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2. ANCA-Associated Glomerulonephritis and Anti-Phospholipid Syndrome in a Patient with SARS-CoV-2 Infection: Just a Coincidence?

Author

Federica Maritati, Maria Ilaria Moretti, Valentina Nastasi, Roberta Mazzucchelli, Manrico Morroni, Patrizia Bagnarelli, Serena Rupoli, Marcello Tavio, Paolo Galiotta, Walter Bisello, and Andrea Ranghino

Subjects
covid-19, rituximab, antineutrophil cytoplasmic antibody-associated vasculitis, antiphospholipid syndrome, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Many reports have described a high incidence of acute kidney injury (AKI) among patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to hemodynamic instability. However, other complex processes may be involved, related to the cytokine storm and the activation of innate and adaptive immunity. Here, we describe a patient who developed an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with rapidly progressive glomerulonephritis and lung involvement and an antiphospholipid syndrome soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After viral pneumonia was excluded by bronchoalveolar lavage, the patient has been treated with rituximab for amelioration of kidney function and resolution of thrombosis without any adverse event. We conclude that COVID-19 may trigger autoimmune diseases including ANCA-associated vasculitis. Thus, this diagnosis should be taken in consideration in COVID-19 patients, especially when they develop AKI with active urinary sediment. In addition, considering the relationship between these 2 diseases, SARS-CoV-2 infection should be excluded in all patients with a new diagnosis ANCA-associated vasculitis before starting immunosuppressive therapy.

Published
2021
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3. A New Dimeric Copper(II) Complex of Hexyl Bis(pyrazolyl)acetate Ligand as an Efficient Catalyst for Allylic Oxidations

Author

Luca Bagnarelli, Alessandro Dolmella, Carlo Santini, Riccardo Vallesi, Roberto Giacomantonio, Serena Gabrielli, and Maura Pellei

Subjects
catalysis, copper, allylic oxidation, X-ray, spectroscopy, Organic chemistry, QD241-441
Abstract

A new dimeric copper(II) bromide complex, [Cu(LOHex)Br(μ-Br)]2 (1), was prepared by a reaction of CuBr2 with the hexyl bis(pyrazol-1-yl)acetate ligand (LOHex) in acetonitrile solution and fully characterized in the solid state and in solution. The crystal structure of 1 was also determined: the complex is interlinked by two bridging bromide ligands and possesses terminal bromide ligands on each copper atom. The two pyrazolyl ligands in 1 coordinate with the nitrogen atoms to complete the Cu coordination sphere, resulting in a five-coordinated geometry—away from idealized trigonal bipyramidal and square pyramidal geometries—which can better be described as distorted square pyramidal, as measured by the τ and χ structural parameters. The pendant hexyloxy chain is disordered over two arrangements, with final site occupancies refined to 0.705 and 0.295. The newly synthesized complex was evaluated as a catalyst in copper-catalyzed C–H oxidation for allylic functionalization through a Kharasch–Sosnovsky reaction without any external reducing agent. Using 0.5 mol% of this catalyst, and tert-butyl peroxybenzoate (Luperox) as an oxidant, allylic benzoates were obtained with up to 90% yield. The general reaction time was only slightly decreased to 24 h but a very significant decrease in the alkene:Luperox ratio to 3:1 was achieved. These factors show relevant improvements with respect to classical Kharasch–Sosnovsky reactions in terms of rate and amount of reagents. The present study highlights the potential of copper(II) complexes containing functionalized bis(pyrazol-1-yl)acetate ligands as efficient catalysts for allylic oxidations.

Published
2021
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4. Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

Author

Sara Caucci, Benedetta Corvaro, Sofia Maria Luigia Tiano, Anna Valenza, Roberta Longo, Katia Marinelli, Monica Lucia Ferreri, Patrik Spiridigliozzi, Giovanna Salvoni, Patrizia Bagnarelli, and Stefano Menzo

Subjects
COVID, SARS, neutralizing antibodies, BAU, anamnestic response, vaccine, Medicine
Abstract

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.

Published
2021
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5. Local Epidemics Gone Viral: Evolution and Diffusion of the Italian HIV-1 Recombinant Form CRF60_BC

Author

Alessia Lai, Francesco Roberto Simonetti, Gaetano Brindicci, Annalisa Bergna, Simona Di Giambenedetto, Gaetana Sterrantino, Cristina Mussini, Stefano Menzo, Patrizia Bagnarelli, Maurizio Zazzi, Gioacchino Angarano, Massimo Galli, Laura Monno, and Claudia Balotta

Subjects
HIV-1 recombinant forms, HIV-1 molecular epidemiology, HIV-1 evolution, HIV-1 outbreak, second generation recombinants, Microbiology, QR1-502
Abstract

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18–37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy.

Published
2019
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6. Syntheses and Reactivity of New Zwitterionic Imidazolium Trihydridoborate and Triphenylborate Species

Author

Maura Pellei, Riccardo Vallesi, Luca Bagnarelli, H. V. Rasika Dias, and Carlo Santini

Subjects
N-heterocyclic carbenes, imidazole, spectroscopy, X-ray, Organic chemistry, QD241-441
Abstract

In this study, four new N-(alkyl/aryl)imidazolium-borates were prepared, and their deprotonation reactions were investigated. Addition of BH3•THF to N-benzylimidazoles and N-mesitylimidazoles leads to imidazolium-trihydridoborate adducts. Ammonium tetraphenylborate reacts with benzyl- or mesityl-imidazoles with the loss of one of the phenyl groups yielding the corresponding imidazolium-triphenylborates. Their authenticity was confirmed by CHN analysis, 1H-NMR, 13C-NMR, 11B-NMR, FT-IR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). 3-Benzyl-imidazolium-1-yl)trihydridoborate, (HImBn)BH3, and (3-mesityl-imidazolium-1-yl)trihydridoborate, (HImMes)BH3, were also characterized by X-ray crystallography. The reactivity of these new compounds as carbene precursors in an effort to obtain borate-NHC complexes was investigated and a new carbene-borate adduct (which dimerizes) was obtained via a microwave-assisted procedure.

Published
2020
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7. Circulating SARS-CoV-2 variants in Italy, October 2020–March 2021

Author

Lai, A., Bergna, A., Menzo, S., Zehender, G., Caucci, S., Ghisetti, V., Rizzo, F., Maggi, F., Cerutti, F., Giurato, G., Weisz, A., Turchi, C., Bruzzone, B., Ceccherini Silberstein, F., Clementi, N., Callegaro, A., Sagradi, F., Francisci, D., Venanzi Rullo, E., Vicenti, I., Clementi, M., Galli, M., Balotta, C., Gori, M., Bagnarelli, P., Baj, A., Novazzi, F., Orsi, A., Caligiuri, P., Boccotti, S., Bellocchi, M. C., Sarmati, L., Andreoni, M., Mancini, N., Criscuolo, E., Gallitelli, R., Testa, S., Dragoni, F., Zazzi, M., Lai, Alessia, Bergna, Annalisa, Menzo, Stefano, Zehender, Gianguglielmo, Caucci, Sara, Ghisetti, Valeria, Rizzo, Francesca, Maggi, Fabrizio, Cerutti, Francesco, Giurato, Giorgio, Weisz, Alessandro, Turchi, Chiara, Bruzzone, Bianca, Ceccherini Silberstein, Francesca, Clementi, Nicola, Callegaro, Annapaola, Sagradi, Fabio, Francisci, Daniela, Venanzi Rullo, Emmanuele, Vicenti, Ilaria, Clementi, Massimo, Galli, Massimo, Balotta, Claudia, Gori, Maria, Bagnarelli, Patrizia, Baj, Andreina, Novazzi, Federica, Orsi, Andrea, Caligiuri, Patrizia, Boccotti, Simona, Bellocchi, Maria Concetta, Sarmati, Loredana, Andreoni, Massimo, Mancini, Nicasio, Criscuolo, Elena, Gallitelli, Rosa, Testa, Sophie, Dragoni, Filippo, and Zazzi, Maurizio

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Short Report, SARS-CoV-2 virus, Infectious and parasitic diseases, RC109-216, Biology, Spike protein, Settore MED/07, COVID-19 RT-PCR testing, Virology, Complete genome sequencing, Viral variants, COVID-19, Humans, Italy, Prevalence, SARS-CoV-2, Epidemics, biochemistry, skin and connective tissue diseases, Whole genome sequencing, fungi, Spike Protein, body regions, Infectious Diseases
Abstract

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

Published
2021

8. Syntheses and Biological Studies of Cu(II) Complexes Bearing Bis(pyrazol-1-yl)- and Bis(triazol-1-yl)-acetato Heteroscorpionate Ligands

Author

Maura Pellei, Valentina Gandin, Luciano Marchiò, Cristina Marzano, Luca Bagnarelli, and Carlo Santini

Subjects
copper, poly(azolyl)acetate ligands, X-ray, spectroscopy, cytotoxicity, Organic chemistry, QD241-441
Abstract

Copper(II) complexes of bis(pyrazol-1-yl)- and bis(triazol-1-yl)-acetate heteroscorpionate ligands have been synthesized. The copper(II) complexes [HC(COOH)(pzMe2)2]Cu[HC(COO)(pzMe2)2]·ClO4, [HC(COOH)(pz)2]2Cu(ClO4)2 (pzMe2 = 3,5-dimethylpyrazole; pz = pyrazole) were prepared by the reaction of Cu(ClO4)2·6H2O with bis(3,5-dimethylpyrazol-1-yl)acetic acid (HC(COOH)(pzMe2)2) and bis(pyrazol-1-yl)acetic acid (HC(COOH)(pz)2) ligands in ethanol solution. The copper(II) complex [HC(COOH)(tz)2]2Cu(ClO4)2·CH3OH (tz = 1,2,4-triazole) was prepared by the reaction of Cu(ClO4)2·6H2O with bis(1,2,4-triazol-1-yl)acetic acid (HC(COOH)(tz)2) ligand in methanol solution. The synthesized Cu(II) complexes, as well as the corresponding uncoordinated ligands, were evaluated for their cytotoxic activity in monolayer and 3D spheroid cancer cell cultures with different Pt(II)-sensitivity. The results showed that [HC(COOH)(pzMe2)2]Cu[HC(COO)(pzMe2)2]·ClO4 was active against cancer cell lines derived from solid tumors at low IC50 and this effect was retained in the spheroid model. Structure and ultra-structure changes of treated cancer cells analyzed by Transmission Electron Microscopy (TEM) highlighted the induction of a cytoplasmic vacuolization, thus suggesting paraptotic-like cancer cell death triggering.

Published
2019
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10. HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users.

