OREY: Phase IIIb Study to Evaluate the Effectiveness and Safety of Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in Human Immunodeficiency Virus (HIV)-Infected Subjects Evidencing Virologic Suppression

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00337467
• Collaborator: (none)
• Enrollment: 61
• Locations: 7
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose is to explore whether atazanavir/ritonavir (ATV/RTV) single enhanced protease inhibitor therapy can maintain virologic suppression without a marked increase in virologic failure.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus (HIV) Infections	Drug: Atazanavir + Ritonavir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IIIb Multicenter, Single Arm, Open-Label Pilot Study to Evaluate the Effectiveness and Safety of Maintenance With Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in HIV-Infected Patients Evidencing Virologic Suppression OREY (Only REYataz) Study
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A1	Drug: Atazanavir + Ritonavir; Capsules, Oral, ATV 300mg + RTV 100mg, once daily, 96 weeks; Other Names: Reyataz BMS-232632

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Treatment Failure Through Week 48 [Week 48]

   Treatment Failure through Week 48 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 48 or study discontinuation before Week 48. Virological rebound is defined as confirmed on-treatment HIV ribonucleic acid (RNA) >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy.

Secondary Outcome Measures

1. Percentage of Participants With Treatment Failure Through Week 96 [Week 96]

   Treatment Failure through Week 96 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 96 or study discontinuation before Week 96. In addition, treatment failure defined based on HIV RNA >= 50 c/mL, latter analysis performed on treated subjects with baseline HIV RNA < 50 c/mL.

2. Percentage of Participants With Virological Rebound Through Week 48 [Week 48]

   Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.

3. Percentage of Participants With Virological Rebound Through Week 96 [Week 96]

   Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.

4. Cumulative Proportion of Participants Without Treatment Failure Through Week 100 [Through Week 100]

   This Kaplan-Meier life table reports the cumulative proportion of participants without treatment failure up to the end of the respective time interval. Failure time is measured from the start of study therapy, and is based on the earliest event defining failure (virologic rebound at or before Week 96, or discontinuation prior to Week 96).

5. Proportion of Participants With Virologic Rebound Through Week 96 [Through Week 96]

   Virologic rebound is defined as confirmed on-study HIV RNA ≥ 400 c/mL or last on-study HIV RNA ≥ 400 c/mL followed by treatment discontinuation.

6. Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 [Baseline, Week 24]

7. Mean Change From Baseline in CD4 Cell Count at Week 48 [Baseline, Week 48]

8. Mean Change From Baseline in CD4 Cell Count at Week 96 [Baseline, Week 96]

9. Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs [From Baseline through Week 96]

   AE=any new untoward medical occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship to treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. AE grades are: mild (1), moderate (2), severe (3), life-threatening (4), and death (5).

10. Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 48 [Baseline, Week 48]

    Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.

11. Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 96 [Baseline, Week 96]

    Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.

12. Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48 [Week 48]

    International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.

13. Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96 [Week 96]

    International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• On continued antiretroviral (ARV) treatment, with no discontinuation periods, for the previous 6 months (24 weeks).

• Absence of evidence or suspected virologic failure on antiretroviral therapy

• Absence of known primary mutations in the protease gene

• Only 1 highly active antiretroviral therapy (HAART) prior to current one

• HIV RNA < 50 copies/mL in the last 6 months (single blip below 200 c/mL allowed)

• On ATV/RTV +2 nucleoside reverse transcriptase inhibitors (NRTIs) (or 1 NRTI + tenofovir [TDF]) for at least 8 weeks before study entry, without treatment-limiting adverse effects

Exclusion Criteria:

• Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.

• Active disease condition (e.g. moderate to severe hepatic impairment/active renal disease/history of clinically significant heart conduction disease)

• Patients with chronic hepatitis B receiving lamivudine (3TC), Tenofovir Disoproxil Fumarate (TDF) or emtricitabine (FTC).

• CD4 < 100 cells/mm3

• Grade IV laboratory values: Hemoglobin < 6.5 g/dL or white blood cells (WBC) <800/mmm3 or absolute neutrophil count < 500/mm3, or platelets < 20,000/mm3 or diffuse petechiae.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Cordoba		Spain	14004
2	Local Institution	Madrid		Spain	28007
3	Local Institution	Madrid		Spain	28034
4	Local Institution	Madrid		Spain	28040
5	Local Institution	Madrid		Spain	28041
6	Local Institution	Madrid		Spain	28046
7	Local Institution	Malaga		Spain	29010

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00337467
• Other Study ID Numbers: AI424-227
• First Posted: Jun 16, 2006
• Last Update Posted: Jul 19, 2010
• Last Verified: Jun 1, 2010

• Keywords provided by , ,: HIV-Infected Patients Evidencing Virologic Suppression
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Ritonavir; Atazanavir Sulfate

Study Results

Participant Flow

Pre-assignment Detail	63 participants were enrolled in this study; 2 were never treated (1 no longer met study criteria and 1 concomitant medication not permitted).

