Equivalence of Boosted Atazanavir Based Regimens and Currently Effective HAART Regimens

Equivalence of Boosted Atazanavir Based Regimens and Currently Effective HAART Regimens With Other PI's/NNRTI's in HIV+ Children and Adolescents With Elevated Lipid Levels

The hypothesis for this study is whether a treatment regimen containing Atazanavir in combination with Ritonavir will work as well as other regimens containing a protease inhibitor and/or a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) at controlling HIV disease in children who are HIV+ and have high cholesterol or high triglycerides. . In this study, children who have high cholesterol or high triglycerides as a result of their HIV medicines, will have the PI or NNRTI in their medication regimen changed to Atazanavir, which is a PI in combination with a low dose of Ritonavir (another PI). Atazanavir has been shown in adults to result in lower cholesterol and triglycerides than other PI's and NNRTI's. The dose of Atazanavir and Ritonavir will be according to the Package Insert for this drug that is FDA approved for children. They will continue taking the other medications from the pre-study regimen. Children will take study drug for 24 weeks, and will be able to continue study drug after the study using commercially available drug. Lab tests and a physical exam will be undertaken at 4 weeks, 12 weeks and 24 weeks after starting study drug to determine how effective the new drug is and to monitor for possible side effects.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Pediatric HIV
• Intervention / Treatment: Drug: Boosted Atazanavir

Detailed Description

The primary objective of this study is to determine if Atazanavir and Ritonavir together will be as effective as the child's previous regimen in keeping the level of virus in the blood stream at such a low level it can't be found and whether that combination will be as effective as the previous regimen in keeping the infection fighting cells in the blood at the same level.

Secondary objectives will be:

• To determine if cholesterol and triglyceride levels drop in children switching to Atazanavir and Ritonavir from other medication regimens.
• To evaluate if Atazanavir and Ritonavir result in an increase in patient satisfaction and patient reported adherence and a decrease in symptoms related to medication side effects.

Inclusion Criteria are:

• On the same medication regimen at least 3 months
• Weight equal to or greater than 25kg
• Able to swallow pills or willing to learn
• Have a parent or guardian willing and able to sign informed consent
• Not be taking a medication which interacts with Atazanavir
• Not be currently taking Sustiva

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV positive children with elevated lipid levels
• on stable HAART for at least 3 months (defined to be on the same regimen with viral load < 1000 for 6 months prior to baseline visit).
• Weight equal to or greater than 25kg
• Able to swallow pills or willing to learn

Exclusion Criteria:

• Patients with underlying hepatitis B or C viral infections
• Previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of Reyataz® (atazanavir).

• Taking other medications that are highly dependent on CYP3A or UGT1A1 for clearance

  • Ergot medicines: dihydroergotamine, ergonovine, ergotamine, and methylergonovine such as Cafergot®, Migranal®, D.H.E. 45®, ergotrate maleate, Methergine®, and others (used for migraine headaches).
  • Orap® (pimozide, used for Tourette's disorder).
  • Propulsid® (cisapride, used for certain stomach problems).
  • Triazolam, also known as Halcion® (used for insomnia).
  • Midazolam, also known as Versed® (used for sedation), when taken by mouth.
  • Camptosar® (irinotecan, used for cancer).
  • Crixivan® (indinavir, used for HIV infection).
  • Cholesterol-lowering medicines Mevacor® (lovastatin) or Zocor® (simvastatin).
  • Rifampin (also known as Rimactane®, Rifadin®, Rifater®, or Rifamate®).
  • St. John's wort (Hypericum perforatum), an herbal product sold as a dietary supplement,
  • Viramune® (nevirapine, used for HIV infection).
  • Vfend® (voriconazole).
• Patients with grade 3 or higher elevations in transaminases (> 10 X ULN)
• Women of Childbearing Potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: boosted Atazanavir; Boosted Atazanavir was switched for the PI or NNRTI in the patients regimen	Drug: Boosted Atazanavir; Boosted Atazanavir, once a day dose adjusted for child's weight for 6 months.; Other Names: Reyataz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Non-fasting Cholesterol	4 Weeks, 12 weeks, 24 weeks
Non-fasting Triglycerides	4 weeks, 12 weeks, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral Load	Number of participants with undetectable viral load	4 weeks, 12 weeks, 24 weeks
CD4 Count		4 Weeks, 12 weeks, 24 weeks

Collaborators and Investigators

• Sponsor: Phoenix Children's Hospital
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2009
• Primary Completion (Actual): October 16, 2013
• Study Completion (Actual): November 23, 2016

Study Registration Dates

• First Submitted: July 15, 2009
• First Submitted That Met QC Criteria: July 15, 2009
• First Posted (Estimate): July 16, 2009

Study Record Updates

• Last Update Posted (Actual): April 20, 2020
• Last Update Submitted That Met QC Criteria: April 15, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Pediatric; Lipids; Atazanavir; treatment experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Atazanavir Sulfate
• Other Study ID Numbers: PCH 09-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No