Author

Alessia Lai, Giorgio Bozzi, Marco Franzetti, Francesca Binda, Francesco R Simonetti, Andrea De Luca, Valeria Micheli, Paola Meraviglia, Patrizia Bagnarelli, Antonio Di Biagio, Laura Monno, Francesco Saladini, Maurizio Zazzi, Gianguglielmo Zehender, Massimo Ciccozzi, and Claudia Balotta

Subjects
Medicine, Science
Abstract

Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype.Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches.The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8%) clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively) compared to those from Africa (20%) (p < .001). Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056) and in women with respect to men (81.4% vs. 53.2%, p < .006). Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece.Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of such variant, probably through sex work.

Published
2016
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11. Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021

Author

Stefanelli, P., Trentini, F., Guzzetta, G., Marziano, V., Mammone, A., Schepisi, M. S., Poletti, P., Grane, C. M., Manica, M., del Manso, M., Andrianou, X., Ajelli, M., Rezza, G., Brusaferro, S., Merler, S., Di Martino, A., Ambrosio, L., Lo Presti, A., Fiore, S., Fabiani, C., Benedetti, E., Di Mario, G., Facchini, M., Puzelli, S., Calzoletti, L., Fontana, S., Venturi, G., Fortuna, C., Marsili, G., Amendola, A., Stuppia, L., Savini, G., Picerno, A., Lopizzo, T., Dell'Edera, D., Minchella, P., Greco, F., Viglietto, G., Atripaldi, L., Limone, A., D'Agaro, P., Licastro, D., Pongolini, S., Sambri, V., Dirani, G., Zannoli, S., Affanni, P., Colucci, M. E., Capobianchi, M. R., Icardi, G., Bruzzone, B., Lillo, F., Orsi, A., Pariani, E., Baldanti, F., Molecolare, U. V., Gismondo, M. R., Maggi, F., Caruso, A., Ceriotti, F., Boniotti, M. B., Barbieri, I., Bagnarelli, P., Menzo, S., Garofalo, S., Scutella, M., Pagani, E., Collini, L., Ghisetti, V., Brossa, S., Ru, G., Bozzetta, E., Chironna, M., Parisi, A., Rubino, S., Serra, C., Piras, G., Coghe, F., Vitale, F., Tramuto, F., Scalia, G., Palermo, C. I., Mancuso, G., Pollicino, T., Di Gaudio, F., Vullo, S., Reale, S., Cusi, M. G., Rossolini, G. M., Pistello, M., Mencacci, A., Camilloni, B., Severini, S., Di Benedetto, M., Terregino, C., Monne, I., Biscaro, V., Stefanelli P, Trentini F, Guzzetta G, Marziano V, Mammone A, Sane Schepisi M, Poletti P, Molina Grané C, Manica M, Del Manso M, Andrianou X, Ajelli M, Rezza G, Brusaferro S, Merler S, Vitale F, Tramuto F, Stefanelli P., Trentini F., Guzzetta G., Marziano V., Mammone A., Sane Schepisi M., Poletti P., Molina Grane C., Manica M., Del Manso M., Andrianou X., Ajelli M., Rezza G., Brusaferro S., Merler S., Sambri V, and (membro del COVID-19 National Microbiology Surveillance Study Group)

Subjects
Epidemiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, co-circulation, lineage, SARS-CoV-2 variant of concern, transmissibility, Humans, Italy, Models, Theoretical, Settore MED/42 - Igiene Generale E Applicata, SARS-COV-2 VARIANT OF CONCERN, CO-CIRCULATION, LINEAGE, TRANSMISSIBILITY, HUMANS, ITALY, MODELS, THEORETICAL, COVID-19, SARS-COV-2, Theoretical, Models, Virology, Human
Abstract

Background Several SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains. Aim We aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility. Methods We conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains. Results The Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55–1.57 times the level of historical lineages (95% CrI: 1.45–1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03–1.23) with complete immune evasion to 1.39 (95% CrI: 1.26–1.56) for complete cross-protection. Conclusion We assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

Published
2022

12. Characteristics of SARS-CoV-2 variants of concern B.1.1.7, B.1.351 or P.1: data from seven EU/EEA countries, weeks 38/2020 to 10/2021

Author

Funk T., Pharris A., Spiteri G., Bundle N., Melidou A., Carr M., Gonzalez G., Garcia-Leon A., Crispie F., O'Connor L., Murphy N., Mossong J., Vergison A., Wienecke-Baldacchino A. K., Abdelrahman T., Riccardo F., Stefanelli P., Di Martino A., Bella A., Lo Presti A., Casaca P., Moreno J., Borges V., Isidro J., Ferreira R., Gomes J. P., Dotsenko L., Suija H., Epstein J., Sadikova O., Sepp H., Ikonen N., Savolainen-Kopra C., Blomqvist S., Mottonen T., Helve O., Gomes-Dias J., Adlhoch C., Macori G., Russell L., Yandle Z., Bennett C., O'Byrne E., Murphy A., Tuite G., Conroy A., Duffy M., Morley U., Keoghan B., Ford I., Kennedy M., McDonnell S., Flynn A., Clarke A., Crowley A., Martin C., Kelly E., Foxton J., Hare D., Dunford L., Connell J., Moran J., Dean J., Fanning S., Rajan L., De Gascun C., Kenny J., Cotter P., Walsh C., Lawton E., Fitzpatrick A., Mullins E., Della Bartola M., McCabe M., Stapleton P., Meaney C., Fanning L., Prentice M., MacSharry J., Dempsey C., Mallon P., Leon A., Chaturvedi A., Coughlan S., McAndrew G., Reddington K., Walsh F., Fitzpatrick D., Smyth C., O'Dwyer T., Chambers T., Clarke L., Jebb D., Klopp J., Kavanagh D., Haslam K., Buckley P., Lemass K., Fitzpatrick F., Burns K., Cafferkey J., Richmond A., Foley M., Sanchez-Morgado J., Chalapati S., Pinnamaneni N., Crosbie C., Limbachiya D., Tinago W., Garcia Leon A. A., Miles S., Alalwan D., Negi R., Macken A., Feeney E., Kenny G., McCann K., Kelly N., Blair M., McCann R., Kenny C., O'Brion C., Waqas S., Savinelli S., Doran P., Bracken T., Varghese P., Lambert J. S., Cotter A., Muldoon E., Sheehan G., McGinty T., Lambert J., Green S., Leamy K., de Barra E., McConkey S., Kelly C., Horgan M., Sadlier C., Yousif O., O'Donnell J., Fitzgerald M., Petty-Saphon N., Cuddihy J., Fiore S., Fabiani C., Benedetti E., Di Mario G., Facchini M., Puzelli S., Calzoletti L., Fontana S., Venturi G., Fortuna C., Marsili G., Amendola A., Stuppia L., Savini G., Picerno A., Lopizzo T., Dell'Edera D., Minchella P., Greco F., Mauro M. V., Viglietto G., Atripaldi L., Limone A., D'Agaro P., Licastro D., Marcello A., Capobianchi M. R., Icardi G., Bruzzone B., Lillo F., Orsi A., Pariani E., Baldanti F., Gismondo M. R., Maggi F., Caruso A., Ceriotti F., Boniotti B., Bagnarelli P., Garofalo S., Scutella M., Pagani E., Collini L., Ghisetti V., Ru G., Chironna M., Parisi A., Rubino S., Serra C., Piras G., Coghe F., Vitale F., Tramuto F., Scalia G., Palermo C. I., Mancuso G., Di Gaudio F., Vullo S., Reale S., Cusi M. G., Rossolini G. M., Pistello M., Mencacci A., Camilloni B., Severini S., Di Benedetto M., Calogero T., Monne I., Biscaro V., COVID Study Groups, Funk T., Pharris A., Spiteri G., Bundle N., Melidou A., Carr M., Gonzalez G., Garcia-Leon A., Crispie F., O'Connor L., Murphy N., Mossong J., Vergison A., Wienecke-Baldacchino A.K., Abdelrahman T., Riccardo F., Stefanelli P., Di Martino A., Bella A., Lo Presti A., Casaca P., Moreno J., Borges V., Isidro J., Ferreira R., Gomes J.P., Dotsenko L., Suija H., Epstein J., Sadikova O., Sepp H., Ikonen N., Savolainen-Kopra C., Blomqvist S., Mottonen T., Helve O., Gomes-Dias J., Adlhoch C., Macori G., Russell L., Yandle Z., Bennett C., O'Byrne E., Murphy A., Tuite G., Conroy A., Duffy M., Morley U., Keoghan B., Ford I., Kennedy M., McDonnell S., Flynn A., Clarke A., Crowley A., Martin C., Kelly E., Foxton J., Hare D., Dunford L., Connell J., Moran J., Dean J., Fanning S., Rajan L., De Gascun C., Kenny J., Cotter P., Walsh C., Lawton E., Fitzpatrick A., Mullins E., Della Bartola M., McCabe M., Stapleton P., Meaney C., Fanning L., Prentice M., MacSharry J., Dempsey C., Mallon P., Leon A., Chaturvedi A., Coughlan S., McAndrew G., Reddington K., Walsh F., Fitzpatrick D., Smyth C., O'Dwyer T., Chambers T., Clarke L., Jebb D., Klopp J., Kavanagh D., Haslam K., Buckley P., Lemass K., Fitzpatrick F., Burns K., Cafferkey J., Richmond A., Foley M., Sanchez-Morgado J., Chalapati S., Pinnamaneni N., Crosbie C., Limbachiya D., Tinago W., Garcia Leon A.A., Miles S., Alalwan D., Negi R., Macken A., Feeney E., Kenny G., McCann K., Kelly N., Blair M., McCann R., Kenny C., O'Brion C., Waqas S., Savinelli S., Doran P., Bracken T., Varghese P., Lambert J.S., Cotter A., Muldoon E., Sheehan G., McGinty T., Lambert J., Green S., Leamy K., de Barra E., McConkey S., Kelly C., Horgan M., Sadlier C., Yousif O., O'Donnell J., Fitzgerald M., Petty-Saphon N., Cuddihy J., Fiore S., Fabiani C., Benedetti E., Di Mario G., Facchini M., Puzelli S., Calzoletti L., Fontana S., Venturi G., Fortuna C., Marsili G., Amendola A., Stuppia L., Savini G., Picerno A., Lopizzo T., Dell'Edera D., Minchella P., Greco F., Mauro M.V., Viglietto G., Atripaldi L., Limone A., D'Agaro P., Licastro D., Marcello A., Capobianchi M.R., Icardi G., Bruzzone B., Lillo F., Orsi A., Pariani E., Baldanti F., Gismondo M.R., Maggi F., Caruso A., Ceriotti F., Boniotti B., Bagnarelli P., Garofalo S., Scutella M., Pagani E., Collini L., Ghisetti V., Ru G., Chironna M., Parisi A., Rubino S., Serra C., Piras G., Coghe F., Vitale F., Tramuto F., Scalia G., Palermo C.I., Mancuso G., Di Gaudio F., Vullo S., Reale S., Cusi M.G., Rossolini G.M., Pistello M., Mencacci A., Camilloni B., Severini S., Di Benedetto M., Calogero T., Monne I., Biscaro V., and COVID Study Groups

