Therapeutic management and evolution of chronic hepatitis B: does HIV still have an impact? The EPIB 2012 study

EA Pôle MERS Hors CT hors EJ; International audience; Background & Aims: To compare the management of chronic hepatitis B (CHB) and its evolution over time in currently followed HIV-positive and HIV-negative patients. Methods: A total of 709 consecutive patients with past or present positive HBs antigenemia seen in October 2012 in 19 French participating centres were included. The data were retrospectively collected from the first visit onwards through standardized questionnaires. Results: Chronic hepatitis B was less often assessed in the 299 HIV-positive patients, who were older, more likely to be male, excessive alcohol drinkers and HBe antigen-, HCV- and HDV-positive. They were also fol…

Role of a 48-week pegylated interferon therapy in hepatitis B e antigen positive HIV-co-infected patients on cART including tenofovir: EMVIPEG study.

In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed.A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72).Fifty-one patients (49 men, median age 46 years, range: 32-6…

Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ cell count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy

OBJECTIVE We explored the impact of lifelong cumulative HIV viremia on immunological recovery during antiretroviral therapy, according to the timing of treatment initiation. METHODS We estimated lifelong cumulative HIV viremia in patients followed in the ANRS PRIMO cohort since primary infection, including 244 patients who started treatment during PHI and had at least one treatment interruption, and 218 patients who started treatment later but with no interruptions. The impact of cumulative viremia on current immunological status was analysed using linear and logistic regression models. RESULTS At the last visit on treatment, median CD4 cell count was 645 cells/μl in the early/intermittent …

Significant reductions in alcohol use after hepatitis C treatment: results from the ANRS CO13-HEPAVIH cohort

BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving pegylated interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioural characteristics were collected by yearly self-administered questionnaires. SETTING: Data were collected across 17 hospitals in France. PARTICIPANTS: All HIV-HCV co-infecte…

High Plasma Concentration of Non-Esterified Polyunsaturated Fatty Acids Is a Specific Feature of Severe COVID-19 Pneumonia

Background: The pathogenesis of severe COVID-19 is frequently associated with an uncontrolled inflammatory response. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Methods: Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological features were assessed. Findings: Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 pat…

Long-term Immune Response to Hepatitis B Virus Vaccination Regimens in Adults With Human Immunodeficiency Virus 1: Secondary Analysis of a Randomized Clinical Trial.

International audience; IMPORTANCE:Data on long-term immune responses to hepatitis B virus (HBV) vaccination in adults with human immunodeficiency virus 1 (HIV-1) infection are scarce.OBJECTIVE:To compare long-term (up to month 42) immune responses to the standard HBV vaccination regimen with a 4-injection intramuscular double-dose regimen and a 4-injection intradermal low-dose regimen.DESIGN, SETTING, AND PARTICIPANTS:The phase 3, open-label, multicenter parallel-group (1:1:1 allocation ratio) randomized clinical trial was conducted from June 28, 2007, to October 23, 2008, at 33 centers in France. Participants included 437 HBV-seronegative adults with HIV-1 and CD4 cell counts of more than…

Direct-acting antivirals for hepatitis C virus infections in patients co-infected with human immunodeficiency virus

Summary Nearly three-quarters of human immunodeficiency virus–hepatitis C virus (HIV-HCV) coinfected patients in France currently need to be cured of their chronic HCV infection. The increase in sustained virological response rates obtained with the recently available HCV protease inhibitors in treatment-naive genotype-1 patients has generated considerable hope in these co-infected patients. However, several particularities (such as a higher baseline HCV load, more advanced liver fibrosis, frequent co-morbidities, and the risk of toxicity and drug–drug interactions) have not allowed the direct extrapolation of the results observed in HCV-monoinfected patients to patients with HIV-HCV co-inf…

Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)

International audience; Background and aims: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV-coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on A…

ESSAI RANDOMISÉ POUR ÉVALUER L’EFFICACITÉ ET LA SÉCURITÉ DE TRAITEMENTS CHEZ DES PATIENTS AMBULATOIRES ATTEINTS DE COVID-19 AYANT DES FACTEURS DE RISQUE ESSAI COVERAGE FRANCE : PRÉSENTATION DU PROTOCOLE

