Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00135356
• Collaborator: (none)
• Enrollment: 219
• Locations: 31
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn if human immunodeficiency virus (HIV)-infected subjects with abdominal fat accumulation on their highly active antiretroviral treatment (HAART) regimen have better changes in fat distribution after switching to atazanavir-ritonavir than those remaining on their current protease inhibitor boosted HAART regimen.

Condition or Disease	Intervention/Treatment	Phase
HIV-Associated Lipodystrophy Syndrome	Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs); Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Open-Label, Randomized, Multicenter Trial Assessing a Reyataz-Based Substitution Approach in the Management of Lipodystrophy Syndrome. Research Into Atazanavir in Lipodystrophy (The REAL Study)
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Jul 1, 2007
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Switch arm	Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs); Capsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks; Other Names: Reyataz
Active Comparator: Control Arm	Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs); Protease inhibitor [PI] combination + 2 NRTIs

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 [Baseline, Week 48]

   Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)

Secondary Outcome Measures

1. Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 [Baseline, Week 96]

   Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.(Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)

2. Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. [Baseline, Week 48, Week 96]

   The mean percent change from baseline in physical signs of lipohypertrophy, as assessed objectively by changes in visceral adipose tissue (VAT) area (cm2) by computed tomography (CT) scans and by changes in trunk fat (kg) by DEXA. Clinical improvement is associated with a decrease in values. (Baseline values can be found in the Baseline Characteristics section.)

3. Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans [Baseline, Week 48, Week 96]

   The mean percent change from baseline in physical signs of lipoatrophy, as assessed objectively by changes in peripheral adipose tissue (ie, limb fat (kg) by DEXA and in subcutaneous adipose tissue (SAT) area by CT scans. Clinical improvement is associated with stable values, or an increase in values. (Baseline values can be found in the Baseline Characteristics section.)

4. Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans [Baseline, Week 48, Week 96]

   The mean percent change from baseline in total body fat by DEXA and in total adipose tissue (TAT) area by CT scans. Total body fat and TAT are both associated many factors (trunk fat + limb fat + other [weight, etc]), and thus clinical improvement cannot be predicted based solely an increase or decrease of these values. (Baseline values can be found in the Baseline Characteristics section.)

5. Mean Percent Changes From Baseline in Fasting Lipids [Baseline, Week 48, Week 96]

   Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B

6. Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 [Baseline, Week 48, Week 96]

7. Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 [Baseline, Week 48, Week 96]

8. Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [Baseline, Week 48, Week 96]

   HOMA-IR is an index used in evaluation of obese patients at risk for type 2 diabetes which requires fasting glucose and insulin concentrations. It is a mathematical model based on the theory of a negative feedback loop between the liver and β-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic β-cell function and degree of insulin resistance. HOMA-IR normal values are between 2 and 2.5. HOMA-IR ≥ 2.5 indicates insulin-resistance.

9. Mean Changes From Baseline in Body Weight at Week 48 and Week 96 [Baseline, Week 48, Week 96]

10. Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 [Baseline, Week 48, Week 96]

11. Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 [Baseline, Week 48, Week 96]

12. Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 [Baseline, Week 48, Week 96]

    Mean changes from baseline in proportion of waist to hip measurements.

13. Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation [Through Week 96 of study therapy]

    Percentage of Participants with AEs, Serious AEs (SAEs), Deaths, and AEs leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

14. Percentage of Participants With Abnormal Liver Function Tests [Week 48, Week 96]

    Percentage of participants with Abnormal Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Total Bilirubin (TBILI) measurements. Values for liver tests are graded using the modified World Health Organization (WHO) criteria. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life threatening or disabling.

15. Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation [Through Week 96]

    Percentage of Participants with AEs leading to discontinuation of study therapy. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. All events listed in this table were SAEs, except for renal impairment and hypertriglycerideamia, which were an AEs (and did not meet the 5 percent threshold reported in Adverse Event module of this record).

16. Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline [Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96]

    Virologic rebound was measured from the first dose of study therapy to the first of the 2 consecutive measurements ≥400 c/mL. Time to virologic rebound was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative proportion of participants without virologic rebound up to the end of the respective interval.

