Following the successful introduction of combined Antiretroviral Therapy (cART), a dramatic decrease in viral burden and opportunistic infections along with a consistent increase in life expectancy has been observed in Human Immunodeficiency Virus (HIV) infected patients [1]. This deep change in the HIV disease evolution has determined that HIV positive subjects were effectively monitored for several alterations of many tissue and organs due to HIV chronic disease and antiretroviral treatment for example, cardiovascular system, bone, adipose tissues, kidney and central nervous system represent the major target of these structural and functional damages during HIV infection. In particular, Cardiovascular Diseases (CVD) were considered important clinical complications in the HIV patient and represent a leading cause of death among HIV-positive patients, accounting for approximately 11% of the total deaths in this population [2]; the risk of CVD is higher in HIV positive individuals compared with HIV negative people, and particularly the reported Myocardial Infarction (MI) incidence in cohort study ranges from 3 to 11 cases per 1000 patients a year in HIV- positive individuals against 2 to 7 cases per 1000 patients-years in HIV-negative population [3,4]. Although initial studies indicated a higher prevalence of traditional CVD risk factors in HIV infected population [5,6] as a possible cause, the molecular mechanisms of increased CVD risk in HIV still remain incompletely defined and should be probably attributable to a combination of multiple factors, including both direct and indirect effects of HIV infection on metabolism. Evidence from experimental and observational studies [7,8] in recent years suggested a more important role of HIV itself in contributing to CVD. Endothelial dysfunction due to gp120, Tat and Nef proteins have been identified as a critical link between infection, inflammation, immune activation, atherosclerosis and cardiovascular system. Moreover, ART may play a role in the exacerbation of risk factors for CVD [9]; since the presentation of findings from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study in 2008 demonstrating a 90% increased risk of MI in HIV- positive individuals receiving ART regimens including Abacavir (ABC), subsequent studies, conducted by FDA [10], GlaxoSmithKline [11] and independent researchers [12], to investigate this risk have yielded conflicting results. Although more recent studies have shown an effective increased risk of CVD associated with use of ABC, many results did not reach statistical significance [13-17]. The absence of a demonstrated underlying biological mechanism for such a risk added interest and confusion about the question, as well as the higher prevalence of risk factors for CVD, such as renal impairment and substance abuse among abacavir recipients; in addition, a recent meta analysis suggests that Relative Risk (RR) for MI is increased within a 6 months exposure to ABC (RR=1.61; 95% confidence interval: 1.48–1.75) and in cART-naive population [18]. While the published evidence remains conflicting and a plausible biological mechanism for this potential association has not yet been identified, in the following study we have tried to verify whether, after introduction of ABC and its discontinuation in the contest of HAART deintensification, common metabolic markers CVD related such as glucose, LDL, HDL, total cholesterol and triglycerides and inflammatory biomarkers such as IL-6 and D-dimer could change in a small cohort of HIV-1 infected patients.
Elevated levels of inflammatory plasma biomarkers are associated with risk of HIV infection