Context. The Covid-19 pandemic is of unprecedented magnitude and has had major social and health consequences. Primary care professionals, mainly general practitioners, ensure the care of most patients with Covid-19. An early-stage treatment administered to patients with risk factors for developing a severe disease could reduce hospitalization and death rates. No treatment is currently validated in this indication. Objectives. To evaluate the safety and efficacy of experimental candidate agents delivered in outpatient settings to reduce the risk of hospitalization or death in at-risk patients with early-stage proven Covid-19 and no indication for hospital admission. Methods. Multicentric, o…

Persistance du risque de décès et d’évènement hépatique après guérison de l’hépatite C chez les patients coinfectés VIH/VHC–cohorte ANRS CO13 Hepavih

Introduction Le risque residuel de deces et d’evenements hepatiques (EH) qui persiste apres la guerison de l’hepatite C, a moyen et long terme, chez le patient co-infecte VIH/VHC est mal connu. Materiels et methodes Au sein d’une cohorte national de patients co-infectes VIH/VHC, nous avons inclus les patients traites pour le VHC et ayant une reponse virologique soutenue (RVS) 3 mois apres la fin du traitement ainsi qu’un resultat disponible de Fibroscan ® (taux d’elastometrie (TE)) realise apres le debut du traitement. Les EH etudies sont : cirrhose decompensee, transplantation hepatique et carcinome hepato-cellulaire (CHC). Ils ont tous ete valides par un comite constitue de cliniciens. Re…

Isolated Anti-HBc: Significance and Management.

Hepatitis B virus (HBV) infection is prevalent worldwide and is associated with dramatic levels of morbidity and mortality. Isolated anti-HBc (IAHBc) is a particular serological pattern that is commonly found in immunocompromised patients. There is ongoing debate regarding the management of patients with IAHBc. Herein, we summarize the current guidelines and the newest evidence. The frequency of IAHBc is variable, with a higher prevalence in some populations, such as persons living with HIV and others immunocompromised patients. The risk of HBV reactivation depends on host factors (including immunosuppression) and viral factors. It is now well established that immunocompromised patients can…

The Respect of Recommendations Provided in an International Travelers' Medical Service: Far From the Cup to the Lips

Equipe plutôt EA Pôle MERS CT3 EJ3; Background: It is not clearly known how frequently the recommendations given to travelers are followed, and what factors could encourage compliance with these recommended measures. Methods: Adults consulting at a Medical Department for International Travelers (International Travelers' Medical Services, ITMS) in October and November 2010 were asked to answer a questionnaire before their journey. They were also contacted for a post-travel telephone interview to determine whether they had followed the recommendations regarding vaccinations and malaria prevention, and the reasons for poor or noncompliance with these recommendations. Results A total of 353 tra…

Mechanical ventilation and Streptococcus pneumoniae pneumonia alter mitochondrial homeostasis.

Abstract Required mechanical ventilation (MV) may contribute to bacterial dissemination in patients with Streptococcus pneumoniae pneumonia. Significant variations in plasma mitochondrial DNA (mtDNA) have been reported in sepsis according to the outcome. The impact of lung stretch during MV was addressed in a model of pneumonia. Healthy or S. pneumoniae infected rabbits were submitted to MV or kept spontaneously breathing (SB). Bacterial burden, cytokines release, mitochondrial DNA levels, integrity and transcription were assessed along with 48-hour mortality. Compared with infected SB rabbits, MV rabbits developed more severe pneumonia with greater concentrations of bacteria in the lungs, …

No effect of vancomycin MIC ≥ 1.5 mg/L on treatment outcome in methicillin-susceptible Staphylococcus aureus bacteraemia

International audience; The vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. In this study, the outcomes of patients with MSSA bacteraemia with a vancomycin MIC ≥ 1.5 mg/L were assessed. A prospective cohort of patients with MSSA bacteraemia in two tertiary-care hospitals was collected. The vancomycin MIC was determined by Etest. Staphylococcus aureus strains were categorised as low (<1.5 mg/L) or high (≥1.5 mg/L) vancomycin MIC. First- and second-line treatments were recorded and classified as optimal, appropriate and inappropriate. The primary endpoint was 30-day mortality. A total o…

Vitamin D supplementation, bone turnover, and inflammation in HIV-infected patients

IF 1.307 (2017); International audience; ObjectiveTo assess whether vitamin D supplementation could be associated with a modification of inflammatory markers and bone turnover in HIV-1-infected patients.Patients and methodsPatients who participated in an initial survey in 2010 and who were followed in the same department were included in a new study in 2012. Between 2010 and 2012, vitamin D supplementation was offered to patients presenting with hypovitaminosis D as per appropriate guidelines. Clinical examinations were performed, and fasting blood samples were taken for inflammation and bone marker evaluations.ResultsOf the 263 patients who participated in the 2010 study, 198 were included…

In vivo efficacy of humanised intermittent versus continuous ceftazidime in combination with tobramycin in an experimental model of pseudomonal pneumonia.

