CD36 deficiency induced by antiretroviral therapy.
BACKGROUND
The molecular basis of lipodystrophy, a syndrome associated with HIV antiretroviral (ARV) therapy, remains unknown.


OBJECTIVE
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.


METHODS
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.
Serghides
Lena
L
Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Nathoo
Salima
S
Walmsley
Sharon
S
Kain
Kevin C
KC
D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018955:CD36 Antigens / Q000097:blood* / Q000378:metabolism; D002460:Cell Line; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D066298:In Vitro Techniques; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000139:chemically induced; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011446:Prospective Studies; D019438:Ritonavir / Q000009:adverse effects; D015215:Zidovudine / Q000009:adverse effects
D019380:Anti-HIV Agents; D018955:CD36 Antigens; D015215:Zidovudine; D019438:Ritonavir