Safety Sudy of Atazanavir Boosted With Ritonavir in the Treatment of HIV Infection in Pediatric Patients

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01691794
• Collaborator: (none)
• Enrollment: 108
• Locations: 27
• Arms: 3
• Actual Duration (Months): 50.7
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to collect safety clinical data in HIV-infected pediatric patients aged 6 and older to younger than18 years and weighing 15 kg or more, who are receiving atazanavir capsule boosted with ritonavir and an optimized nucleoside reverse transcriptase inhibitor backbone therapy as part of their antiretroviral regimen.

Condition or Disease	Intervention/Treatment	Phase
HIV, Pediatric	Drug: Atazanavir; Drug: Ritonavir	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Single Arm, Open-label, International, Multicenter Study to Evaluate the Safety of Atazanavir (ATV) Capsule Boosted With Ritonavir (RTV) With an Optimized NRTI Background Therapy, in HIV Infected, Antiretroviral Naive and Experienced Pediatric Subjects Greater Than or Equal to 6 Years to Less Than 18 Years
• Actual Study Start Date: Nov 30, 2012
• Actual Primary Completion Date: Oct 31, 2014
• Actual Study Completion Date: Feb 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg) Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.	Drug: Atazanavir; Other Names: Reyataz BMS-232632 ; Drug: Ritonavir; Other Names: Norvir
Active Comparator: Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg) Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.	Drug: Atazanavir; Other Names: Reyataz BMS-232632 ; Drug: Ritonavir; Other Names: Norvir
Active Comparator: Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg) Participants with baseline weight ≥ 40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.	Drug: Atazanavir; Other Names: Reyataz BMS-232632 ; Drug: Ritonavir; Other Names: Norvir

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Grade 2-4 Related AEs, Grade 3-4 AEs, and Centers for Disease Control (CDC) Class C AIDS Events [From first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)]

   AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.

2. Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 [After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)]

   Hematocrit (%): Grade (Gr) 1= ≥28.5- <31.5; Gr 2= ≥24- <28.5; Gr 3= ≥19.5- <24; Gr 4= <19.5. Hemoglobin (g/dL): Grade (Gr)1=8.5-10.0; Gr 2=7.5-8.4; Gr 3=6.50-7.4; Gr 4= <6.5. Platelets (/mm^3): Gr 1=100,000-124,999; Gr 2=50,000-99,999; Gr 3=25,000-49,999; Gr 4= <25,000. White blood cells (/mm^3): Gr 1=2000-2500; Gr 2=1500-1999; Gr 3=1000-1499; Gr 4= <1000. Neutrophils (/mm^3): Gr 1=1000-1500; Gr 2= ≥750-1000; Gr 3= ≥500-750; Gr 4= <500. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) (*upper limit of normal [ULN]): Gr 1=1.5-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10.0; Gr 4= >10.0. Total bilirubin (adult and pediatric >14 days) (*ULN): Gr 1=1.1-1.5; Gr 2=1.6-2.5; Gr 3=2.6-5.0; Gr 4= >5.0. Albumin (g/dL): Gr 1= 3.1- <LLN; Gr 2=2.0-2.9; Gr 3= <2.0; Gr 4=NA. Amylase (*ULN): Gr 1=1.10-1.39; Gr 2=1.40-2.09; Gr 3=2.10-5.0; Gr 4= >5. Lipase (*ULN): Gr 1=1.1-1.5; Gr 2=1.6-3.0; Gr 3=3.1-5.0; Gr 4= >5.0.

3. Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 (Continued) [After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)]

   Blood urea nitrogen (*upper limit of normal [ULN]): Grade (Gr) 1=1.25-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10; Gr 4= >10. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12; Gr 3=12.1-15.0; Gr 4= >15.0. Bicarbonate (mEqL): Gr 1= 19.0-21.0; Gr 2=15.0-18.0; Gr 3=41-45; Gr 4= >45. Calcium, low (mg/dL): Gr 1=7.8-8.4; Gr 2=7.0-7.7; Gr 3=6.1-6.9; Gr 4= <6.1.Potassium (mEq/L), high: Gr 1=5.6-6.0; Gr 2=6.1-6.5; Gr 3=6.6-7.0; Gr 4= >7.0. Potassium (mEq/L), low: Gr 1=3.1-3.4; Gr 2=2.5-2.9; Gr 3=2.0-2.4; Gr 4= <2.0. Sodium (mEq/L), low: Gr 1=130-135; Gr 2=125-129; Gr 3=121-124; Gr 4= <1. Total cholesterol, fasting (mg/dL): Gr 1=200-239; Gr 2=240-300; Gr 3= >300; Gr 4=Not applicable (NA). Low-density lipoprotein (LDL) cholesterol, fasting (mg/dL): Gr 1=130-159; Gr 2=160-190; Gr 3= >190; Gr 4= NA. Glucose, low (mg/dL): Gr 1= 55-64; Gr 2=40-54; Gr 3=30-39; Gr 4= <30. Glucose, fasting (mg/dL): Gr 1=110-125; Gr 2=126-250; Gr 3=251-500; Gr 4 >500.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed HIV-1 infection diagnosed by protocol criteria

• Male or female children, ≥ 6 years to <17 years 6 months of age at the time of first treatment

• Antiretroviral-naïve or treatment-experienced participants with a detectable viral load

• Antiretroviral-naïve participants must have genotypic sensitivity at screening to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which have been approved for pediatric use and dosed per local country label

• Antiretroviral-experienced participants must have documented genotypic and phenotypic sensitivity at screening to atazanavir (fold change in susceptibility <2.2) and at least 2 NRTIs, which have been approved for pediatric use and dosed per local country label.

Exclusion Criteria:

• Experienced participants who received atazanavir with or without ritonavir at any time prior to study enrollment

• Antiretroviral-naive or -experienced HIV-1 infected patients with contraindication to study medications

• Documented cardiac conduction abnormality, significant cardiac dysfunction, or a history syncope

• Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval of >440 ms at screening

• One of the following cardiac rhythm abnormalities documented on the screening electrocardiogram:

1. First degree atrioventricular (AV) block, as defined by protocol

2. Type I second degree AV block while awake, type II second degree AV block at any time, complete AV block at any time, or age-adjusted heart rate <2nd percentile

• Coinfection with either hepatitis B or C virus

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children'S Hospital	Phoenix	Arizona	United States	85016
2	Grady Health System Ponce Family And Youth Clinic	Atlanta	Georgia	United States	30322
3	Children'S Medical Center Of Dallas	Dallas	Texas	United States	75235
4	Local Institution	Buenos Aires, Bs As	Buenos Aires	Argentina	1141
5	Local Institution	Buenos Aires		Argentina	1181
6	Local Institution	Buenos Aires		Argentina	1425
7	Local Institution	Salvador	Bahia	Brazil	40110-160
8	Local Institution	Salvador	Bahia	Brazil	40110
9	Local Institution	Porto Alegre	RIO Grande DO SUL	Brazil	90035-903
10	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90035
11	Local Institution	Sao Paulo	SP	Brazil	01416-901
12	Local Institution	Sao Paulo		Brazil	01246
13	Local Institution	Santiago	Metropolitana	Chile	8207257
14	Local Institution	Santiago	Metropolitana	Chile	8380418
15	Local Institution	Guadalajara	Jalisco	Mexico	44280
16	Local Institution	Monterrey	Nuevo LEON	Mexico	64000
17	Local Institution	Merida	Yucatan	Mexico	97000
18	Local Institution	Puebla		Mexico	72000
19	Local Institution	Lima		Peru	1
20	Local Institution	Lima		Peru	LIMA 10
21	Local Institution	Moscow		Russian Federation	129110
22	Local Institution	St. Petersburg		Russian Federation	190103
23	Local Institution	Port Elizabeth	Eastern CAPE	South Africa	6001
24	Local Institution	Bloemfontein	FREE State	South Africa	9301
25	Local Institution	Soweto	Gauteng	South Africa	2013
26	Local Institution	Cape Town	Western CAPE	South Africa	7505
27	Local Institution	Cape Town	Western CAPE	South Africa	7530

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Patient Recruiting
• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01691794
• Other Study ID Numbers: AI424-452; 2011-003300-21
• First Posted: Sep 25, 2012
• Last Update Posted: Apr 27, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Ritonavir; Atazanavir Sulfate

Study Results

Participant Flow

Pre-assignment Detail	Overall, 108 participants were enrolled, and 59 received treatment.

