HIV-1 Infection
Conditions
Keywords
HIV-1, HIV, Treatment Experienced
Brief summary
The purpose of this Phase 2b study was to evaluate the efficacy and safety of the emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) STR, after switching from the efavirenz (EFV)/FTC/TDF STR at baseline, in maintaining HIV-1 RNA \< 50 copies/mL at Week 12. HIV-infected patients were enrolled if they had received EFV/FTC/TDF for ≥ 3 months prior to study start, were experiencing safety or tolerability concerns (in particular, EFV-related intolerance), and wished to change to an alternate, better-tolerated regimen.
Interventions
DRUGFTC/RPV/TDF
Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg single-tablet regimen (STR) administered orally with a meal once daily
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
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 * Receiving EFV/FTC/TDF continuously for ≥ 3 months preceding the screening visit * Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels for ≥ 8 weeks prior to the screening visit and HIV-1 RNA \< 50 copies/mL at the screening visit * On their first antiretroviral drug regimen, and no HIV-1 RNA \> 50 copies/mL measured at two consecutive time points after first achieving HIV RNA \< 50 copies/mL * Had a genotype prior to starting FTC/RPV/TDF and no known resistance to any of the study agents * Normal ECG * Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin * Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL) * Serum amylase ≤ 5 x ULN (subjects with serum amylase \> 5 x ULN eligible if serum lipase ≤ 5 x ULN) * Adequate renal function (estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula) * Males and Females of childbearing potential must have agreed to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be nonheterosexually active, practice sexual abstinence, or have a vasectomized partner) from screening throughout the duration of the study period and for 60 days following the last dose of study drug. * Age ≥ 18 years * Life expectancy ≥ 1 year
Exclusion criteria
* A new AIDS-defining condition diagnosed within 21 days prior to screening * Females who were breastfeeding * Positive serum pregnancy test (female of childbearing potential) * Proven or suspected acute hepatitis in the 21 days prior to study entry * Subjects receiving drug treatment for Hepatitis C, or subjects anticipated to receive treatment for Hepatitis C during the course of the study, or with a history of liver disease * Was experiencing decompensated cirrhosis * Implanted defibrillator or pacemaker * Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject 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 requiring parenteral antibiotic or antifungal therapy within 21 days prior to Baseline * All investigational drugs * Ongoing therapy or anticipated need to initiate drugs or herbal/natural supplements during the study that were contraindicated or not recommended for use as indicated in the protocol, including drugs not to be used with FTC, RPV, and TDF; or subjects with known allergies to the excipients of the FTC/RPV/TDF STR * Participation in any other clinical trial without prior approval from the sponsor was prohibited while participating in this trial * Treatment with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) * 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 | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 (FDA Snapshot Analysis) | Week 12 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 12 was analyzed using the FDA snapshot analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis) | Week 48 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis. |
| Plasma Concentration of RPV and EFV at Week 1 | Week 1 | The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 1. |
| Plasma Concentration of RPV and EFV at Week 2 | Week 2 | The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 2. |
| Plasma Concentration of RPV and EFV at Week 4 | Week 4 | The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 4. |
| Plasma Concentration of RPV and EFV at Week 6 | Week 6 | The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 6. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis) | Week 24 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis. |
| Plasma Concentration of RPV at Week 12 | Week 12 | The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 12. |
| Plasma Concentration of EFV at Week 12 | Week 12 | The mean (SD) plasma concentration (ng/mL) of EFV was measured at Week 12. No analyses of EFV plasma concentrations were conducted after Week 12 |
| Plasma Concentration of RPV at Week 24 | Week 24 | The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 24. |
| Plasma Concentration of RPV at Week 36 | Week 36 | The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 36. |
| Plasma Concentration of RPV at Week 48 | Week 48 | The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 48. |
| Plasma Concentration of RPV and EFV at Week 8 | Week 8 | The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 8. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 18 sites in the United States. The first participant was screened on 27 January 2011. The last participant observation was on 26 June 2012.
