Atazavanir/Ritonavir-based HAART in Children

Study Overview
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Brief Summary
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There are no data on efficacy, safety and pharmacokinetics of ATV/r-based HAART in HIV-infected Asian children. Therefore, the investigators aim to evaluate the pharmacokinetics, efficacy and safety of ATV/r-based HAART in Thai HIV-infected children.

Detailed Description
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Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART have been commonly prescribed as the first-line HAART for HIV-infected children in resource-limited settings. Protease inhibitor (PI)-based HAART are the recommended second-line regimen after failing NNRTI-based HAART. The most commonly used PI in Thailand is lopinavir/ritonavir (LPV/r). However, the metabolic complications of lopinavir/ritonaive (LPV/r) such as hyperlipidemia and lipodyrtrophy are common and a concern for HIV-infected children as it may contribute to the development of cardiovascular disease in the longer term. There are data on efficacy, safety and pharmacokinetics of ATV/r-based HAART in HIV-infected adults but none in children. Furthermore, many studies in both adults and children have shown that different ethnicities can result in different pharmacokinetic response to antiretroviral drugs. As a result of this, this study investigated the efficacy, safety and pharmacokinetics of ATV/r-based HAART in HIV-infected Asian children.

Official Title
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The Study of Atazavanir/Ritonavir-based HAART in Thai HIV-infected Children

Conditions
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HIV

Intervention / Treatment
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* Drug: boosted atazanavir (ATV/r)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected children Age from 6- 18 years old Body weight ≥ 25 kg at screening visit ARV history, the children can be categorized in one of these 2 groups ALT <200 IU/L at screening visit Total bilirubin < 3 mg/dL at the screening visit Can swallow capsule Written informed consent from caregivers and assent (from children aged 7-17 years who know their HIV status) Exclusion Criteria: Active opportunistic infection Relevant history or current condition, illness that might interfere with atazanavir/ritonavir absorption, distribution, metabolism or excretion. Use of concomitant medication that may interfere with the pharmacokinetics of ATV/r (i.e. efavirenz, indinavir, proton pump inhibitor, antacids, cisapride, clarithromycin, rifampin etc.) Pregnancy or lactating at screening visit Liver diseases e.g. hepatitis B carrier, chronic hepatitis, cirrhosis Inability to understand the nature and extent of the study and the procedures required.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PI-experience group<br>Using PI-based HAART for ≥6 months at the screening visit HIV-RNA viral load < 50 copies/ml at the screening visit No history of HIV-RNA ≥ 1,000 copies/ml while using PI-based HAART | Drug: boosted atazanavir (ATV/r)<br>* ATV/r will be taken orally once daily with food plus standard dose of 2 NRTIs according to Thai National HIV treatment guideline<br>|
| Experimental: PI-naïve group<br>Never been exposed to any PI-containing regimen HIV-RNA viral load ≥ 1,000 copies/ml at the screening visit | Drug: boosted atazanavir (ATV/r)<br>* ATV/r will be taken orally once daily with food plus standard dose of 2 NRTIs according to Thai National HIV treatment guideline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics of atazanavir/ritonavir (ATV/r) | Ctrough and Area under the curve (AUC) of atazanavir (ATV) and ritonavir (RTV) will be assessed | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 | Assess CD percent and count at week 48 | 48 weeks | 
| plasma viral load (HIV RNA) | assess HIV RNA at week 24 and 48 | 48 weeks | 
| hyperbilirubin | evaluate total and direct bilirubin at weeks 24 and 48 | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, atazanavir/ritonavir, HIV-infected children