1. Switch to BIC/FTC/TAF
GS-US
GS-US
GS-US

2. GS-US-380-1844 Study: Switch to BIC/FTC/TAF
Design
Randomisation
1 : 1
Double-blind
W48
N = 282
BIC/FTC/TAF 50/200/25 mg QD + DTG/ABC/3TC placebo
HIV+ ≥ 18 years
On DTG, ABC and 3TC
HIV RNA < 50 c/mL ≥ 3 months
eGFR (Cockroft-Gault) > 50 mL/min
No active HBV infection
BIC/FTC/TAF
DTG/ABC/3TC 50/600/300 mg QD + BIC/FTC/TAF placebo
Open-label
extension
N = 281
Endpoints
Primary: proportion of patients with HIV RNA ≥ 50 c/mL at W48 (ITT, snapshot) ; non-inferiority if upper margin of a two-sided % CI for the difference = 4%
GS-US
Molina JM. CROI 2018, Abs. 22

3. GS-US-380-1844 Study: Switch to BIC/FTC/TAF
Baseline characteristics
BIC/FTC/TAF
N = 282
DTG/ABC/3TC
N = 281
Median age, years 47 45
Female, % 12 10
Ethnicity: white / black / hispanic, %
73 / 21 / 16
73 / 22 / 19
CD4 cell count (/mm3), median
732
661
eGFR (Cockroft-Gault), mL/min, median
101
GS-US
Molina JM. CROI 2018, Abs. 22

4. GS-US-380-1844 Study: Switch to BIC/FTC/TAF
Virologic outcome at W48
BIC/FTC/TAF (N = 282)
DTG/ABC/3TC (N = 281)
Difference : 0.7%
(95.002% CI : to 2.8)
1.1
0.4
93.6
5.3
95.0
4.6
HIV RNA < 50 c/mL
No virologic
data 20 40 60 80
100 %
HIV RNA ≥ 50 c/mL
No emergence of resistance in either group
GS-US
Molina JM. CROI 2018, Abs. 22

5. Adverse events between D0 and W48, %
GS-US Study: Switch to BIC/FTC/TAF
Adverse events between D0 and W48, %
BIC/FTC/TAF
N = 282
DTG/ABC/3TC
N = 281
Discontinuation for adverse event
6 (2.1%) *
2 (0.7%) **
Adverse event in ≥ 5% of either arm, %
Upper respiratory tract infection
Nasopharyngitis
Headache
Diarrhea
Arthralgia
Insomnia 10 3
Any study-drug related adverse event
23 (8.2%)
44 (15.7%) p = 0.01
Study drug-related adverse event in ≥ 1%, %
Abnormal dreams
Flatulence
Nausea
Fatigue
3 < 1
< 1 2 1
* Headache (N = 2), vomiting (N = 1), cerebrovascular accident (N = 1), abnormal dreams (N = 1), suicidal ideation (N = 1) ; ** headache (N = 1), pruritus (N = 1)
GS-US
Molina JM. CROI 2018, Abs. 22

6. Grade 3 or 4 laboratory abnormalities, N (%)
GS-US Study: Switch to BIC/FTC/TAF
Grade 3 or 4 laboratory abnormalities, N (%)
BIC/FTC/TAF
N = 282
DTG/ABC/3TC
N = 281
Any
47 (17)
32 (11)
Abnormality in ≥ 2% of either arm
LDL-cholesterol
Amylase
ALT CK
Fasting hyperglycemia
14 (5)
7 (2) *
6 (2) **
6 (2) ***
6 (2)
13 (5)
2 (< 1)
* All elevations transient and not associated with pancreatitis : lipase normal in 4/7
** Acute HCV infection (N = 3), acute HAV infection (N = 1), alcohol (N = 1), NASH (N = 1)
*** No case of rhabdomyolysis
GS-US
Molina JM. CROI 2018, Abs. 22

7. GS-US-380-1844 Study: Switch to BIC/FTC/TAF
DTG/ABC/3TC
Median percent change in quantitative proteinuria at W48
Median change in fasting lipids (mg/dL) at week 48 10 20 30 40 14 % 9 29 21 17
Total cholesterol p = 0.77
LDL cholesterol p = 0.42
HDL cholesterol p = 0.13
Triglycerides p = 0.028
Total cholesterol:
HDL-chol. p = 0.56
Mean % change in bone mineral density
UACR: urine albumin:creatinine ratio
RBP: retinol-binding protein
β-2-m: beta-2 microglobulin
Spine
Hip 2 1 24 48
256
244
233
262
253
0.69
0.42
p = 0.33 2 1 24 48
256
246
229
265
253
242
0.16
0.30
p = 0.47
Median change in eGFRCG at W48:
- 4.3 mL/min BIC/FTC/TAF vs mL/min DTG/ABC/3TC (p < 0.001) n n
GS-US
Molina JM. CROI 2018, Abs. 22

8. GS-US-380-1844 Study: Switch to BIC/FTC/TAF
Conclusion
Switching to BIC/FTC/TAF was non-inferior to remaining on DTG/ABC/3TC, at W48
No treatment emergent resistance
Discontinuation for adverse event was rare: 2% on BIC/FTC/TAF and 1% on DTG/ABC/3TC at W48
Study drug-related adverse events occurred with significantly higher frequency in DTG/ABC/3TC arm
Increased grade 3-4 amylase was seen in 2% of BIC/FTC/TAF and no patient on DTG/ABC/3TC
The lipid, bone and renal parameters of switching to BIC/FTC/TAF were comparable to remaining on DTG/ABC/3TC through 48 weeks
GS-US
Molina JM. CROI 2018, Abs. 22