In this study, we compared the efficacy of ceftazidime (CAZ) intermittent versus continuous infusion with or without tobramycin (TOB) for the treatment of pneumonia caused by Pseudomonas aeruginosa in rabbits. Treatments were humanised and mimicked intermittent CAZ (iCAZ) (2g three times daily), continuous CAZ (cCAZ) (4g once daily (qd)) and TOB (10mg/kg qd). Minimum inhibitory concentrations (MICs) were 1mg/L and 4mg/L for TOB and CAZ, respectively. Bacterial efficacy in lungs was as follows: control, 9+/-0.6 colony-forming units (CFU)/g; TOB monotherapy, 8+/-0.5CFU/g; iCAZ monotherapy, 7.8+/-1.4CFU/g; cCAZ monotherapy, 8+/-0.4CFU/g (P = 0.005); and iCAZ+TOB, 8+/-0.5CFU/g; cCAZ+TOB, 7.2+/-…

Mycotic Aneurysm of Both Internal Iliac Arteries due to Candida albicans.

International audience; : We report the case of a 21-year-old man, with a Candida-related endocarditis causing multiple emboli and bilateral false aneurysms of the internal iliac arteries. As the distal runoff vasculatures of both internal iliac arteries were occluded, these arteries required ligation. Although there were few consequences with the procedure, multiple emboli and recurrence of endocarditis after cardiac surgery led to the patient's death.

A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients.

SUMMARYOptimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of &gt;500 cells/mm3without experiencing AIDS or death. For patients with a baseline HIV viral load ⩾5 log10copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ⩾500/mm3than…

The VIRSTA score, a prediction score to estimate risk of infective endocarditis and determine priority for echocardiography in patients with Staphylococcus aureus bacteremia.

International audience; Objectives - To develop and validate a prediction score, to quantify, within 48 h of Staphylococcus aureus bacteremia (SAB) diagnosis, the risk of IE, and therefore determine priority for urgent echocardiography. Methods - Consecutive adult patients with SAB in 8 French university hospitals between 2009 and 2011 were prospectively enrolled and followed-up 3 months. A predictive model was developed and internally validated using bootstrap procedures. Results - Among the 2008 patients enrolled, 221 (11.0%) had definite IE of whom 39 (17.6%) underwent valve surgery, 25% of them within 6 days of SAB diagnosis. Ten predictors independently associated with IE were used to …

Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study

Background The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. Methods HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. Results 1,062 patients were included from 2005 to 2015 …

Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM.

Abstract Background In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed. Patients and methods In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of…

Optimum combination therapy regimens for HIV/HCV infection

HIV-HCV co-infection mostly affects intravenous drug users, in whom prevalence has tended to decrease in recent years, while it has increased in men who have sex with men, with occurrence of acute hepatitis C. Hepatitis C has a poorer prognosis in patients co-infected with HIV, as clinical progression is faster and degree of hepatic fibrosis is greater. However, optimized ARV treatment is clearly associated with slower progression to hepatic complications. Interactions between HCV and HIV drugs are numerous, which underlines the importance of pharmacological advice for HIV-treated patients before they start HCV treatment. In HIV-HCV co-infection, treatment of hepatitis C has to be offered a…

Prosthetic joint infection caused by Mycobacterium avium complex.

Determinants of high-grade anal intraepithelial lesions in HIV-positive men having sex with men

Background Identifying determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive MSM would allow better targeted screening. Methods APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged ≥35 in six clinics across France. At baseline, participants underwent high resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA. hHSIL diagnosis was established by histopathological review panel consensus, and determinants assessed by logistic regression. Results Baseline hHSIL prevalence was 10.4% and did not differ significantly by…

A New Prognosis Score to Predict Mortality After Acute Pneumonia in Very Elderly Patients

International audience; Objectives: Acute pneumonia (AP) induces an excess of mortality among the elderly. We evaluated the value of a new predictive biomarker index compared to usual prognosis scores for predicting in-hospital and 1-year mortalities in elderly inpatients with AP.Design: Retrospective study in 6 clinical departments of a university hospital.Setting: Burgundy university hospital (France).Participants: All patients aged 75 and over with AP and hospitalized between January 1 and June 30, 2013, in the departments of medicine (5) and intensive care (1) of our university hospital.Measurements: A new index, which we named UBMo, was created by multiplying the uremia (U in the formu…

