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

Chini, Maria; Τσούπρας, Αλέξανδρος; Mangafas, Nikos; Tsogas, Nickolaos; Papakonstantinou, Vasiliki D.; Fragopoulou, Elizabeth; Antonopoulou, Smaragdi; Gargalianos, P.; Demopoulos, Constantinos A.; Lazanas, Marios

doi:10.1177/039463201202500127

Cited by 12 publications

(14 citation statements)

References 30 publications

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“…Our team has already shown that tenofovir-DF/emtricitabine/efavirenz has great in vitro inhibitory effect against PAF [25] and decreases PAF biosynthesis during a 6-month treatment period [34] while abacavir/lamivudine/efavirenz has limited in vitro inhibitory effect [25] against PAF and increases at the 3 rd month lyso-PAF-AT, which is implicated in acute inflammatory processes [35]. The present study expands the previous data by providing the effect of these ART regimens on PAF levels during a 12-month period and the follow-up of PAF metabolic enzymes’ activity at the 9 th and 12 th month along with the levels of selected HIV-implicated cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNFα and VEGF).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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BackgroundPersistent 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.MethodsMale, 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.ResultsBoth 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 3rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen.ConclusionsStudies 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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Section: Discussionmentioning

confidence: 99%

“…The hypothesis states that tenofovir-DF/emtricitabine/efavirenz would down regulate PAF levels in contrast to abacavir/lamivudine/efavirenz based on preliminary data concerning the effect of the above regimens on PAF enzymes [34,35]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…In ART-naive patients, significant immune activation and hypersensivity reactions resulted in induced T cell reactivity associated with initiation of abacavir [46], which may be related to increased CVD risk during the first few months of ABC usage [47]. …”

Section: Antiretroviral Therapymentioning

confidence: 99%

“…Also, given the controversies around abacavir, this drug should be used cautiously in those with higher CVD risk. In particular, given that the significant initial immune activation associated with abacavir increases the risk [46, 47], it is recommended to avoid abacavir in treatment naive patients with significant CVD risk factors.…”

Section: Clinical Considerations In Managing Cardiovascular Disease Rmentioning

confidence: 99%

Coronary Artery Disease in HIV-Infected Patients: Downside of Living Longer

Lacson

Barnes

Bahrami

2017

Curr Atheroscler Rep

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Purpose of Review Introduction of combination antiretroviral therapy (ART) has increased the life expectancy of patients with HIV infection, allowing them to live longer with this chronic medical condition and consequently experiencing conditions such as cardiovascular diseases (CVDs). Several studies have investigated the increased risk of CVD in people living with HIV (PLWH). However, less is known about the exact mechanisms involved in this increased risk. Also, specific guidelines for management of CVD in PLWH have not been developed yet. In this article, we review the recent literature on the mechanisms involved in pathogenesis of CVD in PLWH, with an emphasis on coronary artery disease (CAD). Recent Findings Although initial studies suspected the increased prevalence of traditional CVD risk factors and side effects of ART to be involved in the increased CVD risk in PLWH, recent studies have uncovered the important role of chronic persistent inflammation in this increased risk. In addition, biomarkers of inflammation have been associated with both CVD events and subclinical CAD in this population. Lastly, recent studies and ongoing clinical trials have been investigating medical interventions that aim to reduce inflammation and cardiovascular events. Summary Different mechanisms of inflammation have been examined in PLWH, including subclinical viremia, microbial translocation, and coinfection with other pathogens such as cytomegalovirus. Although inflammatory biomarkers have been consistently associated with CVD and subclinical CVD outcomes, their prognostic value is unknown. Recent and ongoing trials are exploring the benefits of anti-inflammatory drugs, statins, and antimicrobial translocation drugs on both inflammation and CVD risk among PLWH.

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“…Interestingly, it has also been demonstrated that HAART drugs themselves have the ability to induce inflammation [14]–[16], while some commonly used antiretrovirals have been shown to possess the ability to activate platelets [17]–[19], which could therefore contribute to the progression of HAND. Taken all together, we sought to determine if common antiretrovirals could induce the release of sCD40L, and therefore potentially augment the pathogenesis of HAND.…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Inhibits the Release of Soluble CD40L Induced by Non-Nucleoside Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus Infected Individuals

2013

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Despite the use of highly active antiretroviral therapies (HAART), a majority of Human Immunodeficiency Virus Type 1 (HIV) infected individuals continually develop HIV – Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistent with this notion, we have previously shown that levels of the inflammatory mediator soluble CD40 ligand (sCD40L) are elevated in the plasma and cerebrospinal fluid (CSF) of HIV infected, cognitively impaired individuals, and that excess sCD40L can contribute to blood brain barrier (BBB) permeability in vivo, thereby signifying the importance of this inflammatory mediator in the pathogenesis of HAND. Here we demonstrate that the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) induces the release of circulating sCD40L in both HIV infected individuals and in an in vitro suspension of washed human platelets, which are the main source of circulating sCD40L. Additionally, EFV was found to activate glycogen synthase kinase 3 beta (GSK3β) in platelets, and we now show that valproic acid (VPA), a known GSK3β inhibitor, was able to attenuate the release of sCD40L in HIV infected individuals receiving EFV, and in isolated human platelets. Collectively these results have important implications in determining the pro-inflammatory role that some antiretroviral regimens may have. The use of antiretrovirals remains the best strategy to prevent HIV-associated illnesses, including HAND, however these drugs have clear limitations to this end, and thus, these results underscore the need to develop adjunctive therapies for HAND that can also minimize the undesired negative effects of the antiretrovirals.

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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

Cited by 12 publications

References 30 publications

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

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

Coronary Artery Disease in HIV-Infected Patients: Downside of Living Longer

Valproic Acid Inhibits the Release of Soluble CD40L Induced by Non-Nucleoside Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus Infected Individuals

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