Acquired Immunodeficiency Syndrome, HIV Infections
Conditions
Keywords
HIV Infections, Acquired Immunodeficiency Syndrome, TMC125-TiDP2-C238, TMC125-C238, Etravirine, Intelence, HIV, HIV-1, Pharmacokinetics
Brief summary
The purpose of this study is to determine the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) (PK) of ETR when given with ATV/rtv and 1 NRTI in treatment experienced HIV-1 infected patients. In addition, safety, tolerability and anti-HIV effect of this regimen will also be studied. A total of 46 patients will be enrolled.
Detailed description
This is a randomized (study drug assigned by chance), exploratory, open-label (all involved people know the identity of the intervention) trial to evaluate the pharmacokinetics (PK), safety, tolerability and anti-HIV (anti Human Immunodeficiency Virus) activity of etravirine (ETR ) when given with atazanavir/ritonavir (ATV/rtv) and 1 nucleoside reverse transcriptase inhibitor (NRTI) in 46 treatment experienced HIV-1 infected patients. The trial will consist of : 4 weeks of Screening Period, 2 weeks Pre-Treatment Phase, 48-week Treatment Period, and a Final Visit followed by a 4-week Follow-up Period (only for patients not continuing treatment with ETR in another trial or program). Safety evaluations (AE reporting, labs, vital signs, etc.) will be monitored at each study visit. A PK substudy (included in the protocol, with optional participation) with tenofovir (TDF) added to the antiretroviral regimen for 7 days will be conducted in patients with \> 24 weeks of treatment with suppressed HIV-1 viral load. In Pre-Treatment Phase, all patients will receive ATV/rtv 300/100 mg once daily to be taken following a meal each morning + 2 NRTIs (dose as specified in the labels) for 14 days. In Treatment Phase, patients will receive ETR 200 mg twice daily in addition to ATV/rtv (300/100 mg or 400/100 mg) once daily with meals + 1 investigator-selected NRTI for 48 weeks. In substudy TDF 300 mg once daily will be added to the treatment regimen x 7 days.
Interventions
DRUGAtazanavir (ATV) 300 mg
Atazanavir (ATV) 300 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take ATV 300 mg by mouth following a meal each morning on Substudy Days -1 to 7.
DRUGAtazanavir (ATV) 400 mg
Atazanavir (ATV) 400 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take ATV 400 mg by mouth following a meal each morning on Substudy Days -1 to 7.
DRUGRitonavir (rtv) 100 mg
Ritonavir (rtv) 100 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take rtv 100 mg by mouth following a meal each morning on Substudy Days -1 to 7.
DRUGNucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs)
2 investigator-selected NRTIs taken as specified in the individual product labels for 2 weeks during the Pre-Treatment Period followed by 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) taken as specified in the individual product label for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) mg taken as specified in the individual product label during the Substudy.
DRUGEtravirine (ETR) 200 mg
Etravirine (ETR) 200 mg taken twice daily as two 100-mg tablets following a meal (morning and evening) for at least the first two weeks of the 48-week Treatment Period. If participating in the optional substudy, participants will take ETR 200 mg twice daily as two 100-mg tablets following a meal each morning and evening on Substudy Days -1 to 7.
Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.
