Pavie J.,University Paris Diderot |
Porcher R.,University Paris Diderot |
Torti C.,Institute of Infectious Diseases |
Medrano J.,Charles III University of Madrid |
And 7 more authors.
Journal of Antimicrobial Chemotherapy
Background: Limited data are available on the use of unboosted atazanavir in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced HIV-infected patients. Methods: We conducted a multicentre, retrospective study among patients with plasma HIV-1 RNA levels>50 copies/mL under antiretroviral therapy who switched to unboosted atazanavir+NRTIs between January 2002 and December 2008. Virological failure during follow-up was defined as a confirmed plasma HIV-1 RNA level >50 copies/mL. Baseline risk factors for virological failure were identified using Cox proportional hazards models. Results: A total of 886 patients were analysed. At baseline, median age was 44 years, 71.5% were males and median CD4 cell count was 490 cells/mm 3. NRTIs used in combination with atazanavir were tenofovir, abacavir and emtricitabine/lamivudine in 36.9%, 44.1% and 94.4% of patients, respectively. Median follow-up was 21 months. The 3 year probability of virological failure was 20.1%. Only a history of virological failure under NRTIs [hazard ratio (HR) 1.63, P=0.049] and under protease inhibitors (HR 2.04, P=0.006) were significantly associated with the risk of virological failure. Among the 431 patients without a prior history of virological failure, the 3 year probability of virological failure was 11.3%, and only hepatitis C virus co-infection (HR 2.25, P=0.026) and abacavir use (HR 0.43, P=0.04) were associated with the risk of virological failure. Safety of the switch was satisfactory, with improvement of the lipid profile. Conclusions: In patients with virological suppression and no prior history of virological failure, a switch to unboosted atazanavir in combination with NRTIs is associated with a low probability of virological failure and a good safety profile. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source
Ordanini S.,University of Milan |
Varga N.,University of Milan |
Porkolab V.,CNRS Institute of Pharmacology and Structural Biology |
Porkolab V.,French National Center for Scientific Research |
And 16 more authors.
DC-SIGN antagonists were designed combining one selective monovalent glycomimetic ligand with trivalent dendrons separated by a rigid core of controlled length. The design combines multiple multivalency effects to achieve inhibitors of HIV infection, which are active in nanomolar concentration. © The Royal Society of Chemistry. Source
Capraro J.,University of Milan |
Magni C.,University of Milan |
Faoro F.,UNIMI |
Maffi D.,UNIMI |
And 7 more authors.
Biochemical and Biophysical Research Communications
Lupin seed γ-Conglutin is a protein capable of reducing glycaemia in mammalians and increasing glucose uptake by model cells. This work investigated whether γ-Conglutin is internalised into the target cells and undergoes any covalent change during the process, as a first step to understanding its mechanism of action.To this purpose, γ-Conglutin-treated and untreated HepG2 cells were submitted to confocal and transmission electron microscopy. Immune-revelation of γ-Conglutin at various intervals revealed its accumulation inside the cytosol.In parallel, 2D-electrophoresis of the cell lysates and antibody reaction of the blotted maps showed the presence of the protein intact subunits inside the treated cells, whilest no trace of the protein was found in the control cells. However, γ-Conglutin-related spots with an unexpectedly low pI were also observed in the maps. These spots were excised, trypsin-treated and submitted to MS/MS spectrometric analysis. The presence of phosphorylated amino acids was detected.These findings, by showing that γ-Conglutin is internalised by HepG2 cells in an intact form and is modified by multiple phosphorylation, open the way to the understanding of the lupin γ-Conglutin insulin-mimetic activity. © 2013 Elsevier Inc. Source