Subjects
Infecções Respiratórias, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care, Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), variants of concern, Settore MED/42 - Igiene Generale E Applicata, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Medicine, Humans, Intensive care admission, 030212 general & internal medicine, COVID-19, Europe, SARS-CoV-2, surveillance, Surveillance, business.industry, 030503 health policy & services, Public Health, Environmental and Occupational Health, Odds ratio, Confidence interval, Variants of Concern, COVID-19, Europe, SARS-CoV-2, surveillance, variants of concern, 0305 other medical science, business, Rapid Communication, Human
Abstract

COVID study groups - PORTUGAL: Portuguese Laboratory Network for the Diagnosis of COVID-19 and Public Health Department of the Health Administrative Regions, Physicians that provided data and samples from suspected cases and SARS-CoV-2 genetic characterization. INSA laboratory team for the diagnosis of SARS-CoV-2. Algarve Biomedical Center and Unilabs. We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0-2.9; B.1.351: 3.6, 95% CI: 2.1-6.2; P.1: 2.6, 95% CI: 1.4-4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4-3.5; P.1: 2.2, 95% CI: 1.7-2.8). ECDC internal funds. The ICSC and the AIID Cohort are supported by Science Foundation Ireland under the Science Foundation Ireland, Enterprise Ireland, IDA Ireland COVID-19 Rapid Response Funding Call (Grant number: COVID-RRC 20/COV/0103 and COVID-RRC 20/COV/0305). info:eu-repo/semantics/publishedVersion

Published
2021

13. Planificando un sistema de control de calidad interno. Introducción al Análisis Sigma-metric

Author

A. Bagnarelli

Subjects
Biochemistry, QD415-436, Internal medicine, RC31-1245
Abstract

Los principios básicos sobre el diseño de sistemas de control de calidad interno han sido ampliamente estudiados. Sin embargo, la interacción entre las diversas variables que comprende el análisis completo del sistema no ha sido sufi cientemente difundida. La primera etapa en el planeamiento de un sistema de control de calidad interno es elegir las especifi caciones de calidad para el sistema, después se deberá evaluar las características del método analítico (sistema estable) y, fi nalmente, seleccionar el procedimiento de control de calidad (sistema inestable), en términos de reglas de control y número de controles por corrida que dependen de cada prueba. El nivel de calidad obtenido dependerá de la probabilidad del procedimiento en la detección de errores y de falsos rechazos a partir del tamaño de error crítico que deba ser detectado. Este trabajo se focaliza en la planifi cación del proceso de control de calidad interno con la utilización de gráfi cos de potencia y tablas de especifi caciones de calidad. Se incluye, además, una descripción del Análisis Sigma-metric para lograr una mejora en la ejecución y la utilización de las técnicas implementadas, con el fi n de alcanzar objetivos de calidad máxima. Finalmente se brindarán algunos ejemplos.

Published
2009

14. Incertidumbre en los resultados del laboratorio clínico

Author

Dr. Aníbal E. Bagnarelli

Subjects
Biochemistry, QD415-436, Internal medicine, RC31-1245
Abstract

Este documento esta dedicado a tratar el problema de la Incertidumbre de una medición (IM), que es una herramienta metrologica que permite una estimación cuantitativa de la calidad del resultado de una prueba del laboratorio. Hace unos años algunos organismos internacionales desarrollaron un documento para estimar dicha incertidumbre, bajo el titulo Guía para la Medición de la Incertidumbre (GUM) principalmente dedicado a magnitudes físicas y de laboratorios de ensayo, que presentaban un marco adecuado sobre los términos y métodos para ser utilizados en este campo. Posteriormente la norma ISO 15189 los adaptó a la problemática del laboratorio clínico debido a la compleja matriz del material biológico que se utiliza en los ensayos. Hemos estudiado su aplicación en la prueba de calcio en suero y la relación calcio/ creatinina en orina y también se ha estudiado la prueba del antígeno carcino embrionario, para estimar la IM en los niveles de decisión clínica. En estos estudios, las variables introducidas se han obtenido de información brindada por equipos reactivo, instrumental y referencias bibliográficas.

Published
2008

15. Justicia a la carta : el Poder Judicial en la era macrista : un relato imparcial del plan sistemático y estructural de cooptación del Poder Judicial en el gobierno de Cambiemos

Author

Desojo, Emanuel, Coordinador, Bagnarelli, Bruno, Burgos, Luciana, Catoggio, Augusto, Cipolla, Daniela, Desojo, Emanuel, Lovelli, Emanuel, Lovelli, Mariano, Jaureguiberry, Santiago Pavón, Zaffaroni, Eugenio Raúl, Prólogo de, Desojo, Emanuel, Bagnarelli, Bruno, Burgos, Luciana, Catoggio, Augusto, Cipolla, Daniela, Desojo, Emanuel, Lovelli, Emanuel, Lovelli, Mariano, Jaureguiberry, Santiago Pavón, and Zaffaroni, Eugenio Raúl

Published
2020
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16. Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group

Author

Svicher, V., Alteri, C., Montano, M., Nori, A., D’Arrigo, R., Andreoni, M., Angarano, G., Antinori, A., Antonelli, G., Allice, T., Bagnarelli, P., Baldanti, F., Bertoli, A., Borderi, M., Boeri, E., Bon, I., Bruzzone, B., Barresi, R., Calderisi, S., Callegaro, A. P., Capobianchi, M. R., Gargiulo, F., Castelli, F., Cauda, R., Ceccherini-Silberstein, F., Clementi, M., Chirianni, A., Colafigli, M., D’Arminio Monforte, A., De Luca, A., Di Biagio, A., Di Nicuolo, G., Di Perri, G., Di Santo, F., Fadda, G., Galli, M., Gennari, W., Ghisetti, V., Costantini, A., Gori, A., Gulminetti, R., Leoncini, F., Maffongelli, G., Maggiolo, F., Maserati, R., Mazzotta, F., Meini, G., Micheli, V., Monno, L., Mussini, C., Nozza, S., Paolucci, S., Palù, G., Parisi, S., Parruti, G., Pignataro, A. R., Quirino, T., Re, M. C., Rizzardini, G., Sanguinetti, M., Santangelo, R., Scaggiante, R., Sterrantino, G., Turriziani, O., Vatteroni, M. L., Viscoli, C., Vullo, V., Zazzi, M., Lazzarin, A., and Perno, C. F.

Published
2014
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17. Co-circulation of the two influenza B lineages during 13 consecutive influenza surveillance seasons in Italy, 2004-2017

Author

Puzelli S., Martino A. D., Facchini M., Fabiani C., Calzoletti L., Mario G. D., Palmieri A., Affanni P., Camilloni B., Chironna M., D'Agaro P., Giannecchini S., Pariani E., Serra C., Rizzo C., Bella A., Donatelli I., Castrucci M. R., Ansaldi F., Arvia R., Azzi A., Bagnarelli P., Baldanti F., Capobianchi M. R., Castaldi S., Colucci M. E., Galli C., Ghisetti V., Orsi A., Pagani E., Palu G., Sanguinetti M., Smeraglia R., Tramuto F., Vitale F., Puzelli S, Di Martino A, Facchini M, Fabiani C, Calzoletti L, Di Mario G, Palmieri A, Affanni P, Camilloni B, Chironna M, D'Agaro P, Giannecchini S, Pariani E, Serra C, Rizzo C, Bella A, Donatelli I, Castrucci MR, Ansaldi F, Arvia R, Azzi A, Bagnarelli P, Baldanti F, Capobianchi MR, Castaldi S, Colucci ME, Galli C, Ghisetti V, Orsi A, Pagani E, Palù G, Sanguinetti M, Smeraglia R, Tramuto F, Vitale F, Puzelli, S., Martino, A. D., Facchini, M., Fabiani, C., Calzoletti, L., Mario, G. D., Palmieri, A., Affanni, P., Camilloni, B., Chironna, M., D'Agaro, P., Giannecchini, S., Pariani, E., Serra, C., Rizzo, C., Bella, A., Donatelli, I., Castrucci, M. R., Ansaldi, F., Arvia, R., Azzi, A., Bagnarelli, P., Baldanti, F., Capobianchi, M. R., Castaldi, S., Colucci, M. E., Galli, C., Ghisetti, V., Orsi, A., Pagani, E., Palu, G., Sanguinetti, M., Smeraglia, R., Tramuto, F., and Vitale, F.

Subjects
0301 basic medicine, Influenza virological surveillance, Influenza B virus, Victoria lineage, Yamagata lineage, Vaccine match, medicine.medical_specialty, Lineage (evolution), Population, Influenza B viru, Hemagglutinin (influenza), Vaccine match, Settore MED/42 - Igiene Generale E Applicata, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Immunity, Retrospective Studie, Influenza, Human, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, education, Phylogeny, Retrospective Studies, education.field_of_study, biology, Strain (biology), Victoria lineage, Influenza B virus, Influenza virological surveillance, Italy, Yamagata lineage, Virology, Influenza, 030104 developmental biology, Infectious Diseases, Parasitology, Influenza Vaccines, Influenza virological surveillance, Influenza B virus, Victoria lineage, Yamagata lineage, Vaccine match, Italy, Epidemiological Monitoring, biology.protein, Seasons, Influenza Vaccine, Research Article, Human
Abstract

BackgroundSince 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season.MethodsFrom 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene.ResultsCo-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for > 20% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains.ConclusionsThis study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004–2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases.

Published
2019

18. Long-term maintenance of virologic suppression in native and migrant HIV-1 naïve patients: an Italian cohort study

Author

Lagi, F., Kiros, S. T., Di Giambenedetto, Simona, Lombardi, Francesca, Pecorari, Mauro, Borghi, V., Lepore, L., Monno, L., Setti, M., Micheli, V., Bagnarelli, P., Paolini, E., Bai, F., Bartoloni, A., Sterrantino, G., Di Giambenedetto S. (ORCID:0000-0001-6990-5076), Lombardi F. (ORCID:0000-0001-5757-8346), Pecorari M., Lagi, F., Kiros, S. T., Di Giambenedetto, Simona, Lombardi, Francesca, Pecorari, Mauro, Borghi, V., Lepore, L., Monno, L., Setti, M., Micheli, V., Bagnarelli, P., Paolini, E., Bai, F., Bartoloni, A., Sterrantino, G., Di Giambenedetto S. (ORCID:0000-0001-6990-5076), Lombardi F. (ORCID:0000-0001-5757-8346), and Pecorari M.

