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Improvement in Insulin Sensitivity and Dyslipidemia in Protease Inhibitor-Treated Adult Male Patients After Switch to Atazanavir/Ritonavir
  1. Anthony J. Busti, PharmD*†,
  2. Roger Bedimo, MD, MS†‡,
  3. David M. Margolis, MD§,
  4. Dana S. Hardin, MD
  1. From the *Texas Tech University Health Sciences Center School of Pharmacy Dallas Fort Worth Regional Campus; †Dallas Veteran's Affairs Medical Center; ‡University of Texas Southwestern Medical Center, Dallas, TX; §University of North Carolina at Chapel Hill, Chapel Hill, NC; and ¶The Ohio State University, Columbus, OH.
  1. Supported by a research grant from Bristol-Myers Squibb and, in part, by GCRC Grant M01RR000633.
  2. Dr Margolis has received research materials and speaking honoraria from Bristol-Myers Squibb and research materials and consulting honoraria from Abbott.
  3. Reprints: Dana S. Hardin, MD, 700 Children's Dr, W307, Columbus, OH 43205. E-mail: hardind{at}pediatrics.ohio-state.edu.

Abstract

Background Treatment of human immunodeficiency virus (HIV) with protease inhibitors (PIs) is associated with insulin resistance, triglyceride-rich dyslipidemia, and fat redistribution. Atazanavir (ATV), a potent once-daily PI, has been recognized for its convenience to patients, and some studies describe improved lipid metabolism. However, its effects on insulin sensitivity have not been elucidated. We conducted this study to test the hypothesis that ATV improves insulin resistance and dyslipidemia.

Methods We prospectively studied 9 HIV-infected men with dyslipidemia (median age, 53 years; baseline triglyceride level, >200 mg/dL) on stable PI-containing antiretroviral therapy who elected to change PI therapy to ritonavir-boosted ATV therapy, dose of 300/100 mg. We measured insulin resistance at baseline and after 12 weeks of therapy using a hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m2 minute). Fasting lipid profiles and body composition (whole-body dual energy x-ray absorptiometry) were also measured at baseline and after 12 weeks.

Results All 9 patients completed the study and maintained undetectable viral loads (<50 copies/mL) and stable CD4 counts. After 12 weeks, insulin sensitivity significantly improved (+28%; P = 0.008) in all patients. Triglyceride levels also improved.

Conclusions Using the gold-standard euglycemic clamp, ritonavir-boosted ATV therapy improved PI-induced insulin resistance among dyslipidemic HIV-infected men on PI-based antiretroviral therapy. These findings were not attributable to a change in body weight and provide further evidence for ATV's unique metabolic profile among the PIs.

Key Words
  • atazanavir
  • protease inhibitor
  • human immunodeficiency virus
  • insulin resistance
  • hyperlipidemia

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