Acquired Immunodeficiency Syndrome, HIV Infections
Conditions
Keywords
HIV-1, HIV, Treatment Experienced
Brief summary
This study will evaluate the non-inferiority of Stribild® (elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a protease inhibitor (PI) boosted with ritonavir (RTV) plus Truvada® (FTC/TDF) fixed-dose combination in maintaining HIV-1 RNA \< 50 copies/mL at Week 48 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of the two regimens through 96 weeks of treatment.
Interventions
DRUGPI
PI administered according to prescribing information; allowed PIs include atazanavir (ATV), darunavir (DRV), fosamprenavir (FPV), lopinavir (LPV), or saquinavir (SQV)
DRUGRTV
RTV administered according to prescribing information FTC/TDF administered according to prescribing information
DRUGFTC/TDF
FTC/TDF (200/300 mg) administered according to prescribing information
DRUGStribild
Stribild (E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with 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
* Ability to understand and sign a written informed consent form * Be on a stable antiretroviral regimen consisting of a ritonavir boosted PI plus FTC/TDF continuously for ≥ 6 consecutive months preceding the screening visit * Be on the first or second antiretroviral drug regimen documented undetectable plasma HIV 1 RNA levels for ≥ 6 months preceding the screening visit * No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) for any length of time * Documented historical genotype prior to starting initial antiretroviral therapy showing no known resistance to TDF or FTC * HIV RNA \< 50 copies/mL at screening * Normal ECG * Hepatic transaminases ≤ 5 × the upper limit of the normal range (ULN) * Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin * Adequate hematologic function * Serum amylase ≤ 5 × ULN * Estimated glomerular filtration rate ≥ 70 mL/min * Females of childbearing potential must agree to utilize highly effective contraception methods, or be nonheterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug * Female participants who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing * Male participants must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product, or must be nonheterosexually active, or practice sexual abstinence * Age ≥ 18 years
Exclusion criteria
* A new AIDS-defining condition diagnosed within the 30 days prior to screening * Females who are breastfeeding * Positive serum pregnancy test (female of childbearing potential) * Receiving drug treatment for hepatitis C, or participants who are anticipated to receive treatment for hepatitis C during the course of the study * Experiencing decompensated cirrhosis * Have an implanted defibrillator or pacemaker * Current alcohol or substance abuse that would interfere with compliance * A 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 requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline, except for intramuscular penicillin for the treatment of syphilis * 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 * Receiving ongoing therapy with any of the medications, including drugs not to be used with elvitegravir, cobicistat, FTC, or TDF; or those with any known allergies to the excipients of E/C/F/TDF tablets, or FTC/TDF tablets * No anticipated need to initiate drugs during the study that are contraindicated * Receiving other investigational drugs * Participation in any other clinical trial * Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | Week 48 | The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | Week 96 | The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time. |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
| Change From Baseline in CD4+ Cell Count at Week 96 | Baseline; Week 96 | — |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Portugal, Puerto Rico, Spain, Switzerland, 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 18 November 2011. The last study visit occurred on 09 December 2014
Pre-assignment details
632 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Stribild Participants switched from their baseline treatment regimen to Stribild (E/C/F/TDF) (150/150/200/300 mg) STR once daily for up to 96 weeks in the randomized phase, and may have continued to receive Stribild in the extension phase. | 293 |
| PI+RTV+FTC/TDF Participants stayed on their baseline treatment regimen consisting of a PI (ATV, DRV, FPV, LPV, or SQV) boosted with RTV plus FTC/TDF (200/300 mg) (administered according to prescribing information) for up to 96 weeks in the randomized phase, and may have switched to Stribild in the extension phase. | 140 |
| Total | 433 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Phase | Participant Noncompliance | 1 | 0 |
| Randomized Phase | Adverse Event | 6 | 1 |
| Randomized Phase | Investigators Discretion | 1 | 2 |
| Randomized Phase | Lost to Follow-up | 3 | 4 |
| Randomized Phase | Participant Noncompliance | 1 | 5 |
| Randomized Phase | Pregnancy | 0 | 1 |
| Randomized Phase | Protocol Violation | 9 | 4 |
| Randomized Phase | Randomized but Not Treated | 0 | 5 |
| Randomized Phase | Withdrew Consent | 10 | 14 |
Baseline characteristics