Abstract

Little is known about long-term maintenance of virologic suppression in HIV migrants in Italy. The study aims to compare virologic failure rates and associated factors among antiretroviral therapy (ART)-naïve migrants and natives enrolled in the ARCA database since 2007 who achieved virologic suppression within 18 months from the beginning of the ART. Kaplan-Meier method assessed the probability of virologic suppression and failure. Cox regression model was used for multivariate analysis. Of 2515 patients, 2020 (80.3%) were Italian, 286 (10.6%) migrants from low-income countries, of whom 201 (75.0%) from Africa, and 227 (9.0%) from high-income-countries. The median follow-up was 4.5 years (IQR 2.5–7). No difference was observed in the time of achievement of virological suppression in the three groups (log-rank: p = 0.5687). Higher probability of virologic failure was observed in Africans compared to Italians, to patients from high-income-countries and from low-income-countries other than Africans (Log-rank = p < 0.001). In the adjusted analysis, a higher virologic failure risk was found in Africans only compared to Italians. [HR 4.01; 95% CI 2.44–6.56, p < 0.001]. In Italy, African migrants are less likely to maintain virologic suppression compared to natives and other migrants. Targeted interventions could be needed for foreigners, especially for Africans.

Published
2021

19. Prevalence of acquired resistance mutations in a large cohort of perinatally infected HIV-1 patients

Author

Ungaro, R., Taramasso, L., Bruzzone, B., Vicenti, I., Galli, L., Borghi, V., Francisci, D., Pecorari, M., Zoncada, A., Callegaro, A. P., Paolini, E., Monno, L., Bonora, S., Di Biagio, A., ARCA Study Group, Giacometti, A., Butini, L., del Gobbo, R., Bagnarelli, P., Tacconi, D., Corbelli, G., Zanussi, S., Punzi, G., Maggiolo, F., Calza, L., Carla Re, M., Pristera, R., Turconi, P., Mandas, A., Tini, S., Amadio, G., Sighinolfi, L., Corsi, P., Di Pietro, M., Colao, G., Tosti, A., Setti, M., Cenderello, G., Trezzi, M., Orani, A., Arcidiacono, I., Degiuli, A., De Gennaro, M., Chiodera, A., Scalzini, A., Palvarini, L., Todaro, G., Rusconi, S., Gismondo, M. R., Micheli, V., Biondi, M. L., Capetti, A., Meraviglia, P., Boeri, E., Mussini, C., Soria, A., Vecchi, L., Santirocchi, M., Brustia, D., Ravanini, P., Dal Bello, F., Romano, N., Mancuso, S., Calzetti, C., Maserati, R., Filice, G., Baldanti, F., Parruti, G., Polilli, E., Sacchini, D., Martinelli, C., Consolini, R., Vatteroni, L., Vivarelli, A., Nerli, A., Lenzi, L., Magnani, G., Ortolani, P., Andreoni, M., Fimiani, C., Palmisano, L., Di Giambenedetto, S., Vullo, V., Turriziani, O., Montano, M., Antinori, A., Zaccarelli, M., Dentone, C., Gonnelli, A., De Luca, A., Palumbo, M., Ghisetti, V., Delle Foglie, P., Rossi, C., Mondino, V., Malena, M., Grossi, P., Seminari, E., Poletti, F., Ungaro R., Taramasso L., Bruzzone B., Vicenti I., Galli L., Borghi V., Francisci D., Pecorari M., Zoncada A., Callegaro A.P., Paolini E., Monno L., Bonora S., Di Biagio A., Giacometti A., Butini L., del Gobbo R., Bagnarelli P., Tacconi D., Corbelli G., Zanussi S., Punzi G., Maggiolo F., Calza L., Carla Re M., Pristera R., Turconi P., Mandas A., Tini S., Amadio G., Sighinolfi L., Corsi P., Di Pietro M., Colao G., Tosti A., Setti M., Cenderello G., Trezzi M., Orani A., Arcidiacono I., Degiuli A., De Gennaro M., Chiodera A., Scalzini A., Palvarini L., Todaro G., Rusconi S., Gismondo M.R., Micheli V., Biondi M.L., Capetti A., Meraviglia P., Boeri E., Mussini C., Soria A., Vecchi L., Santirocchi M., Brustia D., Ravanini P., Dal Bello F., Romano N., Mancuso S., Calzetti C., Maserati R., Filice G., Baldanti F., Parruti G., Polilli E., Sacchini D., Martinelli C., Consolini R., Vatteroni L., Vivarelli A., Nerli A., Lenzi L., Magnani G., Ortolani P., Andreoni M., Fimiani C., Palmisano L., Di Giambenedetto S., Vullo V., Turriziani O., Montano M., Antinori A., Zaccarelli M., Dentone C., Gonnelli A., De Luca A., Palumbo M., Ghisetti V., Delle Foglie P., Rossi C., Mondino V., Malena M., Grossi P., Seminari E., and Poletti F.

Subjects
Male, antiretroviral treatment, Infectious Disease Transmission, genotype, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, medicine.disease_cause, Retrospective Studie, Genotype, pol Gene Products, Human Immunodeficiency Viru, Prevalence, Medicine, Vertical, HIV Infection, Viral, pol Gene Products, Young adult, General Medicine, Infectious Diseases, Italy, Mutation (genetic algorithm), Female, Human Immunodeficiency Virus, Human, Microbiology (medical), Adult, Settore MED/17 - Malattie Infettive, Adolescent, Anti-HIV Agents, Young Adult, Acquired resistance, Drug Resistance, Viral, Humans, vertical HIV transmission, HIV-1, Mutation, Retrospective Studies, pol Gene Products, Human Immunodeficiency Virus, Infectious Disease Transmission, Vertical, HIV perinatally infection, business.industry, Anti-HIV Agent, Retrospective cohort study, Virology, Large cohort, business
Published
2019

20. HIV-1 subtype F1 epidemiological networks among Italian heterosexual males are associated with introduction events from South America.

Author

Alessia Lai, Francesco R Simonetti, Gianguglielmo Zehender, Andrea De Luca, Valeria Micheli, Paola Meraviglia, Paola Corsi, Patrizia Bagnarelli, Paolo Almi, Alessia Zoncada, Stefania Paolucci, Angela Gonnelli, Grazia Colao, Danilo Tacconi, Marco Franzetti, Massimo Ciccozzi, Maurizio Zazzi, and Claudia Balotta

Subjects
Medicine, Science
Abstract

About 40% of the Italian HIV-1 epidemic due to non-B variants is sustained by F1 clade, which circulates at high prevalence in South America and Eastern Europe. Aim of this study was to define clade F1 origin, population dynamics and epidemiological networks through phylogenetic approaches. We analyzed pol sequences of 343 patients carrying F1 subtype stored in the ARCA database from 1998 to 2009. Citizenship of patients was as follows: 72.6% Italians, 9.3% South Americans and 7.3% Rumanians. Heterosexuals, Homo-bisexuals, Intravenous Drug Users accounted for 58.1%, 24.0% and 8.8% of patients, respectively. Phylogenetic analysis indicated that 70% of sequences clustered in 27 transmission networks. Two distinct groups were identified; the first clade, encompassing 56 sequences, included all Rumanian patients. The second group involved the remaining clusters and included 10 South American Homo-bisexuals in 9 distinct clusters. Heterosexual modality of infection was significantly associated with the probability to be detected in transmission networks. Heterosexuals were prevalent either among Italians (67.2%) or Rumanians (50%); by contrast, Homo-bisexuals accounted for 71.4% of South Americans. Among patients with resistant strains the proportion of clustering sequences was 57.1%, involving 14 clusters (51.8%). Resistance in clusters tended to be higher in South Americans (28.6%) compared to Italian (17.7%) and Rumanian patients (14.3%). A striking proportion of epidemiological networks could be identified in heterosexuals carrying F1 subtype residing in Italy. Italian Heterosexual males predominated within epidemiological clusters while foreign patients were mainly Heterosexual Rumanians, both males and females, and South American Homo-bisexuals. Tree topology suggested that F1 variant from South America gave rise to the Italian F1 epidemic through multiple introduction events. The contact tracing also revealed an unexpected burden of resistance in epidemiological clusters underlying the need of public interventions to limit the spread of non-B subtypes and transmitted drug resistance.

Published
2012
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21. Anti-HIV-1 response elicited in rabbits by anti-idiotype monoclonal antibodies mimicking the CD4-binding site.

Author

Roberto Burioni, Nicasio Mancini, Donata De Marco, Nicola Clementi, Mario Perotti, Giovanni Nitti, Monica Sassi, Filippo Canducci, Krisha Shvela, Patrizia Bagnarelli, John R Mascola, and Massimo Clementi

Subjects
Medicine, Science
Abstract

Antibodies against conserved epitopes on HIV-1 envelope glycoproteins (Env), such as the gp120 CD4-binding site (CD4bs), could contribute to protection against HIV-1. Env-based immunogens inducing such a response could be a major component of future anti-HIV-1 strategies. In this proof-of-concept study we describe the generation of two anti-idiotype (AI) murine antibodies mimicking the CD4bs epitope. Sera were collected from long-term non-progressor patients to obtain CD4bs-directed IgG, through sequential purification steps. The purified IgG were then used as Fab fragments to immunize mice for hybridoma generation. Two hybridomas (P1 and P2), reacting only against the CD4bs-directed IgG, were identified and characterized. The P1 and P2 antibodies were shown to recognize the idiotype of the broadly neutralizing anti-CD4bs human mAb b12. Both P1 and P2 Fabs were able to induce a strong anti-gp120 response in rabbits. Moreover, the rabbits' sera were shown to neutralize two sensitive tier 1 strains of HIV-1 in an Env-pseudotype neutralization assay. In particular, 3/5 rabbits in the P1 group and 1/5 in the P2 group showed greater than 80% neutralizing activity against the HXB2 pseudovirus. Two rabbits also neutralized the pseudovirus HIV-MN. Overall, these data describe the first anti-idiotypic vaccine approach performed to generate antibodies to the CD4bs of the HIV-1 gp120. Although future studies will be necessary to improve strength and breadth of the elicited neutralizing response, this proof-of-concept study documents that immunogens designed on the idiotype of broadly neutralizing Abs are feasible and could help in the design of future anti-HIV strategies.

Published
2008
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23. Comentario editorial

Author

Bagnarelli , Aníbal E.