Pre-assignment details
63 participants were screened, 50 were enrolled; 49 participants were treated, and comprise the Safety Analysis set. Participants in the Safety Analysis Set who had no major protocol violation comprise the Full Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| FTC/RPV/TDF Participants switched from their existing treatment regimen of EFV/FTC/TDF to the FTC/RPV/TDF STR. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Enrolled but not treated | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | FTC/RPV/TDF |
|---|---|
| Age Continuous | 38 years STANDARD_DEVIATION 8.3 |
| Baseline HIV-1 RNA Category < 50 Copies/mL | 47 participants |
| Baseline HIV-1 RNA Category 50 to < 400 Copies/mL | 2 participants |
| EFV plasma concentration | 2204.9 ng/mL STANDARD_DEVIATION 1059.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants |
| Race/Ethnicity, Customized White | 40 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 49 |
| serious Total, serious adverse events | 1 / 49 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 (FDA Snapshot Analysis)
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 12 was analyzed using the FDA snapshot analysis.
Time frame: Week 12
Population: Full Analysis Set: participants who were enrolled into the study, received at least one dose of study drug and had no major protocol violation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 (FDA Snapshot Analysis) | 100 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis) | 100 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis.
Time frame: Week 48
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis) | 93.9 percentage of participants |
Secondary
Plasma Concentration of EFV at Week 12
The mean (SD) plasma concentration (ng/mL) of EFV was measured at Week 12. No analyses of EFV plasma concentrations were conducted after Week 12
Time frame: Week 12
Population: Participants with evaluable measurements for plasma concentration of EFV at Week 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of EFV at Week 12 | 45.2 ng/mL | Inter-Quartile Range 186.46 |
Secondary
Plasma Concentration of RPV and EFV at Week 1
The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 1.
Time frame: Week 1
Population: Participants with evaluable measurements for plasma concentrations of RPV and EFV at Week 1 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 1 | RPV | 31.6 ng/mL | Standard Deviation 11.46 |
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 1 | EFV | 234.5 ng/mL | Standard Deviation 234.09 |
Secondary
Plasma Concentration of RPV and EFV at Week 2
The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 2.
Time frame: Week 2
Population: Participants with evaluable measurements for plasma concentrations of RPV and EFV at Week 2 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 2 | RPV | 52.3 ng/mL | Standard Deviation 24.46 |
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 2 | EFV | 78.5 ng/mL | Standard Deviation 86.91 |
Secondary
Plasma Concentration of RPV and EFV at Week 4
The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 4.
Time frame: Week 4
Population: Participants with evaluable measurements for plasma concentrations of RPV and EFV at Week 4 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 4 | RPV | 65.5 ng/mL | Standard Deviation 33.19 |
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 4 | EFV | 10.0 ng/mL | Standard Deviation 17.97 |
Secondary
Plasma Concentration of RPV and EFV at Week 6
The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 6.
Time frame: Week 6
Population: Participants with evaluable measurements for plasma concentrations of RPV and EFV at Week 6 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 6 | RPV | 67.8 ng/mL | Standard Deviation 36.12 |
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 6 | EFV | 1.9 ng/mL | Standard Deviation 4.66 |
Secondary
Plasma Concentration of RPV and EFV at Week 8
The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 8.
Time frame: Week 8
Population: Participants with evaluable measurements for plasma concentration of RPV and EFV at Week 8 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 8 | RPV | 76.0 ng/mL | Standard Deviation 35.8 |
| FTC/RPV/TDF | Plasma Concentration of RPV and EFV at Week 8 | EFV | NA ng/mL | — |
Secondary
Plasma Concentration of RPV at Week 12
The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 12.
Time frame: Week 12
Population: Participants with measurements for plasma concentration of RPV at Week 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV at Week 12 | 89.0 ng/mL | Standard Deviation 54.13 |
Secondary
Plasma Concentration of RPV at Week 24
The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 24.
Time frame: Week 24
Population: Participants with evaluable measurements for plasma concentration of RPV at Week 24 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV at Week 24 | 74.1 ng/mL | Standard Deviation 37.99 |
Secondary
Plasma Concentration of RPV at Week 36
The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 36.
Time frame: Week 36
Population: Participants with evaluable measurements for plasma concentration of RPV at Week 36 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV at Week 36 | 85.5 ng/mL | Standard Deviation 34.31 |
Secondary
Plasma Concentration of RPV at Week 48
The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 48.
Time frame: Week 48
Population: Participants with evaluable measurements for plasma concentration of RPV at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TDF | Plasma Concentration of RPV at Week 48 | 77.6 ng/mL | Standard Deviation 34.83 |