17. Mean Change From Baseline in CD4 Count [Baseline, Week 48, Week 96]

    Mean change from baseline in CD4 count among treated subjects

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• HIV-1 infected on HAART regimen containing 2 NRTI and boosted PI for at least 12 weeks prior to screening. Subjects may not have experienced virological failure to more than one prior PI-containing regimen. Must be able to swallow tablets

• Viral load <400 c/mL at screening and stable for at least 6 months

• Signs of fat redistribution and lipohypertrophy (abdominal) Waist to Hip Ratio >0.90 and Waist Circumference >88.2 cm for men and Waist Circumference >75.3 for women

Exclusion Criteria:

• Pregnant or breastfeeding women

• New HIV-related opportunistic infections

• Active alcohol or substance use

• Grade 4 lab toxicity

• History of taking atazanavir (ATV)

• Prohibited therapies, including non-nucleoside reverse transcriptase inhibitors (NNRTI)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Ft. Lauderdale	Florida	United States
2	Local Institution	Honolulu	Hawaii	United States
3	Local Institution	Huntersville	North Carolina	United States
4	Local Institution	Houston	Texas	United States
5	Local Institution	Ottawa	Ontario	Canada
6	Local Institution	Toronto	Ontario	Canada
7	Local Institution	Bondy Cedex		France
8	Local Institution	Lagny-sur-Marne		France
9	Local Institution	Lyon Cedex 02		France
10	Local Institution	Lyon Cedex 03		France
11	Local Institution	Nice Cedex		France
12	Local Institution	Paris Cedex 12		France
13	Local Institution	Frankfurt/ Main		Germany
14	Local Institution	Muenchen		Germany
15	Local Institution	Brescia		Italy
16	Local Institution	Milano		Italy
17	Local Institution	Modena		Italy
18	Local Institution	Roma		Italy
19	Local Institution	Guadalajara	Jalisco	Mexico
20	Local Institution	Zapopan	Jalisco	Mexico
21	Local Institution	Puebla		Mexico
22	Local Institution	Szczecin		Poland
23	Local Institution	Wroclaw		Poland
24	Local Institution	Barcelona		Spain
25	Local Institution	Elche (Alicante)		Spain
26	Local Institution	Guipuzcoa		Spain
27	Local Institution	Madrid		Spain
28	Local Institution	Malaga		Spain
29	Local Institution	Valencia		Spain
30	Local Institution	Brighton	East Sussex	United Kingdom
31	Local Institution	London	Greater London	United Kingdom

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: NCT00135356
• Other Study ID Numbers: AI424-131
• First Posted: Aug 26, 2005
• Last Update Posted: May 7, 2010
• Last Verified: Apr 1, 2010

• Keywords provided by , ,: HIV infections
• Additional relevant MeSH terms: HIV-Associated Lipodystrophy Syndrome; Lipodystrophy; Syndrome; Ritonavir; Atazanavir Sulfate; HIV Protease Inhibitors; Reverse Transcriptase Inhibitors; Protease Inhibitors

Study Results

Participant Flow

Pre-assignment Detail	A total of 219 participants were enrolled and 18 were never randomized (1 poor/noncompliance; 10 no longer met study criteria; 5 withdrew consent). 201 participants were randomized; however, 1 participant was never treated and is not included in the participant flow.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Period Title: Overall Study
STARTED	131	69
Discontinued Prior to Week 96 Visit	16	9
Discontinued on or After Week 96 Visit	1	0
COMPLETED	114	60
NOT COMPLETED	17	9

