Antiretroviral Treatment Start-Time during Primary SIVmac Infection in Macaques Exerts a Different Impact on Early Viral Replication and Dissemination

BACKGROUND: The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Six groups of macaques, infected intravenously with SIV(mac251), were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. CONCLUSIONS: Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIV(mac251) exposure

Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

<p>Abstract</p> <p>Background</p> <p>HIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i) the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii) the local concentration of antiviral drugs.</p> <p>Results</p> <p>Here, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis) or before viremia peak (7 days post-infection [pi]), had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi) or during early chronic infection (150 days pi), significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied.</p> <p>Conclusions</p> <p>Our results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.</p

BMJ Med

OBJECTIVE: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). DESIGN: Open label, randomised clinical trial. SETTING: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. PARTICIPANTS: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms 40. MAIN OUTCOME MEASURES: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. RESULTS: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). CONCLUSIONS: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. TRIAL REGISTRATION: ClinicalTrials.gov NCT04345991

Rapid response to the M_w 4.9 earthquake of November 11, 2019 in Le Teil, Lower Rhône Valley, France

On November 11, 2019, a Mw 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE-SW La Rouviere normal fault in reverse faulting in agreement with the present-day E-W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics

Étude de facteurs prédictifs de l'évolution de la maladie hépatique chez les patients co-infectés par le VIH-1 et le VHB suivis à l'hôpital Lariboisière

L infection par le virus de l hépatite B (VHB) et les lésions hépatiques qui en découlent sont une cause importante de mortalité et de morbidité parmi les patients infectés par le virus de l imrnunodéficience humaine (VIH). L Organisation Mondiale de la Santé (OMS), évalue à environ 350 millions le nombre actuel de porteurs du virus de l hépatite B dans le monde, soit une prévalence évaluée à 5%. La fréquence de la co-infection des patients séropositifs pour le VIH par le virus de l hépatite B varie selon les études de 10 à 20%. Les données sur l évolution à long terme des co-infections hépatite B et VIH sont encore limitées. Il n a pas encore été prouvé que le VHB affecte la progression de l infection par le VIH. Nous avons réalisé une étude rétrospective à partir d une cohorte de 137 patients suivis dans le service de médecine interne de l hôpital Lariboisière, recensés de mai 2001 à mai 2005, afin de mettre en évidence les facteurs prédictifs d un mauvais pronostic de la maladie hépatique chez les patients, principalement originaires d Europe et d Afrique sub-Saharienne, co-infectés par le virus de l hépatite B et le VIH- 1. Cent sept patients ont un suivi de plus de 12 mois et répondent aux critères d inclusion, cent patients permettront une comparaison entre les deux populations ethniques majoritaires. La durée moyenne du suivi est de 5,3 ans. 44% des patients ont eu une ponction biopsie hépatique et 81% ont reçu de la Lamivudine au cours de l évolution de la maladie. Durant le suivi, 9 patients sont décédés, dont 5 d une atteinte hépatique. Dix-neuf patients ont développé une atteinte hépatique avancée avec 3 carcinomes hépatocellulaires, 5 cirrhoses, 10 fibroses F3-F4 et une hépatite fulminante à l arrêt de la Lamivudine. Le sexe masculin, l origine Européenne, le génotype du VHB autre que le type E, et la moyenne de la charge virale du VHB et VIH sont associés à un risque important d évolution vers un stade avancé de l atteinte hépatique, mais les facteurs les plus prédictifs retrouvés en analyse multivariée sont la durée moyenne d élévation des transaminases et le temps cumulé de la prise de Lamivudine durant l histoire du patient. 39% des patients avec un taux moyen d ASAT élevé ont développé une atteinte hépatique avancée (versus 7% des patients avec un taux moyen normal). En conclusion, malgré les effets protecteurs de la Lamivudine, une atteinte hépatique avancée est fréquente chez les co-infectés VIH-VHB qui ont une élévation des transaminases persistante. Une meilleure stratégie thérapeutique serait à prévoir pour les groupes de patients à haut risque d atteinte hépatiquePARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

LA TUBERCULOSE DU SEIN (REVUE DE LA LITTERATURE A PROPOS D'UN CAS)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mycobactérioses atypiques pulmonaires de l'adulte séronégatif pour le VIH (A propos de neuf cas cliniques de 1996 à 2001)

Les mycobactéries atypiques sont des saprophytes ubiquitaires. Elles sont à l'origine d'infections appelées mycobactérioses chez les sujets "prédisposésé". Elles donnent essentiellement une atteinte pulmonaire. Elles ont surtout été étudiées depuis l'émergence du SIDA et les mycobactérioses pulmonaires chez les sujets HIV négatifs restent rares. Il n'y a pas de contamination inter humaine. La clinique est peu spécifique et ressemble à la tuberculose ainsi que la biologie et l'histologie. Seule la bactériologie permet de faire la différence. A l'issue de l'identification, il faut distinguer portage et maladie mycobactérienne chez le sujet atteint. L'évolution est lente. Il n'y a pas de codification en matière de traitement et on observe une grande résistance aux antituberculauex classiques. Une grande place est faite aux quinolones et aux macrolides...PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La tuberculose ganglionnaire prouvée bactériologiquement (étude monocentrique de 92 patients)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF