Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients.: Effectiveness of triple therapy in cirrhotic patients

International audienceTriple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P = 0.5), but there was a significant difference in the 50% effective concentrations (EC50) (P = 0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively, P = 0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day(-1)) and was higher in patients who subsequently eradicated HCV (P = 0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Hellénisme et judaïsme

Dorival Gilles. Hellénisme et judaïsme. In: La Méditerranée d'une rive à l'autre : culture classique et cultures périphériques. Actes du 17ème colloque de la Villa Kérylos à Beaulieu-sur-Mer les 20 & 21 octobre 2006. Paris : Académie des Inscriptions et Belles-Lettres, 2007. pp. 155-166. (Cahiers de la Villa Kérylos, 18

Les règles de l'interprétation, édité par Michel Tardieu, 1987. (Patrimoines. Religions du Livre. Centre d'Études des Religions du Livre)

Dorival Gilles. Les règles de l'interprétation, édité par Michel Tardieu, 1987. (Patrimoines. Religions du Livre. Centre d'Études des Religions du Livre). In: Revue des Études Anciennes. Tome 90, 1988, n°1-2. pp. 252-253

Denise Aigle (éd.), Miracles et karâma, Hagiographies médiévales comparées 2, Bibliothèque de l'École des Hautes Études-Section des sciences religieuses 109, Turnhout, Brepols, 2000, 690 pages, 240 x 155.

Bien connue par ses travaux sur les vies de saints orientaux, éditrice du recueil Saints orientaux, qui constitue le volume 1 de la collection « Hagiographies médiévales comparées », parue à Paris chez De Boccard en 1995, Denise Aigle réunit ici les quelque vingt-cinq contributions présentées lors du colloque international « Les saints et leurs miracles à travers l'hagiographie chrétienne et islamique, ive-xve siècles », qui s'est tenu à Ivry-sur-Seine en novembre 1995. Ce gros livre constitu..

Hellénisme et patristique grecque: continuité et discontinuité

The way in which took place the meeting between the Helenism and the Christianity of the Greek Fathers has provoked contradicting opinions: conflict and antagonism, o continuity and ajustments? Actually one could say that the Greek Patristic is at the same time a continuity and a discontinuity of the Hellenism, as has been shown by the studies of the methodology, of the literary forms, of the rhetoric, of the theology and of the patristic values

Hellénisme et patristique. Continuité et discontinuité

Dorival Gilles. Hellénisme et patristique. Continuité et discontinuité. In: Bulletin de la Société Nationale des Antiquaires de France, 1994, 1996. pp. 222-224

Les débuts du christianisme à Alexandrie

Dorival Gilles. Les débuts du christianisme à Alexandrie. In: Alexandrie : une mégapole cosmopolite. Actes du 9ème colloque de la Villa Kérylos à Beaulieu-sur-Mer les 2 & 3 octobre 1998. Paris : Académie des Inscriptions et Belles Lettres, 1999. pp. 157-174. (Cahiers de la Villa Kérylos, 9