Baseline Characteristics

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm	Total
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.	Total of all reporting groups
Overall Participants	131	69	200
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	43	42	43
Sex: Female, Male (Count of Participants)
Female	35 26.7%	14 20.3%	49 24.5%
Male	96 73.3%	55 79.7%	151 75.5%
Race/Ethnicity, Customized (Number) [Number]
White	83 63.4%	43 62.3%	126 63%
Mestizo	31 23.7%	15 21.7%	46 23%
Black/African American	15 11.5%	10 14.5%	25 12.5%
American Indian/Alaska Native	1 0.8%	0 0%	1 0.5%
Latino/Hispanic	1 0.8%	1 1.4%	2 1%
Region of Enrollment (participants) [Number]
Europe	77 58.8%	39 56.5%	116 58%
North America	54 41.2%	30 43.5%	84 42%
Cluster of Differentiation 4 (CD4) Distribution (Number) [Number]
50 to <100 cells/mm3	2 1.5%	0 0%	2 1%
100 to <200 cells/mm3	14 10.7%	3 4.3%	17 8.5%
200 to <350 cells/mm3	24 18.3%	22 31.9%	46 23%
350 to <500 cells/mm3	31 23.7%	16 23.2%	47 23.5%
≥500 cells/mm3	60 45.8%	27 39.1%	87 43.5%
Missing	0 0%	1 1.4%	1 0.5%
Fasting Glucose (participants) [Number]
<100 mg/dL	96 73.3%	49 71%	145 72.5%
100 mg/dL to <126 mg/dL	23 17.6%	13 18.8%	36 18%
>=126 mg/dL	5 3.8%	4 5.8%	9 4.5%
Fasting Lipids (participants) [Number]
Triglycerides <150 mg/dL	29 22.1%	14 20.3%	43 21.5%
Triglycerides 150 mg/dL to <200 mg/dL	28 21.4%	9 13%	37 18.5%
Triglycerides 200 mg/dL to <500 mg/dL	52 39.7%	27 39.1%	79 39.5%
Triglycerides >=500 mg/dL	14 10.7%	12 17.4%	26 13%
Non-HDL Cholesterol <130 mg/dL	22 16.8%	16 23.2%	38 19%
Non-HDL Cholesterol 130 mg/dL to <160 mg/dL	31 23.7%	14 20.3%	45 22.5%
Non-HDL Cholesterol 160 mg/dL to <190 mg/dL	32 24.4%	15 21.7%	47 23.5%
Non-HDL Cholesterol 190 mg/dL to <220 mg/dL	22 16.8%	9 13%	31 15.5%
Non-HDL Cholesterol >=220 mg/dL	16 12.2%	8 11.6%	24 12%
LDL Cholesterol <100 mg/dL	40 30.5%	22 31.9%	62 31%
LDL Cholesterol 100 mg/dL to <130 mg/dL	36 27.5%	25 36.2%	61 30.5%
LDL Cholesterol 130 mg/dL to <160 mg/dL	30 22.9%	11 15.9%	41 20.5%
LDL Cholesterol 160 mg/dL to <190 mg/dL	11 8.4%	1 1.4%	12 6%
LDL Cholesterol >=190 mg/dL	6 4.6%	2 2.9%	8 4%
Total Cholesterol <200 mg/dL	45 34.4%	28 40.6%	73 36.5%
Total Cholesterol 200 mg/dL to 240 mg/dL	42 32.1%	19 27.5%	61 30.5%
Total Cholesterol 240 mg/dL to 300 mg/dL	29 22.1%	11 15.9%	40 20%
Total Cholesterol >=300 mg/dL	7 5.3%	4 5.8%	11 5.5%
HDL Cholesterol <40 mg/dL	23 17.6%	21 30.4%	44 22%
HDL Cholesterol 40 mg/dL to <60 mg/dL	80 61.1%	32 46.4%	112 56%
HDL Cholesterol >=60 mg/dL	20 15.3%	9 13%	29 14.5%
Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution (Number) [Number]
<50 c/mL	117 89.3%	64 92.8%	181 90.5%
50 to <400 c/mL	10 7.6%	5 7.2%	15 7.5%
400 to <1000 c/mL	2 1.5%	0 0%	2 1%
≥1000 c/mL	2 1.5%	0 0%	2 1%
Adipose Tissue at Baseline (cm2) [Median (Inter-Quartile Range) ]
VAT	131.9	128.1	129.4
SAT	209.5	183.9	193.6
TAT	356.2	328.6	352.0
Body Mass Index (BMI) (kg/m2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m2]	25.9	25.7	25.9
Body Weight (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	75	77	76
CD4 Cell Count (cells/mm3) [Median (Full Range) ]
Median (Full Range) [cells/mm3]	470	437	459
Trunk Fat, Limb Fat, Total Body Fat (kg) [Median (Inter-Quartile Range) ]
Trunk Fat	11.8	10.9	11.4
Limb Fat	7.1	6.7	7.0
Total Body Fat	20.8	18.7	19.8
Trunk-to-Limb Fat Ratio (ratio) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ratio]	1.59	1.73	1.62
Waist Circumference (cm) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm]	94	95	94
Waist-to-Hip Ratio (ratio) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ratio]	0.99	0.97	0.99

