PubMed Health⌕ Search

Biomedical subjects

Giuseppe Barbaro

Publications and source records attributed to Giuseppe Barbaro.

At least 19 recordsLinked to original sources
PubMed2005

HIV-associated cardiomyopathy etiopathogenesis and clinical aspects.

Human immunodeficiency virus (HIV) disease is recognized as an important cause of dilated cardiomyopathy. Myocarditis and myocardial infection with HIV-1 are the best-studied causes of cardiomyopathy in HIV disease. HIV-1 virions appear to infect myocardial cells in a patchy distribution with no direct association between the presence of the virus and myocyte dysfunction. Myocardial dendritic cells seem to play a significant pathogenetic role by activating multifunctional cytokines (i. e., tumor necrosis factor-alpha) and the inducible form of nitric oxide synthase that contribute to progressive and late myocardial tissue damage. Coinfection with other viruses (usually, coxsackievirus B3 and cytomegalovirus) may also play an important etiopathogenetic role.The introduction of highly active antiretroviral therapy (HAART) has significantly reduced the incidence of myocarditis in HIV-infected patients living in developed countries. By contrast, in developing countries, where the availability of HAART is scanty and greater is the pathogenetic role of nutritional factors, the incidence of HIV-associated myocarditis and cardiomyopathy is increasing with a high mortality rate for congestive heart failure.A clinical diagnosis of myocarditis or congestive heart failure may be difficult in an HIV-infected patient due to masking of symptoms by concomitant bronchopulmonary disease and/or wasting syndromes, especially in a more advanced stage of HIV disease. Immunomodulatory therapy (intravenous immunoglobulins) may be helpful in adults and children with HIV-associated myocarditis and declining left ventricular function. Data on the role of HAART in the treatment of HIVassociated myocarditis and cardiomyopathy are lacking.

Cardiomyopathies↗
PubMed2005

Highly active antiretroviral therapy: current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome.

Highly active antiretroviral therapy (HAART) dramatically changed the course of HIV infection. Currently, this therapy involves the use of agents from at least two distinct classes of antivirals: a protease inhibitor (PI) in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) in combination with NRTIs. Recently, the third family of antivirals started to be used clinically, with the advent of enfuvirtide, the first fusion inhibitor (FI). Several pharmacological agents are available form these classes of antivirals, NRTIs, NNRTIs, PIs and FIs, which will be briefly reviewed here. Some more agents are in advanced clinical evaluation or have recently been approved (such as tenofovir, a NtRTI; atazanavir, a PI; tipranavir, another PI), mainly against drug-resistant viruses. Compounds inhibiting HIV integrase, the third enzyme of HIV, are also available ultimately, with several such derivatives in clinical trials (L-731, 988 and S-1360). Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes. All steps in the process of HIV entry into the cell may be targeted by specific compounds that might be developed as novel types of antiretrovirals. Thus, inhibitors of the gp120-CD4 interaction have been detected (zintevir, FP-21399 and BMS-378806 in clinical trials). Small molecule chemokine antagonists acting as HIV entry inhibitors also were described in the last period, which interact both with the CXCR4 coreceptor (such as AMD3100; AMD3465; ALX40-4C; T22, T134 and T140), or which are antagonist of the CCR5 coreceptor (TAK-779, TAK-220, SCH-C, SCH-D, E913, AK-602 and NSC 651016 in clinical trials), together with new types of fusion inhibitors possessing the same mechanism of action as enfuvirtide (such as T1249). Compounds interacting with Tat/Tar have also been detected which inhibit HIV replication in low micromolar range (EM2487, tamacrazine, CGP 64222 or CGA 137053 among others). Unexploited viral and cellular targets (such as the maturation process-with a first potent compound available, PA-457; the cellular proteins Tsg101, APOBEC3G, or the viral ones Vif, Rev or RNase H) are also presented, together with recently emerged approaches for eradication of HIV reservoirs. A review on the pharmacology and interactions of these agents with other drugs is presented here, with emphasis on how these pharmacological interferences may improve the clinical use of antivirals, or how side effects due to these drugs may be managed better by taking them into account.

Acquired Immunodeficiency Syndrome↗
PubMed2004

HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis.

HIV-1 infection is associated with serious cardiovascular complications, but the roles of HIV-1, viral proteins, and highly active antiretroviral therapy (HAART) drugs are not understood. HAART decreases the overall risk of heart disease but leads to metabolic disturbances and possibly coronary artery disease. We investigated toxicities of HIV-1, HIV-1 glycoprotein 120 (gp120), and HAART drugs for human coronary artery endothelial cells (CAECs), brain microvascular endothelial cells, and neonatal rat ventricular myocytes (NRVMs). HIV-1 and gp120, but not azidothymidine (AZT), induced apoptosis of NRVMs and CAECs. Ethylisothiourea, an inhibitor of nitric oxide synthase, inhibited apoptosis induction by gp120. AZT, HIV-1, and gp120 all damaged mitochondria of cardiomyocytes. HAART drugs, AZT, and indinavir, but not HIV-1, produced intercellular gaps between confluent endothelial cells and decreased transendothelial electrical resistance. In conclusion, HIV-1 and gp120 induce toxicity through induction of cardiomyocyte and endothelial cell apoptosis. HAART drugs disrupt endothelial cell junctions and mitochondria and could cause vascular damage.