Sponsors
Janssen R&D Ireland
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
\- Documented HIV-1 infection * Failing on a stable ART (anti retroviral therapy) with HIV-1 plasma viral load above 500 HIV-1 RNA copies/ml * Presence of at least 1 documented NNRTI mutation * Demonstrated sensitivity to ATV, ETR and at least one of the selected NRTIs based on the resistance test at screening * General medical condition, in the investigator's opinion, does not interfere with the assessments and completion of the trial * Substudy: patients who have been treated in C238 for more than 24 weeks and are currently suppressed (defined as patients with at least 2 most recent and consecutive viral loads less than 50 cp/mL) will be considered eligible for the substudy
Exclusion criteria
* Primary HIV-1 infection * Previously documented HIV-2 infection * Previously failed 2 or more HIV PI-containing regimens * Previous diagnosis of hereditary hyperbilirubinemia (eg. Gilbert's syndrome, Crigler-Najjar syndrome). Grade 3 or 4 toxicities (according to DAIDS grading) * Acute and chronic viral hepatitis * Receipt of an investigational drug or investigational vaccine within 30 days prior to the trial drug administration * Pregnant or breastfeeding female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48 | Week 48 | The table below shows the percentage of participants wih undetectable plasma viral load (VL) values (\<50 copies/mL) at Week 48 using the Non-Completing = Failure (NC=F) imputation method (ie, participants who discontinued early were counted as nonresponders by having their VL values after discontinuation imputed with their baseline value, thus resulting in a 0 change). |
| Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr) | Day -1 (Reference); Week 2 (Test) | The table below shows pharmacokinetic (PK) results of atazanavir (ATV) when administered as ATV/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr). |
| Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | Day -1 (Reference); Week 2 (Test) | The table below shows the pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax). |
| Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr) | Day -1 (Reference); Week 2 (Test) | The table below shows the pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr). |
| Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | Day -1 (Reference); Week 2 (Test) | The table below shows pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr). |
| Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr) | Day -1 (Reference); Week 2 (Test) | The table below shows pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr). |
| Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | Week 2 | The table below shows pharmacokinetic (PK) results of ETR in the current study expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin) and maximum plasma concentration (Cmax). |
| Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr) | Week 2 | The table below shows pharmacokinetic (PK) results of ETR in the current study expressed as the area under the plasma concentration-time curve from time of intake to 12 hours after dosing (AUC12hr). |
| Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | Day -1 (Pretreatment); Week 2 (Test) | The table below shows pharmacokinetic (PK) results of atazanavir (ATZ) when administered as ATV/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax). |
| Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr) | Day -1 (Pretreatment); Week 2 (Test) | The table below shows pharmacokinetic (PK) results of atazanavir (ATZ) when administered as ATV/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr). |
| Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | Day -1 (Reference); Week 2 (Test) | The table below shows pharmacokinetic (PK) results of atazanavir (ATV) when administered as ATV/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | Baseline, Weeks 4, 12, 24, 48 | The table below shows the percentage of participants per time point with a virologic response defined as having a plasma viral load (VL) \<50 copies/mL, and with plasma VL \<400 copies/mL using the Non-Completing = Failure (NC=F) imputation method (ie, participants who discontinued early were counted as nonresponders by having their VL values after discontinuation imputed with their Baseline value, thus resulting in a 0 change). |
| The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | Baseline, Weeks 4, 12, 24, 48 | The table below shows the percentage of participants with a virologic response defined as a viral load \<50 Copies/mL and \<400 Copies/mL per time point calculated using the time to loss of virologic response (TLOVR) imputation method. |
| The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | Week 48 | The table below provides the results from the snapshot analysis method that includes the percentage of participants with virologic response (\<50 copies/mL), the percentage of participants who were virologic failures (VF) (\>50 copies/mL, discontinued prior to time X for reasons of VF or for other reasons, except for VF or adverse event, with a last viral load \>50 copies/mL), and the percentage of participants with no viral load (VL) data available at Week 48. |
| Change From Pre-Baseline in Log10 Viral Load Over Time | Pre-Baseline, Baseline, Weeks 4, 12, 24, 48 | The table below shows the mean change from prebaseline over time in log10 (Copies/mL) plasma viral load using the Non-Completing = Failure (NC=F) imputation method. |
| Time to Confirmed Virologic Response | Prebaseline to Week 48 | The table below provides the time in days it took participants to reach a confirmed virologic response defined as a plasma viral load (VL) \<50 copies/mL, and plasma VL \<400 copies/mL analyzed according to the Time to Loss of Virologic Response (TLOVR) imputation method. |
| Time to Virologic Failure | Prebaseline to Week 48 | The table below shows the number of days to virologic failure defined as a plasma viral load (VL) \> 50 copies/mL for participants who had been virologic responders (ie, having a plasma VL \<50, and \<400 copies/mL according to the time to loss of virologic response \[TLOVR\] imputation method). Time to virologic failure was the time to subsequent loss of virologic response, and the time was calculated from Prebaseline (Week -2). Participants who never achieved a virologic response were defined as nonresponders and counted as virologic failures on Day 1. |
| Change From Prebaseline in CD4+ Cell Count Over Time | Prebaseline, Baseline, Weeks 4, 12, 24, 48 | The table below shows the mean change from prebaseline over time in CD4+ cell count using the Non-Completing = Failure (NC=F) imputation method. |
Countries
Argentina, France, South Africa, Thailand, United States
Participant flow
Recruitment details
Etravirine coadministered with 2 doses of atazanavir/low-dose ritonavir each combined with 1 nucleoside reverse transcriptase inhibitor was evaluated in human immunodeficiency virus - type 1 infected participants. The study was conducted between 25 June 2009 and 10 April 2012 and participants were recruited by 17 investigators in 4 countries.