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48
Description	Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Treated participants. Observed case (OC) analysis: n=participants with fat measurement at baseline and at the analysis timepoint. Last observation carried forward (LOCF): n=participants with fat measurement at baseline and at or before the analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
LOCF Population (n=112; n=54)	0.02 (0.027)	-0.02 (0.036)
OCPopulation (n=105; n=51)	0.02 (0.029)	-0.01 (0.038)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	0.03
	Confidence Interval	() 95%; -0.06 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	OC
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	P-value not adjusted for multiple testing. 2-sided 95% CI
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	0.07
	Confidence Interval	() 95%; -0.07 to 12.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Description	Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.(Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)
Time Frame	Baseline, Week 96

Outcome Measure Data

Analysis Population Description

Observed case (OC) analysis: n=participants with fat measurement at baseline and at the analysis timepoint. Last observation carried forward (LOCF): n=participants with fat measurement at baseline and at or before the analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
LOCF Population (n=112; n=54)	0.04 (0.035)	0.02 (0.046)
OC Population (n=94; n=45)	0.04 (0.041)	0.05 (0.051)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	0.02
	Confidence Interval	() 95%; -0.10 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	OC
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.14 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA.
Description	The mean percent change from baseline in physical signs of lipohypertrophy, as assessed objectively by changes in visceral adipose tissue (VAT) area (cm2) by computed tomography (CT) scans and by changes in trunk fat (kg) by DEXA. Clinical improvement is associated with a decrease in values. (Baseline values can be found in the Baseline Characteristics section.)
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

VAT analysis population=treated subjects with adipose tissue pairs (LOCF); trunk fat analysis population=treated subjects with fat pairs (LOCF); n=number of subjects with measurement at baseline and at or before the analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 VAT (n=98; n=53)	6.5	-0.4
Week 96 VAT (n=101; n=53)	4.3	2.1
Week 48 Trunk Fat (n=112; n=57)	2.6	-1.8
Week 96 Trunk Fat (n=112; n=57)	1.6	-3.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 48 VAT LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Mean
	Estimated Value	5.2
	Confidence Interval	() 95%; -3.9 to 15.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	VAT, Week 96 LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Mean
	Estimated Value	1.8
	Confidence Interval	() 95%; -6.7 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 48 Trunk Fat LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	4.4
	Confidence Interval	() 95%; -1.4 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 96 Trunk Fat LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	5.3
	Confidence Interval	() 95%; -1.7 to 12.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans
Description	The mean percent change from baseline in physical signs of lipoatrophy, as assessed objectively by changes in peripheral adipose tissue (ie, limb fat (kg) by DEXA and in subcutaneous adipose tissue (SAT) area by CT scans. Clinical improvement is associated with stable values, or an increase in values. (Baseline values can be found in the Baseline Characteristics section.)
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

SAT analysis population=treated subjects with adipose tissue pairs (LOCF); trunk fat analysis population=treated subjects with fat pairs (LOCF); n=number of subjects with measurement at baseline and at or before analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 SAT (n=108; n=59)	-2.2	-5.9
Week 96 SAT (n=111; n=59)	-3.5	-9.7
Week 48 Limb Fat (n=112; 54)	0.9	-3.6
Week 48 Limb Fat (n=112; n=54)	-0.8	-6.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	SAT, Week 48, LOCF
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	4.0
	Confidence Interval	() 95%; -1.6 to 10.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 96 SAT
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Mean
	Estimated Value	6.8
	Confidence Interval	() 95%; -0.2 to 14.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 48, Limb Fat
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	4.6
	Confidence Interval	() 95%; -1.7 to 11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 96, Limb Fat
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	5.7
	Confidence Interval	() 95%; -2.3 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans
Description	The mean percent change from baseline in total body fat by DEXA and in total adipose tissue (TAT) area by CT scans. Total body fat and TAT are both associated many factors (trunk fat + limb fat + other [weight, etc]), and thus clinical improvement cannot be predicted based solely an increase or decrease of these values. (Baseline values can be found in the Baseline Characteristics section.)
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

TAT analysis population=treated subjects with adipose tissue pairs (LOCF); trunk fat analysis population=treated subjects with fat pairs (LOCF); n=number of subjects with measurement at baseline and at or before the analysis timepoint

