HIV-1 Infection
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), or atazanavir (ATV) + ritonavir (RTV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in virologically suppressed HIV-1 infected women.
Interventions
DRUGE/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily with food
DRUGE/C/F/TDF
150/150/200/300 mg FDC administered orally once daily with food
DRUGATV
ATV 300 mg capsules administered orally once daily with food
DRUGRTV
RTV 100 mg tablets administered orally once daily with food
DRUGFTC/TDF
200/300 mg tablet administered orally once daily with food
DRUGB/F/TAF
50/200/25 mg FDC tablet administered orally once daily without regard to food
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria Medically stable HIV-1 infected women who meet the following criteria: * Completion of the Week 48 open-label extension (OLE) visit or any post Week 48 OLE visits in Gilead-sponsored study GS-US-236-0128, or Completion of the Week 96 visit or any post Week 96 visits in Gilead-sponsored study GS-US-292-0109 or completion of the Week 144 visit or any post Week 144 visits in Gilead sponsored studies GS-US-292-0104 or GS-US-292-0111. * Currently on a stable antiretroviral regimen consisting of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF continuously for ≥ 12 consecutive weeks preceding the Screening visit * Documented plasma HIV-1 RNA levels \< 50 copies/mL for ≥ 12 weeks preceding the Screening visit. After reaching HIV-1 RNA \< 50 copies/mL, single values of HIV-1 RNA ≥ 50 copies/mL followed by re-suppression to \< 50 copies/mL is allowed * HIV-1 RNA \<50 copies/mL at screening * Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula at the Screening visit 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 Determined 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 Determined 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. |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
Countries
Dominican Republic, Puerto Rico, Russia, Thailand, Uganda, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Russian Federation, Thailand, Dominican Republic, and Uganda. The first participant was screened on 19 February 2016. The last study visit occurred on 26 November 2018.
Pre-assignment details
491 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| B/F/TAF B/F/TAF (50/200/25 mg) FDC tablet once daily without regard to food for 48 weeks. | 234 |
| Stay on Baseline Regimen Participants remained on their baseline regimen of E/C/F/TAF (150/150/200/10 mg) tablet, E/C/F/TDF (150/150/200/300 mg) tablet, or ATV 300 mg capsule + RTV 100 mg tablet + FTC/TDF (200/300 mg) tablet for 48 weeks. | 236 |
| Total | 470 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase | Adverse Event | 0 | 1 |
| Extension Phase | Lost to Follow-up | 3 | 1 |
| Extension Phase | Pregnancy | 1 | 1 |
| Extension Phase | Withdrew Consent | 0 | 1 |
| Randomized Phase | Death | 0 | 1 |
| Randomized Phase | Investigator's Discretion | 0 | 2 |
| Randomized Phase | Lost to Follow-up | 0 | 1 |
| Randomized Phase | Pregnancy | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Stay on Baseline Regimen | B/F/TAF |
|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 9.3 | 40 years STANDARD_DEVIATION 9.1 | 40 years STANDARD_DEVIATION 9.5 |
| CD4 Cell Count | 725 cells/µL STANDARD_DEVIATION 268.3 | 738 cells/µL STANDARD_DEVIATION 268.4 | 712 cells/µL STANDARD_DEVIATION 268.1 |
| CD4 Cell Count Category ≥ 200 to < 350 cells/µL | 19 Participants | 9 Participants | 10 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 cells/µL | 58 Participants | 25 Participants | 33 Participants |
| CD4 Cell Count Category ≥ 500 cells/µL | 391 Participants | 201 Participants | 190 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 cells/µL | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 74 Participants | 38 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 396 Participants | 198 Participants | 198 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV-1 RNA Category < 50 copies/mL | 467 Participants | 233 Participants | 234 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 3 Participants | 3 Participants | 0 Participants |
| Prior Antiretroviral (ARV) Regimen E/C/F/TAF | 249 Participants | 125 Participants | 124 Participants |
| Prior Antiretroviral (ARV) Regimen E/C/F/TDF | 197 Participants | 98 Participants | 99 Participants |
| Prior Antiretroviral (ARV) Regimen RTV + ATV + FTC/TDF | 24 Participants | 13 Participants | 11 Participants |
| Race/Ethnicity, Customized Asian | 102 Participants | 54 Participants | 48 Participants |
| Race/Ethnicity, Customized Black | 174 Participants | 83 Participants | 91 Participants |
| Race/Ethnicity, Customized Other | 61 Participants | 32 Participants | 29 Participants |
| Race/Ethnicity, Customized White | 133 Participants | 67 Participants | 66 Participants |
| Region of Enrollment Dominican Republic | 58 Participants | 30 Participants | 28 Participants |
| Region of Enrollment Russia | 112 Participants | 54 Participants | 58 Participants |
| Region of Enrollment Thailand | 101 Participants | 54 Participants | 47 Participants |
| Region of Enrollment Uganda | 127 Participants | 62 Participants | 65 Participants |
| Region of Enrollment United States | 72 Participants | 36 Participants | 36 Participants |
| Sex: Female, Male Female | 470 Participants | 236 Participants | 234 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 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 | 0 / 234 | 0 / 236 | 0 / 231 | 1 / 228 |
| other Total, other adverse events | 61 / 234 | 47 / 236 | 52 / 231 | 41 / 228 |
| serious Total, serious adverse events | 7 / 234 | 9 / 236 | 8 / 231 | 10 / 228 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined 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 Determined by the US FDA-Defined Snapshot Algorithm | 1.7 percentage of participants |
| Stay on Baseline Regimen | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-Defined Snapshot Algorithm | 1.7 percentage of participants |
Comparison: The null hypothesis was that the percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 in the B/F/TAF group was at least 4% higher than the rate in the SBR group; the alternative hypothesis was that the percentage of participants with HIV-1 RNA ≥ 50 copies/mL in the B/F/TAF group was less than 4% higher than that in the SBR group.95.001% CI: [-2.9, 2.9]
p-value: 1Fisher 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 | 29 cells/µL | Standard Deviation 159.4 |
| Stay on Baseline Regimen | Change From Baseline in CD4+ Cell Count at Week 48 | 26 cells/µL | Standard Deviation 170.3 |
p-value: 0.8495% CI: [-27, 34]ANOVA
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined 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: 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 Determined by the US FDA-Defined Snapshot Algorithm | 95.7 percentage of participants |
| Stay on Baseline Regimen | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-Defined Snapshot Algorithm | 95.3 percentage of participants |
95.001% CI: [-3.7, 4.5]
p-value: 1Fisher Exact