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

• Published in: International journal of immunopathology and pharmacology Vol. 25; no. 1; pp. 247 - 258
• Main Authors: Chini, M., Tsoupras, A.B., Mangafas, N., Tsogas, N., Papakonstantinou, V.D., Fragopoulou, E., Antonopoulou, S., Gargalianos, P., Demopoulos, C.A., Lazanas, M.C.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2012
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Antiretroviral Therapy, Highly Active; Benzoxazines - administration & dosage; CD4 Lymphocyte Count; Dideoxynucleosides - administration & dosage; Drug Combinations; Drug Therapy, Combination; HIV Infections - drug therapy; HIV Infections - metabolism; Human immunodeficiency virus; Humans; Lamivudine - administration & dosage; Male; Middle Aged; Platelet Activating Factor - metabolism; Viral Load; Highly Active Anti-Retroviral Therapy (HAART); abacavir; Inflammation; Human Immunodeficiency Virus (HIV); Cardiovascular Disease (CVD); Platelet Activating Factor (PAF)
• ISSN: 0394-6320; 2058-7384
• DOI: 10.1177/039463201202500127

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.