Arm/Group Title	Atazanavir, 150 mg + Ritonavir, 100 mg (Weight: 15 to <20 kg)	Atazanavir, 200 mg + Ritonavir, 100 mg (Weight: 20 to <40 kg)	Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: ≥40 kg)
Arm/Group Description	Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir in capsule formation plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight ≥40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.
Period Title: Overall Study
STARTED	3	33	23
COMPLETED	2	15	13
NOT COMPLETED	1	18	10

Baseline Characteristics

Arm/Group Title	Atazanavir, 150 mg + Ritonavir, 100 mg (Weight: 15 to <20 kg)	Atazanavir, 200 mg + Ritonavir, 100 mg (Weight: 20 to <40 kg)	Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: ≥40 kg)	Total
Arm/Group Description	Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir in capsule formation plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight ≥40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Total of all reporting groups
Overall Participants	3	33	23	59
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	6.0 (0.0)	10.7 (2.67)	14.7 (1.72)	12.0 (3.26)
Age, Customized (Years) [Median (Full Range) ]
Median (Full Range) [Years]	6.0	11.0	15.0	12.0
Sex: Female, Male (Count of Participants)
Female	2 66.7%	17 51.5%	11 47.8%	30 50.8%
Male	1 33.3%	16 48.5%	12 52.2%	29 49.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 3%	2 8.7%	3 5.1%
Not Hispanic or Latino	1 33.3%	2 6.1%	2 8.7%	5 8.5%
Unknown or Not Reported	2 66.7%	30 90.9%	19 82.6%	51 86.4%
Race/Ethnicity, Customized (Number) [Number]
White	1 33.3%	5 15.2%	4 17.4%	10 16.9%
Black/African American	2 66.7%	24 72.7%	9 39.1%	35 59.3%
Other	0 0%	4 12.1%	10 43.5%	14 23.7%
Region of Enrollment (Number) [Number]
Africa	2 66.7%	24 72.7%	8 34.8%	34 57.6%
Europe	0 0%	1 3%	0 0%	1 1.7%
North America	1 33.3%	0 0%	3 13%	4 6.8%
South America	0 0%	8 24.2%	12 52.2%	20 33.9%
Country (Number) [Number]
Argentina	0 0%	3 9.1%	0 0%	3 5.1%
Brazil	0 0%	3 9.1%	4 17.4%	7 11.9%
Chile	0 0%	1 3%	2 8.7%	3 5.1%
Mexico	1 33.3%	0 0%	1 4.3%	2 3.4%
Peru	0 0%	1 3%	6 26.1%	7 11.9%
Russia	0 0%	1 3%	0 0%	1 1.7%
South Africa	2 66.7%	24 72.7%	8 34.8%	34 57.6%
United States	0 0%	0 0%	2 8.7%	2 3.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Grade 2-4 Related AEs, Grade 3-4 AEs, and Centers for Disease Control (CDC) Class C AIDS Events
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Time Frame	From first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Atazanavir, 150 mg + Ritonavir, 100 mg (Weight: 15 to <20 kg)	Atazanavir, 200 mg + Ritonavir, 100 mg (Weight: 20 to <40 kg)	Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: ≥40 kg)
Arm/Group Description	Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir in capsule formation plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight ≥40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.
Measure Participants	3	33	23
Deaths	0 0%	0 0%	1 4.3%
SAEs	1 33.3%	3 9.1%	4 17.4%
AEs leading to discontinuation	0 0%	1 3%	2 8.7%
Grade 2-4 related AEs	1 33.3%	3 9.1%	5 21.7%
Grade 3-4 AEs	0 0%	3 9.1%	5 21.7%
CDC Class C AIDS events	0 0%	1 3%	0 0%

