Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2009 Jul 17;23(11):1349-57.
doi: 10.1097/QAD.0b013e32832ba904.

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

Affiliations
Randomized Controlled Trial

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

Takara L Stanley et al. AIDS. .

Abstract

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 micromol/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 cm, 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.

Trial registration: ClinicalTrials.gov NCT00413153.

PubMed Disclaimer

Figures

Fig 1
Fig 1
Fig 1A: Change in serum triglyceride concentrations in each treatment group during the study. p=0.02 for comparison between groups by repeated measures ANCOVA. Fig 1B: Change in serum bilirubin concentrations in each treatment group during the study. p=0.0002 for comparison between groups by repeated measures ANCOVA.
Fig 2
Fig 2
Change in visceral adipose tissue (VAT) after 6 months in each treatment group. p=0.047 for comparison between groups by Student's t-test.

References

    1. Hertel J, Struthers H, Horj CB, Hruz PW. A structural basis for the acute effects of HIV protease inhibitors on GLUT4 intrinsic activity. J Biol Chem. 2004;279:55147–55152. - PMC - PubMed
    1. Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275:20251–20254. - PubMed
    1. Parker RA, Flint OP, Mulvey R, Elosua C, Wang F, Fenderson W, et al. Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors. Mol Pharmacol. 2005;67:1909–1919. - PubMed
    1. Yan Q, Hruz PW. Direct comparison of the acute in vivo effects of HIV protease inhibitors on peripheral glucose disposal. J Acquir Immune Defic Syndr. 2005;40:398–403. - PMC - PubMed
    1. Kim RJ, Wilson CG, Wabitsch M, Lazar MA, Steppan CM. HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism. Obesity (Silver Spring) 2006;14:994–1002. - PubMed

Publication types

MeSH terms

Associated data