Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition:	HIV-Associated Lipodystrophy Syndrome
Interventions:	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)

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
ATV/RTV Switch Arm	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).
PI/RTV Control Arm	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.

Participant Flow:   Overall Study

	ATV/RTV Switch Arm	PI/RTV Control Arm
STARTED	131 [1]	69 [2]
Discontinued Prior to Week 96 Visit	16	9
Discontinued on or After Week 96 Visit	1	0
COMPLETED	114	60
NOT COMPLETED	17	9
Adverse Event	6	2
Lack of Efficacy	2	0
Lost to Follow-up	3	1
Surgery for abdominal fat	1	0
Change in antiviral regimen	0	1
Poor/noncompliance	1	1
No longer meets study criteria	2	0
Withdrawal by Subject	2	4

[1]	Number randomized and treated
[2]	Number randomized and treated(1 randomized and never treated subject not included in this number.)

  Baseline Characteristics

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Population Description

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

	Description
ATV/RTV Switch Arm	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).
PI/RTV Control Arm	Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Total	Total of all reporting groups

Baseline Measures

	ATV/RTV Switch Arm	PI/RTV Control Arm	Total
Overall Participants Analyzed; [Units: Participants]	131	69	200
Age; [Units: Years]; Median (Full Range)	43; (23 to 79)	42; (26 to 65)	43; (23 to 79)
Gender; [Units: Participants]
Female	35	14	49
Male	96	55	151
Race/Ethnicity, Customized; [Units: Participants]
White	83	43	126
Mestizo	31	15	46
Black/African American	15	10	25
American Indian/Alaska Native	1	0	1
Latino/Hispanic	1	1	2
Region of Enrollment; [Units: Participants]
Europe	77	39	116
North America	54	30	84
Cluster of Differentiation 4 (CD4) Distribution [1]; [Units: Participants]
50 to <100 cells/mm3	2	0	2
100 to <200 cells/mm3	14	3	17
200 to <350 cells/mm3	24	22	46
350 to <500 cells/mm3	31	16	47
≥500 cells/mm3	60	27	87
Missing	0	1	1
[1] CD4=a protein marker on the surface of certain types of T lymphocytes and other cells; HIV binds to CD4 receptors to enter host cells.
Fasting Glucose [1]; [Units: Participants]
<100 mg/dL	96	49	145
100 mg/dL to <126 mg/dL	23	13	36
>=126 mg/dL	5	4	9
[1] 7 participants in ATV/RTV arm and 3 participants in PI/RTV arm were missing this baseline measurement.
Fasting Lipids [1]; [Units: Participants]
Triglycerides <150 mg/dL	29	14	43
Triglycerides 150 mg/dL to <200 mg/dL	28	9	37
Triglycerides 200 mg/dL to <500 mg/dL	52	27	79
Triglycerides >=500 mg/dL	14	12	26
Non-HDL Cholesterol <130 mg/dL	22	16	38
Non-HDL Cholesterol 130 mg/dL to <160 mg/dL	31	14	45
Non-HDL Cholesterol 160 mg/dL to <190 mg/dL	32	15	47
Non-HDL Cholesterol 190 mg/dL to <220 mg/dL	22	9	31
Non-HDL Cholesterol >=220 mg/dL	16	8	24
LDL Cholesterol <100 mg/dL	40	22	62
LDL Cholesterol 100 mg/dL to <130 mg/dL	36	25	61
LDL Cholesterol 130 mg/dL to <160 mg/dL	30	11	41
LDL Cholesterol 160 mg/dL to <190 mg/dL	11	1	12
LDL Cholesterol >=190 mg/dL	6	2	8
Total Cholesterol <200 mg/dL	45	28	73
Total Cholesterol 200 mg/dL to 240 mg/dL	42	19	61
Total Cholesterol 240 mg/dL to 300 mg/dL	29	11	40
Total Cholesterol >=300 mg/dL	7	4	11
HDL Cholesterol <40 mg/dL	23	21	44
HDL Cholesterol 40 mg/dL to <60 mg/dL	80	32	112
HDL Cholesterol >=60 mg/dL	20	9	29
[1] Triglycerides, non-high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, total cholesterol, and HDL cholesterol. Values for all baseline fasting lipid measurements were missing for 8 participants in the ATV/RTV arm. Values for baseline fasting LDL cholesterol were missing for 8 participants in the PI/RTV arm; values for all other baseline lipid measurements were missing for 7 participants.
Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution; [Units: Participants]
<50 c/mL	117	64	181
50 to <400 c/mL	10	5	15
400 to <1000 c/mL	2	0	2
≥1000 c/mL	2	0	2
Adipose Tissue at Baseline [1]; [Units: Cm2]; Median (Inter-Quartile Range)
VAT	131.9; (93.8 to 185.8)	128.1; (95.8 to 193.7)	129.4; (94.3 to 186.1)
SAT	209.5; (123.6 to 300.7)	183.9; (151.4 to 282.4)	193.6; (140.3 to 289.2)
TAT	356.2; (263.9 to 446.3)	328.6; (287.3 to 457.8)	352.0; (268.5 to 453.1)
[1] Visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) as assessed by computed tomography (CT). Values for all 3 measurements were missing for 20 participants in the ATV/RTV arm (n=111). Values for all 3 measurements were missing for 10 participants in the PI/RTV arm (n=59).
Body Mass Index (BMI) [1]; [Units: Kg/m2]; Median (Inter-Quartile Range)	25.9; (24.1 to 28.5)	25.7; (24.2 to 28.8)	25.9; (24.2 to 28.5)
[1] 131 participants in ATV/RTV arm and 67 participants in PI/RTV arm had this baseline measurement.
Body Weight; [Units: Kg]; Median (Inter-Quartile Range)	75; (69 to 83)	77; (69 to 87)	76; (69 to 84)
CD4 Cell Count [1]; [Units: Cells/mm3]; Median (Full Range)	470; (90 to 1919)	437; (100 to 1078)	459; (90 to 1919)
[1] CD4 cell=a type of white blood cell that bears the CD4 surface receptor and helps coordinate a range of immune system activities.
Trunk Fat, Limb Fat, Total Body Fat [1]; [Units: Kg]; Median (Inter-Quartile Range)
Trunk Fat	11.8; (8.6 to 15.3)	10.9; (8.8 to 13.8)	11.4; (8.7 to 14.6)
Limb Fat	7.1; (4.6 to 10.4)	6.7; (4.6 to 9.4)	7.0; (4.6 to 10.0)
Total Body Fat	20.8; (14.1 to 26.0)	18.7; (15.6 to 22.4)	19.8; (14.8 to 25.7)
[1] Values for all 3 baseline fat measurements were missing for 14 participants in the ATV/RTV arm (n=117). Values for baseline trunk fat measurements were missing for 10 participants in the PI/RTV arm (n=59); values for baseline limb fat and total body fat measurements were missing for 13 participants in the PI/RTV arm (n=56).
Trunk-to-Limb Fat Ratio [1]; [Units: Ratio]; Median (Inter-Quartile Range)	1.59; (1.27 to 2.04)	1.73; (1.17 to 2.15)	1.62; (1.23 to 2.10)
[1] 117 participants in ATV/RTV arm and 56 participants in PI/RTV arm had this measure at baseline.
Waist Circumference; [Units: Cm]; Median (Inter-Quartile Range)	94; (90 to 103)	95; (91 to 100)	94; (90 to 102)
Waist-to-Hip Ratio [1]; [Units: Ratio]; Median (Inter-Quartile Range)	0.99; (0.95 to 1.03)	0.97; (0.94 to 1.02)	0.99; (0.95 to 1.03)
[1] 131 participants in ATV/RTV arm and 68 participants in PI/RTV arm had this baseline measurement.