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Period Title: Overall Study
STARTED	61
Discontinued Prior to Week 96	10
COMPLETED	51
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Overall Participants	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43 (9.5)
Sex: Female, Male (Count of Participants)
Female	15 24.6%
Male	46 75.4%
Race/Ethnicity, Customized (participants) [Number]
White	61 100%
Cluster of Differentiation 4 (CD4) Categories (participants) [Number]
CD4 Count <200 cells/mm3	3 4.9%
CD4 Count >=200 cells/mm3	58 95.1%
Human Immunodeficiency Ribonucleic Acid (HIV RNA) Categories (Number) [Number]
HIV RNA <50 c/mL	60 98.4%
HIV RNA >=50 c/mL	1 1.6%
CD4 Count (cell/mm3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cell/mm3]	559 (272.8)
Fasting High-Density Lipoprotein (HDL) Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	45 (10.4)
Fasting Low-Density Lipoprotein (LDL) Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	112 (52.3)
Fasting Non-HDL Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	144 (57.9)
Fasting Total Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	189 (57)
Fasting Triglycerides (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	164 (95.7)
HIV RNA (log10 c/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 c/mL]	1.71 (0.152)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment Failure Through Week 48
Description	Treatment Failure through Week 48 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 48 or study discontinuation before Week 48. Virological rebound is defined as confirmed on-treatment HIV ribonucleic acid (RNA) >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Treated participants

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
Number [Percentage of Participants]	21.3 34.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	21.3
	Confidence Interval	(2-Sided) 95%; 11.9 to 33.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Treatment Failure Through Week 96
Description	Treatment Failure through Week 96 defined as virologic rebound (HIV RNA >=400 c/mL) on or before Week 96 or study discontinuation before Week 96. In addition, treatment failure defined based on HIV RNA >= 50 c/mL, latter analysis performed on treated subjects with baseline HIV RNA < 50 c/mL.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Treated participants. For the second row (n=60), one subject was excluded because of baseline HIV RNA > 50 c/mL.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
HIV RNA >= 400 c/mL(n=61)	34.4 56.4%
HIV RNA>=50 c/mL w/Baseline HIV RNA<50 c/mL (n=60)	43.3 71%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	34.4
	Confidence Interval	(2-Sided) 95%; 22.7 to 47.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Virological Rebound Through Week 48
Description	Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Treated participants. For the second row (n=60), one subject was excluded because of baseline HIV RNA > 50 c/mL.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
HIV RNA >= 400 c/mL (n=61)	12 19.7%
HIV RNA>=50 c/mL w/Baseline HIV RNA<50 c/mL (n=60)	26.7 43.8%

4. Secondary Outcome

Title	Percentage of Participants With Virological Rebound Through Week 96
Description	Virological rebound is defined as confirmed on-treatment HIV RNA >= 400 c/mL at 2 consecutive visits or last on-treatment HIV RNA >=400 c/mL followed by discontinuation of study therapy. In addition, virologic rebound defined based on HIV RNA >=50 c/m, latter analysis performed on subjects with baseline HIV RNA < 50 c/mL.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Treated participants. For the second row (n=60), one subject was excluded because of baseline HIV RNA > 50 c/mL.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
HIV RNA >= 400 c/mL (n=61)	14.8 24.3%
HIV RNA>=50 c/mL w/Baseline HIV RNA<50 c/mL (n=60)	33.3 54.6%

5. Secondary Outcome

Title	Cumulative Proportion of Participants Without Treatment Failure Through Week 100
Description	This Kaplan-Meier life table reports the cumulative proportion of participants without treatment failure up to the end of the respective time interval. Failure time is measured from the start of study therapy, and is based on the earliest event defining failure (virologic rebound at or before Week 96, or discontinuation prior to Week 96).
Time Frame	Through Week 100

