HIV-1 Infection
Conditions
Keywords
HIV, HIV-1 Positive, Virologically-Suppressed
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching abacavir/lamivudine (ABC/3TC) fixed-dose combination (FDC) tablets to emtricitabine/tenofovir alafenamide (F/TAF) FDC tablets versus maintaining ABC/3TC in human immunodeficiency virus type 1 (HIV-1) infected adults who are virologically suppressed on regimens containing ABC/3TC.
Interventions
DRUGF/TAF
200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily
DRUGABC/3TC
600/300 mg FDC tablets administered orally once daily
DRUGABC/3TC Placebo
Tablets administered orally once daily
DRUGF/TAF Placebo
Tablets administered orally once daily
DRUG3rd ARV agent
An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).
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: * The ability to understand and sign a written informed consent form * On antiretroviral regimen containing ABC/3TC FDC in combination with one 3rd agent for ≥ 6 consecutive months prior to screening * Plasma HIV-1 RNA levels \< 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and without experiencing two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year * Plasma HIV-1 RNA should be \< 50 copies/mL at the screening visit * Normal ECG * Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance * Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN) * Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin * Adequate hematologic function * Serum amylase ≤ 5 × ULN * Females of childbearing potential and males must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug Key
Exclusion criteria
* A new AIDS-defining condition diagnosed within the 30 days prior to screening * Hepatitis B surface antigen (HBsAg) positive * Individuals experiencing decompensated cirrhosis * Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis) * Pregnant or lactating females * Have an implanted defibrillator or pacemaker * Current alcohol or substance use judged by the investigator to potentially interfere with study compliance * A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. * Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit * 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 dosing requirements * Participation in any other clinical trial (including observational trials) without prior approval * Medications excluded due to the potential for interaction with emtricitabine (FTC), TAF, ABC or 3TC 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 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 |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | Week 96 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 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. |
| 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. |
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | Week 96 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 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. |
| Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | Week 48 | The percentage of participants achieving HIV-1 RNA \< 20 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. |
| Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | Week 96 | The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 96 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. |
| Percent Change From Baseline in Spine BMD at Week 96 | Baseline; Week 96 | — |
| Change From Baseline in CD4 Cell Count at Week 96 | Baseline; Week 96 | — |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | Baseline; Week 48 | — |
| Percent Change From Baseline in Hip BMD at Week 96 | Baseline; Week 96 | — |
| Percent Change From Baseline in Spine BMD at Week 48 | Baseline; Week 48 | — |
| Change From Baseline in CD4 Cell Count at Week 48 | Baseline; Week 48 | — |
Countries
Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Puerto Rico, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America and Europe. The first participant was screened on 29 June 2015. The last study visit occurred on 13 March 2019.
Pre-assignment details
626 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| F/TAF F/TAF (200/10 mg) FDC tablet (with boosted 3rd ARV agent) or F/TAF (200/25 mg) FDC tablet (with unboosted 3rd ARV agent) + ABC/3TC placebo tablet once daily for 96 weeks | 280 |
| ABC/3TC ABC/3TC (600/300 mg) FDC tablet + F/TAF placebo tablet once daily + allowed 3rd ARV agent for 96 weeks | 276 |
| Total | 556 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Phase | Adverse Event | 12 | 9 |
| Double-Blind Phase | Death | 2 | 0 |
| Double-Blind Phase | Investigator's Discretion | 8 | 8 |
| Double-Blind Phase | Lack of Efficacy | 2 | 1 |
| Double-Blind Phase | Lost to Follow-up | 9 | 5 |
| Double-Blind Phase | Non-Compliance with Study Drug | 3 | 1 |
| Double-Blind Phase | Protocol Violation | 1 | 1 |
| Double-Blind Phase | Randomized and Never Treated | 5 | 6 |
| Double-Blind Phase | Withdrew Consent | 25 | 25 |
Baseline characteristics
| Characteristic | ABC/3TC | F/TAF | Total |
|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 9.3 | 51 years STANDARD_DEVIATION 9.4 | 51 years STANDARD_DEVIATION 9.3 |
| CD4 Cell Count | 727 cells/µL STANDARD_DEVIATION 275.2 | 703 cells/µL STANDARD_DEVIATION 298.7 | 715 cells/µL STANDARD_DEVIATION 287.3 |
| CD4 Cell Count Category ≥ 200 to < 350 cells/µL | 16 Participants | 20 Participants | 36 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 cells/µL | 38 Participants | 56 Participants | 94 Participants |
| CD4 Cell Count Category ≥ 500 cells/µL | 221 Participants | 204 Participants | 425 Participants |
| CD4 Cell Count Category < 50 cells/µL | 1 Participants | 0 Participants | 1 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 cells/µL | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 16 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 257 Participants | 264 Participants | 521 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV-1 RNA Category < 50 copies/mL | 273 Participants | 278 Participants | 551 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 3 Participants | 2 Participants | 5 Participants |
| HIV Disease Status AIDS | 50 Participants | 47 Participants | 97 Participants |
| HIV Disease Status Asymptomatic | 201 Participants | 201 Participants | 402 Participants |
| HIV Disease Status Symptomatic HIV Infection | 24 Participants | 31 Participants | 55 Participants |
| HIV Disease Status Unknown | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 66 Participants | 64 Participants | 130 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 199 Participants | 205 Participants | 404 Participants |
| Region of Enrollment Belgium | 6 Participants | 4 Participants | 10 Participants |