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 TAT (n=108; n= 59)	0.0	-3.5
Week 96 TAT (n=111; n=59)	-0.9	-5.0
Week 48 Total Body Fat (n=105; n=51)	1.9	-3.7
Week 96 Total Body Fat (n=94; n=45)	0.5	-7.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 48 TAT
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	DIfference in Means
	Estimated Value	3.6
	Confidence Interval	() 95%; -1.8 to 9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 96 TAT
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	DIfference in Means
	Estimated Value	4.3
	Confidence Interval	() 95%; -1.7 to 10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 48 Total Body Fat
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0385
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	5.0
	Confidence Interval	() 95%; 0.3 to 9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments	Week 96 Total Body Fat
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments	P-value not adjusted for multiple testing, 2-sided 95% CI.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in Means
	Estimated Value	5.9
	Confidence Interval	() 95%; -1.0 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Percent Changes From Baseline in Fasting Lipids
Description	Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

Treated Subjects (LOCF). n=56 for LDL cholesterol in the PI/RTV arm at both timepoints

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	122	57
Week 48 - Total Cholesterol	-13.0	-1.0
Week 48 - HDL Cholesterol	-6.2	-2.6
Week 48 - Non-HDL Cholesterol	-14.8	-0.6
Week 48 - LDL Cholesterol	-10.4	2.6
Week 48 - Triglycerides	-23.8	-11.7
Week 48 - Apolipoprotein B	-7.6	1.1
Week 96 - Total Cholesterol	-12.5	-0.1
Week 96 - HDL Cholesterol	-6.8	-4.6
Week 96 - Non-HDL Cholesterol	-14.0	1.2
Week 96 - LDL Cholesterol	-8.4	3.6
Week 96 - Triglycerides	-25.0	-12.2
Week 96 - Apolipoprotein B	-8.3	8.3

7. Secondary Outcome

Title	Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

Treated participants (LOCF); n=number of participants with baseline value at or before analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 (n=124; n=63)	3.6 (2.60)	-3.3 (2.92)
Week 96 (n=124; n=64)	1.2 (2.82)	3.0 (2.88)

8. Secondary Outcome

Title	Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

Treated participants (LOCF); n=number of participants with baseline value at or before analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Baseline (n=124; n=62)	14.1 (1.04)	21.8 (3.36)
Week 48 (n=124; n=59)	1.3 (1.46)	-4.1 (3.79)
Week 96 (n=124; n=59)	0.0 (1.20)	0.3 (4.76)

9. Secondary Outcome

Title	Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Description	HOMA-IR is an index used in evaluation of obese patients at risk for type 2 diabetes which requires fasting glucose and insulin concentrations. It is a mathematical model based on the theory of a negative feedback loop between the liver and β-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic β-cell function and degree of insulin resistance. HOMA-IR normal values are between 2 and 2.5. HOMA-IR ≥ 2.5 indicates insulin-resistance.
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

Treated participants (LOCF); n=number of participants with baseline value at or before analysis timepoint.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Baseline (n=115; n=59)	3.42 (0.309)	5.43 (1.233)
Week 48 (n=115; n=57)	0.74 (0.589)	-1.73 (1.223)
Week 96 (n=115; n=57)	0.28 (0.500)	1.00 (1.648)

10. Secondary Outcome

Title	Mean Changes From Baseline in Body Weight at Week 48 and Week 96
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

LOCF; n=number of participants with baseline value and value at or before analysis timepoint

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	130	68
Week 48 (n=130; n=68)	1 (0.3)	-1 (0.4)
Week 96 (n=130; n=68)	0 (0.4)	-1 (0.7)

11. Secondary Outcome

Title	Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

LOCF; n=number of participants with baseline value and value at or before analysis timepoint

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 (n=123; n=66)	-1 (0.5)	-1 (0.6)
Week 96 (n=124; n=66)	-1 (0.6)	-1 (0.8)

12. Secondary Outcome

Title	Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

LOCF; n=number of participants with baseline value and value at or before analysis timepoint

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 (n=130; n=67)	0.3 (0.12)	-0.2 (0.13)
Week 96 (n=130; n=67)	0.2 (0.13)	-0.5 (0.25)

