Body Fat and Other Metabolic Effects of Atazanavir and Efavirenz, Each Administered in Combination with Zidovudine plus Lamivudine, in Antiretroviral- Naive HIV-Infected Patients

• Published in: Clinical infectious diseases Vol. 42; no. 2; pp. 273 - 280
• Main Authors: Jemsek, Joseph G, Arathoon, Eduardo, Arlotti, Massimo, Perez, Carlos, Sosa, Nestor, Pokrovskiy, Vadim, Thiry, Alexandra, Soccodato, Michael, Noor, Mustafa A., Giordano, Michael
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 15.01.2006; University of Chicago Press; Oxford University Press
• Subjects: Adipose tissues; Adiposity - drug effects; Adult; AIDS; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Atazanavir Sulfate; Benzoxazines; Body fat; Cholesterols; Double-Blind Method; Drug therapy; Drug Therapy, Combination; Fasting; Female; Glucose; HIV; HIV-Associated Lipodystrophy Syndrome - chemically induced; HIV/AIDS; Human immunodeficiency virus; Humans; Insulin; Insulin resistance; Lamivudine - administration & dosage; Lamivudine - adverse effects; Lipid metabolism; Lipodystrophy; Male; Metabolism; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oxazines - administration & dosage; Oxazines - adverse effects; Protease inhibitors; Pyridines - administration & dosage; Pyridines - adverse effects; Zidovudine - administration & dosage; Zidovudine - adverse effects
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/498505

Background. Protease inhibitor treatment of human immunodeficiency virus (HIV)—infected individuals has been linked to the development of lipodystrophy. The effects of atazanavir on body fat distribution and related metabolic parameters were examined in antiretroviral-naive patients. Methods. HIV-positive patients with CD4 cell counts ⩾100 cells/mm3 were randomized to 1 of 2 treatment arms: (1) atazanavir, 400 mg given once daily, plus efavirenz placebo; or (2) efavirenz, 600 mg given once daily, plus atazanavir placebo; each drug was administered with fixed-dose zidovudine (300 mg) and lamivudine (150 mg) given twice daily, and patients were treated for at least 48 weeks. Fat distribution measurements (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], and total adipose tissue [TAT], as measured by computed tomography; and appendicular fat, truncal fat, and total fat levels, as measured by dual-energy X-ray absorptiometry), metabolic measurements (cholesterol and fasting triglyceride levels), and measurements of insulin resistance (fasting glucose and fasting insulin levels) were made at baseline and at week 48 of treatment for a subgroup of 111 atazanavir recipients and 100 efavirenz recipients. Results. Atazanavir and efavirenz treatments resulted in minimal to modest increases in fat accumulation, as measured by VAT, SAT, TAT, appendicular fat, truncal fat, and total fat levels; results were comparable in both arms. In addition, atazanavir was associated with none of the metabolic abnormalities seen with many other protease inhibitors. Conclusions. Use of atazanavir for 48 weeks neither resulted in abnormal fat redistribution in antiretroviral-naive patients nor induced other metabolic disturbances commonly associated with HIV-related lipodystrophy. Longer-term assessments (e.g., at 96 weeks) will be important to confirm these findings.