Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients

Abstract

Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution or lipodystrophy, hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and diabetes mellitus have been extensively reported in subjects treated with protease inhibitor (PI)-based antiretroviral regimens. In particular, dyslipidaemia occurs in up to 70-80% of HIV-infected individuals receiving HAART and can be associated with all the available PIs, although hypertriglyceridaemia appears to be more frequent in patients treated with ritonavir, ritonavir-saquinavir, or ritonavir-lopinavir. The potential long-term consequences of HAART-associated hyperlipidaemia are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving PIs. Dietary changes, regular aerobic exercise and switching to a PI-sparing regimen may act favourably on dyslipidaemia. Lipid-lowering therapy is often required with statins or fibrates. The choice of hypolipidaemic drugs should take into account potential pharmacological interactions with antiretroviral agents.

Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients

“…Calza et al found that in patients who receive a PIcontaining antiretroviral regimen, the prevalence of hyperlipidaemia ranges from 28% to 80%, and it includes hypertriglyceridaemia in the majority of cases (40%-80%), followed by hypercholesterolaemia (10%-50%) [8].…”

“…The potential long-term consequences of HAART-associated hyperlipidaemia are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIVpositive persons receiving PI. Lipid lowering therapy is often required with statins or fibrates [8].…”

Nuclear Receptors in Vascular Biology

“…Proteases inhibitor use such as ritonavir commonly used to treat HIV is commonly associated with a profound dyslipidaemia [24]. Experimentally ritonavir increased coronary artery wall thickness and foam cell formation, which was associated with a down-regulation of ERα and Erβ, and reversed by addition of estradiol [25].…”

Effects of NO-Hybridization on the Immunomodulatory Properties of the HIV Protease Inhibitors Lopinavir and Ritonavir

“…Lopinavir-NO deserves additional studies for its possible use in T-cell-mediated autoimmune diseases including, but not limited to autoimmune hepatitis. Antiretroviral protease inhibitors (PIs) in combination with nucleoside or non-nucleoside reverse transcriptase inhibitors are the basis for the highly active antiretroviral therapy (HA-ART) that is efficient in suppression of HIV replication and reduction of clinical manifestations of the disease [1].In addition to their primary pharmacological indication, these drugs have also been described to possess antineoplastic and immunomodulatory properties both in in vitro and in vivo pre-clinical settings [2][3][4].However, serious side effects including dyslipidaemia, insulin resistance, lipodystrophy, hepatotoxicity and atherosclerotic cardiovascular complications [5][6][7][8][9] have dampened the possible extension of these drugs to therapeutic areas different than HIV infection.It has been previously demonstrated that nitric oxide (NO)-hybridization may reduce toxicity of parental compounds while enhancing the pharmacological potency of the drugs [10]. Along this line of research, several derivatives of PIs have been synthesized at OncoNOx (Copenhagen, Denmark) by covalent attachment of NO moiety to the parental molecules.…”

“…However, serious side effects including dyslipidaemia, insulin resistance, lipodystrophy, hepatotoxicity and atherosclerotic cardiovascular complications [5][6][7][8][9] have dampened the possible extension of these drugs to therapeutic areas different than HIV infection.…”