title: Effects of HAART on platelet-activating factor metabolism in naive HIV-infected patients I: study of the tenofovir-DF/emtricitabine/efavirenz HAART regimen.
abstract: Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive 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 measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated.
authors: 3rd Internal Medicine Department-Infectious Diseases Unit, Red Cross General Hospital, Athens, Greece.
authors: Maria
authors: M
authors: Chini
authors: Alexandros B
authors: AB
authors: Tsoupras
authors: Nikos
authors: N
authors: Mangafas
authors: Nikos
authors: N
authors: Tsogas
authors: Vasiliki D
authors: VD
authors: Papakonstantinou
authors: Elizabeth
authors: E
authors: Fragopoulou
authors: Smaragdi
authors: S
authors: Antonopoulou
authors: Panagiotis
authors: P
authors: Gargalianos
authors: Constantinos A
authors: CA
authors: Demopoulos
authors: Marios C
authors: MC
authors: Lazanas
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004338:Drug Combinations; D000068257:Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D019562:Viral Load
chemical_list: D004338:Drug Combinations; D000068257:Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D063065:Organophosphonates; D010078:Oxazines; D010972:Platelet Activating Factor; D003841:Deoxycytidine; D000225:Adenine