Official Title: “Phase I/II Safety and Efficacy Investigation of Atorvastatin for Treatment of PI-Associated Increased LDL Cholesterol in HIV-Infected Children and Adolescents”

Treatment of HIV with antiretroviral regimens that include protease inhibitors (PIs) frequently results in the suppression of HIV viral load, significant immune recovery, and delayed disease progression. However, treatment with PIs has been associated with significant increases in cholesterol and triglycerides in HIV infected adults and children. The purpose of this study is 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 antiretroviral regimens containing at least one PI.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2010

Antiretroviral regimens 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 is to evaluate the safety and effectiveness of escalating doses of atorvastatin, based on low-density lipoprotein (LDL) cholesterol levels, in HIV-infected children receiving antiretroviral regimens containing at least one PI.

This study will last no longer than 48 weeks. Participants will be assigned to one of two groups according to age. One group will include participants from ages 10 to 14 years with participants from ages 15 to 18 years in the other. The first six participants enrolled in the study will be from the 15 to 18 year old age group. Once safety data through Week 8 on these 6 participants has been analyzed, the remaining participants will be enrolled. All participants will receive atorvastatin in combination with a stable antiretroviral regimen including at least one PI. Each participant will be followed independently according to a dose escalation algorithm for atorvastatin. Participants will begin dosing at 10 mg daily. If efficacy criteria are not met, dosing will increase to no more than 20 mg daily. Atorvastatin will be provided by the study, but antiretrovirals will not.

This study will consist of seven study visits after screening. Visits will occur at study entry and Weeks 4, 8, 12, 24, 36, and 48. A physical exam, medical history, and adherence questionnaire will occur at all study visits. Blood collection will occur at most visits.

Urine collection will occur at some visits.

Intervention(s) in this Clinical Trial

• Drug: Atorvastatin
  • 10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable PI-based antiretroviral regimen
• Experimental: 2
  • Participants ages 15 to 18 years receiving oral atorvastatin for 48 weeks while on a stable PI-based antiretroviral regimen

Primary Measures

• Occurence of Grade 3 or 4 toxicity
  • Time Frame: Throughout study
    Safety Issue?: Yes
• Low density lipoprotein cholesterol levels
  • Time Frame: Throughout study
    Safety Issue?: No

Secondary Measures

• Atorvastatin pharmacokinetic parameters
  • Time Frame: Throughout study
    Safety Issue?: No
• Fasting lipids
  • Time Frame: Throughout study
    Safety Issue?: No
• Inflammatory markers for cardiac disease risk
  • Time Frame: Throughout study
    Safety Issue?: No
• Viral load
  • Time Frame: Throughout study
    Safety Issue?: No

Inclusion Criteria:

• HIV infected
• CD4 count of at least 15 at screening
• Viral load of at least 10,000 copies/ml at screening
• Receiving stable antiretroviral therapy regimen containing at least one protease inhibitor for at least 6 months
• Tanner stage of 2 or higher
• Certain fasting LDL cholesterol values and cardiovascular risk factors/co-morbidities.
• More information on this criterion can be found in the protocol.
• Able to fast overnight for 8 hours
• Agree to use two appropriate forms of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• Certain abnormal laboratory values
• Any laboratory or unresolved clinical toxicity equal to Grade 3 or higher
• Unlikely to remain on current antiretroviral therapy for at least six months after study entry
• Use of statin, fibrate, or niacin within 3 months prior to study entry
• Evidence of chronic ongoing myositis or history of myopathy or neuromuscular disorder
• Symptomatic peripheral neuropathy within 6 months prior to study entry
• Pharmacologic treatment for depression or other mental disorder excluding Attention
• Deficit Disorder within 30 days prior to study entry
• Presence of an active CDC Stage C opportunistic infection or serious bacterial infection requiring therapy within 2 weeks prior to study entry.
• Chemotherapy for malignancy within 3 months prio to study entry
• Hepatitis B Surface Antigen positive
• Hepatitis C viremia
• Insulin-dependent diabetes mellitus
• Required treatment with an agent contraindicated with either atorvastatin or PIs. More information on this criterion can be found in the protocol.
• Pregnant or breastfeeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 10 Years

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Ann Melvin, MD Study Chair Seattle Children's Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00663234

Study ID Number: IMPAACT P1063

ClinicalTrials.gov Identifier: NCT00663234

Health Authority: United States: Food and Drug Administration

Click here for the AIDSinfo Hyperlipidemia Fact Sheet