  Outcome Measures

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1. Primary:

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

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2. Secondary:

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

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3. Secondary:

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

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4. Secondary:

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 [ Time Frame: Baseline, Week 48, Week 96 ]

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5. Secondary:

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

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6. Secondary:

Mean Percent Changes From Baseline in Fasting Lipids [ Time Frame: Baseline, Week 48, Week 96 ]

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7. Secondary:

Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ]

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8. Secondary:

Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ]

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9. Secondary:

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

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10. Secondary:

Mean Changes From Baseline in Body Weight at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ]

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11. Secondary:

Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ]

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12. Secondary:

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

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13. Secondary:

Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ]

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14. Secondary:

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

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15. Secondary:

Percentage of Participants With Abnormal Liver Function Tests [ Time Frame: Week 48, Week 96 ]

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16. Secondary:

Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation [ Time Frame: Through Week 96 ]

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17. Secondary:

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 [ 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 ]

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18. Secondary:

Mean Change From Baseline in CD4 Count [ Time Frame: Baseline, Week 48, Week 96 ]

  Show Outcome Measure 18

  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

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Certain Agreements:  

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: 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.

Results Point of Contact:  

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00135356 History of Changes
Other Study ID Numbers:	AI424-131
First Submitted:	August 25, 2005
First Posted:	August 26, 2005
Results First Submitted:	December 15, 2009
Results First Posted:	May 7, 2010
Last Update Posted:	May 7, 2010