13. Secondary Outcome

Title	Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96
Description	Mean changes from baseline in proportion of waist to hip measurements.
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

LOCF; n=number of participants with baseline value and value at or before analysis timepoint

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Week 48 (n=123; n=65)	-0.01 (0.005)	-0.01 (0.007)
Week 96 (n=124; n=65)	-0.01 (0.006)	-0.01 (0.007)

14. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation
Description	Percentage of Participants with AEs, Serious AEs (SAEs), Deaths, and AEs leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time Frame	Through Week 96 of study therapy

Outcome Measure Data

Analysis Population Description

Treated participants

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Death	0 0%	0 0%
SAE	8 6.1%	7 10.1%
AE Leading to Discontinuation	5 3.8%	3 4.3%
Any AEs (all grades) through Week 96	90 68.7%	83 120.3%

15. Secondary Outcome

Title	Percentage of Participants With Abnormal Liver Function Tests
Description	Percentage of participants with Abnormal Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Total Bilirubin (TBILI) measurements. Values for liver tests are graded using the modified World Health Organization (WHO) criteria. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life threatening or disabling.
Time Frame	Week 48, Week 96

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Wk 48 ALT Grades 1-4	34 26%	23 33.3%
Wk 48 ALT Grades 3-4	1 0.8%	0 0%
Wk 48 ALT Grade 4	0 0%	0 0%
Wk 96 ALT Grades 1-4	37 28.2%	32 46.4%
Wk 96 ALT Grades 3-4	2 1.5%	0 0%
Wk 96 ALT Grade 4	0 0%	0 0%
Wk 48 AST Grade 1-4	19 14.5%	15 21.7%
Wk 48 AST Grades 3-4	1 0.8%	0 0%
Wk 48 AST Grade 4	0 0%	0 0%
Wk 96 AST Grades 1-4	24 18.3%	19 27.5%
Wk 96 AST Grades 3-4	1 0.8%	0 0%
Wk 96 AST Grade 4	0 0%	0 0%
Wk 48 TBILI Grades 1-4	94 71.8%	19 27.5%
Wk 48 TBILI Grades 3-4	53 40.5%	0 0%
Wk 48 TBILI Grade 4	13 9.9%	0 0%
Wk 96 TBILI Grades 1-4	95 72.5%	21 30.4%
Wk 96 TBILI Grades 3-4	60 45.8%	0 0%
Wk 96 TBILI Grade 4	17 13%	0 0%

16. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation
Description	Percentage of Participants with AEs leading to discontinuation of study therapy. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. All events listed in this table were SAEs, except for renal impairment and hypertriglycerideamia, which were an AEs (and did not meet the 5 percent threshold reported in Adverse Event module of this record).
Time Frame	Through Week 96

Outcome Measure Data

Analysis Population Description

Treated subjects

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	69
Any adverse experience leading to discontinuation	5 3.8%	3 4.3%
Hyperbilirubinemia	2 1.5%	0 0%
Jaundice	1 0.8%	0 0%
Drug abuse	1 0.8%	0 0%
Renal impairment	1 0.8%	0 0%
Stevens-Johnson syndrome	1 0.8%	0 0%
Hypertriglyceridemia	0 0%	1 1.4%
Squamous cell carcinoma	0 0%	1 1.4%

17. Secondary Outcome

Title	Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline
Description	Virologic rebound was measured from the first dose of study therapy to the first of the 2 consecutive measurements ≥400 c/mL. Time to virologic rebound was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative proportion of participants without virologic rebound up to the end of the respective interval.
Time Frame	Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96

Outcome Measure Data

Analysis Population Description

Treated subjects with HIV RNA <400 c/mL at baseline.

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	127	69
By Weeks 8-12	0.9837 0.8%	1.000 1.4%
By Weeks 20-24	0.9837 0.8%	1.000 1.4%
By Weeks 32-36	0.9753 0.7%	0.9841 1.4%
By Weeks 44-48	0.9669 0.7%	0.9841 1.4%
By Weeks 56-60	0.9585 0.7%	0.9841 1.4%
By Weeks 68-72	0.9585 0.7%	0.9841 1.4%
By Weeks 80-84	0.9585 0.7%	0.9674 1.4%
By Weeks 92-96	0.9585 0.7%	0.9309 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ATV/RTV Switch Arm, PI/RTV Control Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.3 to 3.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Mean Change From Baseline in CD4 Count
Description	Mean change from baseline in CD4 count among treated subjects
Time Frame	Baseline, Week 48, Week 96