Subjects
Biochemistry, QD415-436, Internal medicine, RC31-1245
Published
2006

24. Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Author

Rossetti, B., Giambenedetto, Di, Torti, S, Postorino, C. c., Punzi, M. C., Saladini, G., Gennari, F., Borghi, W. f., Monno, V., Pignataro, L., Polilli, A. R., Colafigli, E., Poggi, M., Tini, A., Zazzi, S., Luca, De, Mellace, A., Capetti, V., Gismondo, A., Biondi, M. R., Mussini, M. L., Pecorari, C., Gianotti, M., Sacchini, N., Parruti, D., Baldelli, F., Zanussi, S., Nerli, A., Lenzi, L., Calzetti, C., Vivarelli, A., Maserati, R., Baldanti, F., Poletti, F., Mondino, V., Malena, M., Cascio, A., Filice, G., Magnani, G., Zerbini, A., Lombardi, F., Gaimbenedetto, Di, Andreoni, S., Montano, M., Vullo, M., Turriziani, V., Gonnelli, O., Boeri, A., Bonora, E., Ghisetti, S., Francisci, D., Grossi, P., Bagnarelli, P., Butini, L., Del, Gobbo, Giacometti, R., Tacconi, A., Callegaro, D., Maggiolo, A., Zoncada, F., Paolini, A., Sighinolfi, E., Colao, L., Corsi, G., Blanc, P., Galli, P., Meraviglia, L., Tosti, P., Bruzzone, A., Setti, B., Penco, M., Biagio, Di, Nencioni, A., Pardelli, C., Arcidiacono, R., Degiuli, I., Gennaro, De, Soria, M., Foc, A., Latella, A., Cosco, S., Malandrin, L., Milini, S., Cicconi, P., Rusconi, P., Micheli, S., the Antiviral Response Cohort Analysis (ARCA) Collaborative Group, Rossetti B., Di Giambenedetto S., Torti C., Postorino M.C., Punzi G., Saladini F., Gennari W., Borghi V., Monno L., Pignataro A.R., Polilli E., Colafigli M., Poggi A., Tini S., Zazzi M., De Luca A., Mellace V., Capetti A., Gismondo M.R., Biondi M.L., Mussini C., Pecorari M., Gianotti N., Sacchini D., Parruti G., Baldelli F., Zanussi S., Nerli A., Lenzi L., Calzetti C., Vivarelli A., Maserati R., Baldanti F., Poletti F., Mondino V., Malena M., Cascio A., Filice G., Magnani G., Zerbini A., Lombardi F., Di Gaimbenedetto S., Andreoni M., Montano M., Vullo V., Turriziani O., Gonnelli A., Boeri E., Bonora S., Ghisetti V., Francisci D., Grossi P., Bagnarelli P., Butini L., del Gobbo R., Giacometti A., Tacconi D., Callegaro A., Maggiolo F., Zoncada A., Paolini E., Sighinolfi L., Colao G., Corsi P., Blanc P., Galli L., Meraviglia P., Tosti A., Bruzzone B., Setti M., Penco G., Di Biagio A., Nencioni C., Pardelli R., Arcidiacono I., Degiuli A., De Gennaro M., Soria A., Foc A., Latella S., Cosco L., Malandrin S., Milini P., Cicconi P., Rusconi S., and Micheli V.

Subjects
0301 basic medicine, Male, antiretroviral therapy, HIV, recent HIV infection, resistance epidemiology, transmitted HIV drug resistance, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Female, HIV Infections, HIV-1, Humans, Italy, Middle Aged, Mutation, Odds Ratio, Prevalence, Viral Proteins, Drug Resistance, Viral, Health Policy, Infectious Diseases, Pharmacology (medical), Drug Resistance, Drug resistance, Gastroenterology, Interquartile range, HIV Infection, Viral, biology, Integrase, Viral load, Human, medicine.medical_specialty, 030106 microbiology, Settore MED/17 - MALATTIE INFETTIVE, Virus, 03 medical and health sciences, Internal medicine, medicine, Viral Protein, business.industry, Anti-HIV Agent, Odds ratio, Reverse transcriptase, Confidence interval, biology.protein, business
Abstract

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169–521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR 4.1–5.3 log 10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P=0.003): TDR to NRTIs from 9.9 to 2.9% (P=0.003) and TDR to NNRTIs from 5.1 to 3.7% (P=0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P&nbsp

Published
2018

25. Interim 2017/18 influenza seasonal vaccine effectiveness: combined results from five European studies

Author

Rondy, M, Kissling, E, Emborg, Hd, Gherasim, A, Pebody, R, Trebbien, R, Pozo, F, Larrauri, A, Mcmenamin, J, Valenciano, M, Kaic, B, Kurecic Filipovic, S, Visekruna-Vucina, V, Pem Novosel, I, Lovric, Z, Petrović, G, Krause, Tg, Fischer, Tk, Lina, B, Falchi, Antonella, Vilcu, Am, Souty, C, Blanchon, T, van der Werf, S, Enouf, V, Behillil, S, Valette, M, Bernard-Stoecklin, S, Lévy-Bruhl, D, Launay, O, Loulergue, P, Lenzi, N, Lesieur, Z, L'Honneur, As, Galtier, F, Agostini, C, Serrand, C, Merle, C, Foulongne, V, Vanhems, P, Lainé, F, Lagathu, G, Carrat, F, Buda, S, Preuss, U, Prahm, K, Schweiger, B, Wedde, M, Heider, A, Martin, M, Biere, B, Duerrwald, R, Domegan, L, Coughlan, L, O’Donnell, J, Joyce, M, Collins, C, Dunford, L, Martin Moran, Josè Manuel, Tuite, G, Duffy, M, Connell, J, de Gascun, C, Rizzo, C, Bella, A, Alfonsi, V, Castrucci, Mr, Puzelli, S, Pagani, E, Ghisetti, V, Pariani, E, Baldanti, F, Palù, G, D'Agaro, P, Ansaldi, F, Affanni, P, Rossolini, Gm, Camilloni, B, Bagnarelli, P, Sanguinetti, M, Atripaldi, L, Chironna, M, Serra, C, Vitale, F, Germinario, C, Orsi, A, Manini, I, Montomoli, E, Napoli, C, Orsi, Gb, Casado, I, Castilla, J, Fernandino, L, Martínez-Baz, I, Ezpeleta, G, Navascués, A, Pérez-García, A, Aguinaga, A, Ezpeleta, C, Meijer, A, van den Brink, S, van der Hoek, W, Goderski, G, Wijsman, L, Bagheri, M, Dijkstra, F, de Lange, M, Marzec, T, Overduin, P, Teirlinck, A, Wentink, E, Donker, G, Marbus, S, van Gageldonk- Lafeber, R, Schneeberger, P, van Oosterheert JJ, Schweitzer, V, Groeneveld, G, Nunes, B, RIBEIRO MACHADO, CARLOS AUGUSTO, Rodrigues, Ap, DIAZ GOMEZ, MARIA VANESSA, Kislaya, I, Guiomar, R, Pechirra, P, Cristóvão, P, Costa, I, Panarra, A, Côrte-Real, R, Poças, J, João Peres, M, García Comas, L, Marisquerena, Mei, Galán, Jc, Folgueira, D, Gonzalez Carril, F, Sancho Martínez, R, Cilla, G, García Cenoz, M, Quiñones Rubio, C, Martinez Ochoa, E, Blasco, M, Gimenez Duran, J, Vanrell, Jm, Reina, J, Castrillejo, D, Gherasim, Am, Delgado, C, Oliva, J, Casas, I, García, M, Latorre, M, Milagro Beamonte AM, Martinez Sapiñ, A, Oribe Amores, M, Aizpurúa, A, Montes, Marco, Zakikhany, K, Brytting, M, Wiman, Å, Carnahan, A, Warburton, F, Djennad, A, Ellis, J, Andrews, N, Marques, D, Cottrell, S, Reynolds, Alexander, Gunson, R, Galiano, M, Lackenby, A, Robertson, C, O’Doherty, M, Sinnathamby, M, Yonova, I, Moore, C, Sartaj, M, de Lusignan, S, Zambon, M, Moren, A, Penttinen, P., Unión Europea, EpiConcept [Paris], Statens Serum Institut [Copenhagen], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Rondy M., Kissling E., Emborg H.-D., Gherasim A., Pebody R., Trebbien R., Pozo F., Larrauri A., McMenamin J., Valenciano M., Kaic B., Filipovic S.K., Visekruna-Vucina V., Novosel I.P., Lovric Z., Petrovic G., Krause T.G., Fische T.K., Lina B., Falchi A., Vilcu A.-M., Souty C., Blanchon T., van der Werf S., Enouf V., Behillil S., Valette M., Bernard-Stoecklin S., Levy-Bruhl D., Launay O., Loulergue P., Lenzi N., Lesieur Z., L'Honneur A.-S., Galtier F., Agostini C., Serrand C., Merle C., Foulongne V., Vanhems P., Laine F., Lagathu G., Carrat F., Buda S., Preuss U., Prahm K., Schweiger B., Wedde M., Heider A., Martin M., Biere B., Duerrwald R., Domegan L., Coughlan L., O'Donnell J., Joyce M., Collins C., Dunford L., Moran J., Tuite G., Duffy M., Connell J., de Gascun C., Rizzo C., Bella A., Alfonsi V., Castrucci M.R., Puzelli S., Pagani E., Ghisetti V., Pariani E., Baldanti F., Palu G., D'Agaro P., Ansaldi F., Affanni P., Rossolini G.M., Camilloni B., Bagnarelli P., Sanguinetti M., Atripaldi L., Chironna M., Serra C., Vitale F., Germinario C., Orsi A., Manini I., Montomoli E., Napoli C., Orsi G.B., Casado I., Castilla J., Fernandino L., Martinez-Baz I., Ezpeleta G., Navascues A., Perez-Garcia A., Aguinaga A., Ezpeleta C., Meijer A., van den Brink S., van der Hoek W., Goderski G., Wijsman L., Bagheri M., Dijkstra F., de Lange M., Marzec T., Overduin P., Teirlinck A., Wentink E., Donker G., Marbus S., van Gageldonk-Lafeber R., Schneeberger P., van Oosterheert J.J., Schweitzer V., Groeneveld G., Nunes B., Machado A., Rodrigues A.P., Gomez V., Kislaya I., Guiomar R., Pechirra P., Cristovao P., Costa I., Panarra A., Corte-Real R., Pocas J., Peres M.J., Comas L.G., Marisquerena M.E.I., Galan J.C., Folgueira M.D., Carril F.G., Martinez R.S., Cilla G., Cenoz M.G., Rubio C.Q., Ochoa E.M., Blasco M., Duran J.G., Vanrell J.M., Reina J., Castrillejo D., Gherasim A.M., Delgado C., Oliva J., Casas I., Garcia M., Latorre M., Beamonte A.M.M., Sapina A.M., Amores M.O., Aizpurua A., Montes M., Zakikhany K., Brytting M., Wiman A., Carnahan A., Warburton F., Djennad A., Ellis J., Andrews N., Marques D., Cottrell S., Reynolds A., Gunson R., Galiano M., Lackenby A., Robertson C., O'Doherty M., Sinnathamby M., Yonova I., Moore C., Sartaj M., de Lusignan S., Zambon M., Moren A., Penttinen P., Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Marc, Rondy, Esther, Kissling, Hanne-Dorthe, Emborg, Alin, Gherasim, Richard, Pebody, Ramona, Trebbien, Francisco, Pozo, Amparo, Larrauri, Jim, Mcmenamin, Marta, Valenciano, D'Agaro, Pierlanfranco, De Lusignan, S, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)

