Metabolic Effects of Switching Kaletra to Boosted Reyataz

Not Applicable

Completed

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

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
1	atazanavir/ritonavir	Boosted Reyataz (300mg atazanavir + 100mg ritonavir)
2	lopinavir/ritonavir	Kaletra (pre-study dose)

Primary Outcome Measures

Name	Time	Method
Glucose Trafficking	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Liver Enzymes -- Alanine Aminotransferase (ALT)	6 months	6 month mean and standard deviation for ALT.
Total Bilirubin	6 months	6 month mean and standard deviation for total bilirubin.
Fasting Glucose	6 months	6 month mean and standard deviation for fasting glucose.
Liver Enzymes -- Aspartate Aminotransferase (AST)	6 months	6 month mean and standard deviation for AST.
Insulin Sensitivity	6 months	6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp.
Lipid Metabolism - Serum Triglyceride	6 months	6 month mean and standard deviation for serum triglyceride.
Body Composition - Visceral Adipose Tissue	6 months	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).
Immune Parameters -- CD4 Count	6 months	6 month mean and standard deviation for CD4+ count.