Outcome Measure Data

Analysis Population Description

Observed Cases (OC)

Arm/Group Title	ATV/RTV Switch Arm	PI/RTV Control Arm
Arm/Group Description	Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Measure Participants	131	68
Week 48 (n=114; n=56)	14 (13.1)	44 (19.4)
Week 96 (n=96; n=54)	3 (16.9)	82 (22.0)

Adverse Events

Arm/Group Title	ATV/RTV Switch Arm		PI/RTV Control Arm
Arm/Group Description
All Cause Mortality
	ATV/RTV Switch Arm		PI/RTV Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ATV/RTV Switch Arm		PI/RTV Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/131 (8.4%)		5/69 (7.2%)
Cardiac disorders
MYOCARDIAL INFARCTION	1/131 (0.8%)		0/69 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	0/131 (0%)		1/69 (1.4%)
IRRITABLE BOWEL SYNDROME	1/131 (0.8%)		0/69 (0%)
Hepatobiliary disorders
JAUNDICE	1/131 (0.8%)		0/69 (0%)
HYPERBILIRUBINAEMIA	3/131 (2.3%)		0/69 (0%)
Infections and infestations
PNEUMONIA	1/131 (0.8%)		0/69 (0%)
NEUROSYPHILIS	1/131 (0.8%)		0/69 (0%)
URINARY TRACT INFECTION	0/131 (0%)		1/69 (1.4%)
Injury, poisoning and procedural complications
JAW FRACTURE	0/131 (0%)		1/69 (1.4%)
DRUG TOXICITY	1/131 (0.8%)		1/69 (1.4%)
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION	0/131 (0%)		1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	1/131 (0.8%)		0/69 (0%)
SQUAMOUS CELL CARCINOMA	0/131 (0%)		1/69 (1.4%)
Nervous system disorders
PARALYSIS	1/131 (0.8%)		0/69 (0%)
CONVULSION	0/131 (0%)		1/69 (1.4%)
CEREBROVASCULAR ACCIDENT	1/131 (0.8%)		0/69 (0%)
Psychiatric disorders
DRUG ABUSE	1/131 (0.8%)		0/69 (0%)
DRUG DEPENDENCE	1/131 (0.8%)		0/69 (0%)
Renal and urinary disorders
CALCULUS BLADDER	0/131 (0%)		1/69 (1.4%)
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	1/131 (0.8%)		0/69 (0%)
Skin and subcutaneous tissue disorders
STEVENS-JOHNSON SYNDROME	1/131 (0.8%)		0/69 (0%)
Other (Not Including Serious) Adverse Events
	ATV/RTV Switch Arm		PI/RTV Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/131 (71.8%)		35/69 (50.7%)
Gastrointestinal disorders
DIARRHOEA	10/131 (7.6%)		5/69 (7.2%)
Hepatobiliary disorders
JAUNDICE	35/131 (26.7%)		0/69 (0%)
HYPERBILIRUBINAEMIA	38/131 (29%)		1/69 (1.4%)
Infections and infestations
INFLUENZA	10/131 (7.6%)		1/69 (1.4%)
SINUSITIS	5/131 (3.8%)		4/69 (5.8%)
BRONCHITIS	14/131 (10.7%)		4/69 (5.8%)
PHARYNGITIS	7/131 (5.3%)		0/69 (0%)
NASOPHARYNGITIS	8/131 (6.1%)		2/69 (2.9%)
URINARY TRACT INFECTION	4/131 (3.1%)		5/69 (7.2%)
Investigations
BLOOD BILIRUBIN INCREASED	10/131 (7.6%)		2/69 (2.9%)
Metabolism and nutrition disorders
HYPERTRIGLYCERIDAEMIA	13/131 (9.9%)		13/69 (18.8%)
Musculoskeletal and connective tissue disorders
BACK PAIN	6/131 (4.6%)		6/69 (8.7%)
Nervous system disorders
HEADACHE	10/131 (7.6%)		3/69 (4.3%)
Respiratory, thoracic and mediastinal disorders
COUGH	11/131 (8.4%)		4/69 (5.8%)

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.