Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

TMC125-TiDP2-C238: An Exploratory Pharmacokinetics, Safety and Anti-HIV Activity Study of Etravirine (ETR) When Given With Boosted Atazanavir (ATV/Rtv) at Two Different Doses and 1 Nucleoside Reverse Transcriptase Inhibitor (NRTI) in Treatment Experienced HIV Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT00896051
First received: May 7, 2009
Last updated: September 27, 2013
Last verified: September 2013
Results First Received: April 10, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV Infections
Acquired Immunodeficiency Syndrome
Interventions: Drug: Atazanavir (ATV) 300 mg
Drug: Atazanavir (ATV) 400 mg
Drug: Ritonavir (rtv) 100 mg
Drug: Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs)
Drug: Etravirine (ETR) 200 mg
Drug: Tenofovir disoproxil fumarate (TDF) 300 mg

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.
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.

Participant Flow:   Overall Study
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
STARTED     25     25  
COMPLETED     15     16  
NOT COMPLETED     10     9  
Adverse Event                 2                 1  
Lost to Follow-up                 3                 2  
Withdrawal by Subject                 3                 2  
Subject noncompliant                 1                 3  
Not specified                 1                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.
Total Total of all reporting groups

Baseline Measures
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)     Total  
Number of Participants  
[units: participants]
  25     25     50  
Age  
[units: participants]
     
<=18 years     0     1     1  
Between 18 and 65 years     25     24     49  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  41.2  ± 10.44     39.8  ± 9.37     40.5  ± 9.85  
Gender  
[units: participants]
     
Female     12     13     25  
Male     13     12     25  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)   [ Time Frame: Day -1 (Pretreatment); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 300/100 mg (Test) 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 + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks during the treatment period (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 300/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  21     19  
Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)  
[units: ng/ml]
Mean ± Standard Deviation
   
C0h, ng/ml (Reference, n=21; Test, n=19)     1339  ± 1728     845.7  ± 703.3  
Cmin, ng/ml (Reference, n=20; Test, n=18)     1104  ± 1511     758.6  ± 610.5  
Cmax, ng/ml (Reference, n=20; Test, n=19)     5652  ± 2735     5232  ± 2166  


Statistical Analysis 1 for Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
Groups [1] All groups
Method [2] Linear mixed effects model
Least Squares (LS) Means Ratio [3] 0.82
90% Confidence Interval ( 0.55 to 1.22 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Parameter: minimum plasma concentration (Cmin)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A linear mixed effects model was used controlling for treatment as fixed effect, and participant as a random effect.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
Groups [1] All groups
Method [2] Linear mixed effects model
Least Squares (LS) Mean Ratio [3] 0.96
90% Confidence Interval ( 0.80 to 1.16 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Parameter: maximum plasma concentration (Cmax)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A linear mixed effects model was used controlling for treatment as fixed effect, and participant as a random effect.
[3] Other relevant estimation information:
  No text entered.



2.  Primary:   Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)   [ Time Frame: Day -1 (Pretreatment); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 300/100 mg (Test) 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 + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks during the treatment period (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 300/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  19     18  
Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)  
[units: ng.h/mL]
Mean ± Standard Deviation
  60030  ± 39690     55070  ± 21860  


Statistical Analysis 1 for Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)
Groups [1] All groups
Method [2] Linear mixed effects model
Least Squares (LS) Means Ratio [3] 0.96
90% Confidence Interval ( 0.76 to 1.22 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Parameter: area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  linear mixed effects model was used controlling for treatment as fixed effect, and participant as a random effect.
[3] Other relevant estimation information:
  No text entered.



3.  Primary:   Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)   [ Time Frame: Day -1 (Reference); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 400/100 mg (Test) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 400/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  21     20  
Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)  
[units: ng/ml]
Mean ± Standard Deviation
   
C0h, ng/ml (Reference, n=22; Test, n=20)     1898  ± 2298     1545  ± 1296  
Cmin, ng/ml (Reference, n=21;Test, n=18)     1671  ± 2310     1107  ± 866.8  
Cmax, ng/ml (Reference, n=22; Test, n=20)     6419  ± 2853     6950  ± 2693  


Statistical Analysis 1 for Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
Groups [1] All groups
Method [2] Linear mixed effects model
Least Squares (LS) Means Ratio [3] 0.91
90% Confidence Interval ( 0.63 to 1.33 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Parameter: Minimum plasma concentration (Cmin)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A linear mixed effects model was used controlling for treatment as fixed effect, and participant as a random effect.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
Groups [1] All groups
Method [2] Linear mixed effects model
Least Squares (LS) Means Ratio [3] 1.05
90% Confidence Interval ( 0.86 to 1.27 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Parameter: maximum plasma concentration (Cmax)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A linear mixed effects model was used controlling for treatment as fixed effect, and participant as a random effect.
[3] Other relevant estimation information:
  No text entered.