Outcome Measure Data

Analysis Population Description

treated participants; n= the number at risk entering interval

Arm/Group Title	Proportion of Participants
Arm/Group Description	Proportion of participants without treatment failure at the end of interval
Measure Participants	61
Interval Week 4 - 8 (n=61)	0.9836 1.6%
Interval Week 8 - 12 (n=60)	0.9508 1.6%
Interval Week 12 - 16 (n=58)	0.9016 1.5%
Interval Week 16 - 20 (n=55)	0.8852 1.5%
Interval Week 20 - 24 (n=54)	0.8689 1.4%
Interval Week 24 - 28 (n=53)	0.8525 1.4%
Interval Week 32 - 36 (n=52)	0.8197 1.3%
Interval Week 36 - 40 (n=50)	0.7869 1.3%
Interval Week 48 - 52 (n=48)	0.7541 1.2%
Interval Week 56 - 60 (n=46)	0.7377 1.2%
Interval Week 64 - 68 (n=45)	0.7049 1.2%
Interval Week 68 - 72 (n=43)	0.6885 1.1%
Interval Week 72 - 76 (n=42)	0.6721 1.1%
Interval Week 84 - 88 (n=41)	0.6557 1.1%
Interval Week 92 - 96 (n=40)	0.6557 1.1%
Interval Week 96 - 100 (n=31)	0.6557 1.1%

6. Secondary Outcome

Title	Proportion of Participants With Virologic Rebound Through Week 96
Description	Virologic rebound is defined as confirmed on-study HIV RNA ≥ 400 c/mL or last on-study HIV RNA ≥ 400 c/mL followed by treatment discontinuation.
Time Frame	Through Week 96

Outcome Measure Data

Analysis Population Description

This analysis was not done; however, percentage of participants with virologic rebound through Weeks 48 and 96 are reported in Secondary Outcome Measures 3 and 4. Time to reatment failure (defined as the earlier of virologic rebound or treatment discontinuation) is reported in Secondary Outcome Measure 5.

Arm/Group Title	Proportion of Participants
Arm/Group Description	Proportion of participants without virologic rebound at the end of interval
Measure Participants	0

7. Secondary Outcome

Title	Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

n=number of participants with CD4 cell count at baseline and at Week 24

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
Baseline Value (n=61)	559 (272.8)
Change at Week 24 (n=51)	61 (173.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change (Final Values)
	Estimated Value	61
	Confidence Interval	(2-Sided) 95%; 12.3 to 109.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 24.3
	Estimation Comments

8. Secondary Outcome

Title	Mean Change From Baseline in CD4 Cell Count at Week 48
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

n=number of participants with CD4 cell count at baseline and at Week 48.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
Baseline Value (n=61)	559 (272.8)
Change at Week 48 (n=46)	53 (203.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change (Final Values)
	Estimated Value	53
	Confidence Interval	(2-Sided) 95%; -7.1 to 113.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 30.0
	Estimation Comments

9. Secondary Outcome

Title	Mean Change From Baseline in CD4 Cell Count at Week 96
Time Frame	Baseline, Week 96

Outcome Measure Data

Analysis Population Description

n=number of participants with CD4 cell count at baseline and at Week 96.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
Baseline Value (n=61)	559 (272.8)
Change at Week 96 (n=40)	63 (208.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change (Final Values)
	Estimated Value	63
	Confidence Interval	(2-Sided) 95%; -4.0 to 129.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 32.9
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition that does not necessarily have a causal relationship to treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. AE grades are: mild (1), moderate (2), severe (3), life-threatening (4), and death (5).
Time Frame	From Baseline through Week 96

Outcome Measure Data

Analysis Population Description

Treated Participants

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
All Grades AEs	75.4 123.6%
All Grades AEs Related to Study Therapy	13.1 21.5%
Grade 3 to Grade 4 AEs	18 29.5%
Grade 3 to Grade 4 AEs Related to Study Therapy	3.3 5.4%
Deaths	3.3 5.4%
SAEs	19.7 32.3%
SAEs Related to Study Therapy	0 0%
AEs Leading to Discontinuation	4.9 8%
Lipodystrophy-Related AEs	1.6 2.6%

11. Secondary Outcome

Title	Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 48
Description	Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

n= number of treated participants with baseline measure and measure at Week 48

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
Total Cholesterol (n=36)	9 (18.0)
HDL Cholesterol (n=35)	2 (18.5)
Non-HDL Cholesterol (n=35)	12 (24.4)
LDL Cholesterol (n=33)	20 (33.4)
Triglycerides (n=36)	17 (51.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting Total Cholesterol at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	9
	Confidence Interval	(2-Sided) 95%; 2.5 to 14.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting HDL Cholesterol at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	2
	Confidence Interval	(2-Sided) 95%; -3.9 to 8.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting Non-HDL Cholesterol at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	12
	Confidence Interval	(2-Sided) 95%; 4.0 to 20.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting LDL Cholesterol at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	20
	Confidence Interval	(2-Sided) 95%; 8.0 to 31.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.8
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting Triglycerides at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	17
	Confidence Interval	(2-Sided) 95%; -0.4 to 34.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.6
	Estimation Comments

