HIV, HIV Infections
Conditions
Keywords
Treatment Naive, HIV 1 Infected
Brief summary
To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI \[GS-9350\])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla®) in HIV-1 infected, antiretroviral treatment-naive adults. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor-based STRs.
Interventions
DRUGStribild
Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR administered orally once daily
DRUGAtripla
Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet administered orally once daily prior to bedtime
DRUGStribild Placebo
Placebo to match Stribild STR administered orally once daily
DRUGAtripla Placebo
Placebo to match Atripla tablet administered orally once daily prior to bedtime
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures * Plasma HIV-1 RNA levels ≥ 5,000 copies/mL * No prior use of any approved or investigational antiretroviral drug for any length of time * Screening genotype report must show sensitivity to FTC, TDF, and EFV * Normal electrocardiogram (ECG) * Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula) * Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) ≤ 5 x the upper limit of the normal range (ULN) * Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin * Adequate hematologic function * Serum amylase ≤ 5 x ULN * Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug * Age ≥ 18 years * Life expectancy ≥ 1 year
Exclusion criteria
* A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening * Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C * Subjects experiencing decompensated cirrhosis * Females who are breastfeeding * Positive serum pregnancy test (female of childbearing potential) * Implanted defibrillator or pacemaker * Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance * History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma * Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline * Medications contraindicated for use with EVG, COBI, FTC, EFV, or TDF; or subjects with any known allergies to the excipients of Stribild or Atripla tablets * Participation in any other clinical trial without prior approval * Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 | Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 | Week 96 | — |
| The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 | Week 144 | — |
| The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 | Week 192 | — |
| The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Baseline; Weeks 48, 96, 144, and 192 | Change = value of the relevant time point minus the baseline value |
| The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | Week 48 | — |
| The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm | Week 48 | — |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at sites in the United States and Puerto Rico. The first participant was screened on 16 March 2010. The last study visit occurred on 02 September 2014.
Pre-assignment details
917 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Stribild Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime | 348 |
| Atripla Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily | 352 |
| Total | 700 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 19 |
| Overall Study | Death | 3 | 2 |
| Overall Study | Investigator's Discretion | 7 | 2 |
| Overall Study | Lack of Efficacy | 5 | 3 |
| Overall Study | Lost to Follow-up | 27 | 29 |
| Overall Study | Participant Noncompliance | 5 | 10 |
| Overall Study | Participant Transferred to Another Study | 215 | 200 |
| Overall Study | Pregnancy | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Randomized but Not Treated | 5 | 2 |
| Overall Study | Withdrew Consent | 16 | 22 |
Baseline characteristics
| Characteristic | Stribild | Atripla | Total |
|---|---|---|---|
| Age, Continuous | 38 years STANDARD_DEVIATION 10.4 | 38 years STANDARD_DEVIATION 10.6 | 38 years STANDARD_DEVIATION 10.5 |
| CD4 Cell Count (/µL) 201 to ≤ 350 | 112 participants | 96 participants | 208 participants |
| CD4 Cell Count (/µL) 351 to ≤ 500 | 113 participants | 136 participants | 249 participants |
| CD4 Cell Count (/µL) ≤ 50 | 7 participants | 6 participants | 13 participants |
| CD4 Cell Count (/µL) > 500 | 80 participants | 69 participants | 149 participants |
| CD4 Cell Count (/µL) 51 to ≤ 200 | 36 participants | 45 participants | 81 participants |
| Hepatitis B Virus (HBV) Infection Status Negative | 343 participants | 343 participants | 686 participants |
| Hepatitis B Virus (HBV) Infection Status Positive | 5 participants | 9 participants | 14 participants |
| Hepatitis C Virus (HCV) Infection Status Negative | 331 participants | 337 participants | 668 participants |
| Hepatitis C Virus (HCV) Infection Status Positive | 17 participants | 15 participants | 32 participants |
| HIV-1 RNA Category (copies/mL) ≤ 100,000 | 230 participants | 236 participants | 466 participants |
| HIV-1 RNA Category (copies/mL) > 100,000 | 118 participants | 116 participants | 234 participants |
| HIV Disease Status AIDS | 28 participants | 24 participants | 52 participants |
| HIV Disease Status Asymptomatic | 290 participants | 295 participants | 585 participants |
