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 boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.
Interventions
DRUGRTV
100 mg capsule coadministered orally with ATV or DRV once daily with food
DRUGATV
300 mg capsule administered orally once daily with food
DRUGDRV
800 mg tablet administered orally once daily with food
DRUGCOBI
150 mg tablet coadministered orally with ATV or DRV once daily with food
DRUGATV/co
300/150 mg FDC tablet administered orally once daily with food
DRUGDRV/co
800/150 mg FDC tablet administered orally once daily with food
DRUGFTC/TDF
200/300 mg FDC tablet administered orally once daily without regard to food
DRUGABC/3TC
600/300 mg tablet administered orally once daily with or without regard to 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
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Currently receiving a once daily antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for ≥ 6 months preceding the screening visit * Adequate renal function: * Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec) according to the Cockcroft-Gault formula * Life expectancy ≥ 1 year * Currently on a stable regimen for ≥ 6 months preceding the screening visit with documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 6 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). Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or blip) prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL \[e.g., \< 20 copies/mL\], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests) * Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I * No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) Key
Exclusion criteria
* An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening * Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) * Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies) * Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance * A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study * Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 * Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial * Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with the dosing requirements * Any known allergies to the excipients of B/F/TAF FDC or ATV, RTV, DRV, COBI, FTC/TDF or ABC/3TC * Females who are pregnant (as confirmed by positive serum pregnancy test) * Females who are breastfeeding * Acute hepatitis in the 30 days prior to study entry * Chronic hepatitis B infection in individuals not on a TDF containing regimen, as determined by either: * Positive hepatitis B virus (HBV) surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit * Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit * Active tuberculosis infection Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the 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 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 to Week 48 | — |
Countries
Australia, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Dominican Republic, North America, Australia, and Europe. The first participant was screened on 20 November 2015. The last study visit occurred on 23 December 2019.
Pre-assignment details
707 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| B/F/TAF Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.
Extension Phase: After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first. | 290 |
| Stay on Baseline Regimen (SBR) Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablets or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.
Extension Phase: After Week 48, participants in countries where B/F/TAF was not available were given the option to receive B/F/TAF for up to 96 additional weeks or until the product became accessible to participants through an access program, or until Gilead Sciences elected to discontinue the study in that country, whichever occurred first. | 287 |
| Total | 577 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Optional Extension Phase | Adverse Event | 0 | 2 |
| Optional Extension Phase | Investigator's discretion | 2 | 2 |
| Optional Extension Phase | Lost to Follow-up | 3 | 3 |
| Optional Extension Phase | Not treated in extension phase | 0 | 1 |
| Optional Extension Phase | Pregnancy | 0 | 3 |
| Optional Extension Phase | Protocol Violation | 1 | 0 |
| Optional Extension Phase | Withdrew consent | 3 | 2 |
| Randomized Phase | Adverse Event | 2 | 0 |
| Randomized Phase | Death | 1 | 1 |
| Randomized Phase | Investigator's discretion | 0 | 1 |
| Randomized Phase | Lack of Efficacy | 1 | 0 |
| Randomized Phase | Lost to Follow-up | 1 | 3 |
| Randomized Phase | Non-compliance with study drug | 1 | 1 |
| Randomized Phase | Protocol Violation | 1 | 0 |
| Randomized Phase | Withdrew consent | 8 | 15 |
Baseline characteristics
| Characteristic | Stay on Baseline Regimen (SBR) | B/F/TAF | Total |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 10.5 | 47 years STANDARD_DEVIATION 10.5 | 46 years STANDARD_DEVIATION 10.5 |
| CD4 Cell Count | 657 cells/μL STANDARD_DEVIATION 285 | 669 cells/μL STANDARD_DEVIATION 303.4 | 663 cells/μL STANDARD_DEVIATION 294.2 |
| CD4 Cell Count Category ≥ 200 to < 350 cells/μL | 30 Participants | 26 Participants | 56 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 cells/μL | 60 Participants | 62 Participants | 122 Participants |
| CD4 Cell Count Category ≥ 500 cells/μL | 189 Participants | 198 Participants | 387 Participants |
| CD4 Cell Count Category < 50 cells/μL | 0 Participants | 0 Participants | 0 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 cells/μL | 8 Participants | 4 Participants | 12 Participants |
| HIV-1 RNA Category < 50 copies/mL | 277 Participants | 285 Participants | 562 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 10 Participants | 5 Participants | 15 Participants |
| HIV Disease Status Acquired Immunodeficiency Syndrome (AIDS) | 33 Participants | 34 Participants | 67 Participants |
| HIV Disease Status Asymptomatic | 234 Participants | 240 Participants | 474 Participants |
| HIV Disease Status Symptomatic HIV Infection | 20 Participants | 16 Participants | 36 Participants |
| Prior ARV Regimen Boosted ATV + ABC/3TC | 23 Participants | 21 Participants | 44 Participants |
| Prior ARV Regimen Boosted ATV + FTC/TDF | 110 Participants | 105 Participants | 215 Participants |
| Prior ARV Regimen Boosted DRV + ABC/3TC | 21 Participants | 24 Participants | 45 Participants |
| Prior ARV Regimen Boosted DRV + FTC/TDF | 133 Participants | 140 Participants | 273 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 6 Participants | 16 Participants |
| Race/Ethnicity, Customized Black | 72 Participants | 79 Participants | 151 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 47 Participants | 60 Participants | 107 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 240 Participants | 230 Participants | 470 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 14 Participants | 26 Participants |
| Race/Ethnicity, Customized White | 190 Participants | 188 Participants | 378 Participants |
| Region of Enrollment Australia | 16 Participants | 15 Participants | 31 Participants |
| Region of Enrollment Belgium | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Canada | 15 Participants | 18 Participants | 33 Participants |
| Region of Enrollment Dominican Republic | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment France | 17 Participants | 17 Participants | 34 Participants |
| Region of Enrollment Germany | 33 Participants | 28 Participants | 61 Participants |
| Region of Enrollment Italy | 5 Participants | 3 Participants | 8 Participants |
| Region of Enrollment Spain | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 23 Participants | 31 Participants | 54 Participants |
| Region of Enrollment United States | 164 Participants | 166 Participants | 330 Participants |
| Sex: Female, Male Female | 53 Participants | 47 Participants | 100 Participants |
| Sex: Female, Male Male | 234 Participants | 243 Participants | 477 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 | 1 / 290 | 1 / 287 | 0 / 272 | 1 / 244 |
| other Total, other adverse events | 117 / 290 | 126 / 287 | 108 / 272 | 113 / 244 |
| serious Total, serious adverse events | 17 / 290 | 21 / 287 | 20 / 272 | 29 / 244 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the 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: Full Analysis Set: all 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 HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 1.7 percentage of participants |
| Stay on Baseline Regimen (SBR) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the 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.95.002% CI: [-2.5, 2.5]
p-value: 1Fisher Exact
Secondary
Change From Baseline in CD4 Cell Count at Week 48
Time frame: Baseline to 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 | 25 cells/μL | Standard Deviation 151.2 |
| Stay on Baseline Regimen (SBR) | Change From Baseline in CD4 Cell Count at Week 48 | 0 cells/μL | Standard Deviation 159.4 |
p-value: 0.06895% CI: [-2, 52]ANOVA
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the 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: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 92.1 percentage of participants |
| Stay on Baseline Regimen (SBR) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 88.9 percentage of participants |
95.002% CI: [-1.6, 8.2]
p-value: 0.2Fisher Exact