12. Secondary Outcome

Title	Mean Percent Changes From Baseline in Fasting Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Non-HDL Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, and Triglycerides at Week 96
Description	Lipid values after starting lipid-reducing agents are excluded from analyses. Baseline values are provided in Baseline Characteristics.
Time Frame	Baseline, Week 96

Outcome Measure Data

Analysis Population Description

n=number of treated participants with baseline measure and measure at Week 96

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	61
Total Cholesterol (n=29)	14 (17.4)
HDL Cholesterol (n=29)	2 (21.2)
Non-HDL Cholesterol (n=29)	19 (23.7)
LDL Cholesterol (n=28)	29 (34.4)
Triglycerides (n=29)	16 (67.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting Total Cholesterol at Week 96
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	14
	Confidence Interval	() 95%; 6.9 to 20.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting HDL Cholesterol at Week 96
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	2
	Confidence Interval	(2-Sided) 95%; -6.0 to 10.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.9
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting Non-HDL Cholesterol at Week 96
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	19
	Confidence Interval	(2-Sided) 95%; 10.3 to 28.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.4
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting LDL Cholesterol at Week 96
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	29
	Confidence Interval	(2-Sided) 95%; 15.3 to 42.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.5
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
	Comments	Percent Change from Baseline in Fasting Triglycerides at Week 96
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Change
	Estimated Value	16
	Confidence Interval	(2-Sided) 95%; -9.5 to 41.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.5
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 48
Description	International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Number of participants with virologic rebounds (HIV-RNA ≥ 400 c/mL) through Week 48.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy.
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	7
IAS-USA-defined major PI substitutions	1 1.6%
RT substitutions	0 0%

14. Secondary Outcome

Title	Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96
Description	International Aids Society of the United States (IAS-USA)-defined major protease inhibitor (PI) substitutions are V32I, L33F, M46I/L, I47V, G48V, I50L/V, I54M/L, I76V, I82A/F/T/S, I84V, N88S, and L90M. Reverse Transcriptase (RT) are TAMS and M184V.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Number of participants with virologic rebounds (HIV-RNA ≥ 400 c/mL) through Week 96.

Arm/Group Title	Atazanavir (ATV)/Ritonavir (RTV) Monotherapy
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
Measure Participants	9
IAS-USA-defined major PI substitutions	2 3.3%
RT substitutions	0 0%

Adverse Events

Arm/Group Title	ATV/RTV Monotherapy
Arm/Group Description	ATV/RTV treatment regimen was administered once daily. ATV: 2 x 150 mg capsules once daily with food (meal or snack), RTV: 1 x 100 mg capsule once daily with food (meal or snack)
All Cause Mortality
	ATV/RTV Monotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ATV/RTV Monotherapy
	Affected / at Risk (%)	# Events
Total	12/61 (19.7%)
General disorders
MULTI-ORGAN FAILURE	1/61 (1.6%)
Infections and infestations
SEPSIS	1/61 (1.6%)
PNEUMONIA	2/61 (3.3%)
APPENDICITIS	1/61 (1.6%)
EYE INFECTION SYPHILITIC	1/61 (1.6%)
Injury, poisoning and procedural complications
ACCIDENT	1/61 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER CANCER	1/61 (1.6%)
Nervous system disorders
HEADACHE	1/61 (1.6%)
ISCHAEMIC STROKE	1/61 (1.6%)
Psychiatric disorders
SUICIDAL IDEATION	1/61 (1.6%)
DYSTHYMIC DISORDER	1/61 (1.6%)
PSYCHOTIC DISORDER	1/61 (1.6%)
DEPRESSION SUICIDAL	1/61 (1.6%)
Reproductive system and breast disorders
TESTICULAR ATROPHY	1/61 (1.6%)
Vascular disorders
PERIPHERAL ISCHAEMIA	1/61 (1.6%)
Other (Not Including Serious) Adverse Events
	ATV/RTV Monotherapy
	Affected / at Risk (%)	# Events
Total	25/61 (41%)
Infections and infestations
TOOTH INFECTION	4/61 (6.6%)
RESPIRATORY TRACT INFECTION	5/61 (8.2%)
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA	7/61 (11.5%)
HYPERTRIGLYCERIDAEMIA	6/61 (9.8%)
Nervous system disorders
HEADACHE	5/61 (8.2%)
Psychiatric disorders
DEPRESSION	4/61 (6.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.