Pre-assignment details
Fifty (50) participants were enrolled in the study and received treatment with study drug during a 2-week Pre-treatment Period (Week -2 to Day -1) and a 48-week Treatment Period (Day 1 to Week 48). Efficacy data are reported for the 48-week Treatment Period.
Participants by arm
| Arm | Count |
|---|---|
| ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced human immunodeficiency virus - type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/low-dose ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for pre-treatment for 2 weeks followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks. | 25 |
| ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced human immunodeficiency virus - type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/low-dose ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) pretreatment for 2 weeks followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Subject noncompliant | 1 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | ATV/Rtv 300/100 mg (Treatment A) | ATV/Rtv 400/100 mg (Treatment B) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 24 Participants | 49 Participants |
| Age Continuous | 41.2 years STANDARD_DEVIATION 10.44 | 39.8 years STANDARD_DEVIATION 9.37 | 40.5 years STANDARD_DEVIATION 9.85 |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 25 | 15 / 25 |
| serious Total, serious adverse events | 4 / 25 | 2 / 25 |
Outcome results
Primary
Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48
The table below shows the percentage of participants wih undetectable plasma viral load (VL) values (\<50 copies/mL) at Week 48 using the Non-Completing = Failure (NC=F) imputation method (ie, participants who discontinued early were counted as nonresponders by having their VL values after discontinuation imputed with their baseline value, thus resulting in a 0 change).
Time frame: Week 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48 | 50.0 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48 | 45.5 Percentage of Participants |
Primary
Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)
The table below shows pharmacokinetic (PK) results of atazanavir (ATZ) when administered as ATV/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
Time frame: Day -1 (Pretreatment); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the PK parameter reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr) | 60030 ng.h/mL | Standard Deviation 39690 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr) | 55070 ng.h/mL | Standard Deviation 21860 |
Comparison: Parameter: area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr)90% CI: [0.76, 1.22]Linear mixed effects model
Primary
Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
The table below shows pharmacokinetic (PK) results of atazanavir (ATZ) when administered as ATV/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax).
Time frame: Day -1 (Pretreatment); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the PK parameter reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=21; Test, n=19) | 1339 ng/ml | Standard Deviation 1728 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml (Reference, n=20; Test, n=18) | 1104 ng/ml | Standard Deviation 1511 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=20; Test, n=19) | 5652 ng/ml | Standard Deviation 2735 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=21; Test, n=19) | 845.7 ng/ml | Standard Deviation 703.3 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml (Reference, n=20; Test, n=18) | 758.6 ng/ml | Standard Deviation 610.5 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=20; Test, n=19) | 5232 ng/ml | Standard Deviation 2166 |
Comparison: Parameter: minimum plasma concentration (Cmin)90% CI: [0.55, 1.22]Linear mixed effects model
Comparison: Parameter: maximum plasma concentration (Cmax)90% CI: [0.8, 1.16]Linear mixed effects model
Primary
Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)
The table below shows pharmacokinetic (PK) results of atazanavir (ATV) when administered as ATV/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
Time frame: Day -1 (Reference); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr) | 74210 ng.h/mL | Standard Deviation 55480 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr) | 72220 ng.h/mL | Standard Deviation 34600 |
Comparison: Parameter: area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr)90% CI: [0.81, 1.21]Llinear mixed effects model
Primary
Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
The table below shows pharmacokinetic (PK) results of atazanavir (ATV) when administered as ATV/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
Time frame: Day -1 (Reference); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=22; Test, n=20) | 1898 ng/ml | Standard Deviation 2298 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml (Reference, n=21;Test, n=18) | 1671 ng/ml | Standard Deviation 2310 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=22; Test, n=20) | 6419 ng/ml | Standard Deviation 2853 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=22; Test, n=20) | 1545 ng/ml | Standard Deviation 1296 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml (Reference, n=21;Test, n=18) | 1107 ng/ml | Standard Deviation 866.8 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=22; Test, n=20) | 6950 ng/ml | Standard Deviation 2693 |
Comparison: Parameter: Minimum plasma concentration (Cmin)90% CI: [0.63, 1.33]Linear mixed effects model
Comparison: Parameter: maximum plasma concentration (Cmax)90% CI: [0.86, 1.27]Linear mixed effects model
Primary
Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)
The table below shows pharmacokinetic (PK) results of ETR in the current study expressed as the area under the plasma concentration-time curve from time of intake to 12 hours after dosing (AUC12hr).
