1,721,009 research outputs found

    Do the HIV-1 subtypes circulating in Italy resemble the Red Queen running in Carroll's novel?

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    The human immunodeficiency virus type 1 (HIV-1) pandemic is currently in its third decade and approximately 35 million people are infected worldwide. HIV-1 genetic variability results in 9 phylogenetic subtypes and several circulating recombinant forms (CRFs). In Italy, the first phase of the HIV epidemic was mainly confined to the intravenous drug users (IDU) risk group, moreover most studies have focused on different aspects of the non B subtype such as drugs and therapeutic protocols, laboratory methodologies (heteroduplex mobility assay, PCR screening methods) for the identification of phenotypic variants. These studies were mostly locally conducted. In this context, the Red Queen Hypothesis might be suggestive. In the first original expression that comes from Chapter 2, Through the Looking Glass. To improve our knowledge, in the near future, we will need to investigate the demographic and spatiotemporal history of different HIV-1 subtypes circulating in Italy in a large data set of sequences, involving a sample size comparable with the Italian population. To monitor the genetic evolution of the HIV-1 in a large data-set represent an essential strategy to control the local as well as the global HIV-1 epidemic and to develop efficient preventive and therapeutic strategies, with a great impact in clinical practice

    Comparison of the Aptima HIV-1 Quant Dx Assay with the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 v2.0 Test for HIV-1 Viral Load Quantification in Plasma Samples from HIV-1-Infected Patients.

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    Background and aims: HIV‐1 RNA viral load (VL) in plasma samples of HIV‐1–positive patients is used to assess the level of viral replication, the risk of disease progression, and the response and efficacy to antiretroviral treatment. Knowing the performance of different tests for HIV‐1 RNA detection is, therefore, important for clinical care. This study compared the performance of the recently introduced Aptima HIV‐1 Quant Dx assay (Hologic, Inc) and the standard COBAS AmpliPrep/COBAS TaqMan HIV‐1 v2.0 Test (CAP/CTM2) (Roche Molecular System, Inc) for HIV‐1 RNA quantitation. Methods: Assay performance was assessed using 335 clinical samples, a standard HIV‐1 low VL panel, and 2 diluted samples from well‐characterized patients infected with different HIV‐1 subtypes tested in 5 replicates over 3 days. All samples were tested on both assays to evaluate inter‐assay agreement, both qualitatively and quantitively. Altogether, we evaluated assay sensitivity, linearity, accuracy, precision, repeatability, and reproducibility. Results: Assay agreement for qualitative results in 335 clinical samples was fair (80.6%). Correlation of quantitative assay results (n = 164) was excellent (R2 = 0.97), with 96.3% of the results within the 95% limit of assay agreement (−0.42 to +0.86 log), and 98.8% within 1 log of each other. Aptima‐HIV‐1 yielded results, on average, 0.22 log higher than CAP/CTM2. Both assays accurately quantitated the HIV‐1 standard at low VL (R2 ≥ 0.94), with all samples within 0.5 log of the target. Conclusion: Aptima‐HIV‐1 assay demonstrated sensitivity, accuracy, reproducibility, and precision for the detection and quantitation of HIV‐1 RNA across a wide dynamic range of VLs. Its performance, together with full automation and high throughput, suggests that Aptima‐HIV‐1 could be a suitable assay for reliable monitoring of HIV‐1 VL in patients undergoing treatment

    No correlation between statin exposure and incident diabetes mellitus in HIV-1-infected patients receiving combination antiretroviral therapy

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    Objectives: Recent clinical studies and one meta-analysis have shown a modest but significant increase in the incidence of diabetes mellitus associated with statin exposure, so this correlation was investigated in a cohort of HIV-positive subjects. Methods: A retrospective cohort study including adult HIV-1-infected patients followed at our Clinic of Infectious Diseases between 2007 and 2014 was performed. Results: We assessed 3170 HIV-positive patients with a median follow-up of 5.2 years. The incidence of diabetes mellitus was 1.2 per 100 person-years and it was not significantly associated with the prescription of statins [hazard ratio (HR) 1.09 per year of statin exposure; 95% confidence interval (CI) 0.7-1.49; P = 0.067], while it was associated with older age, chronic hepatitis C, antiretroviral-naïve vs. antiretroviral experienced condition, high body mass index, and high serum concentration of triglycerides. Conclusions: In our study, a higher risk of diabetes mellitus was not associated with statin treatment, but with some traditional risk factors

