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Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on muscle glucose uptake and visceral fat in HIV-infected patients

Stanley, Takara La; Joy, Tishaa; Hadigan, Colleen Md; Liebau, James Ga; Makimura, Hideoa; Chen, Cindy Ya; Thomas, Bijoy Jc; Weise, Steven Bc; Robbins, Gregory Kb; Grinspoon, Steven Ka

doi: 10.1097/QAD.0b013e32832ba904
Clinical Science

Objective: To determine the effects of switching from lopinavir/ritonavir (LPV/r) to atazanavir/ritonavir (ATV/r) on muscle glucose uptake, glucose homeostasis, lipids, and body composition.

Methods: Fifteen HIV-infected men and women on a regimen containing LPV/r and with evidence of hyperinsulinemia and/or dyslipidemia were randomized to continue LPV/r or to switch to ATV/r (ATV 300 mg and ritonavir 100 mg daily) for 6 months. The primary endpoint was change in thigh muscle glucose uptake as measured by positron emission tomography. Secondary endpoints included abdominal visceral adipose tissue, fasting lipids, and safety parameters. The difference over time between treatment groups (treatment effect of ATV/r relative to LPV/r) was determined by repeated measures ANCOVA.

Results: After 6 months, anterior thigh muscle glucose uptake increased significantly (treatment effect +18.2 ± 5.9 μmol/kg per min, ATV/r vs. LPV/r, P = 0.035), and visceral adipose tissue area decreased significantly in individuals who switched to ATV/r (treatment effect −31 ± 11 cm2, ATV/r vs. LPV/r, P = 0.047). Switching to ATV/r significantly decreased triglyceride (treatment effect −182 ± 64 mg/dl, ATV/r vs. LPV/r, P = 0.02) and total cholesterol (treatment effect −23 ± 8 mg/dl, ATV/r vs. LPV/r, P = 0.01), whereas high-density lipoprotein and low-density lipoprotein did not change significantly. Fasting glucose also decreased significantly following switch to ATV/r (treatment effect −15 ± 4 mg/dl, ATV/r vs. LPV/r, P = 0.002).

Conclusion: Switching from LPV/r to ATV/r significantly increases glucose uptake by muscle, decreases abdominal visceral adipose tissue, improves lipid parameters, and decreases fasting glucose over 6 months.

aProgram in Nutritional Metabolism, USA

bDivision of Infectious Diseases, USA

cDepartment of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

dNational Institutes of Health, Bethesda, Maryland, USA.

Received 26 January, 2009

Revised 11 March, 2009

Accepted 15 March, 2009

Correspondence to Steven K. Grinspoon, MD, Director, Program in Nutritional Metabolism, Massachusetts General Hospital, Boston, MA 02114, USA. Tel: +1 617 724 9109; fax: +1 617 724 8998; e-mail: sgrinspoon@partners.org

© 2009 Lippincott Williams & Wilkins, Inc.