Subjects
0301 basic medicine, Male, Pediatrics, Epidemiology, viruses, Influenza B viru, influenza, influenza vaccine effectiveness, influenza vaccination, case control study, multicentre study, Europe, Europe, case control study, influenza, influenza vaccination, influenza vaccine effectiveness, multicentre study, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interim, Pandemic, Influenza A Virus, 030212 general & internal medicine, QA, Influenza vaccine effectiveness, Child, media_common, Vaccine Effectiveness, Vaccination, virus diseases, Middle Aged, 3. Good health, Treatment Outcome, Influenza Vaccines, Child, Preschool, H3N2 Subtype, Female, Seasons, Influenza Vaccine, Rapid Communication, Human, Adult, RM, medicine.medical_specialty, Adolescent, Influenza vaccine, 030106 microbiology, Case control study, Multicentre study, European studies, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, 03 medical and health sciences, Virology, Influenza, Human, medicine, media_common.cataloged_instance, Humans, H1N1 Subtype, Vacina Antigripal, European Union, European union, Preschool, Pandemics, Aged, Influenza A Virus, H3N2 Subtype, Cuidados de Saúde, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Influenza a, influenza vaccine effectivene, Newborn, Influenza, respiratory tract diseases, Influenza vaccination, Influenza B virus, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Determinantes da Saúde e da Doença, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract

Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates. Funding: The five studies have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446 to conduct the study in individuals aged 65 years or more. ECDC has contributed to fund some study sites of the EU-PC study under the Framework contract No ECDC/2014/026 for the individuals aged less than 65 years. All study teams are very grateful to all patients, general practitioners, paediatricians, hospital teams, laboratory teams, regional epidemiologists who have contributed to the studies. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu Database used for this study. All submitters of data may be contacted directly via the GISAID website www.gisaid.org Sí

Published
2018
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27. Local Epidemics Gone Viral: Evolution and Diffusion of the Italian HIV-1 Recombinant Form CRF60_BC

Author

Lai, A., Simonetti, F. R., Brindicci, G., Bergna, A., Di Giambenedetto, S., Sterrantino, G., Mussini, C., Menzo, S., Bagnarelli, P., Zazzi, M., Angarano, G., Galli, M., Monno, L., and Balotta, C.

Subjects
second generation recombinants, HIV-1 outbreak, HIV-1 evolution, HIV-1 molecular epidemiology, HIV-1 recombinant forms, Second generation recombinants, lcsh:QR1-502, Settore MED/17 - MALATTIE INFETTIVE, Microbiology, lcsh:Microbiology, Original Research
Abstract

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18–37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy.

Published
2019

30. Hepatitis E in Italy: 5 years of national epidemiological, virological and environmental surveillance, 2012 to 2016

Author

Alfonsi, V., Romano, L., Ciccaglione, A. R., La Rosa, G., Bruni, R., Zanetti, A., Libera, S. D., Iaconelli, M., Bagnarelli, P., Capobianchi, M. R., Garbuglia, A. R., Riccardo, F., Tosti, M. E., Ferrigno, L., Crateri, S., Galli, C., Tagliacarne, C., Giordani, M. T., Morelli, E., Vit, A., Bertin, T., Marinello, S., De Checchi, G., Zotti, C., Amprino, V., Rossati, A., Di Vito, A., Guidoni, C., Fiacchini, D., Marinelli, K., Loffredo, M., De Angelis, G., Citarella, A., and Megnia, A. S.

Subjects
0301 basic medicine, Swine, Sewage, Wastewater, medicine.disease_cause, Surveillance and Outbreak Report, 0302 clinical medicine, Hepatitis E virus, Epidemiology, Genotype, 80 and over, risk factors, 030212 general & internal medicine, Viral, Child, Phylogeny, Aged, 80 and over, Travel, Transmission (medicine), Middle Aged, Hepatitis E, 6. Clean water, 3. Good health, One Health, Italy, surveillance, RNA, Viral, epidemiology, Travel-Related Illness, Environmental Monitoring, Adult, medicine.medical_specialty, Adolescent, viral infections, Food Contamination, 03 medical and health sciences, Young Adult, Virology, Environmental health, medicine, Animals, Humans, Waste Water, Risk factor, Aged, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, 030104 developmental biology, RNA, business
Abstract

Increasing numbers of hepatitis E cases are being reported in several European countries, including Italy, but the burden of hepatitis E virus (HEV) infection is largely unknown in the latter. To gain a better understanding of HEV epidemiology at national level in Italy, we piloted a strengthened and integrated human (epidemiological and virological) and environmental HEV surveillance system between 2012 and 2016. Over the 5-year period, 169 confirmed hepatitis E cases were identified, with a national annual incidence of 0.72 cases per 1,000,000. Of 65 HEV-RNA positive samples of sufficient quality for molecular analysis, 66% were genotype HEV3, 32% HEV1 and 1% HEV4. The most frequent risk factor reported by all HEV3 infected cases, was the consumption of undercooked pork and sausage. For the environmental surveillance, 679 urban sewage samples were collected from 53 wastewater treatment plants and HEV-RNA was detected in 38/679 of the samples. Among these, 25 (66%) were genotype HEV3 and the remaining were HEV1. We demonstrate that autochthonous transmission and environmental circulation of genotype HEV3 is adding to travel-related HEV transmission in Italy. We recommend the ‘One Health’ approach to integrated surveillance, and to include HEV-related messages within health information campaigns focussing on food security.

Published
2018

31. Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy

Author

Costantini Andrea, Marinelli Katia, Biagioni Giulia, Monachetti Alessia, Ferreri Monica L, Butini Luca, Montroni Maria, Manzin Aldo, and Bagnarelli Patrizia

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Occult hepatitis B virus (HBV) infection (OBI) is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease. Case presentation We report the case of an individual with human immunodeficiency virus (HIV) infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART). HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels. Conclusion This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals.

Published
2011
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32. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

Author

Micheli Valeria, Bagnarelli Patrizia, Penco Giovanni, Callegaro Annapaola, Bruzzone Bianca, Meini Genny, Fanti Iuri, Di Giambenedetto Simona, Prosperi Mattia CF, Paolini Elisabetta, Di Biagio Antonio, Ghisetti Valeria, Di Pietro Massimo, Zazzi Maurizio, and De Luca Andrea

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

Published
2011
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34. Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects

Author

Mazzi Benedetta, Gallotta Giulia, Degano Massimo, Bagnarelli Patrizia, Berrè Stefano, Sampaolo Michela, Marinozzi Maria, Canducci Filippo, Lemey Philippe, Burioni Roberto, and Clementi Massimo

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract The characteristics of intra-host human immunodeficiency virus type 1 (HIV-1) env evolution were evaluated in untreated HIV-1-infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term non-progressor [LTNP] patients. High-resolution phylogenetic analysis of the C2-C5 env gene sequences of the replicating HIV-1 was performed in sequential samples collected over a 3–5 year period; overall, 301 HIV-1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3rd codon mutation rate was equal or even lower than that observed at the 1st and 2nd positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximum-likelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of N-linked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4-binding site (CD4bs). In addition, localized pressure in the area of the IgG-b12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3-dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV-1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV-1 infection.

Published
2009
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35. Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

Author

Sisti Stefano, Marinelli Katia, Bagnarelli Patrizia, Ciavattini Andrea, Menzo Stefano, and Clementi Massimo

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Human papillomavirus (HPV) tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR) HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings. Results In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000–2007, were analyzed using PCR amplification of a 173–206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer. Conclusion Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.

Published
2008
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37. Interim 2017/18 influenza seasonal vaccine effectiveness: Combined results from five European studies