4.  Primary:   Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)   [ Time Frame: Day -1 (Reference); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 300/100 mg (Test) 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 + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks during the treatment period (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 300/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  21     19  
Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)  
[units: ng.h/mL]
Mean ± Standard Deviation
  74210  ± 55480     72220  ± 34600  


Statistical Analysis 1 for Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)
Groups [1] All groups
Method [2] Llinear mixed effects model
Least Squares (LS) Means Ratio [3] 0.99
90% Confidence Interval ( 0.81 to 1.21 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Parameter: area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A linear mixed effects model was used controlling for treatment as fixed effect, and participant as a random effect.
[3] Other relevant estimation information:
  No text entered.



5.  Primary:   Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)   [ Time Frame: Day -1 (Reference); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 300/100 mg (Test) 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 + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks during the treatment period (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 300/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  21     19  
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)  
[units: ng/ml]
Mean ± Standard Deviation
   
C0h, ng/ml (Reference, n=21; Test, n=19)     143.4  ± 269.8     102.5  ± 157.2  
Cmin, ng/ml (Reference, n=20; Test, n=18)     60.42  ± 73.17     43.97  ± 36.29  
Cmax, ng/ml (Reference, n=20; Test, n=19)     1834  ± 1009     1740  ± 1149  

No statistical analysis provided for Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)



6.  Primary:   Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)   [ Time Frame: Day -1 (Reference); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 300/100 mg (Test) 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 + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks during the treatment period (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 300/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  19     18  
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)  
[units: ng.h/ml]
Mean ± Standard Deviation
  12560  ± 6643     11120  ± 6658  

No statistical analysis provided for Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)



7.  Primary:   Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)   [ Time Frame: Day -1 (Reference); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 400/100 mg (Test) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks (Day 1 to Week 48). Pharmacokinetic results for rtv provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 400/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  20     19  
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)  
[units: ng/ml]
Mean ± Standard Deviation
   
C0h, ng/ml (Reference, n=22; Test, n=20)     109.2  ± 94.50     163.4  ± 240.2  
Cmin, ng/ml     64.70  ± 51.80     75.68  ± 69.98  
Cmax, ng/ml (Reference, n=22)     1882  ± 1026     1847  ± 859.9  

No statistical analysis provided for Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)



8.  Primary:   Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)   [ Time Frame: Day -1 (Reference); Week 2 (Test) ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Reference) 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 14 days during the pre-treatment period. Pharmacokinetic results for ATV provided in the table below are at Day -1.
ATV/Rtv 300/100 mg (Test) 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 + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI) for 48 weeks during the treatment period (Day 1 to Week 48). Pharmacokinetic results for ATV provided in the table below are at Week 2.

Measured Values
    ATV/Rtv 300/100 mg (Reference)     ATV/Rtv 300/100 mg (Test)  
Number of Participants Analyzed  
[units: participants]
  20     19  
Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)  
[units: ng.h/ml]
Mean ± Standard Deviation
  13880  ± 8198     13660  ± 6778  

No statistical analysis provided for Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)



9.  Primary:   Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)   [ Time Frame: Week 2 ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  19     20  
Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)  
[units: ng/ml]
Mean ± Standard Deviation
   
C0h (Treatment B, n=19)     422.2  ± 327.9     316.6  ± 215.4  
Cmin (Treatment A, n=16; Treatment B, n=18)     425.1  ± 328.1     286.5  ± 198.0  
Cmax (Treatment A, n=18; Treatment B, n=18)     773.0  ± 360.5     628.7  ± 294.0  

No statistical analysis provided for Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)



10.  Primary:   Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)   [ Time Frame: Week 2 ]

Measure Type Primary
Measure Title Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 nucleoside reverse transcriptase inhibitor (NRTI).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  18     18  
Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)  
[units: ng.h/mL]
Mean ± Standard Deviation
  7629  ± 4213     5171  ± 2695  

No statistical analysis provided for Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)



11.  Primary:   Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced human immunodeficiency virus – type 1 (HIV-1) infected participants took by mouth atazanavir (ATV)/ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48  
[units: Percentage of Participants]
Number ( 95% Confidence Interval )
  50.0  
  ( 28.2 to 71.8 )  
  45.5  
  ( 45.5 to 67.8 )  

No statistical analysis provided for Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48



12.  Secondary:   Change From Prebaseline in CD4+ Cell Count Over Time   [ Time Frame: Prebaseline, Baseline, Weeks 4, 12, 24, 48 ]

Measure Type Secondary
Measure Title Change From Prebaseline in CD4+ Cell Count Over Time
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
Change From Prebaseline in CD4+ Cell Count Over Time  
[units: CD4+ cell count]
Mean ± Standard Error
   
Baseline     16  ± 11.8     8  ± 18  
Week 4     55  ± 15.4     46  ± 27.4  
Week 12     31  ± 15.0     72  ± 23.5  
Week 24     54  ± 22.0     83  ± 23.2  
Week 48     105  ± 31.1     132  ± 32.6  

