Τίτλος:
Effects of highly active antiretroviral therapy on platelet activating factor metabolism in naïve HIV-infected patients: II study of the abacavir/lamivudine/efavirenz haart regimen
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Human Immunodeficiency Virus (HIV)-infected patients are at increased risk for cardiovascular diseases partly due to chronic inflammation. Some antiretroviral drugs and Highly Active Anti-Retroviral Therapy (HAART) regimens seem to be related and amplify this increased risk, especially the ones containing abacavir. Platelet-Activating-Factor (PAF) is a potent inflammatory mediator that is implicated in both cardiovascular diseases and HIV-related manifestations. Our objective is to study the in vivo effect of the abacavir/Iamivudine/efavirenz first-line HAART regimen on PAF metabolism in HIV-infected patients. The specific activities of PAF basic biosynthetic enzymes in leukocytes and platelets, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAFAT), but also those of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets and Lipoprotein-associated-Phospholipase-A2 (LpPLA2) in plasma, were measured in blood samples of 10 asymptomatic naïve male HIV-infected patients just before and after 1,3 and 6 months of treatment. CD4 cell counts, viral load and several biochemical markers were also measured in the same blood samples of these patients. The repeated ANOVA measures and the Pearson r criterion were used for studying statistical differences and correlations - partial correlations respectively. Even though viral load was decreased and CD4 cell counts were beneficially increased after treatment with the abacavir/lamivudine/efavirenz regimen, the main enzyme of the remodelling PAF-synthesis that is implicated in pro-atherogenic inflammatory procedures, Lyso-PAF-AT activity, was increased at 3 months of treatment in both leukocytes and platelets, while the main enzyme of PAF-degradation, PAF-AH, was increased as a response only in leukocytes at the 3rd month. Although the abacavir/lamivudine/efavirenz HAART regimen exhibits very efficient antiretroviral activities, on the other hand it induces an in vivo transient increase in the inflammation-related remodeling PAF-biosynthetic pathway. This finding supports the hypothesis of inflammation-mediated increased cardiovascular risk in HIV-infected patients during the first months of abacavir-containing HAART. Copyright © by BIOLIFE, s.a.s.
Συγγραφείς:
Chini, M.
Tsoupras, A.B.
Mangafas, N.
Tsogas, N.
Papakonstantinou, V.D.
Fragopoulou, E.
Antonopoulou, S.
Gargalianos, P.
Demopoulos, C.A.
Lazanas, M.C.
Περιοδικό:
International Journal of Immunopathology and Pharmacology
Λέξεις-κλειδιά:
abacavir; acyltransferase; cholinephosphotransferase; efavirenz; lamivudine; thrombocyte activating factor; 1 alkyl 2 acetylglycerophosphocholine esterase; abacavir plus lamivudine; phospholipase A2, adult; analysis of variance; article; biosynthesis; blood sampling; cardiovascular risk; catabolism; CD4 lymphocyte count; cell activation; correlation coefficient; drug effect; highly active antiretroviral therapy; human; Human immunodeficiency virus infected patient; Human immunodeficiency virus infection; in vivo study; inflammation; leukocyte; male; priority journal; protein degradation; virus load; Article; clinical article; controlled study; enzyme activity; enzyme synthesis; human cell; metabolism; protein induction
DOI:
10.1177/039463201202500127