Author

Rondy, M., Kissling, E., Emborg, H. -D., Gherasim, A., Pebody, R., Trebbien, R., Pozo, F., Larrauri, A., Mcmenamin, J., Valenciano, M., Kaic, B., Filipovic, S. K., Visekruna-Vucina, V., Novosel, I. P., Lovric, Z., Petrovic, G., Krause, T. G., Fische, T. K., Lina, B., Falchi, A., Vilcu, A. -M., Souty, C., Blanchon, T., van der Werf, S., Enouf, V., Behillil, S., Valette, M., Bernard-Stoecklin, S., Levy-Bruhl, D., Launay, O., Loulergue, P., Lenzi, N., Lesieur, Z., L'Honneur, A. -S., Galtier, F., Agostini, C., Serrand, C., Merle, C., Foulongne, V., Vanhems, P., Laine, F., Lagathu, G., Carrat, F., Buda, S., Preuss, U., Prahm, K., Schweiger, B., Wedde, M., Heider, A., Martin, M., Biere, B., Duerrwald, R., Domegan, L., Coughlan, L., O'Donnell, J., Joyce, M., Collins, C., Dunford, L., Moran, J., Tuite, G., Duffy, M., Connell, J., de Gascun, C., Rizzo, C., Bella, A., Alfonsi, V., Castrucci, M. R., Puzelli, S., Pagani, E., Ghisetti, V., Pariani, E., Baldanti, F., Palu, G., D'Agaro, P., Ansaldi, F., Affanni, P., Rossolini, G. M., Camilloni, B., Bagnarelli, P., Sanguinetti, Maurizio, Atripaldi, L., Chironna, M., Serra, C., Vitale, F., Germinario, C., Orsi, A., Manini, I., Montomoli, E., Napoli, C., Orsi, G. B., Casado, I., Castilla, J., Fernandino, L., Martinez-Baz, I., Ezpeleta, G., Navascues, A., Perez-Garcia, A., Aguinaga, A., Ezpeleta, C., Meijer, A., van den Brink, S., van der Hoek, W., Goderski, G., Wijsman, L., Bagheri, M., Dijkstra, F., de Lange, M., Marzec, T., Overduin, P., Teirlinck, A., Wentink, E., Donker, G., Marbus, S., van Gageldonk-Lafeber, R., Schneeberger, P., van Oosterheert, J. J., Schweitzer, V., Groeneveld, G., Nunes, B., Machado, A., Rodrigues, A. P., Gomez, V., Kislaya, I., Guiomar, R., Pechirra, P., Cristovao, P., Costa, I., Panarra, A., Corte-Real, R., Pocas, J., Peres, M. J., Comas, L. G., Marisquerena, M. E. I., Galan, J. C., Folgueira, M. D., Carril, F. G., Martinez, R. S., Cilla, G., Cenoz, M. G., Rubio, C. Q., Ochoa, E. M., Blasco, M., Duran, J. G., Vanrell, J. M., Reina, J., Castrillejo, D., Gherasim, A. M., Delgado, C., Oliva, J., Casas, I., Garcia, M., Latorre, M., Beamonte, A. M. M., Sapina, A. M., Amores, M. O., Aizpurua, A., Montes, M., Zakikhany, K., Brytting, M., Wiman, A., Carnahan, A., Warburton, F., Djennad, A., Ellis, J., Andrews, N., Marques, D., Cottrell, S., Reynolds, A., Gunson, R., Galiano, M., Lackenby, A., Robertson, C., O'Doherty, M., Sinnathamby, M., Yonova, I., Moore, C., Sartaj, M., de Lusignan, S., Zambon, M., Moren, A., Penttinen, P., Sanguinetti M. (ORCID:0000-0002-9780-7059), Rondy, M., Kissling, E., Emborg, H. -D., Gherasim, A., Pebody, R., Trebbien, R., Pozo, F., Larrauri, A., Mcmenamin, J., Valenciano, M., Kaic, B., Filipovic, S. K., Visekruna-Vucina, V., Novosel, I. P., Lovric, Z., Petrovic, G., Krause, T. G., Fische, T. K., Lina, B., Falchi, A., Vilcu, A. -M., Souty, C., Blanchon, T., van der Werf, S., Enouf, V., Behillil, S., Valette, M., Bernard-Stoecklin, S., Levy-Bruhl, D., Launay, O., Loulergue, P., Lenzi, N., Lesieur, Z., L'Honneur, A. -S., Galtier, F., Agostini, C., Serrand, C., Merle, C., Foulongne, V., Vanhems, P., Laine, F., Lagathu, G., Carrat, F., Buda, S., Preuss, U., Prahm, K., Schweiger, B., Wedde, M., Heider, A., Martin, M., Biere, B., Duerrwald, R., Domegan, L., Coughlan, L., O'Donnell, J., Joyce, M., Collins, C., Dunford, L., Moran, J., Tuite, G., Duffy, M., Connell, J., de Gascun, C., Rizzo, C., Bella, A., Alfonsi, V., Castrucci, M. R., Puzelli, S., Pagani, E., Ghisetti, V., Pariani, E., Baldanti, F., Palu, G., D'Agaro, P., Ansaldi, F., Affanni, P., Rossolini, G. M., Camilloni, B., Bagnarelli, P., Sanguinetti, Maurizio, Atripaldi, L., Chironna, M., Serra, C., Vitale, F., Germinario, C., Orsi, A., Manini, I., Montomoli, E., Napoli, C., Orsi, G. B., Casado, I., Castilla, J., Fernandino, L., Martinez-Baz, I., Ezpeleta, G., Navascues, A., Perez-Garcia, A., Aguinaga, A., Ezpeleta, C., Meijer, A., van den Brink, S., van der Hoek, W., Goderski, G., Wijsman, L., Bagheri, M., Dijkstra, F., de Lange, M., Marzec, T., Overduin, P., Teirlinck, A., Wentink, E., Donker, G., Marbus, S., van Gageldonk-Lafeber, R., Schneeberger, P., van Oosterheert, J. J., Schweitzer, V., Groeneveld, G., Nunes, B., Machado, A., Rodrigues, A. P., Gomez, V., Kislaya, I., Guiomar, R., Pechirra, P., Cristovao, P., Costa, I., Panarra, A., Corte-Real, R., Pocas, J., Peres, M. J., Comas, L. G., Marisquerena, M. E. I., Galan, J. C., Folgueira, M. D., Carril, F. G., Martinez, R. S., Cilla, G., Cenoz, M. G., Rubio, C. Q., Ochoa, E. M., Blasco, M., Duran, J. G., Vanrell, J. M., Reina, J., Castrillejo, D., Gherasim, A. M., Delgado, C., Oliva, J., Casas, I., Garcia, M., Latorre, M., Beamonte, A. M. M., Sapina, A. M., Amores, M. O., Aizpurua, A., Montes, M., Zakikhany, K., Brytting, M., Wiman, A., Carnahan, A., Warburton, F., Djennad, A., Ellis, J., Andrews, N., Marques, D., Cottrell, S., Reynolds, A., Gunson, R., Galiano, M., Lackenby, A., Robertson, C., O'Doherty, M., Sinnathamby, M., Yonova, I., Moore, C., Sartaj, M., de Lusignan, S., Zambon, M., Moren, A., Penttinen, P., and Sanguinetti M. (ORCID:0000-0002-9780-7059)

Abstract

Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates.

Published
2018

38. Locally acquired hepatitis E virus in Marche Italy: Clinical/laboratory features and outcome.

Author

Tarantino, Giuseppe, Ortolani, Alessio, Marinelli, Katia, Benedetti, Antonio, Marconi, Giulia, Calzolari, Manuela, Dalton, Harry R., Marzioni, Marco, Schiadà, Laura, Fava, Giammarco, Chiodera, Alessandro, Amadio, Giorgio, Fiorentini, Alessandro, Riva, Alessandra, Fraticelli, Paolo, Menzo, Stefano, and Bagnarelli, Patrizia

Abstract

Hepatitis E Virus is endemic in Europe with increasing numbers of cases in recent years, also in Italy where this phenomenon has hitherto been modest. The aim of this study was to document the clinical features/natural history of locally acquired hepatitis E in our territory and explore factors which determine adverse outcome. Retrospective study of patients with locally-acquired HEV (hepatitis E virus) in Marche, Italy (2011–2019). 1189 patients were tested for HEV with 89 confirmed cases. 81 (6.8%) had locally acquired infection; 54 (66%) were male (mean age 55.5 years) and 32 (39.5%) had active co-morbidities. 41 cases were viraemic (all HEV-3 (HEV genotype 1,2,3,4)); acute infection was found in 79 and chronic infection in 2. Forty-five cases (55%) required admission to hospital, for a total of 785 days. 4 patients developed acute on-chronic liver failure, 6 developed acute kidney injury and 8 died: all had active comorbidities. Univariate analysis showed that bilirubin, INR, immunosuppression, cirrhosis and diabetes were associated with death. On multivariant analysis the only predictor of death was the presence of diabetes (p = 0.04). Hepatitis E in Marche Italy is mostly locally acquired and caused by HEV-3 that impacts on the morbidity and mortality particularly for fragile patients. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Molecular surveillance of pandemic influenza A(H1N1) viruses circulating in Italy from May 2009 to February 2010: association between haemagglutinin mutations and clinical outcome

Author

Puzelli, S, Facchini, M, De Marco, M. A, Palmieri, A, Spagnolo, D, Boros, S, Corcioli, F, Trotta, D, Bagnarelli, P, Azzi, Anna, Cassone, A, Rezza, G, Pompa, M. G, Oleari, F, Donatelli, I, Capobianchi, Mr, Fadda, Giuseppe, Palu', Giorgio, Vitale, F, D'Agaro, P, Esposito, C, Ghisetti, V, Ansaldi, F, Zanetti, A, Nelli, Lc, Baldanti, F., Puzelli, S., Facchini, M., De Marco, M. A., Palmieri, A., Spagnolo, D., Boros, S., Corcioli, F., Trotta, D., Bagnarelli, P., Azzi, A., Cassone, A., Rezza, G., Pompa, M. G., Oleari, F., Donatelli, I., Influnet Surveillance Group for Pandemic A., 2009 Influenza Virus in Italy, D'Agaro, Pierlanfranco, Puzelli, S, Facchini, M, De Marco, MA, Palmieri, A, Spagnolo, D, Boros, S, Corcioli, F, Trotta, D, Bagnarelli, P, Azzi, A, Cassone, A, Rezza, G, Pompa, MG, Oleari, F, Donatelli, I, and Vitale, F

Subjects
Male, Molecular surveillance, Pandemic influenza A(H1N1), Haemagglutinin mutations, Italy from May 2009 to February 2010, pandemic influenza, surveillance of pandemic influenza A(H1N1), Epidemiology, viruses, Settore MED/42 - Igiene Generale E Applicata, medicine.disease_cause, Severity of Illness Index, Influenza A Virus, H1N1 Subtype, Pandemic, Influenza A Virus, A(H1N1), Child, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), Adolescent, Adult, Age Distribution, Aged, Amino Acid Substitution, Child, Preschool, Female, Hemagglutinins, Humans, Infant, Influenza, Human, Italy, Middle Aged, Population Surveillance, Sex Distribution, Young Adult, Pandemics, haemagglutinin mutations, Human, Biology, Disease cluster, Disease course, Virology, medicine, H1N1 Subtype, Preschool, Molecular epidemiology, Public Health, Environmental and Occupational Health, Pandemic influenza, Influenza, Mutational analysis
Abstract

Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in Italy were examined, focusing on amino acid changes at position 222 because of its suggested pathogenic relevance. Among 169 patients, the D222G substitution was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild cases, whereas the D222E mutation was more frequent and evenly distributed in mild (31.6%) and severe cases (38.4%). A cluster of D222E viruses among school children confirms reported human-to-human transmission of viruses mutated at amino acid position 222.

Published
2010
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40. Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice

Author

Prosperi, Mc, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, ARCA Collaborative Group, Giacometti, A, Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, A, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, Clinic of Infectious Diseases, Università cattolica del Sacro Cuore [Roma] (Unicatt), Molecular Biology, Microbiology and Virology, Bari University Hospital, Clinical Infectious Diseases, Careggi University Hospital, Unit of Infectious Diseases, Catholic Universisty of Sacred Heart, A. Savoia Hospital, infectiuos diseases, Università degli studi di Torino (UNITO), Modena University Hospital, L. Sacco University Hospital, Ancona University Hospital, Grosseto General Hospital, Institute of Infectious Diseases, Sacro Cuore Catholic University, Infectious Diseases Unit, University Hospital of Siena, Prosperi, M, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, M, Bagnarelli, P, Carli, T, De Luca, A, Mancuso, S, Prosperi MC, Zazzi M, Punzi G, Monno L, Colao G, Corsi P, Di Giambenedetto S, Meini G, Ghisetti V, Bonora S, Pecorari M, Gismondo MR, Bagnarelli P, Carli T, De Luca A, ARCA Collaborative Group [.., Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Maggiolo F, Callegaro A, Calza L, Re MC, Raffaele P, Turconi P, Mandas A, Tini S, Zoncada A, Paolini E, Amadio G, Sighinolfi L, and ]

Subjects
Male, Lopinavir/ritonavir, HIV Infections, boosted protease inhibitor, Lopinavir, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, virologic failure, HIV Infection, Treatment Failure, 030212 general & internal medicine, Pyrimidinone, 0303 health sciences, education.field_of_study, lopinavir/ritonavir, Viral Load, Resistance mutation, first-line antiretroviral therapy, Reverse Transcriptase Inhibitor, 3. Good health, Treatment Outcome, Infectious Diseases, RNA, Viral, Reverse Transcriptase Inhibitors, Medicine, Drug Therapy, Combination, Female, Survival Analysi, Viral load, Human, medicine.drug, Anti-HIV Agents, Population, Pyrimidinones, Settore MED/17 - MALATTIE INFETTIVE, Emtricitabine, human immunodeficiency virus type 1, 03 medical and health sciences, Virology, Drug Resistance, Viral, antiretroviral drug resistance, medicine, Humans, Protease inhibitor (pharmacology), education, HIV Protease Inhibitor, Ritonavir, 030306 microbiology, business.industry, Anti-HIV Agent, HIV Protease Inhibitors, Survival Analysis, HIV-1, Cohort Studie, business
Abstract

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.

