Heart failure in patients with human immunodeficiency virus: a review of the literature.

Coronary artery disease represents the leading cause of death for HIV patients treated with highly active antiretroviral treatment. Besides this, an extensive amount of data related to the risk of overt heart failure and consequently of atrial fibrillation and sudden cardiac death (SCD) in this population has been reported. It seems that persistent deregulation of immunity in HIV-infected patients is a common pathway related to both of these adverse clinical outcomes.

Intracellular accumulation of atazanavir/ritonavir according to plasma concentrations and OATP1B1, ABCB1 and PXR genetic polymorphisms.

Objectives: The rate of accumulation of atazanavir and ritonavir within cells is still debated due to methodological limitations. Our aim was to measure peripheral blood mononuclear cell (PBMC) concentrations of atazanavir and ritonavir and investigate whether single-nucleotide polymorphisms of OATP, ABCB1, CYP3A4 and PXR genes are involved in intracellular drug penetration.

Methods: HIV-positive patients administered 300 mg of atazanavir/100 mg of ritonavir were enrolled.

A meta-analysis investigating incidence and features of stroke in HIV-infected patients in the highly active antiretroviral therapy era.

Objective: Recent studies have suggested a close biological and clinical association between HIV infection and risk of myocardial infarction, whereas contrasting data have been reported about incidence of stroke and its clinical predictors.

Design And Setting: Studies including HIV-infected patients developing a cerebral ischemic event were systematically searched for in MEDLINE/PubMed.

Patients And Main Outcome Measures: Baseline, treatment and outcome data were appraised and pooled with random-effects methods computing summary estimates (95% confidence intervals).

Prevalence and predictors of blood-brain barrier damage in the HAART era.

Blood-brain barrier damage (BBBD) is prevalent in HIV-positive patients and may enhance cell trafficking to the central nervous system. A retrospective analysis in adult HIV-positive patients with no central nervous system disease was conducted in order to estimate the prevalence and risk factors of BBBD (according to cerebrospinal fluid to plasma albumin ratios). One hundred fifty-eight HIV-positive adult patients were included.

Etravirine plasma exposure is associated with virological efficacy in treatment-experienced HIV-positive patients.

Etravirine is a non-nucleoside reverse transcriptase inhibitor used in combination with other antiretrovirals for the treatment of HIV infection. Given previous conflicting results aim of this study was to investigate whether etravirine plasma exposure was associated with virological outcome. Adult HIV-positive patients starting etravirine with detectable HIV viral loads were included if highly adherent (<90% of the doses) and if steady-state plasma concentrations were available (measured through a validated HPLC-PDA method).

Intracellular antiviral activity of low-dose ritonavir in boosted protease inhibitor regimens.

Protease inhibitors are largely used for the treatment of HIV infection in combination with other antiretroviral drugs. Their improved pharmacokinetic profiles can be achieved through the concomitant administration of low doses of ritonavir (RTV), a protease inhibitor currently used as a booster, increasing the exposure of companion drugs. Since ritonavir-boosted regimens are associated with long-term adverse events, cobicistat, a CYP3A4 inhibitor without antiviral activity, has been developed.

Transcatheter aortic valve implantation in a 54-year-old patient with aggressive HIV.

We report a case of a 54-year-old patient who was denied surgical replacement for severe aortic stenosis because of complicated acquired immunodeficiency syndrome and who successfully underwent transcatheter aortic valve implantation at our institution.

Immune activation and microbial translocation in liver disease progression in HIV/hepatitis co-infected patients: results from the Icona Foundation study.

Background: We evaluated whether immune activation (IA) and microbial translocation (MT) might play a role in accelerating liver disease progression in HIV-HBV/HCV co-infected patients.

Methods: ART-naïve HIV/viral hepatitis co-infected patients from Icona with a CD4 cell count >200/μl and with a known date of prior HIV neg/pos tests and ≥1 plasma sample stored were included in the study. Plasma MT (LPS, sCD14) and IA (IL-6,TNFα) were measured using ELISA while activated CD8 + CD38 + HLA-DR +  were measured by flow cytometry, with one measurement being performed for all patients and two measurements for a smaller group of subjects.

Plasma and intracellular imatinib concentrations in patients with chronic myeloid leukemia.

Background: Imatinib (Gleevec, STI-571), a 2-phenylaminopyrimidine-type competitive inhibitor of Bcr-Abl kinase, is the current frontline therapy for patients with chronic myeloid leukemia, and it induces durable responses and prolonging event-free and progression-free survival. Monitoring imatinib trough plasma concentration is a simple and rapid way to determine if the drug exposure exceeds the clinical efficacy threshold (1 mcg/mL). Because the target enzyme is located within cells, adequate drug intracellular concentrations are needed to inhibit its function.

Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production.

Mammals possess two types of adipose tissue, white (WAT) and brown (BAT). The uncoupling protein 1 (UCP1) is a hallmark of BAT, being the pivotal player for cold-induced thermogenesis. WAT can acquire BAT characteristics with up-regulation of UCP1 after cold exposure or adrenergic stimulation.

Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases.

Context: Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50% of affected subjects.

Objective: The purpose of this study was to determine whether a systematic diagnostic workup could achieve better etiologic diagnosis in children and adolescents presenting with polyuria and polydipsia.

Design And Setting: This is a prospective study conducted at a tertiary referral center.

High interpatient variability of raltegravir CSF concentrations in HIV-positive patients: a pharmacogenetic analysis.

Objectives: To analyse the determinants of raltegravir CSF penetration, including the pharmacogenetics of drug transporters located at the blood-brain barrier or blood-CSF barrier.

Methods: Plasma and CSF raltegravir concentrations were determined by a validated HPLC coupled with mass spectrometry method in adults on raltegravir-based combination antiretroviral therapy undergoing a lumbar puncture. Single nucleotide polymorphisms in the genes encoding drugs transporters (ABCB1 3435, SLCO1A2, ABCC2 and SLC22A6) and the gene encoding hepatocyte nuclear factor 4 α (HNF4α) were determined by real-time PCR.

A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection.

Background: In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.

Objectives: To assess the contribution of HA-RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009-2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.

Pharmacokinetics of caspofungin increased dosage in a patient on rifampin-containing anti-tubercular treatment.

We describe a patient treated with caspofungin and rifampin; after increasing the dosage of the former (70 mg/day) we observed an unexpectedly lower plasma exposure (AUC0-24 79.5 μg/ml*h vs. 108.

FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS.

Insulin resistance is the putative key underlying mechanism linking adipose tissue (AT) dysfunction with liver inflammation and steatosis in metabolic syndrome (MetS). We have recently demonstrated that the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA) ameliorates insulin resistance and the metabolic profile with a marked reduction in the amount of visceral AT (VAT) in a high-fat diet (HFD)-induced rabbit model of MetS. These effects were mediated by the activation of FXR, since treatment with the selective TGR5 agonist INT-777 was not able to ameliorate the metabolic parameters evaluated.