Time frame: Week 2
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr) | 7629 ng.h/mL | Standard Deviation 4213 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr) | 5171 ng.h/mL | Standard Deviation 2695 |
Primary
Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)
The table below shows pharmacokinetic (PK) results of ETR in the current study expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin) and maximum plasma concentration (Cmax).
Time frame: Week 2
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | C0h (Treatment B, n=19) | 422.2 ng/ml | Standard Deviation 327.9 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | Cmin (Treatment A, n=16; Treatment B, n=18) | 425.1 ng/ml | Standard Deviation 328.1 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | Cmax (Treatment A, n=18; Treatment B, n=18) | 773.0 ng/ml | Standard Deviation 360.5 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | C0h (Treatment B, n=19) | 316.6 ng/ml | Standard Deviation 215.4 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | Cmin (Treatment A, n=16; Treatment B, n=18) | 286.5 ng/ml | Standard Deviation 198 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax) | Cmax (Treatment A, n=18; Treatment B, n=18) | 628.7 ng/ml | Standard Deviation 294 |
Primary
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)
The table below shows the pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
Time frame: Day -1 (Reference); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr) | 12560 ng.h/ml | Standard Deviation 6643 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr) | 11120 ng.h/ml | Standard Deviation 6658 |
Primary
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)
The table below shows the pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/rtv 300/100 mg pretreatment (Reference) and at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), and maximum plasma concentration (Cmax).
Time frame: Day -1 (Reference); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=21; Test, n=19) | 143.4 ng/ml | Standard Deviation 269.8 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml (Reference, n=20; Test, n=18) | 60.42 ng/ml | Standard Deviation 73.17 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=20; Test, n=19) | 1834 ng/ml | Standard Deviation 1009 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=21; Test, n=19) | 102.5 ng/ml | Standard Deviation 157.2 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml (Reference, n=20; Test, n=18) | 43.97 ng/ml | Standard Deviation 36.29 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=20; Test, n=19) | 1740 ng/ml | Standard Deviation 1149 |
Primary
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)
The table below shows pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
Time frame: Day -1 (Reference); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr) | 13880 ng.h/ml | Standard Deviation 8198 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr) | 13660 ng.h/ml | Standard Deviation 6778 |
Primary
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)
The table below shows pharmacokinetic (PK) results of low-dose ritonavir (rtv) when administered as atazanavir (ATV)/ritonavir (rtv) 300/100 mg pretreatment (Reference) and when administered as ATV/rtv 400/100 mg at Week 2 after treatment (Test). Results are expressed as the predose plasma concentration (C0h), minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr).
Time frame: Day -1 (Reference); Week 2 (Test)
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population) for which data was available for the parameter reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=22; Test, n=20) | 109.2 ng/ml | Standard Deviation 94.5 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml | 64.70 ng/ml | Standard Deviation 51.8 |
| ATV/Rtv 300/100 mg (Reference) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=22) | 1882 ng/ml | Standard Deviation 1026 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | C0h, ng/ml (Reference, n=22; Test, n=20) | 163.4 ng/ml | Standard Deviation 240.2 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmin, ng/ml | 75.68 ng/ml | Standard Deviation 69.98 |
| ATV/Rtv 300/100 mg (Test) | Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax) | Cmax, ng/ml (Reference, n=22) | 1847 ng/ml | Standard Deviation 859.9 |
Secondary
Change From Prebaseline in CD4+ Cell Count Over Time
The table below shows the mean change from prebaseline over time in CD4+ cell count using the Non-Completing = Failure (NC=F) imputation method.
