ObjectivesThe aim of the study was to investigate the relationship between metabolic comorbidities, cardiovascular risk factors or common carotid intima-media thickness (cIMT) and cognitive performance in HIV-infected patients. MethodsAsymptomatic HIV-infected subjects were consecutively enrolled during routine out-patient visits at two clinical centres. All patients underwent an extensive neuropsychological battery and assessment of metabolic comorbidities and cardiovascular risk factors. Moreover, cIMT was assessed by ultrasonography. Cognitive performance was evaluated by calculating a global cognitive impairment (GCI) score obtained by summing scores assigned to each test (0 if normal and 1 if pathological). ResultsA total of 245 patients (median age 46 years; 84.1% with HIV RNA < 50 copies/mL; median CD4 count 527 cells/mL) were enrolled in the study. Cardiovascular risk factors were highly prevalent in our population: the most frequent were dyslipidaemia (61.2%), cigarette smoking (54.3%) and hypertension (15.1%). cIMT was abnormal (Ն 0.9mm) in 31.8% of patients. Overall, the median GCI score was 2 [interquartile range (IQR) 1-4]; it was higher in patients with diabetes (P = 0.004), hypertension (P = 0.030) or cIMT Ն 0.9 mm (P < 0.001). In multivariate analysis, it was confirmed that diabetes (P = 0.007) and cIMT Ն 0.9 mm (P = 0.044) had an independent association with lower cognitive performance. In an analysis of patients on combination antiretroviral therapy (cART), abacavir use was independently associated with a better cognitive performance (P = 0.011), while no association was observed for other drugs or neuroeffectiveness score. ConclusionsDiabetes, cardiovascular risk factors and cIMT showed a strong association with lower cognitive performance, suggesting that metabolic comorbidities could play a relevant role in the pathogenesis of HIV-associated neurocognitive disorders in the recent cART era.Keywords: cardiovascular risk factors, carotid intima-media thickness, dementia, diabetes, HIV-associated neurocognitive disorders Accepted 27 July 2012 IntroductionAlthough combination antiretroviral therapy (cART) has markedly changed the prognosis of HIV-infected patients by reducing AIDS-related morbidity and mortality [1], HIVassociated neurocognitive disorders (HANDs) are increasingly recognized in such populations. In particular, while the incidence of HIV-associated dementia (HAD) has significantly decreased in recent years, the prevalence of milder forms of HAND has gradually increased [2][3][4]. Several factors may contribute to these epidemiological changes, such as a lower mortality leading to aging and a HIV-infected patients show a high prevalence of cardiovascular (CV) risk factors (including diabetes, hypertension, obesity, dyslipidaemia, atherosclerosis and coronary heart disease) [9,10] which can contribute to the increased mortality of a such population [11]. These factors have been linked to a lower cognitive performance in the general population [12][13][14][15]. It has been postulated ...
Background: Gastrointestinal basidiobolomycosis (GIB) is a rare mycosis affecting almost exclusively immunocompetent subjects. Methods: We describe a case of GIB caused by Basidiobolus ranarum in a 25-year-old Italian immunocompetent man resident in Ireland who presented a 2-month history of epigastric pain. Suspecting colon cancer he underwent a right hemicolectomy subsequently leading to a diagnosis of GIB by means of molecular biology. After surgery a 9-month therapy with itraconazole was employed with a good outcome. A review of medical literature regarding GIB cases published in the period 1964-2017 is presented. Results: One-hundred and two cases of GIB were included in this analysis. The disease was observed predominantly in male gender (74.5%) and children (41.2%). Abdominal pain was the single most common complaint (86.3%) followed by fever (40.2%) and evidence of an abdominal mass (30.4%). Peripheral blood eosinophilia was detected in 85.7% of cases. Most of the patients were diagnosed in Saudi Arabia (37.2%) followed by USA (21.6%) and Iran (20.6%). Surgery plus antifungal therapy was employed in the majority of patients (77.5%). An unfavourable outcome was documented globally in 18.6% of patients. Conclusions: GIB seems to be an emerging intestinal mycosis among immunocompetent patients living in the Middle East and Arizona. 1 MDP and VDC contributed equally to this work.
BackgroundNevirapine has been used as antiretroviral agent since early ‘90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity.MethodsWe retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3–4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ2 test. A multivariable logistic regression model was constructed using a backward elimination method.ResultsThree hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04–0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27–50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02–0.47; p = 0.004) was associated with a lower risk.ConclusionsAccording to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine.
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