1. Treatment-Naïve Adults
Phase 3 Randomized, Controlled, Clinical Trial of Bictegravir Coformulated With FTC/TAF in a Fixed-Dose Combination vs Dolutegravir + FTC/TAF in Treatment-Naïve HIV-1–Positive Adults: Week 48 Results
Study Design
Primary Endpoint
Week 0 48 96
144
B/F/TAF QD
n=320
Treatment-Naïve Adults
DTG + F/TAF Placebo QD
HIV-1 RNA ≥500 copies/mL
eGFRCG ≥30 mL/min
1:1
DTG + F/TAF QD
n=325
B/F/TAF Placebo QD
Phase 3, randomized, double-blind, active-controlled Study 1490 (ClinicalTrials.gov NCT )
Stratified by HIV-1 RNA, CD4 cell count, and geographic region (USA vs ex-USA)
North America, Europe, Australia, and Latin America
Chronic hepatitis B/C virus (HBV/HCV) infection allowed
Primary endpoint: proportion with HIV-1 RNA <50 copies/mL at Week 48
Noninferiority margin of 12% based on US Food and Drug Administration-defined snapshot algorithm
Background
Inclusion criteria includes
Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) or PEP (post-exposure prophylaxis), up to one month prior to screening
Screening genotype report must show sensitivity to FTC and TFV. Screening IN genosure was not performed.
Exclusion criteria did not include
HBV or HCV coinfection, except acute hepatitis in the 30 days prior to study entry
eGFRCG, estimated glomerular filtration rate by Cockcroft-Gault equation.

2. Virologic Outcome at Week 48 Snapshot Analysis
% Treatment Difference (95% CI)
>99 1°
B/F/TAF
DTG + F/TAF PP
Favors
DTG + F/TAF
Favors
B/F/TAF
-3.5 1°
HIV-1 RNA <50 Copies/mL, %
-7.9
1.0
-0.7
1.2
-2.6 PP
HIV-1 RNA <50
Copies/mL
HIV-1 RNA ≥50
Copies/mL
No Virologic
Data
-12%
12%
For modified snapshot:
HIV-1 RNA > 50:
BFTAF 91.4% (286/313)
DTG+F/TAF 92·9% (302/325)
difference-1·5% (−5.8% to 2.8%), p=0·48
HIV RNA >/=50:
BFTAF 2.6% (8/313)
DTG+FTAF 1.2% (4/325)
Missing:
BFTAF 6.1% (19/313)
DTG+FTAF 5.8% (19/325)
BFTAF
286
320
302
325
279
282
296
297 14
320 4
325 3
282 1
297 20
320 19
325
282
297
Primary endpoint of noninferiority met
No resistance to any components of the treatment regimens occurred
Sensitivity analyses confirmed noninferiority of B/F/TAF
1°, primary; CI, confidence interval; PP, per protocol.

3. Virologic Outcome at Week 48 Primary Endpoint
Patients, n (%)
B/F/TAF
n=320
DTG + FTC/TAF
n=325
HIV-1 RNA <50 copies/mL
286 (89.4)
302 (92.9)
Difference for <50 copies/mL, % (95.002% CI)
-3.5 (-7.9, 1.0; p=0.12)
HIV-1 RNA ≥50 copies/mL
14 (4.4)
4 (1.2)
3 (0.9)
1 (0.3)
D/C due to lack of efficacy
D/C due to other reason* and last VL ≥50 copies/mL
11 (3.4)
No virologic data in Week 48 window
20 (6.3)
19 (5.8)
D/C due to AE/death
D/C due to other reason* and last VL <50 copies/mL
14 (4.3)
On study drug, but missing data in window
6 (1.9)
2 (0.6)
This table describes the Snapshot outcome shown previously in greater detail. As you can see, there were a total of 4 subjects with VL ≥ 50 copies/mL in the Week 48 window, 3 on B/F/TAF and 1 on DTG + F/TAF.
1 B/F/TAF subject had a BL VL of 45,000. He was undetectable through Week 36, then was 1,690 copes/mL at Week 48
1 B/F/TAF subject had BL VL 25, 200 copies/mL. He was undetectable Weeks 4-36, then 15,400 copies at Week 48
1 B/F/TAF had a screening VL of 3.83 million copies/mL, which was 3.15 million on Day 1. He was never < 50 and had a VL of 315 copies/mL at Week 48.
The 1 subject with HIV-1 RNA ≥ 50 at Week 48 on the DTG arm had a BL of 577,000 copies, and had 56 copies per mL at Week 48.
This table also shows that a total of 14 subjects discontinued for a reason other than an AE or death but had HIV-1 RNA ≥ 50 copies at their last visit. Six of these subjects had their labs done, then took 1 dose of study medication on Day 1 and never returned for follow up. All 6 of these subjects were in the B/F/TAF arm, as shown in the next slide. In a post-hoc analysis which excluded only those 6 subjects+1 who dc’d due to AE/death (from no data category) and also did not provide postbaseline HIV RNA, the difference in response rates was 91.4% on B/F/TAF vs 92.9% for DTG + F/TAF.
*Other reasons included investigator’s discretion, patient decision, lost to follow-up, noncompliance with study drug, protocol violation, and pregnancy. VL, viral load.

4. Reason for Discontinuation
Patients Discontinued for Reasons Other Than Adverse Event/Death and Last HIV-1 RNA ≥50 Copies/mL
Group
Patient
Day of Last
HIV-1 RNA
Last HIV-1 RNA,
Copies/mL
Reason for Discontinuation
B/F/TAF 1
1 (baseline)
438*
Patient decision (did not want to participate in study) 2
185,000*
Protocol violation (incarcerated) 3
56,500*
Lost to follow-up (moved away) 4
71,900*
Investigator discretion (inconsistent state of residency) 5
17,300*
Patient decision (no reason provided) 6
9600*
Patient decision (moved away) 7 58
317,000
Investigator discretion (erratic behavior) 8 62
9000
Lost to follow-up (unresponsive to contact attempts) 9
169
23,400
Patient decision (wanted drug holiday) 10
176
4440
Investigator discretion (multiple missed appointments) 11
253
8630
DTG +
F/TAF 12
213
Pregnancy 13
22,800
Lost to follow-up (incarcerated) 14
12,000
Noncompliance with study drug
*Pretreatment baseline result

5. Further Results and Conclusions
B/F/TAF was safe and well tolerated
Treatment discontinuations due to adverse events were rare in both arms
Lipid changes did not differ significantly between study arms
Less decrease in eGFRCG was observed with B/F/TAF vs DTG + F/TAF
No treatment discontinuations due to renal adverse events
Further details of results in poster TUPDB0201LB
Conclusions:
Virologic suppression at Week 48 was high in both arms, and B/F/TAF was noninferior to DTG + F/TAF in treatment-naïve adults
No patient discontinued due to lack of efficacy
No treatment-emergent resistance to any study medication was observed
These data reinforce the non-inferiority of B/F/TAF vs. DTG-based regimens seen in Study 1489 (abstract MOAB0105LB), presented yesterday