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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.
AuthorsMaria Chini, Alexandros B Tsoupras, Nikos Mangafas, Nikos Tsogas, Vasiliki D Papakonstantinou, Elizabeth Fragopoulou, Smaragdi Antonopoulou, Panagiotis Gargalianos, Constantinos A Demopoulos, Marios C Lazanas
JournalAIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 28 Issue 8 Pg. 766-75 (Aug 2012) ISSN: 1931-8405 [Electronic] United States
PMID22050695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drug Combinations
  • Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
  • Organophosphonates
  • Oxazines
  • Platelet Activating Factor
  • Deoxycytidine
  • Adenine
Topics
  • Adenine (analogs & derivatives, pharmacology)
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Deoxycytidine (analogs & derivatives, pharmacology)
  • Drug Combinations
  • Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
  • HIV Infections (drug therapy, metabolism, virology)
  • Humans
  • Male
  • Organophosphonates (pharmacology)
  • Oxazines (pharmacology)
  • Platelet Activating Factor (metabolism)
  • Viral Load

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