HIV-1 Infection
Conditions
Keywords
HIV 1 Infection, HIV, Virologically-Suppressed
Brief summary
The primary objective of this study is to evaluate the safety of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected participants aged ≥ 60 years.
Interventions
DRUGE/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily
DRUGTDF
300 mg tablet administered orally once daily
DRUGFTC
200 mg capsule administered orally once daily
DRUGFTC/TDF
200/300 mg tablet administered orally once daily
DRUG3TC
Tablet administered orally
DRUGThird agent
Third agent may include one of the following regimens: lopinavir+ritonavir (LPV/r; Kaletra®), atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®), ATV + cobicistat (COBI;Tybost®) (or ATV/COBI FDC), DRV + RTV, darunavir (DRV; Prezista®) + COBI (or DRV/COBI FDC), fosamprenavir (FPV; Lexiva®) + RTV , saquinavir (SQV; Invirase®; Fortovase®) + RTV, efavirenz (EFV;Sustiva®), rilpivirine (RPV;Edurant®), nevirapine (NVP;Viramune®), etravirine (ETR;Intelence®), raltegravir (RAL; Isentress®), elvitegravir (EVG) + COBI, or dolutegravir (DTG;Tivicay®) 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
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Currently receiving a TDF and FTC or 3TC-containing 'backbone' (maximum 2 NRTIs) regimen plus a third agent for ≥ 6 consecutive months prior to screening visit. For individuals with 3 or more ART regimens, a regimen history must be provided for approval by the Sponsor. Refer to assigned interventions for allowed third agents of the current regimen. * 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 level \< 50 copies/mL at screening visit * Adequate renal function * Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert * All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. If historical plasma prior to first ART is not available or individual has 3 or more ART regimens, individuals will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC. * Study performed dual energy x-ray absorptiometry (DXA) scan and T-score received prior to Day 1 Key
Exclusion criteria
* Previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time) if the current regimen contains a PI/r * Individuals will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV) * A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4+ cell count and/or percentage criteria) * Hepatitis C virus that would require therapy during the study * Individuals receiving ongoing treatment for bone disease (eg, osteoporosis), including bisphosphonates, denosumab, and strontium ranelate Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline to Week 48 in Spine BMD | Baseline; Week 48 |
| Percent Change From Baseline to Week 48 in Hip BMD | Baseline; Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm | Week 24 | The percentage of participants with 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. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined 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. |
| Percent Change From Baseline to Week 24 in Spine BMD | Baseline; Week 24 | — |
| Change in Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
| Change From Baseline in CD4+ Cell Count at Week 24 | Baseline; Week 24 | — |
| Percent Change From Baseline to Week 24 in Hip BMD | Baseline; Week 24 | — |
Countries
Belgium, France, Italy, Spain, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe. The first participant was screened on 22 December 2015. The last study visit occurred on 21 March 2018.
Pre-assignment details
214 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| E/C/F/TAF Participants switched from TDF and FTC or 3TC plus a third agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily for 48 weeks. | 110 |
| Stay on Baseline Regimen Participants stayed on current regimen of TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent for 48 weeks. | 56 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Non-Compliance with Study Drug | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Randomized but Not Treated | 1 | 0 |
| Overall Study | Withdrew Consent | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Stay on Baseline Regimen | E/C/F/TAF |
|---|---|---|---|
| Age, Continuous | 66 Years STANDARD_DEVIATION 4.7 | 66 Years STANDARD_DEVIATION 4.9 | 65 Years STANDARD_DEVIATION 4.6 |
| CD4+ Cell Count | 658 cells/µL STANDARD_DEVIATION 277 | 676 cells/µL STANDARD_DEVIATION 316.5 | 649 cells/µL STANDARD_DEVIATION 255.6 |
| CD4+ Cell Count Category ≥ 200 to < 350 cells/µL | 20 Participants | 8 Participants | 12 Participants |
| CD4+ Cell Count Category ≥ 350 to < 500 cells/µL | 25 Participants | 7 Participants | 18 Participants |
| CD4+ Cell Count Category ≥ 500 cells/µL | 119 Participants | 39 Participants | 80 Participants |