| HIV Disease Status Symptomatic HIV Infections | 30 participants | 33 participants | 63 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Asian | 6 participants | 10 participants | 16 participants |
| Race/Ethnicity, Customized Black or African Heritage | 106 participants | 91 participants | 197 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Other | 16 participants | 19 participants | 35 participants |
| Race/Ethnicity, Customized White | 214 participants | 227 participants | 441 participants |
| Region of Enrollment United States | 348 participants | 352 participants | 700 participants |
| Sex: Female, Male Female | 41 Participants | 36 Participants | 77 Participants |
| Sex: Female, Male Male | 307 Participants | 316 Participants | 623 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 313 / 348 | 326 / 352 |
| serious Total, serious adverse events | 69 / 348 | 50 / 352 |
Outcome results
Primary
The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48
Time frame: Week 48
Population: Intent-to-treat (ITT) Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 | 87.6 percentage of participants |
| Atripla | The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 | 84.1 percentage of participants |
Comparison: The null hypothesis was that the percentage of participants achieving HIV-1 RNA \< 50 copies/mL (as defined by the snapshot analysis algorithm) at Week 48 in the Stribild group is at least 12% worse than the response rate in the Atripla group; the alternative hypothesis was that the response rate in the Stribild group is less than 12% worse than that in the Atripla Group.95.2% CI: [-1.6, 8.8]
Secondary
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192
Change = value of the relevant time point minus the baseline value
Time frame: Baseline; Weeks 48, 96, 144, and 192
Population: ITT Analysis Set. The missing = excluded (M = E) method was used in which all participants with missing data were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stribild | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 48 (Stribild, n=325; Atripla, n=315) | 239 cells/µL | Standard Deviation 167.2 |
| Stribild | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 96 (Stribild, n=307; Atripla, n=302) | 295 cells/µL | Standard Deviation 213.3 |
| Stribild | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 144 (Stribild, n=294; Atripla, n=283) | 321 cells/µL | Standard Deviation 227 |
| Stribild | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 192 (Stribild, n=62; Atripla, n=69) | 360 cells/µL | Standard Deviation 285.9 |
| Atripla | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 192 (Stribild, n=62; Atripla, n=69) | 328 cells/µL | Standard Deviation 227.6 |
| Atripla | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 48 (Stribild, n=325; Atripla, n=315) | 206 cells/µL | Standard Deviation 153.4 |
| Atripla | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 144 (Stribild, n=294; Atripla, n=283) | 300 cells/µL | Standard Deviation 202.3 |
| Atripla | The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change at Wk 96 (Stribild, n=307; Atripla, n=302) | 273 cells/µL | Standard Deviation 189.7 |
Secondary
The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm
Time frame: Week 48
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm | 85.9 percentage of participants |
| Atripla | The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm | 83.2 percentage of participants |
Secondary
The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Time frame: Week 48
Population: ITT Analysis Set. The missing = failure (M = F) method was used in which all missing data were considered as failure (HIV-1 RNA ≥ 50 copies/mL).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 88.8 percentage of participants |
| Atripla | The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 85.5 percentage of participants |
Secondary
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144
Time frame: Week 144
Population: ITT Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 | 80.2 percentage of participants |
| Atripla | The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 | 75.3 percentage of participants |
Secondary
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192
Time frame: Week 192
Population: Week 192 Modified Intent-to-treat (MITT) Analysis Set: Participants in the ITT analysis set, excluding those who either 1) transferred to other Gilead-sponsored studies after completing their Week 144 Visit and before the lower limit of the Week 192 analysis window, or 2) prematurely discontinued study drug prior to the Week 144 Visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 | 76.1 percentage of participants |
| Atripla | The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 | 78.1 percentage of participants |
Secondary
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96
Time frame: Week 96
Population: ITT Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 | 84.2 percentage of participants |
| Atripla | The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 | 81.5 percentage of participants |