No statistical analysis provided for Change From Prebaseline in CD4+ Cell Count Over Time



13.  Secondary:   The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method   [ Time Frame: Baseline, Weeks 4, 12, 24, 48 ]

Measure Type Secondary
Measure Title The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method  
[units: Percentage of Participants]
   
<50 copies/mL, Baseline     9.1     9.1  
<50 copies/mL, Week 4     31.8     36.4  
<50 copies/mL, Week 12     59.1     59.1  
<50 copies/mL, Week 24     63.6     63.6  
<50 copies/mL, Week 48     50.0     45.5  
<400 copies/mL, Baseline     40.9     40.9  
<400 copies/mL, Week 4     77.3     77.3  
<400 copies/mL, Week 12     68.2     81.8  
<400 copies/mL, Week 24     72.7     72.7  
<400 copies/mL, Week 48     50.0     59.1  

No statistical analysis provided for The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method



14.  Secondary:   The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method   [ Time Frame: Baseline, Weeks 4, 12, 24, 48 ]

Measure Type Secondary
Measure Title The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment A)  
Number of Participants Analyzed  
[units: participants]
  22     22  
The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method  
[units: Percentage of Particpants]
   
<50 copies/mL, Baseline     9.1     4.5  
<50 copies/mL, Week 4     31.8     36.4  
<50 copies/mL, Week 12     59.1     54.5  
<50 copies/mL, Week 24     63.6     59.1  
<50 copies/mL, Week 48     45.5     50.0  
<400 copies/mL, Baseline     36.4     40.9  
<400 copies/mL, Week 4     77.3     77.3  
<400 copies/mL, Week 12     68.2     86.4  
<400 copies/mL, Week 24     68.2     68.2  
<400 copies/mL, Week 48     59.1     54.5  

No statistical analysis provided for The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method



15.  Secondary:   The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method  
[units: Percentage of Participants]
   
Virologic Response     50.0     45.5  
Virologic Failure     31.8     36.4  
No VL Data Available     18.2     18.2  

No statistical analysis provided for The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method



16.  Secondary:   Change From Pre-Baseline in Log10 Viral Load Over Time   [ Time Frame: Pre-Baseline, Baseline, Weeks 4, 12, 24, 48 ]

Measure Type Secondary
Measure Title Change From Pre-Baseline in Log10 Viral Load Over Time
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
Change From Pre-Baseline in Log10 Viral Load Over Time  
[units: log10 (Copies/mL)]
Mean ± Standard Error
   
Baseline     -1.4  ± 0.14     -1.4  ± 0.18  
Week 4     -1.9  ± 0.18     -1.8  ± 0.15  
Week 12     -1.7  ± 0.26     -2.0  ± 0.23  
Week 24     -1.8  ± 0.24     -1.8  ± 0.27  
Week 48     -1.4  ± 0.24     -1.4  ± 0.29  

No statistical analysis provided for Change From Pre-Baseline in Log10 Viral Load Over Time



17.  Secondary:   Time to Confirmed Virologic Response   [ Time Frame: Prebaseline to Week 48 ]

Measure Type Secondary
Measure Title Time to Confirmed Virologic Response
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
Time to Confirmed Virologic Response  
[units: Days]
Median ( 95% Confidence Interval )
   
Plasma VL < 50 copies/mL     71.0  
  ( 44.0 to 129.0 )  
  76.0  
  ( 42.0 to 99.0 )  
Plasma VL < 400 copies/mL     28.0  
  ( 15.0 to 43.0 )  
  28.0  
  ( 15.0 to 43.0 )  

No statistical analysis provided for Time to Confirmed Virologic Response



18.  Secondary:   Time to Virologic Failure   [ Time Frame: Prebaseline to Week 48 ]

Measure Type Secondary
Measure Title Time to Virologic Failure
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups
  Description
ATV/Rtv 300/100 mg (Treatment A) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment A).
ATV/Rtv 400/100 mg (Treatment B) Treatment-experienced 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 2 weeks (Pre-treatment Period) followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks (Treatment B).

Measured Values
    ATV/Rtv 300/100 mg (Treatment A)     ATV/Rtv 400/100 mg (Treatment B)  
Number of Participants Analyzed  
[units: participants]
  22     22  
Time to Virologic Failure  
[units: Days]
Median ( 95% Confidence Interval )
   
Virologic Responders (Plasma VL < 50 copies/mL)     318.0  
  ( 78.0 to NA ) [1]
  NA  
  ( NA to NA ) [2]
Virologic Responders (Plasma VL < 400 copies/mL)     NA  
  ( NA to NA ) [3]
  NA  
  ( NA to NA ) [3]
[1] The upper limit of the 95% CI could not be assessed because a sufficient number of participants did not experience virologic failure.
[2] Median cannot be assessed since less than 50% of participants experienced virologic failure.
[3] Median cannot be assessed since less than 50% of participants experienced virologic failure

No statistical analysis provided for Time to Virologic Failure




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information