdominal pain
12.7
11.5
10.2
7.3
6.4
13.0 **
Grade 3-4 laboratory abnormalities, %
CK elevation
LDL-cholesterol elevation
Amylase
Neutropenia
3.5
2.3
1.9
1.6
2.2
3.2
* Nausea, rash ; thrombocytopenia ; chronic pancreatitis, steatorrhea ; depression
** p < 0.001
GS-US
Gallant J. Lancet Nov 4;390(10107): 6

7. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Renal parameters, bone mineral density and lipid changes at W48
BIC/F/TAF
N = 314
DTG/ABC/3TC
N = 315
Median change in eGFR (Cockroft-Gault), mL/min
- 10.5
- 10.8
Median percent changes in quantitative proteinuria, %
Urine albumin: creatinine
Retinol binding protein : creatinine
Beta2-microglobulin : creatinine 6 20
- 18
Mean % changes in bone mineral density, %
Hip
Spine
- 0.6
- 0.78
- 0.83
- 1.02
Mean changes in fasting lipids, mg/dL
Total cholesterol
LDL cholesterol
HDL cholesterol
Triglycerides 13 7 5 9
11 4 3
None of the differences between groups were significant
No discontinuations due to renal adverse events and no proximal tubulopathy in either arm
GS-US
Gallant J. Lancet Nov 4;390(10107): 7

8. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
Steady-state pharmacokinetic parameters of BIC/F/TAF (N = 17)
Bictegravir
FTC
TAF
AUCtau (hr*ng/mL)
Mean (% CV ; min-max
(33.5 ; )
(29.8 ; )
206.0
(51.2 ; )
Cmax (ng/mL)
Mean (% CV ; min-max)
(27.5 ; )
1 868
(34.5 ; )
225.5
(68.3 ; )
Ctau (ng/mL) * *
(40.7 ; )
80.9
(37.1 ; ) -
Tmax (h)
Median (Q1-Q3)
1.53 ( )
1.50 ( )
0.53 ( )
t1/2 (h)
15.93 ( )
6.66 ( )
0.42 ( )
* BIC mean Ctau about 14 times higher than the protein adjusted effective concentration (162 ng/mL) against wild type HIV-1 virus
GS-US
Gallant J. Lancet Nov 4;390(10107):

9. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Summary of week 48 results
Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W48 by snapshot algorithm
92.4% of patients on BIC/F/TAF and 93.0% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL
Sensitivity analyses confirmed non inferiority
No treatment emergent resistance
BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation
Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001)
Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC
Changes from baseline in bone mineral density, lipid parameters and renal markers were comparable between treatment arms
GS-US
Gallant J. Lancet Nov 4;390(10107): 9

10. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
Virologic outcome at week 96, ITT snapshot
BIC/F/TAF (N = 314)
DTG/3TC/ABC (N = 315)
HIV RNA
< 50 c/mL
≥ 50 c/mL
No virologic data
87.9
0.6
89.8
2.2
11.5
7.9 %
100 80 60 40 20
Difference (95 % CI)
-12 %
12 %
DTG/3TC/ABC
BIC/F/TAF
- 1.9
3.1
- 6.9
Secondary endpoints at week 96
BIC/F/TAF
DTG/3TC/ABC
HIV RNA < 50 c/mL (sensitivity analyses)
Per protocol
99.6%
98.9%
Missing = failure
87.9%
90,8%
Missing = excluded
99.3%
Virologic failure with confirmed HIV RNA > 200 c/mL
N assessed for resistance
N with emergence of resistance 5
Mean change in CD4 at W96
+ 287/mm3
+ 288/mm3
GS-US
Wohl DA Lancet HIV 2019 ; 6:e355-63

11. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
Adverse events at W96
Discontinuation for adverse event
BIC/F/TAF (N = 314)
DTG/3TC/ABC (N = 315)
5 (1.6%)
Nausea, rash (D4)
Thrombocytopenia (D50)
Chronic pancreatitis (D134)
Depression (D248)
Renal failure (D621)
Adverse events all grades (%)
BIC/F/TAF (N = 314)
DTG/3TC/ABC (N = 315)
Nausea
11 *
24 *
Headache 13 16
Diarrhea 15
Fatigue 9 11
Insomnia 7 10
* p < 0.001
GS-US
Wohl DA Lancet HIV 2019 ; 6:e355-63

12. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
Laboratory parameters (W96)
BIC/F/TAF
(N = 314)
DTG/3TC/ABC
(N = 315) p
CK grade 3-4, % 6 5 -
LDL-cholesterol grade 3-4, % 3 4
Median change in eGFR CG, mL/min
- 7.8
- 9.6
0.01
Median % change in urine albumine:creatinine ratio
- 0.3
+ 5.2
0.25
Median % change in urine retinol binding protein:creatinine ratio
+ 21.2
+ 22.1
0.91
Median % change in urine beta-2-microglobulin:creatinine ratio
- 30.8
- 29.4
0.96
Bone DXA: mean % change in BMD between D0 and W96
BIC/F/TAF
(N = 314)
DTG/3TC/ABC
(N = 315) p
Spine, %
- 0.71
- 0.22
0.14
Hip, %
- 1.13
- 1.26
0.59
GS-US
Wohl DA Lancet HIV 2019 ; 6:e355-63

13. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
Mean changes in fasting lipids at W96, mg/dL
Total cholesterol:
HDL-cholesterol
Ratio
p = 0.003
0.5
-0.5 -1
3.7
-0.2
- 0.1
Total cholesterol
LDL-
cholesterol
HDL-
Triglycerides
p = 0.002
p < 0.001
p = 0.17
p = 0.28 15 10 20 30
87,9 8 17 7 4 5 6
Mean baseline
value, mg/dL
162
159
101 42 96 93
BIC/FTC/TAF
DTG/ABC/3TC
% of patients on lipid-lowering agents at baseline
3.8 %
2.2 %
% of patients initiating lipid-lowering agents during study
4.1%
GS-US
Wohl DA Lancet HIV 2019 ; 6:e355-63

14. Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD
ARV-trial.com
Study GS-US : BIC/F/TAF QD vs DTG/ABC/3TC QD
Summary of week 96 results
Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W96 by snapshot algorithm
87.9% of patients on BIC/F/TAF and 89.8% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL
No treatment emergent resistance
BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation
Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001)
Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC
Decrease in eGFR was significantly higher on DTG/ABC/3TC
Increase in total-cholesterol and LDL-cholesterol was significantly higher on BIC/F/TAF, but the proportion of participants initiating lipid-lowering agents was not different between arms
GS-US
Wohl DA Lancet HIV 2019 ; 6:e355-63 14