HIV-1-infection
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of switching from a regimen of either dolutegravir (DTG) and emtricitabine /tenofovir alafenamide (F/TAF) or DTG and emtricitabine/tenofovir disoproxil fumarate (F/TDF) to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus DTG+F/TAF in virologically suppressed HIV-1 infected adults with or without antiretroviral (ARV) resistance.
Interventions
DRUGB/F/TAF
50/200/25 mg FDC tablet(s) administered orally once daily
DRUGF/TAF
200/25 mg FDC tablet(s) administered orally once daily
DRUGDTG
50 mg tablet(s) administered orally once daily
DRUGDTG Placebo
Tablet(s) administered orally once daily
DRUGF/TAF Placebo
Tablet(s) administered orally once daily
DRUGB/F/TAF Placebo
Tablet(s) administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Currently receiving an ARV regimen of DTG+F/TAF or DTG+F/TDF for the following minimum time periods: * ≥ 6 months (if there is documented or suspected nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance prior to the screening visit) * ≥ 3 months (if there is no documented or suspected NRTI resistance prior to the screening visit) * Documented plasma HIV-1 ribonucleic acid (RNA) \< 50 copies/mL during treatment with DTG+F/TAF or DTG+F/TDF (for a minimum period of ≥ 6 or ≥ 3 months, as applicable) preceding the screening visit * Plasma HIV-1 RNA levels \< 50 copies/mL at screening visit * Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance * No documented resistance to integrase stand transfer inhibitors (INSTIs) or confirmed virologic failure * Eligible adults with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection are permitted to enroll NOTE: Other protocol defined Inclusion/
Exclusion criteria
may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | Week 48 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | Week 48 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
Countries
Austria, Canada, France, Germany, Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America and Europe. The first participant was screened on 12 June 2017. The last study visit occurred on 10 Feb 2021.
Pre-assignment details
633 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| B/F/TAF B/F/TAF (50/200/25 mg) FDC tablet + DTG placebo tablet + F/TAF placebo tablet administered orally once daily without regard to food for at least 48 weeks. | 284 |
| DTG + F/TAF DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for at least 48 weeks. | 281 |
| Total | 565 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Treatment Phase | Adverse Event | 3 | 3 | 0 | 0 |
| Double-Blind Treatment Phase | Death | 2 | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Investigator's Discretion | 1 | 3 | 0 | 0 |
| Double-Blind Treatment Phase | Lost to Follow-up | 4 | 3 | 0 | 0 |
| Double-Blind Treatment Phase | Non-Compliance with Study Drug | 1 | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Protocol Violation | 0 | 1 | 0 | 0 |
| Double-Blind Treatment Phase | Randomized but not Treated | 0 | 2 | 0 | 0 |
| Double-Blind Treatment Phase | Withdrew Consent | 10 | 16 | 0 | 0 |
| Open-label B/F/TAF Extension Phase | Adverse Event | 0 | 0 | 0 | 1 |
| Open-label B/F/TAF Extension Phase | Lost to Follow-up | 0 | 0 | 3 | 1 |
| Open-label B/F/TAF Extension Phase | Withdrew Consent | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | B/F/TAF | DTG + F/TAF |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 11.3 | 50 years STANDARD_DEVIATION 11.3 | 49 years STANDARD_DEVIATION 11.3 |
| CD4 Cell Count | 686 Cells/μL STANDARD_DEVIATION 303.1 | 714 Cells/μL STANDARD_DEVIATION 309.1 | 658 Cells/μL STANDARD_DEVIATION 294.7 |
| CD4 Cell Count Category ≥ 200 to < 350 Cells/μL | 52 Participants | 18 Participants | 34 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 Cells/μL | 97 Participants | 53 Participants | 44 Participants |
| CD4 Cell Count Category ≥ 500 Cells/ μL | 403 Participants | 207 Participants | 196 Participants |
| CD4 Cell Count Category < 50 Cells/ μL | 1 Participants | 0 Participants | 1 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 Cells/μL | 12 Participants | 6 Participants | 6 Participants |
| HIV-1 RNA Category < 50 copies/mL | 551 Participants | 276 Participants | 275 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 14 Participants | 8 Participants | 6 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 110 Participants | 61 Participants | 49 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 449 Participants | 220 Participants | 229 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black | 129 Participants | 68 Participants | 61 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 22 Participants | 9 Participants | 13 Participants |
| Race/Ethnicity, Customized Race White | 399 Participants | 200 Participants | 199 Participants |
| Region of Enrollment Austria | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Canada | 49 Participants | 24 Participants | 25 Participants |
| Region of Enrollment France | 26 Participants | 12 Participants | 14 Participants |
| Region of Enrollment Germany | 56 Participants | 30 Participants | 26 Participants |
| Region of Enrollment Puerto Rico | 32 Participants | 19 Participants | 13 Participants |
| Region of Enrollment United States | 399 Participants | 197 Participants | 202 Participants |
| Sex: Female, Male Female | 80 Participants | 39 Participants | 41 Participants |
| Sex: Female, Male Male | 485 Participants | 245 Participants | 240 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 284 | 2 / 283 | 0 / 125 | 0 / 117 |
| other Total, other adverse events | 181 / 284 | 170 / 281 | 30 / 125 | 33 / 116 |
| serious Total, serious adverse events | 36 / 284 | 27 / 281 | 12 / 125 | 11 / 116 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 48
Population: The Full Analysis Set included participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 0.4 percentage of participants |
| DTG + F/TAF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 1.1 percentage of participants |
Comparison: The null hypothesis was that the B/F/TAF group is at least 4% higher than the DTG + F/TAF group with respect to the percentage of participants with HIV-1 RNA ≥ 50 copies/mL as determined by the US FDA-defined snapshot algorithm at Week 48; the alternative hypothesis was that the B/F/TAF group is less than 4% higher than the DTG + F/TAF group with respect to the percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48.95.001% CI: [-2.8, 1]
p-value: 0.37Fisher Exact
Secondary
Change From Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | Change From Baseline in CD4+ Cell Count at Week 48 | 18 cells/µL | Standard Deviation 179.1 |
| DTG + F/TAF | Change From Baseline in CD4+ Cell Count at Week 48 | 36 cells/µL | Standard Deviation 152.6 |
p-value: 0.2395% CI: [-46, 11]ANOVA
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 93.3 percentage of participants |
| DTG + F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 91.1 percentage of participants |
95.001% CI: [-2.3, 6.8]