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S. Nathoo*, L. Serghides, S. L. Walmsley, and K. C. Kain .
Univ.of Toronto, Toronto, Ontario, Canada.
Background:The HIV lipodystrophy syndrome (LS) is a recognized complication of antiretroviral (ARV) therapy. Treatment options for LS are limited, and predictors to identify those at risk of LS are not available. Several lines of evidence suggest an important role for CD36 in lipid metabolism. We hypothesized that ARV therapy, and in particular protease inhibitors (PI), might inhibit the expression of CD36 and that this defect might contribute to the metabolic complications observed in LS.
Methods:Five healthy controls, participating in a pharmacokinetic study of ritonavir, and 15 HIV positive, treatment-naïve patients have been enrolled in this on-going prospective study. HIV-infected subjects were initiated on combination ARV therapy and were randomized to receive either nelfinavir or ABT-378 /ritonavir as the PI component. CD36 surface levels from peripheral blood monocytes were measured using flow cytometry at baseline (pre-treatment), after 7 days (controls) and after 1 month of ARV therapy (HIV-positive subjects). In addition, the in vitro effects of ritonavir on CD36 surface levels of human monocyte-derived cell lines were assessed using flow cytometry.
Results:One healthy control withdrew due to adverse drug effects. Three of the 4 remaining healthy controls demonstrated a marked decrease in CD36 surface levels after 7 days (steady state) of PI therapy. Ten of 15 HIV subjects showed a striking decrease in CD36 surface levels (50—75% decrease) after 1 month of ARV therapy. Two of the remaining 15 subjects exhibited a moderate decrease (30%) while three subjects displayed an increase
in CD36 surface levels. Controls not on ARV therapy had no change in their CD36 levels over the same period. These results were also observed in vitro. Exposure of monocyte cell lines to 10mM ritonavir for 3 days resulted in a marked reduction in CD36 surface levels (30%) (P < 0.05, N = 4, Student t-test).
Conclusions:Our data indicate that ARV including PI therapy markedly decreases CD36 surface levels in a proportion of users (~70%). The in vitro results also support our hypothesis that the PI ritonavir decreases CD36 surface expression in vivo. These results are the first to show prospective changes in CD36 surface levels due to ARV therapy. Long-term studies of the relationship between CD36, PIs and the development of LS are ongoing.
© 8th Conference on Retroviruses and Opportunistic Infections