HIV-1 Infection
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of switching from a regimen of dolutegravir (DTG) and abacavir/lamivudine (ABC/3TC) or a fixed dose combination (FDC) of abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) to a FDC of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing DTG and ABC/3TC as the FDC ABC/DTG/3TC in virologically suppressed Human Immunodeficiency Virus- 1 (HIV-1) infected adults.
Interventions
DRUGABC/DTG/3TC
600/50/300 mg FDC tablets administered orally once daily without regard to food
DRUGB/F/TAF
50/200/25 mg FDC tablets administered orally once daily without regard to food
Tablets administered orally once daily without regard to food
DRUGB/F/TAF Placebo
Tablets administered orally once daily without regard to food
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: * Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec). * Currently receiving an antiretroviral regimen of DTG + ABC/3TC, or ABC/DTG/3TC FDC for ≥ 3 months prior to the screening visit. * HIV ribonucleic acid (RNA) \< 50 copies/mL at the screening visit. * Currently on a stable regimen for ≥ 3 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 3 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). * Have no documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), DTG, ABC or 3TC. Key
Exclusion criteria
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance. * Active tuberculosis infection. * Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding). * Females who are pregnant. * Females who are breastfeeding. * Acute hepatitis in the 30 days prior to study entry. * Chronic Hepatitis B Virus (HBV) infection. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Virologic Failure (HIV-1 RNA ≥ 50 Copies/mL) as Defined by the Modified 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
| Spine Bone Mineral Density (BMD) at Baseline | Baseline | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL 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. |
| Hip Bone Mineral Density at Baseline | Baseline | — |
| Percentage Change From Baseline in Hip BMD at Week 48 | Baseline; Week 48 | — |
| Percentage Change From Baseline in Spine BMD at Week 48 | Baseline; Week 48 | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Puerto Rico, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, and Australia. The first participant was screened on 11 November 2015. The last study visit occurred on 23 October 2019.
Pre-assignment details
646 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| B/F/TAF Double-Blind Phase: B/F/TAF 50/200/25 mg FDC tablet + ABC/DTG/3TC placebo orally once daily for at least 48 weeks, without regard to food.
OL Extension Phase: After Week 48, participants in a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. | 282 |
| ABC/DTG/3TC Double-Blind Phase: ABC/DTG/3TC (600/50/300 mg) FDC tablet + B/F/TAF placebo orally once daily for at least 48 weeks, without regard to food.
OL Extension Phase: After Week 48, participants in a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. | 281 |
| Total | 563 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Phase | Adverse Event | 3 | 3 |
| Double-Blind Treatment Phase | Death | 2 | 0 |
| Double-Blind Treatment Phase | Did not receive study drug | 2 | 2 |
| Double-Blind Treatment Phase | Investigator's discretion | 2 | 0 |
| Double-Blind Treatment Phase | Lost to Follow-up | 4 | 2 |
| Double-Blind Treatment Phase | Non-compliance with study drug | 1 | 0 |
| Double-Blind Treatment Phase | Pregnancy | 1 | 1 |
| Double-Blind Treatment Phase | Withdrew consent | 4 | 8 |
| OL Extension B/F/TAF Treatment Phase | Adverse Event | 0 | 1 |
| OL Extension B/F/TAF Treatment Phase | Death | 0 | 1 |
| OL Extension B/F/TAF Treatment Phase | Investigator's discretion | 1 | 2 |
| OL Extension B/F/TAF Treatment Phase | Lack of Efficacy | 0 | 1 |
| OL Extension B/F/TAF Treatment Phase | Lost to Follow-up | 3 | 4 |
| OL Extension B/F/TAF Treatment Phase | Withdrew consent | 1 | 2 |
Baseline characteristics
| Characteristic | Total | B/F/TAF | ABC/DTG/3TC |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 11.3 | 46 years STANDARD_DEVIATION 11.1 | 45 years STANDARD_DEVIATION 11.5 |
| CD4 Cell Count | 723 cell/µL STANDARD_DEVIATION 298.1 | 752 cell/µL STANDARD_DEVIATION 302.2 | 694 cell/µL STANDARD_DEVIATION 291.6 |
| CD4 Cell Count Category ≥ 200 to < 350 cells/μL | 46 Participants | 16 Participants | 30 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 cells/μL | 75 Participants | 33 Participants | 42 Participants |
| CD4 Cell Count Category ≥ 500 cells/μL | 432 Participants | 227 Participants | 205 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 cells/μL | 10 Participants | 6 Participants | 4 Participants |