Evolution of patients’ socio-behavioral characteristics in the context of DAA: Results from the French ANRS CO13 HEPAVIH cohort of HIV-HCV co-infected patients

International audience; BACKGROUND:Direct-acting antivirals (DAA) have dramatically increased HCV cure rates with minimal toxicity in HIV-HCV co-infected patients. This study aimed to compare the socio-behavioral characteristics of patients initiating pegylated-interferon (PEG-IFN)-based HCV treatment with those of patients initiating DAA-based treatment.METHODS:ANRS CO13 HEPAVIH is a national multicenter prospective cohort started in 2005, which enrolled 1,859 HIV-HCV co-infected patients followed up in French hospital outpatient units. Both clinical/biological and socio-behavioral data were collected during follow-up. We selected patients with socio-behavioral data available before HCV tr…

Recombinant virus-like particles of a norovirus (genogroup II strain) administered intranasally and orally with mucosal adjuvants LT and LT(R192G) in BALB/c mice induce specific humoral and cellular Th1/Th2-like immune responses

We investigated the immune response induced by mucosal immunization of BALB/c mice with virus-like particles (VLPs) of a genogroup II norovirus, Dijon171/96 virus, produced in the baculovirus system. VLPs administered alone by the intranasal route induced a high serum antibody response as well as fecal IgA, which were enhanced when the heat-labile Escherichia coli toxin or its non toxic mutant LT(R192G) was coadministered. In these conditions, the oral route was also efficient. Cytokine production by cells from different lymphoid tissues was then assessed after in vitro restimulation. A Th1/Th2-like response was observed in cervical lymph node and Peyer's patch (PP) cell cultures from mice …

Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial

Equipe CHU UB (EA) Pôle MERS CT3 Hors Enjeu ANRS HB04 B-BOOST study group : Hugues Aumaitre (Centre Hospitalier Marechal Joff re, Perpignan, France); Jean-Luc Berger (Centre Hospitalier Universitaire de Reims– Hopital Robert Debre, Reims, France); Alain Devidas (Hopital Gilles de Corbeil–Centre Hospitalier Sud Francilien, Corbeil Essonne, France); Sophie Abgrall (Centre Hospitalier Universitaire Avicenne, Avicenne, France); Olivier Patey (Centre Hospitalier Intercommunal de Villeneuve St Georges, Villeneuve Saint Georges, France); Marie-Christine Drobacheff Thiebaut (Centre Hospitalier Universitaire de Besancon–Hopital Saint Jacques, Besancon, France); Frederic Lucht (Centre Hospitalier Uni…

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing como…

Head and neck squamous cell carcinoma in people living with HIV in France.

Abstract Objectives Head and neck squamous cell carcinoma (HNSCC), mainly due to smoking, is one of the leading causes of cancer deaths. However, an increasing number of tumors – especially oropharyngeal cancer – are reported in non-smokers in association with the human papillomavirus (HPV). As HIV-infected individuals are particularly at risk of HPV-related disease, we aimed to describe the burden of HNSCC in this population. Methods Retrospective chart review of patients from HIV clinics diagnosed with HNSCC between 2004 and 2014. Case patients were defined using the International Classification of Disease for Oncology (3rd edition). Age at HIV diagnosis and time from HIV diagnosis to HNS…

Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: The HEPAIG study

Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log10 IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interf…

Low Trough Plasma Concentrations of Nevirapine Associated with Virologic Rebounds in HIV-Infected Patients Who Switched from Protease Inhibitors

BACKGROUND:The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants.OBJECTIVE:To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine.METHODS:Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels &gt;1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL &gt;20 copies/mL but &lt;1000 copies/mL. Virolog…

Cancer and Infective Endocarditis: Characteristics and Prognostic Impact

Background: The interplay between cancer and IE has become of increasing interest. This study sought to assess the prevalence, baseline characteristics, management, and outcomes of IE cancer patients in the ESC EORP EURO-ENDO registry.Methods: Three thousand and eighty-five patients with IE were identified based on the ESC 2015 criteria. Three hundred and fifty-nine (11.6%) IE cancer patients were compared to 2,726 (88.4%) cancer-free IE patients.Results: In cancer patients, IE was mostly community-acquired (74.8%). The most frequently identified microorganisms were S. aureus (25.4%) and Enterococci (23.8%). The most frequent complications were acute renal failure (25.9%), embolic events (2…