2. Primary Outcome

Title	Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4
Description	Hematocrit (%): Grade (Gr) 1= ≥28.5- <31.5; Gr 2= ≥24- <28.5; Gr 3= ≥19.5- <24; Gr 4= <19.5. Hemoglobin (g/dL): Grade (Gr)1=8.5-10.0; Gr 2=7.5-8.4; Gr 3=6.50-7.4; Gr 4= <6.5. Platelets (/mm^3): Gr 1=100,000-124,999; Gr 2=50,000-99,999; Gr 3=25,000-49,999; Gr 4= <25,000. White blood cells (/mm^3): Gr 1=2000-2500; Gr 2=1500-1999; Gr 3=1000-1499; Gr 4= <1000. Neutrophils (/mm^3): Gr 1=1000-1500; Gr 2= ≥750-1000; Gr 3= ≥500-750; Gr 4= <500. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) (*upper limit of normal [ULN]): Gr 1=1.5-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10.0; Gr 4= >10.0. Total bilirubin (adult and pediatric >14 days) (*ULN): Gr 1=1.1-1.5; Gr 2=1.6-2.5; Gr 3=2.6-5.0; Gr 4= >5.0. Albumin (g/dL): Gr 1= 3.1- <LLN; Gr 2=2.0-2.9; Gr 3= <2.0; Gr 4=NA. Amylase (*ULN): Gr 1=1.10-1.39; Gr 2=1.40-2.09; Gr 3=2.10-5.0; Gr 4= >5. Lipase (*ULN): Gr 1=1.1-1.5; Gr 2=1.6-3.0; Gr 3=3.1-5.0; Gr 4= >5.0.
Time Frame	After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Atazanavir, 150 mg + Ritonavir, 100 mg (Weight: 15 to <20 kg)	Atazanavir, 200 mg + Ritonavir, 100 mg (Weight: 20 to <40 kg)	Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: ≥40 kg)
Arm/Group Description	Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir in capsule formation plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight ≥40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.
Measure Participants	3	33	23
Hematocrit	0 0%	3 9.1%	0 0%
Hemoglobin	0 0%	5 15.2%	0 0%
Platelets	0 0%	0 0%	1 4.3%
White blood cells	0 0%	3 9.1%	0 0%
Neutrophils+bands (absolute)	1 33.3%	13 39.4%	4 17.4%
ALT	1 33.3%	6 18.2%	9 39.1%
AST	0 0%	6 18.2%	5 21.7%
ALP	1 33.3%	11 33.3%	12 52.2%
Total bilirubin	3 100%	26 78.8%	17 73.9%
Albumin	2 66.7%	15 45.5%	6 26.1%
Amylase	2 66.7%	27 81.8%	14 60.9%
Lipase	0 0%	15 45.5%	8 34.8%

