HIV-1 Infection
Conditions
Keywords
HIV 1 Infection, HIV, Virologically-Suppressed, Antiretroviral agents
Brief summary
The primary objective of this study is to evaluate the efficacy of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) relative to continuing on a baseline regimen consisting of abacavir/lamivudine (ABC/3TC) plus a 3rd antiretroviral agent in HIV-1 infected participants.
Interventions
DRUGE/C/F/TAF
150/150/200/10 mg FDC tablets administered orally once daily
DRUGABC/3TC
600/300 mg tablets administered orally once daily
DRUGThird Antiretroviral Agent
Third antiretroviral agents could include one of the following: * ATV+cobicistat (COBI; Tybost®) or ATV/COBI FDC * DRV+COBI or DRV/COBI FDC * darunavir (DRV; Prezista®) + RTV * lopinavir/ritonavir (LPV/r; Kaletra®) * atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®) * efavirenz (EFV; Sustiva®) * etravirine (ETR; Intelence®) * nevirapine (NVP; Viramune®) * rilpivirine (RPV; Edurant®) * dolutegravir (DTG; Tivicay®) * raltegravir (RAL; Isentress®) * fosamprenavir (FPV; Lexiva®) + RTV * saquinavir (SQV; Invirase®) + RTV * ATV (no booster) Drug classes: * Protease inhibitors (PI): LPV/r, ATV, RTV, ATV, DRV, FPV and SQV * Pharmacokinetic enhancer: COBI * Non-nucleoside reverse transcriptase inhibitors (NNRTI): EFV, RPV, NVP, and ETR * Integrase inhibitors: RAL and DTG
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: HIV-infected adult participants who meet the following criteria will be given the option to participate in the study: * Currently receiving ABC/3TC plus a third antiretroviral (ARV) agent for ≥ 6 consecutive months preceding the screening visit. For subjects with 3 or more ART regimens, a regimen history must be provided to the Sponsor for approval. Allowed third antiretroviral agents include LPV/r, ATV+RTV, ATV+COBI (or ATV/COBI FDC), DRV+RTV, DRV + COBI (or DRV/COBI FDC) FPV + RTV, SQV + RTV, ATV (no booster), EFV, RPV, NVP, ETR, RAL or DTG * Documented plasma HIV-1 RNA levels \< 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay). In the preceding 6 months prior to screening, one episode of blip (HIV-1 RNA \> 50 and \< 400 copies/mL) is acceptable, only if HIV-1 RNA is \< 50 copies/mL immediately before and after the blip. * Plasma HIV-1 RNA \< 50 copies/mL at screening visit * Individuals will have no evidence of previous virologic failure on a PI+RTV or integrase strand transfer inhibitor-based regimen (with or without resistance to either class of ARV). * All documented historical plasma genotype(s) must not show resistance to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC), including, but not limited to the presence of reverse transcriptase resistance mutants K65R, K70E, M184V/I, or thymidine analog associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype is not available or subject has 3 or more ART regimens, subject will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC. * Adequate renal function defined as having an estimated glomerular filtration rate of ≥ 30 mL/min as calculated by Cockcroft-Gault (eGFR-CG) Note: Other protocol defined Inclusion/
Exclusion criteria
may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24 | Week 24 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 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 Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12 | Week 12 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at week 12 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 Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48 | 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 24 | Baseline; Week 24 | — |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe and North America. The first participant was screened on 18 November 2015. The last study visit occurred on 24 Jan 2018.