| CD4+ Cell Count Category ≥ 50 to < 200 cells/µL | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 8 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 130 Participants | 42 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 6 Participants | 6 Participants |
| Hip BMD | 0.924 g/cm^2 STANDARD_DEVIATION 0.1332 | 0.927 g/cm^2 STANDARD_DEVIATION 0.1346 | 0.922 g/cm^2 STANDARD_DEVIATION 0.1332 |
| HIV-1 RNA Category < 50 copies/mL | 165 Participants | 56 Participants | 109 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Permitted | 9 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 152 Participants | 49 Participants | 103 Participants |
| Region of Enrollment Belgium | 9 Participants | 1 Participants | 8 Participants |
| Region of Enrollment France | 52 Participants | 23 Participants | 29 Participants |
| Region of Enrollment Italy | 51 Participants | 15 Participants | 36 Participants |
| Region of Enrollment Spain | 43 Participants | 14 Participants | 29 Participants |
| Region of Enrollment United Kingdom | 11 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 19 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 147 Participants | 51 Participants | 96 Participants |
| Spine Bone Mineral Density (BMD) | 1.042 g/cm^2 STANDARD_DEVIATION 0.185 | 1.052 g/cm^2 STANDARD_DEVIATION 0.1789 | 1.036 g/cm^2 STANDARD_DEVIATION 0.1886 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 110 | 0 / 56 |
| other Total, other adverse events | 47 / 110 | 20 / 56 |
| serious Total, serious adverse events | 10 / 110 | 1 / 56 |
Outcome results
Primary
Percent Change From Baseline to Week 48 in Hip BMD
Time frame: Baseline; Week 48
Population: Participants in the Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF | Percent Change From Baseline to Week 48 in Hip BMD | 1.330 Percent change | Standard Deviation 2.1968 |
| Stay on Baseline Regimen | Percent Change From Baseline to Week 48 in Hip BMD | -0.726 Percent change | Standard Deviation 3.2069 |
p-value: <0.00195% CI: [1.168, 2.904]ANOVA
Primary
Percent Change From Baseline to Week 48 in Spine BMD
Time frame: Baseline; Week 48
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF | Percent Change From Baseline to Week 48 in Spine BMD | 2.237 Percent change | Standard Deviation 3.2727 |
| Stay on Baseline Regimen | Percent Change From Baseline to Week 48 in Spine BMD | -0.104 Percent change | Standard Deviation 3.3854 |
p-value: <0.00195% CI: [1.337, 3.517]ANOVA
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 | 48 cells/μL | Standard Deviation 161.9 |
| Stay on Baseline Regimen | Change From Baseline in CD4+ Cell Count at Week 24 | -4 cells/μL | Standard Deviation 153.9 |
p-value: 0.05395% CI: [-1, 106]ANOVA
Secondary
Change in 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 |
|---|---|---|---|
| E/C/F/TAF | Change in Baseline in CD4+ Cell Count at Week 48 | 56 cells/μL | Standard Deviation 177.7 |
| Stay on Baseline Regimen | Change in Baseline in CD4+ Cell Count at Week 48 | -1 cells/μL | Standard Deviation 149.1 |
p-value: 0.05195% CI: [0, 115]ANOVA
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants with 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 included all participants who were randomized into the study, received at least 1 dose of study drug, and did not have any major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm | 94.5 Percentage of participants |
| Stay on Baseline Regimen | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm | 100.0 Percentage of participants |
p-value: 0.1895% CI: [-11.8, 1.6]Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined 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: Full Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and did not have any major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 93.6 Percentage of participants |
| Stay on Baseline Regimen | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 94.5 Percentage of participants |
p-value: 195% CI: [-8.5, 9.3]Fisher Exact
Secondary
Percent Change From Baseline to Week 24 in Hip BMD
Time frame: Baseline; Week 24
Population: Participants in the Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF | Percent Change From Baseline to Week 24 in Hip BMD | 0.808 Percent change | Standard Deviation 1.9084 |
| Stay on Baseline Regimen | Percent Change From Baseline to Week 24 in Hip BMD | -0.537 Percent change | Standard Deviation 2.7647 |
p-value: <0.00195% CI: [0.602, 2.099]ANOVA
Secondary
Percent Change From Baseline to Week 24 in Spine BMD
Time frame: Baseline; Week 24
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF | Percent Change From Baseline to Week 24 in Spine BMD | 1.625 Percent change | Standard Deviation 3.2346 |
| Stay on Baseline Regimen | Percent Change From Baseline to Week 24 in Spine BMD | -0.027 Percent change | Standard Deviation 2.9875 |
p-value: <0.00195% CI: [0.726, 2.771]ANOVA