3. Primary Outcome

Title	Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 (Continued)
Description	Blood urea nitrogen (*upper limit of normal [ULN]): Grade (Gr) 1=1.25-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10; Gr 4= >10. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12; Gr 3=12.1-15.0; Gr 4= >15.0. Bicarbonate (mEqL): Gr 1= 19.0-21.0; Gr 2=15.0-18.0; Gr 3=41-45; Gr 4= >45. Calcium, low (mg/dL): Gr 1=7.8-8.4; Gr 2=7.0-7.7; Gr 3=6.1-6.9; Gr 4= <6.1.Potassium (mEq/L), high: Gr 1=5.6-6.0; Gr 2=6.1-6.5; Gr 3=6.6-7.0; Gr 4= >7.0. Potassium (mEq/L), low: Gr 1=3.1-3.4; Gr 2=2.5-2.9; Gr 3=2.0-2.4; Gr 4= <2.0. Sodium (mEq/L), low: Gr 1=130-135; Gr 2=125-129; Gr 3=121-124; Gr 4= <1. Total cholesterol, fasting (mg/dL): Gr 1=200-239; Gr 2=240-300; Gr 3= >300; Gr 4=Not applicable (NA). Low-density lipoprotein (LDL) cholesterol, fasting (mg/dL): Gr 1=130-159; Gr 2=160-190; Gr 3= >190; Gr 4= NA. Glucose, low (mg/dL): Gr 1= 55-64; Gr 2=40-54; Gr 3=30-39; Gr 4= <30. Glucose, fasting (mg/dL): Gr 1=110-125; Gr 2=126-250; Gr 3=251-500; Gr 4 >500.
Time Frame	After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	Atazanavir, 150 mg + Ritonavir, 100 mg (Weight: 15 to <20 kg)	Atazanavir, 200 mg + Ritonavir, 100 mg (Weight: 20 to <40 kg)	Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: ≥40 kg)
Arm/Group Description	Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir in capsule formation plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.	Participants with baseline weight ≥40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.
Measure Participants	3	33	23
Blood urea nitrogen	0 0%	3 9.1%	0 0%
Uric acid	0 0%	2 6.1%	3 13%
Bicarbonate, low	3 100%	29 87.9%	17 73.9%
Calcium, low	0 0%	2 6.1%	3 13%
Potassium, high	0 0%	2 6.1%	1 4.3%
Potassium, low	0 0%	2 6.1%	0 0%
Total cholesterol, fasting (n=3, 31, 21)	0 0%	10 30.3%	6 26.1%
Sodium, low	1 33.3%	13 39.4%	0 0%
LDL cholesterol, fasting (n=3, 31, 21)	0 0%	7 21.2%	3 13%
Glucose, low (n=1, 11, 9)	0 0%	3 9.1%	0 0%
Glucose, fasting, high (3, 31, 22)	0 0%	3 9.1%	1 4.3%
Calcium, high	0 0%	2 6.1%	0 0%
Chloride, high	0 0%	0 0%	2 8.7%
Chloride, low	0 0%	0 0%	0 0%
Glucose, Non-Fasting, High	0 0%	0 0%	0 0%
Sodium, high	0 0%	1 3%	1 4.3%
Creatinine	0 0%	1 3%	0 0%
Triglycerides, fasting	0 0%	0 0%	0 0%