Pre-assignment details
346 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| E/C/F/TAF E/C/F/TAF (150/150/200/10 mg) FDC tablets administered orally once daily with food for 48 weeks | 183 |
| ABC/3TC+3rd Agent ABC/3TC (600/300 mg) tablets plus a third antiretroviral agent administered orally once daily for 24 weeks followed by a delayed switch to E/C/F/TAF FDC | 91 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 |
| Overall Study | Investigator's Discretion | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Non-Compliance with Study Drug | 1 | 0 |
| Overall Study | Randomized but not treated | 0 | 1 |
| Overall Study | Withdrew Consent | 2 | 2 |
Baseline characteristics
| Characteristic | ABC/3TC+3rd Agent | Total | E/C/F/TAF |
|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 10.7 | 49 years STANDARD_DEVIATION 11.3 | 50 years STANDARD_DEVIATION 11.6 |
| CD4 Cell Count | 753 cells/µL STANDARD_DEVIATION 312.8 | 718 cells/µL STANDARD_DEVIATION 291.8 | 701 cells/µL STANDARD_DEVIATION 280.1 |
| CD4 Cell Count Category ≥ 200 to < 350 cells/µL | 7 Participants | 18 Participants | 11 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 cells/µL | 13 Participants | 43 Participants | 30 Participants |
| CD4 Cell Count Category ≥ 500 cells/µL | 71 Participants | 211 Participants | 140 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 cells/µL | 0 Participants | 2 Participants | 2 Participants |
| HIV-1 RNA Categories < 50 copies/mL | 91 Participants | 268 Participants | 177 Participants |
| HIV-1 RNA Categories 50 ≥ copies/mL | 0 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Black | 15 Participants | 42 Participants | 27 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 16 Participants | 43 Participants | 27 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 73 Participants | 228 Participants | 155 Participants |
| Race/Ethnicity, Customized Not Permitted | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 75 Participants | 225 Participants | 150 Participants |
| Region of Enrollment France | 23 Participants | 63 Participants | 40 Participants |
| Region of Enrollment Germany | 2 Participants | 8 Participants | 6 Participants |
| Region of Enrollment Italy | 16 Participants | 59 Participants | 43 Participants |
| Region of Enrollment Spain | 30 Participants | 86 Participants | 56 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 19 Participants | 55 Participants | 36 Participants |
| Sex: Female, Male Female | 17 Participants | 44 Participants | 27 Participants |
| Sex: Female, Male Male | 74 Participants | 230 Participants | 156 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 / 183 | 0 / 91 | 0 / 89 | 0 / 272 |
| other Total, other adverse events | 71 / 183 | 21 / 91 | 17 / 89 | 88 / 272 |
| serious Total, serious adverse events | 12 / 183 | 1 / 91 | 4 / 89 | 16 / 272 |
Outcome results
Primary
Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 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 24
Population: Full Analysis Set: participants who were randomized and received at least one dose of study drug (either E/C/F/TAF or ABC/3TC+3rd agent on or after Day 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24 | 93.4 percentage of participants |
| ABC/3TC+3rd Agent | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24 | 97.8 percentage of participants |
| Delayed E/C/F/TAF | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24 | 96.6 percentage of participants |
p-value: 0.1595% CI: [-9.4, 1.9]Fisher Exact
Secondary
Change From Baseline in CD4+ Cell Count at Week 24
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF | Change From Baseline in CD4+ Cell Count at Week 24 | -28 cells/µL | Standard Deviation 161.4 |
| ABC/3TC+3rd Agent | Change From Baseline in CD4+ Cell Count at Week 24 | 8 cells/µL | Standard Deviation 192.9 |
| Delayed E/C/F/TAF | Change From Baseline in CD4+ Cell Count at Week 24 | -23 cells/µL | Standard Deviation 201.7 |
p-value: 0.1195% CI: [-80, 9]ANOVA
Secondary
Change From Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline; Week 48
Population: Participants in the E/C/F/TAF group with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF | Change From Baseline in CD4+ Cell Count at Week 48 | -32 cells/µL | Standard Deviation 147.1 |
Secondary
Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at week 12 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 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12 | 95.1 percentage of participants |
| ABC/3TC+3rd Agent | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12 | 98.9 percentage of participants |
| Delayed E/C/F/TAF | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12 | 96.6 percentage of participants |
p-value: 0.1795% CI: [-8.3, 1.6]Fisher Exact
Secondary
Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at 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.
Time frame: Week 48
Population: Only the participants who were randomized to E/C/F/TAF group were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48 | 86.9 percentage of participants |