Published
2010
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41. Quantitative HIV-1 proviral DNA detection: a multicentre analysis

Author

De Rossi A, Zanchetta M, Vitone F, Antonelli G, Bagnarelli P, Luigi Buonaguro, Capobianchi MR, Clementi M, Abbate I, Canducci F, Monachetti A, Riva E, Rozera G, Scagnolari C, Tagliamonte M, Mc, Re, Sivim, Group, De Rossi, A, Zanchetta, M, Vitone, F, Antonelli, G, Bagnarelli, P, Buonaguro, L, Capobianchi, Mr, Clementi, Massimo, Abbate, I, Canducci, F, Monachetti, A, Riva, E, Rozera, G, Scagnolari, C, Tagliamonte, M, Re, Mc, De Rossi A, Zanchetta M, Vitone F, Antonelli G, Bagnarelli P, Buonaguro L, Capobianchi MR, Clementi M, Abbate I, Canducci F, Monachetti A, Riva E, Rozera G, Scagnolari C, Tagliamonte M, and Re MC

Subjects
DNA detection, HIV, HIV Infections, Viral Load, Polymerase Chain Reaction, Sensitivity and Specificity, gag Gene Products, Human Immunodeficiency Virus, dna detection, hiv, standardization, Standardization, Cell Line, Italy, Proviruses, HIV, DNA detection, Standardization, DNA, Viral, HIV-1, Humans, Telomerase
Abstract

Despite the widespread use of molecular biology techniques, standardized methods for the measurement of HIV-1 proviral DNA are currently lacking and several discordant results are still present in different studies. To assess the clinical meaning of the proviral DNA load, a study group comprising seven different laboratories was set up to standardize a HIV-1 proviral DNA quantification method able to assess the DNA proviral load of the most relevant circulating HIV-1 subtypes. Reference samples (24 cellular samples infected with HIV-1 clade B, and 40 samples of peripheral blood mononuclear cells containing different concentrations of plasmids expressing different HIV-1 clades) were distributed and tested blindly. All laboratories employed hTERT gene as housekeeping gene and primers within the gag gene to quantify different HIV-1 clades. Inter-laboratory results did not differ statistically but showed only minor variations concerning HIV-1 DNA amounts and different HIV clades, with a good agreement among the laboratories participating in the study. Since test standardization represents a key step for future application in clinical practice, further studies of the patients' samples are in progress to establish the real meaning and utility of the proviral DNA load for clinical management of HIV-1 infected patients.

Published
2010

42. Synergistic effect of antimicrobial peptide LL-37 and colistin combination against multidrug-resistant Escherichia coliisolates

Author

Morroni, Gianluca, Sante, Laura Di, Simonetti, Oriana, Brescini, Lucia, Kamysz, Wojciech, Kamysz, Elzbieta, Mingoia, Marina, Brenciani, Andrea, Giovanetti, Eleonora, Bagnarelli, Patrizia, Giacometti, Andrea, and Cirioni, Oscar

Abstract

Overview:The global spread of antibiotic resistance represents a serious threat for public health. Aim:We evaluated the efficacy of the antimicrobial peptide LL-37 as antimicrobial agent against multidrug-resistant Escherichia coli. Results:LL-37 showed good activity against mcr-1 carrying, extended spectrum β-lactamase- and carbapenemase-producing E. coli(minimum inhibitory concentration, MIC, from 16 to 64 mg/l). Checkerboard assays demonstrated synergistic effect of LL-37/colistin combination against all tested strains, further confirmed by time–kill and post antibiotic effect assays. MIC and sub-MIC concentrations of LL-37 were able to reduce biofilm formation. Conclusion:Our preliminary data indicated that LL-37/colistin combination was effective against multidrug-resistant E. colistrains and suggested a new possible clinical application.

Published
2021
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43. Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis

Author

Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, MANCUSO, Salvatrice, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, Poletti, F., Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, and Poletti, F

Subjects
Male, Time Factors, Cross-sectional study, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, medicine.disease_cause, Cohort Studies, Antiretroviral Therapy, Highly Active, Ritonavir-boosted darunavir, Genotype, HIV Infection, Treatment Failure, Viral, Genotypic resistance, Darunavir, Sulfonamides, General Medicine, Middle Aged, Virological failure, Infectious Diseases, Female, Human, medicine.drug, Adult, Microbiology (medical), Logistic Model, Time Factor, Antiretroviral Therapy, Settore MED/17 - MALATTIE INFETTIVE, Sulfonamide, Drug Resistance, Viral, medicine, Humans, Highly Active, Protease inhibitors, Cross-Sectional Studies, HIV Protease Inhibitors, HIV-1, Logistic Models, Mutation, HIV Protease Inhibitor, Cross-Sectional Studie, business.industry, Antiretroviral therapy, Virology, Protease inhibitor, Cohort Studie, business
Abstract

Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. Discussion The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. Conclusion: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon. © Springer-Verlag 2011.

Published
2012

44. HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users

Author

Lai, A, Bozzi, G, Franzetti, M, Binda, F, Simonetti, Fr, De Luca, Andrea, Micheli, V, Meraviglia, P, Bagnarelli, P, Di Biagio, A, Monno, L, Saladini, F, Zazzi, M, Zehender, G, Ciccozzi, M, Balotta, C., De Luca, Andrea (ORCID:0000-0002-8311-6935), Lai, A, Bozzi, G, Franzetti, M, Binda, F, Simonetti, Fr, De Luca, Andrea, Micheli, V, Meraviglia, P, Bagnarelli, P, Di Biagio, A, Monno, L, Saladini, F, Zazzi, M, Zehender, G, Ciccozzi, M, Balotta, C., and De Luca, Andrea (ORCID:0000-0002-8311-6935)

Abstract

Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype.

Published
2016

45. Immune reconstitution in HIV-1 infected children with discordant response to antiretroviral therapies: patterns of HIV-1 env gene evolution driven by restoration of thymic function

Author

Vecchi, M., Burighel, N., Bellanova, D., Menzo, S., Anita De Rossi, Clementi, M., Bagnarelli, P., Vecchi, M, Burighel, N, Bellanova, D, Menzo, S, De Rossi, A, Clementi, Massimo, and Bagnarelli, P.

Subjects
recocombinant virus, CD4-Positive T-Lymphocytes, DNA, Complementary, Anti-HIV Agents, T-Lymphocytes, Molecular Sequence Data, HIV Infections, CD8-Positive T-Lymphocytes, HIV Envelope Protein gp120, Genes, env, Evolution, Molecular, evolution, Humans, Amino Acid Sequence, Selection, Genetic, Child, env, V3, HIV-1, evolution, env, V3, recocombinant virus, thymic output, Sequence Analysis, DNA, Peptide Fragments, CD4 Lymphocyte Count, Protein Structure, Tertiary, thymic output, Mutation, HIV-1, RNA, Viral
Abstract

The evolution of human immunodeficiency virus type 1 (HIV-1) env gp120 region was addressed in HIV-1 infected children showing virological failure to antiretroviral therapy (ART). Sequence analysis of the replicating plasma virus at baseline and after one year of therapy documented evolution of gp120 in all subjects but one. Analysis of the host's selective pressure showed that the values of Ka/Ks ratios were higher in the V3 sequence than in the whole C2-V5 region in 4 of 5 children with improvement of thymic output. Moreover, in 2 of the 4 chidren, the V3 evolution paralleled with a reverse shift of the viral phenotype (from CXCR4-tropic to CCR5-tropic). These results suggest that, under ART, the V3 evolution towards less pathogenic viral variants may be driven by the host's increased selective pressure following restoration of thymic function and immune reconstitution.

Published
2005

47. Intra-host evolution of human immunodeficiency virus type 1 and viral fitness

Author

Clementi, M., Filippo Canducci, Bagnarelli, P., Menzo, S., Clementi, Massimo, Canducci, E, Bagnarelli, P, and Menzo, S.

Subjects
AIDS Vaccines, Evolution, Molecular, Anti-HIV Agents, Drug Resistance, Viral, Adaptation, Biological, HIV-1, Humans, Drug Therapy, Combination, HIV Infections, Selection, Genetic
Abstract

RNA viruses are frequently tolerant to high levels of mutagenesis. In contrast, DNA viruses are less errorprone and coevolve along with their specific hosts over long time periods. Although both strategies have been successful, the "RNA-strategy" (directly linked to the pathogenic potential of these agents) most often generates novelty (new variants, new strains, and even new viral pathogens). For several decades, intra-host virus evolution has been considered to be a speculative field, far from the main issues of clinical virology. This concept is now changed, due to the evidence that RNA virus evolution is intimately linked to failures in viral disease control and prevention. Antiviral strategies using single and fixed elements (i.e. treatments using one antiviral compound, immunizations using a single recombinant protein) have been unable to control highly dynamic quasispecies, such as human immunodeficiency virus type I (HIV-1) and hepatitis C virus (HCV). The development of combinatorial treatments in HIV-1 infection and the recognition that vaccines should be multivalent are important steps in adapting disease control strategies to the complexity of viral populations. The present report summarizes the strategies adopted to address HIV-1 evolution and its phenotypic consequences, including changes in susceptibility to antiviral compounds, viral fitness, and pathogenic potential. In particular, it is highlighted that sequence-function analyses of the intra-host HIV-I evolution, including studies of viral fitness, have opened up new perspectives not only to studying the pathogenic mechanisms and the virus-host relationships, but also to designing new strategies for monitoring antiviral therapies.

Published
2004

48. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

Author

PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, CALZA, LEONARDO, RE, MARIA CARLA, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Prosperi, M, Di Giambenedetto, S, Fanti, I, Meini, G, Bruzzone, B, Callegaro, A, Penco, G, Bagnarelli, P, Micheli, V, Paolini, E, Di Biagio, A, Ghisetti, V, Di Pietro, M, Zazzi, M, De Luca, A, and Mancuso, S

Subjects
Oncology, Male, Adult, Anti-HIV Agents, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Middle Aged, Proportional Hazards Models, Treatment Failure, Viral Load, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Medicine, HIV Infection, 030212 general & internal medicine, 0303 health sciences, Health Policy, 3. Good health, Computer Science Applications, Censoring (clinical trials), Cohort, Combination, lcsh:R858-859.7, Viral load, Human, Research Article, Cart, medicine.medical_specialty, antiretroviral therapy, Health Informatics, Settore MED/17 - MALATTIE INFETTIVE, lcsh:Computer applications to medicine. Medical informatics, 03 medical and health sciences, Drug Therapy, Internal medicine, Survival analysis, 030306 microbiology, business.industry, Proportional hazards model, ANTIRETROVIRAL DRUGS, Anti-HIV Agent, HIV, GENOTYPES, Discontinuation, Regimen, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

Published
2011
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