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CD36 deficiency induced by antiretroviral therapy

Serghides, Lena; Nathoo, Salima; Walmsley, Sharon; Kain, Kevin C.

Basic Science: Concise Communication

Background: The molecular basis of lipodystrophy, a syndrome associated with HIV antiretroviral (ARV) therapy, remains unknown.

Objectives: To examine whether ARV therapy might inhibit the expression of CD36, which is known to play an important role in fatty acid and glucose metabolism, and if this might contribute to the metabolic alterations associated with lipodystrophy.

Design: The effects of ARV therapy on CD36 levels was examined in vivo in a prospective cohort of individuals treated with ARV therapy and in vitro in assays of human cell lines exposed to ARV drugs.

Methods: Monocyte CD36 levels were assessed by flow cytometry at baseline and after 7 days of therapy in five healthy volunteers and 10 treatment-naive HIV-1-infected individuals. ARV therapy included protease inhibitors (ritonavir, nelfinavir or lopinavir/ritonavir). In addition, human cell lines (THP-1 and C32) were assessed for CD36 levels pre and post-ritonavir treatment.

Results: Three of four healthy controls (one withdrew because of adverse effects) and 6 of 10 HIV-1-infected individuals had a 50 to > 90% decrease in monocyte CD36 levels after 7 days of therapy. One of ten HIV-infected subjects had a 30% decrease, and the remaining individuals had no change or an increase in CD36 levels. CD36 levels decreased significantly in human cell lines treated with ritonavir but not in those treated with zidovudine.

Conclusions: ARV therapy resulted in a marked decrease in CD36 in approximately 70% of our participants. Sustained ARV therapy-induced CD36 deficiency may contribute to insulin resistance and other metabolic complications of lipodystrophy.

From the the Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada.

Requests for reprints to: Dr K. C. Kain, Toronto General Hospital, EN G-224, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4.

Sponsorship: This work was supported by the Ontario HIV Treatment Network (302479), the Medical Research Council of Canada/CIHR (MT-13721) and the Heart and Stroke Foundation of Canada (NA-3391). L. Serghides is the recipient of a Medical Research of Canada Studentship. K. C. Kain is supported by a Career Scientist Award from the Ontario Ministry of Health.

Note: L. Serghides and S. Nathoo have contributed equally to this work.

Received: 9 March 2001;

revised: 3 September 2001; accepted: 3 October 2001.

© 2002 Lippincott Williams & Wilkins, Inc.