Animals↗
PubMed2003

HIV infection, highly active antiretroviral therapy and the cardiovascular system.

Cardiovascular complications in the course of human immunodeficiency virus (HIV) infection are multifactorial and may be caused by the virus itself or by the related opportunistic infections and neoplasms. Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in peripheral artery and coronary artery diseases. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients candidate to antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk with the available guidelines.

Anti-HIV Agents↗
PubMed2003

An open-label, prospective, observational study of the incidence of coronary artery disease in patients with HIV infection receiving highly active antiretroviral therapy.

BACKGROUND: The association of highly active antiretroviral therapy (HAART) regimens that include protease inhibitors (PIs) with metabolic and somatic disorders has raised concerns about the possibility of an increased risk of coronary artery disease (CAD) in patients with HIV infection. OBJECTIVE: The aim of this study was to assess the incidence of CAD in previously untreated HIV infected outpatients who received reverse transcriptase inhibitors with or without PIs. METHODS: In this open-label, multicenter, prospective, observational trial, previously untreated and asymptomatic HIV-infected Italian patients were followed to assess the incidence of CAD (primary end point) according to the HAART regimen they received: 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) in combination with PIs (group PI+) or 1 non-nucleoside reverse transcriptase inhibitor in combination with 2 NRTIs (group PI-). Patients underwent clinical examination and laboratory testing every 4 months. RESULTS: A total of 1551 HIV-infected patients (994 [64%] men; median age, 35 years; range, 22-50 years) were followed for a median 36 months (range, 34-42 months). The cumulative annual incidence of CAD-related events was 9.8/1000 in group PI+ and 0.8/1000 in group PI- (P < 0.001). The annual incidence of myocardial infarction was 5.1/1000 in group PI+ and 0.4/1000 in group PI- (P < 0.001). Independent of patient age, the incidence of CAD was greater among men (P < 0.001) and patients who smoked >20 cigarettes per day (P < 0.001). Lipodystrophy and metabolic alterations were observed in 62% of patients in group PI+ and in 4% of patients in group PI- (P < 0.001). Of 23 patients receiving PIs who developed CAD, 17 (73.9%) had lipodystrophy and all 23 had hypertriglyceridemia and hypercholesterolemia. CONCLUSIONS: According to our findings, HAART that includes PIs may accelerate the onset of CAD-related events in young, male, heavy smokers who develop metabolic disorders and lipodystrophy during therapy. Patients with increased coronary risk should receive careful cardiac monitoring if treated with PIs.

Adult↗
PubMed2003

Pathogenesis of HIV-associated heart disease.

As longevity increases in HIV-infected individuals after the introduction of highly active antiretroviral therapy regimens, long-term effects such as cardiovascular disease and, more specifically, symptomatic heart failure are emerging as leading health issues. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on etiopathogenetic mechanisms that may play a role in diagnosis, management, and therapy of HIV-associated heart failure in the highly active antiretroviral therapy era.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Kawasaki-like syndromes and other vasculitic syndromes in HIV-infected patients.

Excluding drug-related hypersensitivity reactions, vasculitic syndromes are not common in HIV-positive patients. Review of the existing literature suggests that HIV positive patients may be predisposed to polyarteritis nodosa, microscopic polyarteritis, Kawasaki-like syndromes, acute occlusion syndromes, primary angiitis of the central nervous system and erythema elevatum diutinum. With the exception of erythema elevatum diutinum, these vasculitic syndromes have significant morbidities and mortality if they are not treated. It is therefore important to make these diagnoses and to initiate appropriate therapy in a timely fashion. Because fevers, malaise, weakness, rashes, headaches and neurologic symptoms are common in HIV-positive patients, it is probable that some cases of vasculitis go undiagnosed. In this report, we review vasculitic syndromes seen in HIV-positive patients. We also re-examine a previously published case of a young HIV-positive male who died of an acute myocardial infarction without atherosclerotic disease. Immunohistopathology of the affected arteries suggests that he died of a Kawasaki-like syndrome.

AIDS-Related Opportunistic Infections↗
PubMed2003

Highly active antiretroviral therapy and the cardiovascular system: the heart of the matter.

Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in coronary artery disease and stroke. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients are candidates for antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk according to the available guidelines.

Antiretroviral Therapy, Highly Active↗