| HIV-1 RNA Categories < 50 copies/mL | 550 Participants | 278 Participants | 272 Participants |
| HIV-1 RNA Categories ≥ 50 copies/mL | 13 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants | 9 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 121 Participants | 59 Participants | 62 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 98 Participants | 46 Participants | 52 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 463 Participants | 236 Participants | 227 Participants |
| Race/Ethnicity, Customized Not Permitted | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 408 Participants | 206 Participants | 202 Participants |
| Region of Enrollment Australia | 15 Participants | 9 Participants | 6 Participants |
| Region of Enrollment Belgium | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Canada | 35 Participants | 13 Participants | 22 Participants |
| Region of Enrollment France | 12 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Germany | 28 Participants | 17 Participants | 11 Participants |
| Region of Enrollment Italy | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Spain | 62 Participants | 31 Participants | 31 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 401 Participants | 203 Participants | 198 Participants |
| Sex: Female, Male Female | 64 Participants | 35 Participants | 29 Participants |
| Sex: Female, Male Male | 499 Participants | 247 Participants | 252 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 | 2 / 282 | 0 / 281 | 1 / 259 | 1 / 265 |
| other Total, other adverse events | 122 / 282 | 132 / 281 | 84 / 259 | 82 / 265 |
| serious Total, serious adverse events | 17 / 282 | 26 / 281 | 24 / 259 | 11 / 265 |
Outcome results
Primary
Percentage of Participants With Virologic Failure (HIV-1 RNA ≥ 50 Copies/mL) as Defined by the Modified 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: The Full Analysis Set included participants who were randomized into the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | Percentage of Participants With Virologic Failure (HIV-1 RNA ≥ 50 Copies/mL) as Defined by the Modified US FDA-defined Snapshot Algorithm | 1.1 percentage of participants |
| ABC/DTG/3TC | Percentage of Participants With Virologic Failure (HIV-1 RNA ≥ 50 Copies/mL) as Defined by the Modified US FDA-defined Snapshot Algorithm | 0.4 percentage of participants |
95.002% CI: [-1, 2.8]
p-value: 0.62Fisher 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 | -31 cells/µL | Standard Deviation 181.3 |
| ABC/DTG/3TC | Change From Baseline in CD4+ Cell Count at Week 48 | 4 cells/µL | Standard Deviation 191 |
p-value: 0.03195% CI: [-67, -3]ANOVA
Secondary
Hip Bone Mineral Density at Baseline
Time frame: Baseline
Population: The Hip DXA Analysis Set included participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | Hip Bone Mineral Density at Baseline | 1.006 g/cm^2 | Standard Deviation 0.1471 |
| ABC/DTG/3TC | Hip Bone Mineral Density at Baseline | 0.996 g/cm^2 | Standard Deviation 0.1363 |
Secondary
Percentage Change From Baseline in Hip BMD at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | Percentage Change From Baseline in Hip BMD at Week 48 | 0.156 percentage change | Standard Deviation 2.2138 |
| ABC/DTG/3TC | Percentage Change From Baseline in Hip BMD at Week 48 | 0.299 percentage change | Standard Deviation 2.1077 |
p-value: 0.4795% CI: [-0.534, 0.248]ANOVA
Secondary
Percentage Change From Baseline in Spine BMD at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | Percentage Change From Baseline in Spine BMD at Week 48 | 0.692 percentage change | Standard Deviation 3.1296 |
| ABC/DTG/3TC | Percentage Change From Baseline in Spine BMD at Week 48 | 0.416 percentage change | Standard Deviation 2.9973 |
p-value: 0.3395% CI: [-0.275, 0.827]ANOVA
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL 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 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Defined by the US FDA-defined Snapshot Algorithm | 93.6 percentage of participants |
| ABC/DTG/3TC | Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Defined by the US FDA-defined Snapshot Algorithm | 95.0 percentage of participants |
95.002% CI: [-5.5, 2.6]
p-value: 0.59Fisher Exact
Secondary
Spine Bone Mineral Density (BMD) at Baseline
Time frame: Baseline
Population: The Spine dual X-ray absorptiometry (DXA) analysis Set included participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline spine BMD values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | Spine Bone Mineral Density (BMD) at Baseline | 1.124 g/cm^2 | Standard Deviation 0.1833 |
| ABC/DTG/3TC | Spine Bone Mineral Density (BMD) at Baseline | 1.103 g/cm^2 | Standard Deviation 0.1548 |