Time frame: Prebaseline, Baseline, Weeks 4, 12, 24, 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 4 | 55 CD4+ cell count | Standard Error 15.4 |
| ATV/Rtv 300/100 mg (Reference) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 24 | 54 CD4+ cell count | Standard Error 22 |
| ATV/Rtv 300/100 mg (Reference) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 12 | 31 CD4+ cell count | Standard Error 15 |
| ATV/Rtv 300/100 mg (Reference) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 48 | 105 CD4+ cell count | Standard Error 31.1 |
| ATV/Rtv 300/100 mg (Reference) | Change From Prebaseline in CD4+ Cell Count Over Time | Baseline | 16 CD4+ cell count | Standard Error 11.8 |
| ATV/Rtv 300/100 mg (Test) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 48 | 132 CD4+ cell count | Standard Error 32.6 |
| ATV/Rtv 300/100 mg (Test) | Change From Prebaseline in CD4+ Cell Count Over Time | Baseline | 8 CD4+ cell count | Standard Error 18 |
| ATV/Rtv 300/100 mg (Test) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 4 | 46 CD4+ cell count | Standard Error 27.4 |
| ATV/Rtv 300/100 mg (Test) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 12 | 72 CD4+ cell count | Standard Error 23.5 |
| ATV/Rtv 300/100 mg (Test) | Change From Prebaseline in CD4+ Cell Count Over Time | Week 24 | 83 CD4+ cell count | Standard Error 23.2 |
Secondary
Change From Pre-Baseline in Log10 Viral Load Over Time
The table below shows the mean change from prebaseline over time in log10 (Copies/mL) plasma viral load using the Non-Completing = Failure (NC=F) imputation method.
Time frame: Pre-Baseline, Baseline, Weeks 4, 12, 24, 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Change From Pre-Baseline in Log10 Viral Load Over Time | Baseline | -1.4 log10 (Copies/mL) | Standard Error 0.14 |
| ATV/Rtv 300/100 mg (Reference) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 4 | -1.9 log10 (Copies/mL) | Standard Error 0.18 |
| ATV/Rtv 300/100 mg (Reference) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 12 | -1.7 log10 (Copies/mL) | Standard Error 0.26 |
| ATV/Rtv 300/100 mg (Reference) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 24 | -1.8 log10 (Copies/mL) | Standard Error 0.24 |
| ATV/Rtv 300/100 mg (Reference) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 48 | -1.4 log10 (Copies/mL) | Standard Error 0.24 |
| ATV/Rtv 300/100 mg (Test) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 48 | -1.4 log10 (Copies/mL) | Standard Error 0.29 |
| ATV/Rtv 300/100 mg (Test) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 24 | -1.8 log10 (Copies/mL) | Standard Error 0.27 |
| ATV/Rtv 300/100 mg (Test) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 4 | -1.8 log10 (Copies/mL) | Standard Error 0.15 |
| ATV/Rtv 300/100 mg (Test) | Change From Pre-Baseline in Log10 Viral Load Over Time | Baseline | -1.4 log10 (Copies/mL) | Standard Error 0.18 |
| ATV/Rtv 300/100 mg (Test) | Change From Pre-Baseline in Log10 Viral Load Over Time | Week 12 | -2.0 log10 (Copies/mL) | Standard Error 0.23 |
Secondary
The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method
The table below provides the results from the snapshot analysis method that includes the percentage of participants with virologic response (\<50 copies/mL), the percentage of participants who were virologic failures (VF) (\>50 copies/mL, discontinued prior to time X for reasons of VF or for other reasons, except for VF or adverse event, with a last viral load \>50 copies/mL), and the percentage of participants with no viral load (VL) data available at Week 48.
Time frame: Week 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | Virologic Response | 50.0 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | Virologic Failure | 31.8 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | No VL Data Available | 18.2 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | Virologic Response | 45.5 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | Virologic Failure | 36.4 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method | No VL Data Available | 18.2 Percentage of Participants |
Secondary
The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method
The table below shows the percentage of participants per time point with a virologic response defined as having a plasma viral load (VL) \<50 copies/mL, and with plasma VL \<400 copies/mL using the Non-Completing = Failure (NC=F) imputation method (ie, participants who discontinued early were counted as nonresponders by having their VL values after discontinuation imputed with their Baseline value, thus resulting in a 0 change).