| Characteristic | Total | PI+RTV+FTC/TDF | Stribild |
|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 9.4 | 41 years STANDARD_DEVIATION 8.9 | 41 years STANDARD_DEVIATION 9.7 |
| Age, Customized ≥ 40 to < 50 years | 158 participants | 49 participants | 109 participants |
| Age, Customized < 40 years | 198 participants | 68 participants | 130 participants |
| Age, Customized ≥ 50 years | 77 participants | 23 participants | 54 participants |
| CD4+ Cell Count | 610 cells/µL STANDARD_DEVIATION 272.9 | 624 cells/µL STANDARD_DEVIATION 269.9 | 604 cells/µL STANDARD_DEVIATION 274.6 |
| CD4+ Cell Count Category 201 to ≤ 350 cells/µL | 51 participants | 14 participants | 37 participants |
| CD4+ Cell Count Category 351 to ≤ 500 cells/µL | 95 participants | 26 participants | 69 participants |
| CD4+ Cell Count Category > 500 cells/µL | 272 participants | 94 participants | 178 participants |
| CD4+ Cell Count Category ≤ 50 cells/µL | 0 participants | 0 participants | 0 participants |
| CD4+ Cell Count Category 51 to ≤ 200 cells/µL | 15 participants | 6 participants | 9 participants |
| HIV-1 RNA Category 200 to < 400 copies/mL | 0 participants | 0 participants | 0 participants |
| HIV-1 RNA Category ≥ 400 copies/mL | 1 participants | 1 participants | 0 participants |
| HIV-1 RNA Category < 50 copies/mL | 428 participants | 137 participants | 291 participants |
| HIV-1 RNA Category 50 to < 200 copies/mL | 4 participants | 2 participants | 2 participants |
| HIV Disease Status AIDS | 59 participants | 18 participants | 41 participants |
| HIV Disease Status Asymptomatic | 319 participants | 105 participants | 214 participants |
| HIV Disease Status Symptomatic HIV Infections | 55 participants | 17 participants | 38 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 9 participants | 2 participants | 7 participants |
| Race/Ethnicity, Customized Black or African Heritage | 63 participants | 20 participants | 43 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 59 participants | 17 participants | 42 participants |
| Race/Ethnicity, Customized Non-Hispanic/Latino | 372 participants | 123 participants | 249 participants |
| Race/Ethnicity, Customized Not Permitted | 4 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Other | 7 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized White | 347 participants | 113 participants | 234 participants |
| Region of Enrollment Austria | 15 participants | 4 participants | 11 participants |
| Region of Enrollment Belgium | 8 participants | 2 participants | 6 participants |
| Region of Enrollment Canada | 8 participants | 3 participants | 5 participants |
| Region of Enrollment France | 54 participants | 15 participants | 39 participants |
| Region of Enrollment Germany | 57 participants | 21 participants | 36 participants |
| Region of Enrollment Italy | 60 participants | 16 participants | 44 participants |
| Region of Enrollment Portugal | 19 participants | 7 participants | 12 participants |
| Region of Enrollment Puerto Rico | 5 participants | 2 participants | 3 participants |
| Region of Enrollment Spain | 49 participants | 21 participants | 28 participants |
| Region of Enrollment Switzerland | 20 participants | 8 participants | 12 participants |
| Region of Enrollment United Kingdom | 14 participants | 1 participants | 13 participants |
| Region of Enrollment United States | 124 participants | 40 participants | 84 participants |
| Sex: Female, Male Female | 62 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Male | 371 Participants | 121 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 169 / 293 | 67 / 140 | 169 / 313 |
| serious Total, serious adverse events | 24 / 293 | 11 / 140 | 24 / 313 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.
Time frame: Week 48
Population: Full Analysis Set: Participants who were randomized and treated, and had no major eligibility criteria violations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 93.8 percentage of participants |
| PI+RTV+FTC/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 87.1 percentage of participants |
p-value: 0.02595% CI: [0.4, 13.7]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; the missing-equals-excluded approach where participants with missing data were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stribild | Change From Baseline in CD4+ Cell Count at Week 48 | 40 cells/µL | Standard Deviation 169.5 |
| PI+RTV+FTC/TDF | Change From Baseline in CD4+ Cell Count at Week 48 | 32 cells/µL | Standard Deviation 166.1 |
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 while on study drug were analyzed; the missing-equals-excluded approach where participants with missing data were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stribild | Change From Baseline in CD4+ Cell Count at Week 96 | 61 cells/µL | Standard Deviation 196.5 |
| PI+RTV+FTC/TDF | Change From Baseline in CD4+ Cell Count at Week 96 | 71 cells/µL | Standard Deviation 173.4 |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.
Time frame: Week 96
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 86.9 percentage of participants |
| PI+RTV+FTC/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 69.8 percentage of participants |