| Region of Enrollment Canada | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment Denmark | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment France | 17 Participants | 18 Participants | 35 Participants |
| Region of Enrollment Germany | 19 Participants | 20 Participants | 39 Participants |
| Region of Enrollment Ireland | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment Italy | 17 Participants | 26 Participants | 43 Participants |
| Region of Enrollment Spain | 34 Participants | 32 Participants | 66 Participants |
| Region of Enrollment Sweden | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United Kingdom | 59 Participants | 50 Participants | 109 Participants |
| Region of Enrollment United States | 101 Participants | 105 Participants | 206 Participants |
| Sex: Female, Male Female | 61 Participants | 40 Participants | 101 Participants |
| Sex: Female, Male Male | 215 Participants | 240 Participants | 455 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 | 5 / 280 | 0 / 276 | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 190 / 280 | 199 / 276 | 1 / 6 | 2 / 5 |
| serious Total, serious adverse events | 55 / 280 | 32 / 276 | 0 / 6 | 0 / 5 |
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 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 all participants who were randomized into the study and received at least 1 dose of study drug. Participants were grouped according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 88.6 percentage of participants |
| ABC/3TC | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 92.4 percentage of participants |
Comparison: The analysis purpose of the primary efficacy endpoint was to assess the noninferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent.p-value: 0.1595.002% CI: [-8.9, 1.1]Fisher 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 |
|---|---|---|---|
| F/TAF | Change From Baseline in CD4 Cell Count at Week 48 | -30 cells/µL | Standard Deviation 152.3 |
| ABC/3TC | Change From Baseline in CD4 Cell Count at Week 48 | 2 cells/µL | Standard Deviation 171.2 |
p-value: 0.02695% CI: [-61, -4]ANOVA
Secondary
Change From Baseline in CD4 Cell Count at Week 96
Time frame: Baseline; Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF | Change From Baseline in CD4 Cell Count at Week 96 | -29 cells/μL | Standard Deviation 160.7 |
| ABC/3TC | Change From Baseline in CD4 Cell Count at Week 96 | 10 cells/μL | Standard Deviation 178.2 |
p-value: 0.01395% CI: [-70, -8]ANOVA
Secondary
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 20 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) |
|---|---|---|
| F/TAF | Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 85.7 percentage of participants |
| ABC/3TC | Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 87.3 percentage of participants |
Comparison: The analysis purpose of this efficacy endpoint was to assess the noninferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent.p-value: 0.6295% CI: [-7.4, 4.2]Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 96 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 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF | Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 80.4 percentage of participants |
| ABC/3TC | Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 86.2 percentage of participants |
Comparison: The analysis purpose of this efficacy endpoint was to assess the noninferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent.p-value: 0.06995% CI: [-12.2, 0.4]Fisher Exact
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: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 1.8 percentage of participants |
| ABC/3TC | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 0.7 percentage of participants |
Comparison: The analysis purpose of this efficacy endpoint was to assess the non-inferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent.p-value: 0.4595.002% CI: [-1, 3.5]Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 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 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 82.1 percentage of participants |
| ABC/3TC | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 88.4 percentage of participants |
Comparison: The analysis purpose of this efficacy endpoint was to assess the non-inferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent.p-value: 0.04295% CI: [-12.3, -0.3]Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 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 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 2.5 percentage of participants |
| ABC/3TC | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 1.1 percentage of participants |
Comparison: The analysis purpose of this efficacy endpoint was to assess the non-inferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent.p-value: 0.3495% CI: [-1, 4.2]Fisher Exact
Secondary
Percent Change From Baseline in Hip BMD at Week 96
Time frame: Baseline; Week 96
Population: Participants in the Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF | Percent Change From Baseline in Hip BMD at Week 96 | 0.169 percent change | Standard Deviation 2.7277 |
| ABC/3TC | Percent Change From Baseline in Hip BMD at Week 96 | 0.021 percent change | Standard Deviation 2.7212 |
p-value: 0.5395% CI: [-0.348, 0.678]ANOVA
Secondary
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set (all participants who are randomized and have received at least one dose of study drug, and have nonmissing baseline hip BMD values) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | 0.246 percent change | Standard Deviation 2.2914 |
| ABC/3TC | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | 0.086 percent change | Standard Deviation 2.3315 |
p-value: 0.495% CI: [-0.24, 0.598]ANOVA
Secondary
Percent Change From Baseline in Spine BMD at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Spine DXA Analysis Set (all participants who are randomized and have received at least one dose of study drug, and have nonmissing baseline spine BMD values) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF | Percent Change From Baseline in Spine BMD at Week 48 | 0.081 percent change | Standard Deviation 3.0051 |
| ABC/3TC | Percent Change From Baseline in Spine BMD at Week 48 | -0.052 percent change | Standard Deviation 3.755 |
p-value: 0.6395% CI: [-0.465, 0.767]ANOVA
Secondary
Percent Change From Baseline in Spine BMD at Week 96
Time frame: Baseline; Week 96
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF | Percent Change From Baseline in Spine BMD at Week 96 | 0.178 percent change | Standard Deviation 3.8881 |
| ABC/3TC | Percent Change From Baseline in Spine BMD at Week 96 | 0.235 percent change | Standard Deviation 4.3066 |
p-value: 0.8995% CI: [-0.825, 0.713]ANOVA