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      In vivo effect of two first-line ART regimens on inflammatory mediators in male HIV patients

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          Abstract

          Background

          Persistent immune activation and inflammation are lying behind HIV-infection even in the setting of ART mediated viral suppression. The purpose of this study is to define the in vivo effect of two first-line ART regimens on certain inflammatory mediators in male HIV patients.

          Methods

          Male, naive, HIV-infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month period. Differences within each group were determined by non-parametric Friedman and Wilcoxon test, while the differences between the groups were checked by ANOVA repeated measures.

          Results

          Both ART regimens present pronounced effect on inflammatory mediators, resulting in decreased PAF levels and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen and same as baseline PAF levels with a peak though at the 3 rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen.

          Conclusions

          Studies regarding the effect of first-line ART regimens on inflammation may be beneficial in preventing chronic morbidities during HIV-treatment. From this point of view, the present study suggests an anti-inflammatory effect of tenofovir-containing ART, while the temporary increase of PAF levels in abacavir-containing ART may be the link between the reported cardiovascular risk and abacavir administration.

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          Most cited references43

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          HIV and inflammation: mechanisms and consequences.

          Persistent immune activation and inflammation despite sustained antiretroviral therapy (ART)-mediated viral suppression has emerged as a major challenge of the modern HIV treatment era. While immune activation, inflammatory, and coagulation markers typically decline during suppressive ART, they remain abnormally elevated in many HIV-infected individuals and predict subsequent mortality and non-AIDS morbidities including cardiovascular disease. The goal of this review is to summarize the current state of our knowledge regarding the underlying causes of persistent immune activation during ART-mediated viral suppression as well as the link between persistent immune activation and morbidity and mortality in this setting. Several recent studies have linked surrogate markers of this persistent inflammatory state to clinical outcomes, validating persistent immune activation as a viable therapeutic target. Other recent studies have helped clarify the roles of persistent HIV expression and/or replication, microbial translocation, and co-infections in driving this persistent inflammatory state, identifying targets for novel interventions.
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            The role of HIV in serious diseases other than AIDS.

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              The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis.

              To review the platelet-activating factor (PAF) signaling system, its regulation, and its dysregulation in acute inflammation and thrombosis and in syndromes that involve these cascades, including sepsis. A summary of published literature from MEDLINE search files and published reviews. DATA EXTRACTION, SYNTHESIS, AND SUMMARY: PAF, a phospholipid signaling molecule, transmits outside-in signals to intracellular transduction systems and effector mechanisms in a variety of cell types, including key cells of the innate immune and hemostatic systems: neutrophils, monocytes, and platelets. Thus, the PAF signaling system is a point of convergence at which injurious stimuli can trigger and amplify both acute inflammatory and thrombotic cascades. The biological activities of PAF are regulated by several precise mechanisms that, together, constrain and control its action in physiologic inflammation. Unregulated synthesis of PAF or defects in the mechanisms that limit its biological activities have the potential to cause pathologic inflammation and thrombosis. In addition, nonenzymatic generation of oxidized phospholipids that are recognized by the PAF receptor can trigger inflammatory and thrombotic events. There is evidence that the PAF signaling system is dysregulated in sepsis, shock, and traumatic injury and that interruption or termination of its effector responses leads to beneficial outcomes. Plasma PAF acetylhydrolase, an enzyme that hydrolyzes PAF and structurally related oxidized phospholipids, yielding products that are no longer recognized by the PAF receptor, may be a particularly important signal terminator. The PAF signaling system can trigger inflammatory and thrombotic cascades, amplify these cascades when acting with other mediators, and mediate molecular and cellular interactions (cross talk) between inflammation and thrombosis. Evidence from in vitro experiments, studies of experimental animals, and clinical observations in humans indicates that the PAF signaling system is important in sepsis and other syndromes of inflammatory injury and that therapeutic strategies to interrupt or terminate signaling via the PAF signaling system may be useful in these conditions.
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                Author and article information

                Contributors
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2014
                29 May 2014
                : 13
                : 90
                Affiliations
                [1 ]Faculty of Chemistry, National & Kapodistrian University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece
                [2 ]3rd Internal Medicine Department-Infectious Diseases Unit, Red Cross General Hospital, Athens, Greece
                [3 ]Department of Immunology and Histocompatibility, Evangelismos Hospital, Athens, Greece
                [4 ]Department of Science Nutrition-Dietetics, Harokopio University, Athens, Greece
                [5 ]1st Internal Medicine Department-Infectious Diseases Unit, “G. Gennimatas” Hospital, Athens, Greece
                Article
                1476-511X-13-90
                10.1186/1476-511X-13-90
                4055908
                24884881
                0da53c73-6a0e-4be1-b6d3-f0d2deaff3af
                Copyright © 2014 Papakonstantinou et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 April 2014
                : 24 May 2014
                Categories
                Research

                Biochemistry
                platelet activating factor,cytokines,inflammation,human immunodeficiency virus,cardiovascular disease,tenofovir-df,abacavir,efavirenz

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