Metabolic Effects of Switching Kaletra to Boosted Reyataz

Study Overview
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Brief Summary
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To study the effects of switching from Kaletra to Boosted Reyataz on glucose, lipids and fat in HIV-infected patients.

Detailed Description
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The primary objective of this study is to determine tissue specific glucose trafficking in patients before and after switching from a regimen containing Lopinavir/ritonavir (LPV/r) to one containing atazanavir/ritonavir (ATV/r). Secondary outcome measures of interest will include insulin sensitivity determined by clamp testing, and lipid metabolism and hepatic glucose production assessed using stable isotope techniques. We hypothesize that switching protease inhibitor (PI) to ATV/r from LPV/r will result in direct increases in glucose uptake in muscle and visceral adipose tissue in association with improvements in overall whole body insulin sensitivity compared to remaining on LPV/r. We will complete a prospective randomized trial of Human Immunodeficiency Virus (HIV) infected patients who have been on a stable antiretroviral (ARV) regimen containing LPV/r for at least 6 months and who will be randomized to either switch to a regimen containing ATV/r or remain on LPV/r for 6 months. Each subject will complete Positron Emission Tomography (PET) 18-fluorodeoxyglucose (FDG) imaging during a hyperinsulinemic clamp study at baseline and 6 months after randomization.

Official Title
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Metabolic Effects of Switching Kaletra to Boosted Reyataz

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: atazanavir/ritonavir
* Drug: lopinavir/ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously diagnosed HIV infection Age between 18-65 years Stable antiviral regimen containing at least 2 nucleoside reverse transcriptase inhibitors (NRTI's) and LPV/r for ³ 6 mos CD4 count > 400 cell/mm3 Metabolic complication as indicated by one or more of hyperinsulinemia (fasting insulin >= 15 mIU/ml), hypercholesteremia (fasting total cholesterol >= 200 mg/dL), hypertriglyceridemia (fasting triglycerides >= 150 mg/dL), or treatment with a lipid lowering medication. Exclusion Criteria: Hemoglobin < 11.0 g/dL History of Diabetes Mellitus Currently on medication for Diabetes Therapy with glucocorticoid, growth hormone or other anabolic agents currently or within the past 3 months Current substance abuse, including alcohol, cocaine and/or heroin Any contraindication to ATV/r or known allergy to ATV Concurrent therapy with: Bepridil; cisapride; ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine); indinavir; irinotecan; lovastatin; midazolam; pimozide; proton pump inhibitors (esomeprazole, lansoprazole, omeprazole); rifampin; simvastatin; St John's wort; or triazolam New or serious opportunistic infection in the past 3 months Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: 1<br>Boosted Reyataz (300mg atazanavir + 100mg ritonavir) | Drug: atazanavir/ritonavir<br>* atazanavir 300mg + ritonavir 100mg once daily<br>* Other names: Boosted Reyataz;|
| Active Comparator: 2<br>Kaletra (pre-study dose) | Drug: lopinavir/ritonavir<br>* patient remains on their pre-study dose of lopinavir/ritonavir<br>* Other names: Kaletra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Trafficking | 6 month mean and standard deviation for glucose uptake into anterior thigh muscle as measured by FDG/PET scanning during euglycemic hyperinsulinemic clamp. During the hyperinsulinemic conditions of the clamp, glucose and 18-FDG [labeled glucose] are taken up by muscle. The quantity of 18-FDG taken up is measured by the PET scan. Although there are no well-accepted norms for this measurement, a higher value indicates that more glucose is being taken up by (or trafficked to) muscle. Increased uptake of glucose indicates increased muscle insulin sensitivity. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | 6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp. | 6 months | 
| Fasting Glucose | 6 month mean and standard deviation for fasting glucose. | 6 months | 
| Lipid Metabolism - Serum Triglyceride | 6 month mean and standard deviation for serum triglyceride. | 6 months | 
| Body Composition - Visceral Adipose Tissue | 6 month mean and standard deviation for visceral adipose tissue (VAT) as measured by single slice computed tomography (CT) scan at the L4 pedicle (pedicle of 4th lumbar vertebra). | 6 months | 
| Immune Parameters -- CD4 Count | 6 month mean and standard deviation for CD4+ count. | 6 months | 
| Liver Enzymes -- Aspartate Aminotransferase (AST) | 6 month mean and standard deviation for AST. | 6 months | 
| Liver Enzymes -- Alanine Aminotransferase (ALT) | 6 month mean and standard deviation for ALT. | 6 months | 
| Total Bilirubin | 6 month mean and standard deviation for total bilirubin. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Kaletra, Reyataz, Insulin sensitivity, Lipids, Body Composition, Receiving Kaletra, Treatment Experienced