Adverse Events

Time Frame	From first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)
Arm/Group Title	B/L Weight 15 to Less Than 20 kg		B/L Weight 20 to Less Than 40 kg		B/L Weight Greater Than and Equal 40 kg
Arm/Group Description	Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir in capsule formation plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.		Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.		Participants with baseline weight ≥40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients were eligible to receive study treatment, with regular 12-week visits, until the age of 18 years.
All Cause Mortality
	B/L Weight 15 to Less Than 20 kg		B/L Weight 20 to Less Than 40 kg		B/L Weight Greater Than and Equal 40 kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/33 (0%)		1/23 (4.3%)
Serious Adverse Events
	B/L Weight 15 to Less Than 20 kg		B/L Weight 20 to Less Than 40 kg		B/L Weight Greater Than and Equal 40 kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		3/33 (9.1%)		4/23 (17.4%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		0/33 (0%)		1/23 (4.3%)
Infections and infestations
Appendicitis	0/3 (0%)		0/33 (0%)		1/23 (4.3%)
Meningitis bacterial	0/3 (0%)		0/33 (0%)		1/23 (4.3%)
Injury, poisoning and procedural complications
Accidental overdose	1/3 (33.3%)		0/33 (0%)		0/23 (0%)
Overdose	0/3 (0%)		1/33 (3%)		0/23 (0%)
Nervous system disorders
Seizure	0/3 (0%)		1/33 (3%)		0/23 (0%)
Psychiatric disorders
Abnormal behaviour	0/3 (0%)		0/33 (0%)		1/23 (4.3%)
Renal and urinary disorders
Glomerulonephritis	0/3 (0%)		1/33 (3%)		0/23 (0%)
Haematuria	0/3 (0%)		1/33 (3%)		0/23 (0%)
Post streptococcal glomerulonephritis	0/3 (0%)		1/33 (3%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	B/L Weight 15 to Less Than 20 kg		B/L Weight 20 to Less Than 40 kg		B/L Weight Greater Than and Equal 40 kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		26/33 (78.8%)		20/23 (87%)
Cardiac disorders
Atrioventricular block first degree	0/3 (0%)		3/33 (9.1%)		0/23 (0%)
Sinus bradycardia	0/3 (0%)		2/33 (6.1%)		2/23 (8.7%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		2/33 (6.1%)		0/23 (0%)
Tympanic membrane perforation	0/3 (0%)		2/33 (6.1%)		0/23 (0%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		1/33 (3%)		5/23 (21.7%)
Diarrhoea	0/3 (0%)		3/33 (9.1%)		1/23 (4.3%)
Nausea	0/3 (0%)		2/33 (6.1%)		4/23 (17.4%)
Toothache	0/3 (0%)		3/33 (9.1%)		0/23 (0%)
Vomiting	0/3 (0%)		7/33 (21.2%)		3/23 (13%)
General disorders
Pyrexia	0/3 (0%)		2/33 (6.1%)		0/23 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		2/33 (6.1%)		4/23 (17.4%)
Jaundice	1/3 (33.3%)		2/33 (6.1%)		6/23 (26.1%)
Ocular icterus	0/3 (0%)		1/33 (3%)		3/23 (13%)
Infections and infestations
Bronchitis	1/3 (33.3%)		2/33 (6.1%)		0/23 (0%)
Conjunctivitis	0/3 (0%)		2/33 (6.1%)		2/23 (8.7%)
Gastroenteritis	1/3 (33.3%)		3/33 (9.1%)		0/23 (0%)
Impetigo	0/3 (0%)		1/33 (3%)		2/23 (8.7%)
Influenza	1/3 (33.3%)		3/33 (9.1%)		3/23 (13%)
Nasopharyngitis	1/3 (33.3%)		3/33 (9.1%)		6/23 (26.1%)
Oral herpes	0/3 (0%)		4/33 (12.1%)		1/23 (4.3%)
Otitis media	1/3 (33.3%)		2/33 (6.1%)		2/23 (8.7%)
Tonsillitis	1/3 (33.3%)		4/33 (12.1%)		0/23 (0%)
Upper respiratory tract infection	2/3 (66.7%)		13/33 (39.4%)		4/23 (17.4%)
Abscess	0/3 (0%)		2/33 (6.1%)		0/23 (0%)
Pharyngitis	1/3 (33.3%)		1/33 (3%)		0/23 (0%)
Pharyngotonsillitis	1/3 (33.3%)		0/33 (0%)		0/23 (0%)
Urinary tract infection	1/3 (33.3%)		1/33 (3%)		0/23 (0%)
Injury, poisoning and procedural complications
Head injury	1/3 (33.3%)		0/33 (0%)		0/23 (0%)
Nervous system disorders
Headache	0/3 (0%)		4/33 (12.1%)		2/23 (8.7%)
Psychiatric disorders
Depression	0/3 (0%)		2/33 (6.1%)		1/23 (4.3%)
Hallucination	1/3 (33.3%)		0/33 (0%)		0/23 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		9/33 (27.3%)		4/23 (17.4%)
Rhinorrhoea	0/3 (0%)		2/33 (6.1%)		1/23 (4.3%)
Asthma	0/3 (0%)		0/33 (0%)		2/23 (8.7%)
Nasal congestion	0/3 (0%)		0/33 (0%)		2/23 (8.7%)
Oropharyngeal pain	1/3 (33.3%)		0/33 (0%)		0/23 (0%)
Skin and subcutaneous tissue disorders
Acne	0/3 (0%)		1/33 (3%)		2/23 (8.7%)
Dermatitis	0/3 (0%)		4/33 (12.1%)		0/23 (0%)
Rash	0/3 (0%)		4/33 (12.1%)		2/23 (8.7%)
Eczema	0/3 (0%)		2/33 (6.1%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

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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.