    Conflicting interpretations of the prevalence of mutations associated with drug resistance in antiviral naive HIV-1 patients with acute and chronic infection

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    The routine determination of drug resistance in newly HIV-1 infected individuals records a potential increase in transmissions of drug-resistant variants. Plasma samples from 38 individuals classified as newly infected (seroconversion time <12 months) and twenty four individuals with an established infection (seroconversion time ranging from 3 to 10 years) were analyzed for the presence of mutations by Trugene HIV-1 genotyping assay and Virtual phenotype. Results on the newly infected and the chronically infected individuals showed a limited number of relevant mutations associated with substantial resistance to reverse transcriptase and protease inhibitors. In particular, three patients (4.8%) carried viral major mutations (T69D and M41L) associated with resistance to reverse transcriptase inhibitors, whereas only one showed the presence of M46L, which is correlated with partial resistance to some protease inhibitors. The clinical interpretation based on different approaches to monitor resistance showed that the Virconet interpretation was less grave than Trugene, suggesting that these interpretations need standardization for the currently used sequencing methods and that they may be associated with different outcomes when eventually are used

    Acute onset myopericarditis as unusual presentation of primary HIV infection

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    A 30-year-old man was admitted to hospital after complaining of a retrosternal burning pain, radiating to the jugular region, and to both upper limbs. An electrocardiography examination showed a ST segment elevation involving the lower-lateral leads. A trans-thoracic ultrasonography showed findings compatible with an acute myopericarditis. All performed serological testings excluded other recent infections with cardiac tropism. Among screening tests, a peripheral lymphocyte subset analysis was performed and an inversion of the CD4/CD8 ratio was found. Therefore, HIV testing was performed and proved positive for HIV-1 antibodies. The discovery of a primary HIV infection with involvement of a vital organ led us to start HAART. On day 20, our patient underwent a right heart catheterization and endomyocardial biopsy. During the following days, the clinical conditions of our patient improved, and a further heart ultrasonography documented a mild pericardial thickening as a result of the recent myopericarditis. Also the evolving changes of ECG were compatible with a benign evolution of myopericarditis. The histopathologic studies revealed a mild fibrosis of the myocardial right ventricular tissue, and inflammatory findings compatible with a recent myocarditis. At the real-time PCR analysis on bioptic sample, only HHV6 DNA and HIV-DNA were reactive. An immunofluorescence staining was performed to highlight the HIV p24 protein and a positive signal was detected in myocardial tissue. Considering the low avidity level of the anti-HIV IgG antibodies and the positivity of HIV-DNA in the endomyocardial tissue, we believe that the clinical manifestation presented can be referred to the recent primary HIV-infection

    Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients

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    The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents

    Ivermectin concentration in breastmilk of a woman with Strongyloides stercoralis and human T-lymphotropic virus-I co-infection

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    Ivermectin is a widely used drug for the treatment of various neglected tropical diseases, such as lymphatic filariasis, onchocerciasis, and strongyloidiasis among others. Despite its excellent safety profile, there are few published studies of the use of ivermectin in children, pregnant and nursing women. In the present study, we report clinical data on ivermectin concentrations in breastmilk of a woman with Strongyloides stercoralis and HTLV-I coinfection. Ivermectin levels in breastmilk ranged from 1.4 to 20.8 ng/ml, with a mean of 9.26 ng/ml after a single dose of 200 μg/kg. We estimated the possible ivermectin exposure of the infant to be 1.1 μg/kg, 0.55% of the weight-adjusted percentage of the maternal dose. This value is largely under the threshold established by the World Health Organization for safe breastfeeding. Our results bolster previous findings on the secretion of ivermectin into breastmilk in healthy volunteers. The findings from this case study do not support exclusion of lactating women or interrupting lactation to accommodate it

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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