Treatment of HIV with combination antiretroviral regimens frequently results in the suppression of HIV viral load, significant immune recovery, and delayed disease progression. However, treatment with these regimens, particularly protease inhibitors (PIs), has been associated with significant increases in cholesterol and triglycerides in HIV-infected adults and children. The purpose of this study was to evaluate the safety and effectiveness of escalating doses of atorvastatin, a FDA-approved drug which lowers cholesterol and triglyceride levels, in HIV-infected children receiving stable antiretroviral regimens.
Antiretroviral regimens, particularly those containing PIs, often cause hyperlipidemia, which is an increase in the amount of fat (such as cholesterol and triglycerides) in the blood. These increases can lead to heart disease and pancreatitis. Although the mechanism by which PIs cause hyperlipidemia is not clearly understood, there are medications to combat this side effect. The primary purpose of this study was to evaluate the safety and effectiveness of escalating doses of atorvastatin, based on low-density lipoprotein cholesterol (LDL-C) levels, in HIV-infected children receiving stable antiretroviral therapy. Participants were assigned to one of two groups based on age (10 to 14 years or 15 to 23 years) and were treated for a maximum of 48 weeks. The first six participants enrolled in the study were in the 15 to 23 year old age group. Once safety data through week 8 on these 6 participants was analyzed, the remaining participants were enrolled. All participants received atorvastatin in combination with a stable antiretroviral regimen. Each participant was followed independently according to a dose escalation algorithm for atorvastatin. Participants began dosing at 10 mg daily. If efficacy criteria were not met, dosing increased to 20 mg daily at week 8. Since dose escalations were done within subject, safety and efficacy rates were presented for the dose-escalation strategy overall and not for individual doses. Atorvastatin was provided by the study, but antiretrovirals were not. Study visits occurred at study entry and weeks 4, 8, 12, 24, 36, and 48. Safety labs were collected at all study visits. Blood collection for lipid measurements occurred at weeks 4, 12, 24 and 48.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Univ. of Colorado Denver NICHD CRS (5052)
Aurora, Colorado, United States
Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
Miami, Florida, United States
University of South Florida Tampa (5018)
Tampa, Florida, United States
Chicago Children's CRS (4001)
Chicago, Illinois, United States
Tulane University (5095)
New Orleans, Louisiana, United States
Boston Medical Center Ped. HIV Program NICHD CRS (5011)
Boston, Massachusetts, United States
New York University NY (5012)
New York, New York, United States
Metropolitan Hospital (5003)
New York, New York, United States
Bronx-Lebanon Hospital IMPAACT CRS (6901)
The Bronx, New York, United States
St. Jude/UTHSC CRS (6501)
Memphis, Tennessee, United States
...and 1 more locations
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)
AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the core study team. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.
Time frame: Study entry to weeks 12, 24, and 48
Percentage of Participants Experiencing at Least One Adverse Event (AE)
AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.
Time frame: Study entry to weeks 12, 24, and 48
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Intention to Treat)
Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.
Time frame: Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Data Available)
Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.
Time frame: Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Per Protocol)
Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.
Time frame: Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria and Did Not Experience a Primary Safety Endpoint Attributable to Study Drug
Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.
Time frame: Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by Age Group
Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.
Time frame: Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by NNRTI Treatment
Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.
Time frame: Study entry and weeks 4, 12, 24, and 48
Percent Change in LDL Cholesterol (LDL-C) From Study Entry
Time frame: Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) by Age Group
AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the core study team. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.
Time frame: Study entry to weeks 12, 24, and 48
Percentage of Participants Experiencing at Least One Adverse Event (AE) by Age Group
AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.
Time frame: Study entry to weeks 12, 24, and 48
Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Time frame: Study entry and weeks 4, 12, 24, and 48
Percent Change in Triglycerides (TG) From Study Entry
Time frame: Study entry and weeks 4, 12, 24, and 48
Percent Change in HDL-cholesterol (HDL-C) From Study Entry
Time frame: Study entry and weeks 4, 12, 24, and 48
Percent Change in Apolipoprotein A1 (Apo A-1) From Study Entry
Time frame: Study entry and weeks 12, 24, and 48
Percent Change in Apolipoprotein B (Apo B) From Study Entry
Time frame: Study entry and weeks 12, 24, and 48
Percent Change in High-sensitivity CRP (Hs-CRP) From Study Entry
Time frame: Study entry and weeks 12, 24, and 48
Percent Change in Interleukin 6 (IL-6) From Study Entry
Time frame: Study entry and weeks 12, 24, and 48
Percentage of Participants With Undetectable Plasma HIV-1 RNA
Undetectable is defined as plasma HIV-1 RNA below the lower limit of quantification of the assay used.
Time frame: Study entry and weeks 12, 24, and 48
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