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

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00896051
• Collaborator: (none)
• Enrollment: 50
• Locations: 19
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Acquired Immunodeficiency Syndrome	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	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TMC125-TiDP2-C238: A Randomized, Exploratory, Open-label 48-week Trial to Investigate the Pharmacokinetics, Safety, Tolerability and Antiviral Activity of Etravirine (ETR) in Combination With Ritonavir-boosted Atazanavir (ATV/Rtv) and 1 NRTI in Treatment-experienced HIV-1 Infected Subjects
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ATV/rtv 300/100 mg (Treatment A) Treatment-experienced human immunodeficiency virus - type 1 (HIV-1) infected participants will take by mouth atazanavir (ATV)/low-dose ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 2 weeks pre-treatment followed by ATV/rtv 300/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks. If particpating in an optional substudy to assess the effect of adding tenofovir disoproxil fumarate (TDF) for 7 days on ATV and ETR pharmacokinetics, participants will receive TDF 300 mg once daily for 7 days in addition to their antiretroviral regimen (ETR+ATV/rtv+NRTI).	Drug: Atazanavir (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.; Drug: Ritonavir (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.; Drug: Nucleo(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.; Drug: Etravirine (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.; Drug: Tenofovir disoproxil fumarate (TDF) 300 mg; Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.
Experimental: ATV/rtv 400/100 mg (Treatment B) Treatment-experienced human immunodeficiency virus - type 1 (HIV-1) infected participants will take by mouth atazanavir (ATV)/low-dose ritonavir (rtv) 300/100 mg once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 2 weeks pretreatment followed by ATV/rtv 400/100 mg once daily + etravirine (ETR) 200 mg twice daily + 1 NRTI for 48 weeks. If particpating in an optional substudy to assess the effect of adding tenofovir disoproxil fumarate (TDF) for 7 days on ATV and ETR pharmacokinetics, participants will take TDF 300 mg once daily for 7 days in addition to their antiretroviral regimen (ETR+ATV/rtv+NRTI).	Drug: Atazanavir (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.; Drug: Ritonavir (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.; Drug: Nucleo(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.; Drug: Etravirine (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.; Drug: Tenofovir disoproxil fumarate (TDF) 300 mg; Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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).

5. 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).

6. 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).

7. 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).

8. 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).

9. 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).

10. 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).

11. 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).

Secondary Outcome Measures

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.

2. 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).

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Little Rock	Arkansas	United States
2		Bakersfield	California	United States
3		Beverly Hills	California	United States
4		Orlando	Florida	United States
5		Tampa	Florida	United States
6		Vero Beach	Florida	United States
7		West Palm Beach	Florida	United States
8		Macon	Georgia	United States
9		Dallas	Texas	United States
10		Houston	Texas	United States
11		Buenos Aires		Argentina
12		Cordoba		Argentina
13		Paris Cedex 10		France
14		Paris		France
15		Tourcoing		France
16		Bloemfontein		South Africa
17		Cape Town		South Africa
18		George		South Africa
19		Bangkok		Thailand

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Janssen R&D Ireland Clinical Trial, Janssen R&D Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT00896051
• Other Study ID Numbers: CR016045; TMC125-TiDP2-C238
• First Posted: May 11, 2009
• Last Update Posted: Sep 30, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Janssen R&D Ireland: HIV Infections; Acquired Immunodeficiency Syndrome; TMC125-TiDP2-C238; TMC125-C238; Etravirine; Intelence; HIV; HIV-1; Pharmacokinetics
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Ritonavir; Atazanavir Sulfate; Tenofovir; Etravirine; Reverse Transcriptase Inhibitors

Study Results

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 Detail	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.

Arm/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	25	25
COMPLETED	15	16
NOT COMPLETED	10	9

Baseline Characteristics

Arm/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	25	25	50
Age (Count of Participants)
<=18 years	0 0%	1 4%	1 2%
Between 18 and 65 years	25 100%	24 96%	49 98%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.2 (10.44)	39.8 (9.37)	40.5 (9.85)
Sex: Female, Male (Count of Participants)
Female	12 48%	13 52%	25 50%
Male	13 52%	12 48%	25 50%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for C0h, Cmin, and Cmax)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 300/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	21	19
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