Time frame: Baseline, Weeks 4, 12, 24, 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Baseline | 9.1 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 4 | 31.8 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 12 | 59.1 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 24 | 63.6 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 48 | 50.0 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Baseline | 40.9 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 4 | 77.3 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 12 | 68.2 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 24 | 72.7 Percentage of Participants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 48 | 50.0 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 12 | 81.8 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Baseline | 9.1 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Baseline | 40.9 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 4 | 36.4 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 48 | 59.1 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 12 | 59.1 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 4 | 77.3 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 24 | 63.6 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <400 copies/mL, Week 24 | 72.7 Percentage of Participants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method | <50 copies/mL, Week 48 | 45.5 Percentage of Participants |
Secondary
The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method
The table below shows the percentage of participants with a virologic response defined as a viral load \<50 Copies/mL and \<400 Copies/mL per time point calculated using the time to loss of virologic response (TLOVR) imputation method.
Time frame: Baseline, Weeks 4, 12, 24, 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Baseline | 9.1 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 4 | 31.8 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 12 | 59.1 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 24 | 63.6 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 48 | 45.5 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Baseline | 36.4 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 4 | 77.3 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 12 | 68.2 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 24 | 68.2 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Reference) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 48 | 59.1 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 12 | 86.4 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Baseline | 4.5 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Baseline | 40.9 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 4 | 36.4 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 48 | 54.5 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 12 | 54.5 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 4 | 77.3 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 24 | 59.1 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <400 copies/mL, Week 24 | 68.2 Percentage of Particpants |
| ATV/Rtv 300/100 mg (Test) | The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method | <50 copies/mL, Week 48 | 50.0 Percentage of Particpants |
Secondary
Time to Confirmed Virologic Response
The table below provides the time in days it took participants to reach a confirmed virologic response defined as a plasma viral load (VL) \<50 copies/mL, and plasma VL \<400 copies/mL analyzed according to the Time to Loss of Virologic Response (TLOVR) imputation method.
Time frame: Prebaseline to Week 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Time to Confirmed Virologic Response | Plasma VL < 50 copies/mL | 71.0 Days | 95% Confidence Interval 10.87 |
| ATV/Rtv 300/100 mg (Reference) | Time to Confirmed Virologic Response | Plasma VL < 400 copies/mL | 28.0 Days | 95% Confidence Interval 5.02 |
| ATV/Rtv 300/100 mg (Test) | Time to Confirmed Virologic Response | Plasma VL < 50 copies/mL | 76.0 Days | 95% Confidence Interval 9.95 |
| ATV/Rtv 300/100 mg (Test) | Time to Confirmed Virologic Response | Plasma VL < 400 copies/mL | 28.0 Days | 95% Confidence Interval 6.47 |
Secondary
Time to Virologic Failure
The table below shows the number of days to virologic failure defined as a plasma viral load (VL) \> 50 copies/mL for participants who had been virologic responders (ie, having a plasma VL \<50, and \<400 copies/mL according to the time to loss of virologic response \[TLOVR\] imputation method). Time to virologic failure was the time to subsequent loss of virologic response, and the time was calculated from Prebaseline (Week -2). Participants who never achieved a virologic response were defined as nonresponders and counted as virologic failures on Day 1.
Time frame: Prebaseline to Week 48
Population: The population analyzed included all randomized participants with at least 1 etravirine (ETR) intake regardless of their compliance with the protocol (ie, the efficacy ITT population).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| ATV/Rtv 300/100 mg (Reference) | Time to Virologic Failure | Virologic Responders (Plasma VL < 50 copies/mL) | 318.0 Days | 95% Confidence Interval 31.9 |
| ATV/Rtv 300/100 mg (Reference) | Time to Virologic Failure | Virologic Responders (Plasma VL < 400 copies/mL) | NA Days | 95% Confidence Interval 28.92 |
| ATV/Rtv 300/100 mg (Test) | Time to Virologic Failure | Virologic Responders (Plasma VL < 50 copies/mL) | NA Days | 95% Confidence Interval 22.46 |
| ATV/Rtv 300/100 mg (Test) | Time to Virologic Failure | Virologic Responders (Plasma VL < 400 copies/mL) | NA Days | 95% Confidence Interval 17.28 |