The progress of ART over the years has turned HIV-infection from lethal into a chronic disease. However, immune activation and inflammation are lying behind effectively treated patients causing various non-AIDS morbidities as cardiovascular or renal diseases and cancers . Consequently chronic HIV-associated inflammation is now considered a significant factor for the above-mentioned conditions while elevated inflammatory and coagulation markers can predict higher morbidity and even mortality in HIV infected population [2–4].
During HIV-infection specific cells of the immune system become targets of the virus and secrete in response several inflammatory factors as cytokines and chemokines . The effect of antiretrovirals on cytokines’ levels seems contradictory. Abacavir is thought to be associated with increased cardiovascular risk as it up-regulates pro-inflammatory cytokines and CRP [6, 7]. Nevertheless, its use was not always associated with increased levels of inflammatory markers , showing a similar effect with tenofovir-DF . In addition both antiretrovirals had no effect on coronary endothelial cell gene transcription and protein expression of cytokines, supporting that the increased cardiovascular risk is probably not through the direct endothelial activation pathways . The inconsistent effect of ART on cytokines’ levels maybe indicates another inflammatory mediator to be responsible for the increased cardiovascular risk associated with abacavir use.
Platelet Activating Factor (PAF) is one of the most potent inflammatory factors and a significant signaling molecule of the immune system, considered as a primitive and universal cellular mediator [11, 12] that participates in both physiological and pathological processes [13, 14]. Concerning PAF biosynthesis, there are two distinctive pathways named de novo, responsible for the constant PAF biosynthesis, and remodeling, activated as a direct response to acute inflammatory processes , with key-enzymes being dithiothreitol-insensitive PAF-cholinephosphotransferase (PAF-CPT, EC 188.8.131.52) and lyso-PAF:acetyl-CoA acetyltransferase (lyso-PAF-AT, EC 184.108.40.206) [16, 17], respectively. PAF catabolism is moderated by PAF-specific acetylhydrolase (PAF-AH, EC 220.127.116.11), and its plasma isoform, Lipoprotein-associated phospholipase A2 (Lp-PLA2) .
PAF is thought to be implicated in the progression of HIV-infection as studies have revealed that HIV-infected monocytes overexpress PAF through Tat protein [19, 20]. It was found that altered host cells and their sub-products as Tat protein induce PAF biosynthesis via cytokines, as Tumor Necrosis Factor-alpha (TNFα), and growth factors, as Vascular Endothelial Growth Factor (VEGF) [21, 22]. The produced PAF, as a secondary mediator, participates in several processes like monocyte cell recruitment and increased vascular permeability, which can lead to various morbidities [2, 23, 24]. A great variety of antiretrovirals, backbone and HAART regimens exhibit in vitro inhibitory effect against PAF activity  while many studies have underlined the need for combined antiretroviral and anti-PAF action in drugs like piperazine and its developed derivatives [26–28]. Patients with early or asymptomatic HIV-infection before ART initiation have shown increased activity of PAF biosynthetic enzymes and Lp-PLA2 indicating a persistent inflammatory condition . It has also been proposed that Lp-PLA2 could play the role of a sensitive marker as its increased levels in HIV and AIDS patients may be a physiological response protecting the host against PAF or other oxidized phospholipids . The implication of PAF in HIV-infection is further supported by the beneficial effect of PAF antagonists administration in animal models for HIV-1 encephalitis [31, 32] as well by the improvement of neuropsychological test scores in HIV-patients under lexipafant, the first PAF antagonist used in HIV-associated cognitive impairment .
The scope of this paper is to determine for the first time the in vivo effect of two first line ART regimens on PAF levels in HIV naive patients along with several already established inflammatory biomarkers implicated in HIV-infection. 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].