Statistical Analysis Overview	Comparison Group Selection	ATV/Rtv 300/100 mg (Reference), ATV/Rtv 300/100 mg (Test)
	Comments	Parameter: minimum plasma concentration (Cmin)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Means Ratio
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 90%; 0.55 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/Rtv 300/100 mg (Reference), ATV/Rtv 300/100 mg (Test)
	Comments	Parameter: maximum plasma concentration (Cmax)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90%; 0.80 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetic Results of Atazanavir (ATV): Treatment A: ATV/Low-Dose Ritonavir (Rtv) 300/100 mg (Results for AUC24hr)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 300/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	19	18
Mean (Standard Deviation) [ng.h/mL]	60030 (39690)	55070 (21860)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/Rtv 300/100 mg (Reference), ATV/Rtv 300/100 mg (Test)
	Comments	Parameter: area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Means Ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90%; 0.76 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for C0h, Cmin, and Cmax)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 400/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	21	20
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

Statistical Analysis Overview	Comparison Group Selection	ATV/Rtv 300/100 mg (Reference), ATV/Rtv 300/100 mg (Test)
	Comments	Parameter: Minimum plasma concentration (Cmin)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Means Ratio
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 90%; 0.63 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/Rtv 300/100 mg (Reference), ATV/Rtv 300/100 mg (Test)
	Comments	Parameter: maximum plasma concentration (Cmax)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Means Ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 90%; 0.86 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Pharmacokinetic Results of Atazanavir (ATV): Treatment B: ATV/Low-Dose Ritonavir (Rtv) 400/100 mg (Results for AUC24hr)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 300/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	21	19
Mean (Standard Deviation) [ng.h/mL]	74210 (55480)	72220 (34600)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/Rtv 300/100 mg (Reference), ATV/Rtv 300/100 mg (Test)
	Comments	Parameter: area under the plasma concentration-time curve from time of intake to 24 hours after dosing (AUC24hr)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Means Ratio
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 90%; 0.81 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for C0h, Cmin, and Cmax)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 300/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	21	19
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)

6. Primary Outcome

Title	Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment A: Atazanavir (ATV)/Rtv 300/100 mg (Results for AUC24hr)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 300/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	19	18
Mean (Standard Deviation) [ng.h/ml]	12560 (6643)	11120 (6658)

7. Primary Outcome

Title	Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for C0h, Cmin, and Cmax)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 400/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	20	19
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)

8. Primary Outcome

Title	Pharmacokinetic Results of Low-Dose Ritonavir (Rtv): Treatment B: Atazanavir (ATV)/Rtv 400/100 mg (Results for AUC24hr)
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)

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Reference)	ATV/Rtv 300/100 mg (Test)
Arm/Group Description	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.	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.
Measure Participants	20	19
Mean (Standard Deviation) [ng.h/ml]	13880 (8198)	13660 (6778)

9. Primary Outcome

Title	Pharmacokinetic Results of Etravirine (ETR) (Results for C0h, Cmin, and Cmax)
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	19	20
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)

10. Primary Outcome

Title	Pharmacokinetic Results of Etravirine (ETR) (Results for AUC12hr)
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	18	18
Mean (Standard Deviation) [ng.h/mL]	7629 (4213)	5171 (2695)

11. Primary Outcome

Title	Percentage of Participants With Undetectable Plasma Viral Load (VL) Values (<50 Copies/mL) at Week 48
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
Number (95% Confidence Interval) [Percentage of Participants]	50.0 200%	45.5 182%

12. Secondary Outcome

Title	Change From Prebaseline in CD4+ Cell Count Over Time
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
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)

13. Secondary Outcome

Title	The Percentage of Participants With a Virologic Response Using the Non-Completing = Failure (NC=F) Imputation Method
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
<50 copies/mL, Baseline	9.1 36.4%	9.1 36.4%
<50 copies/mL, Week 4	31.8 127.2%	36.4 145.6%
<50 copies/mL, Week 12	59.1 236.4%	59.1 236.4%
<50 copies/mL, Week 24	63.6 254.4%	63.6 254.4%
<50 copies/mL, Week 48	50.0 200%	45.5 182%
<400 copies/mL, Baseline	40.9 163.6%	40.9 163.6%
<400 copies/mL, Week 4	77.3 309.2%	77.3 309.2%
<400 copies/mL, Week 12	68.2 272.8%	81.8 327.2%
<400 copies/mL, Week 24	72.7 290.8%	72.7 290.8%
<400 copies/mL, Week 48	50.0 200%	59.1 236.4%

14. Secondary Outcome

Title	The Percentage of Participants With a Virologic Response Using the Time to Loss of Virologic Response (TLOVR) Imputation Method
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment A)
Arm/Group Description	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).	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).
Measure Participants	22	22
<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

