title: Effects of highly active antiretroviral therapy on platelet activating factor metabolism in naive HIV-infected patients: ii) study of the abacavir/lamivudine/efavirenz HAART regimen.
abstract: 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/lamivudine/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-PAF-AT), 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.
authors.affiliation: 3rd Internal Medicine Department-Infectious Diseases Unit, Red Cross General Hospital, Athens,  Greece.
authors.forename: M
authors.initials: M
authors.lastname: Chini
authors.forename: A B
authors.initials: AB
authors.lastname: Tsoupras
authors.forename: N
authors.initials: N
authors.lastname: Mangafas
authors.forename: N
authors.initials: N
authors.lastname: Tsogas
authors.forename: V D
authors.initials: VD
authors.lastname: Papakonstantinou
authors.forename: E
authors.initials: E
authors.lastname: Fragopoulou
authors.forename: S
authors.initials: S
authors.lastname: Antonopoulou
authors.forename: P
authors.initials: P
authors.lastname: Gargalianos
authors.forename: C A
authors.initials: CA
authors.lastname: Demopoulos
authors.forename: M C
authors.initials: MC
authors.lastname: Lazanas
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000378:metabolism*; D019562:Viral Load; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; D010972:Platelet Activating Factor; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir; C098320:efavirenz