15. Secondary Outcome

Title	The Percentage of Participants With a Virologic Response (Plasma Viral Load < 50 Copies/mL) at Week 48 Using the Snapshot Analysis Method
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
Virologic Response	50.0 200%	45.5 182%
Virologic Failure	31.8 127.2%	36.4 145.6%
No VL Data Available	18.2 72.8%	18.2 72.8%

16. Secondary Outcome

Title	Change From Pre-Baseline in Log10 Viral Load Over Time
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
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)

17. Secondary Outcome

Title	Time to Confirmed Virologic Response
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
Plasma VL < 50 copies/mL	71.0 (10.87)	76.0 (9.95)
Plasma VL < 400 copies/mL	28.0 (5.02)	28.0 (6.47)

18. Secondary Outcome

Title	Time to Virologic Failure
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

Outcome Measure Data

Analysis Population Description

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/Group Title	ATV/Rtv 300/100 mg (Treatment A)	ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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).	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).
Measure Participants	22	22
Virologic Responders (Plasma VL < 50 copies/mL)	318.0 (31.90)	NA (22.46)
Virologic Responders (Plasma VL < 400 copies/mL)	NA (28.92)	NA (17.28)

Adverse Events

Time Frame	Up to a maximum of 56 weeks.
Adverse Event Reporting Description	To also include the safety data of 6 participants who discontinued during the Pretreatment Period, the safety analyses were performed on the ITT population defined as all participants who had at least 1 atazanavir (ATV)/low dose ritonavir (rtv) intake regardless of their compliance with the protocol (ie, the 'safety ITT population').
Arm/Group Title	ATV/Rtv 300/100 mg (Treatment A)		ATV/Rtv 400/100 mg (Treatment B)
Arm/Group Description	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.		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.
All Cause Mortality
	ATV/Rtv 300/100 mg (Treatment A)		ATV/Rtv 400/100 mg (Treatment B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ATV/Rtv 300/100 mg (Treatment A)		ATV/Rtv 400/100 mg (Treatment B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/25 (16%)		2/25 (8%)
Blood and lymphatic system disorders
Anaemia	1/25 (4%)		0/25 (0%)
Infections and infestations
Gastroenteritis	1/25 (4%)		0/25 (0%)
Meningitis aseptic	1/25 (4%)		0/25 (0%)
Pneumonia	1/25 (4%)		1/25 (4%)
Sinusitis	1/25 (4%)		0/25 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/25 (4%)		0/25 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease	0/25 (0%)		1/25 (4%)
Metastatic malignant melanoma	1/25 (4%)		0/25 (0%)
Nervous system disorders
Headache	0/25 (0%)		1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/25 (4%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	ATV/Rtv 300/100 mg (Treatment A)		ATV/Rtv 400/100 mg (Treatment B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/25 (84%)		15/25 (60%)
Gastrointestinal disorders
Abdominal pain	0/25 (0%)		2/25 (8%)
Diarrhoea	2/25 (8%)		2/25 (8%)
Nausea	4/25 (16%)		1/25 (4%)
Vomiting	2/25 (8%)		0/25 (0%)
General disorders
Fatigue	2/25 (8%)		1/25 (4%)
Pyrexia	2/25 (8%)		0/25 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	3/25 (12%)		0/25 (0%)
Jaundice	2/25 (8%)		2/25 (8%)
Infections and infestations
Bronchitis	2/25 (8%)		1/25 (4%)
Influenza	2/25 (8%)		3/25 (12%)
Sinusitis	2/25 (8%)		0/25 (0%)
Upper respiratory tract infection	2/25 (8%)		3/25 (12%)
Investigations
Blood bilirubin increased	3/25 (12%)		2/25 (8%)
Nervous system disorders
Headache	3/25 (12%)		3/25 (12%)
Neuropathy peripheral	2/25 (8%)		0/25 (0%)
Psychiatric disorders
Anxiety disorder	2/25 (8%)		0/25 (0%)
Depression	2/25 (8%)		0/25 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	5/25 (20%)		4/25 (16%)
Oropharyngeal pain	2/25 (8%)		1/25 (4%)
Skin and subcutaneous tissue disorders
Pruritus	0/25 (0%)		2/25 (8%)
Rash	3/25 (12%)		1/25 (4%)
Rash maculo-papular	1/25 (4%)		2/25 (8%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

It is the policy of the sponsor not to allow investigators to publish their results or findings from the study prior to the sponsor's publication of the overall trial results. The investigator agrees that before he/she publishes any results of this trial, he/she shall allow at least 45 days for the sponsor to review the prepublication manuscript prior to submission of the manuscript to the publisher.