Staphylococcus aureus bloodstream infection in patients with prosthetic joint included in the prospective VIRSTA cohort study: frequency and time of occurrence of periprosthetic joint infection

International audience; Among 143 patients of the VIRSTA cohort study with Staphylococcus aureus bacteremia and an arthroplasty implanted for more than a year, S. aureus periprosthetic joint infection was observed in 19%. Signs of infection (pain and swelling) were always present, in median 1 day (range, 0-21 days) after onset of bacteremia. Staphylococcus aureus has both a high potential for metastatic infection and a high affinity for foreign material. Possible prosthesis infection is of clinical concern in all patients with preexisting prosthetic materials experiencing S. aureus bloodstream infection (SAB). Prosthetic joints are especially prone to infection during the course of bacterem…

Correction to: The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared.At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients …

Prevalence and Risk Factors for Anal Human Papillomavirus Infection in Human Immunodeficiency Virus–Positive Men Who Have Sex with Men

A correction has been published:The Journal of Infectious Diseases, Volume 218, Issue 8, 15 October 2018, Page 1350, https://doi.org/10.1093/infdis/jiy315; International audience; Background:We assessed prevalence and risk factors for anal human papillomavirus (HPV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), who are at high-risk of HPV-related anal cancer.Methods:APACHES is a multicentric, prospective study of anal HPV infection and lesions in HIV-positive MSM aged ≥35 years. At baseline, participants underwent anal swabs for HPV and cytology, plus high-resolution anoscopy. High-risk HPV (HR-HPV) was tested by Cobas4800, with genotyping of HR-HPV positiv…

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Invasive mechanical ventilation; COVID-19; Critical care Ventilación mecánica invasiva; COVID-19; Cuidado crítico Ventilació mecànica invasiva; COVID-19; Atenció crítica Background Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods This is a multin…

Oral delivery of homologous and heterologous strains of rotavirus to BALB/c mice induces the same profile of cytokine production by spleen cells.

Abstract In this work, we wanted to clarify if differences in antibody (Ab) and particularly in secretory immunoglobulin A (IgA) responses following homologous or heterologous rotavirus infection could be explained by different priming of specific T helper (Th) cells. We compared the Ab responses from suckling BALB/c mice orally inoculated with either a heterologous simian (SA11) or bovine (RF) rotavirus or a homologous murine rotavirus (EHP w ), as well as the profile of cytokines produced by spleen cells after in vitro restimulation. Oral inoculation of EHP w and SA11 induced a similar pattern of Ab with mucosal and serum IgA associated with serum IgG with equal levels of IgG1 and IgG2a, …

Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with external ventricular drain

International audience; Background: Due to its antibacterial properties ceftaroline could be attractive for the treatment of bacterial postneurosurgicalmeningitis. However only few data are available concerning its meningeal concentrations. The aim of this studywas to investigate ceftaroline cerebrospinal fluid (CSF) pharmacokinetics (PK) in intensive care unit (ICU) patients with anexternal ventricular drain (EVD).Materials/methods: Patients received a single 600 mg dose of ceftaroline as a one-hour intravenous infusion . Blood and CSFsamples were collected before and 0.5, 1, 3, 6, 12 and 24 hours after the end of the infusion. Concentrations were assayed inplasma and CSF by LC-MS/MS. A tw…

Vaccination Against Hepatitis B Virus (HBV) in HIV-1-Infected Patients With Isolated Anti-HBV Core Antibody: The ANRS HB EP03 CISOVAC Prospective Study.

International audience;  Although an isolated anti-hepatitis B virus (HBV) core antibody (anti-HBc) serological profile is frequent in human immunodeficiency virus (HIV)-infected patients, data on HBV vaccination in these patients are scarce.  A prospective multicenter study was conducted to assess the immunogenicity of HBV vaccination in 54 patients with an isolated anti-HBc profile and undetectable HIV load. They were vaccinated with 1 dose (20 µg) of recombinant HBV vaccine. Those with an anti-HBV surface antibody (anti-HBs) level of 100 mIU/mL 4 weeks after a single recall dose of HBV vaccine should be further vaccinated with a reinforced triple double-dose scheme.

Patients With Isolated Hepatitis B Core Antibody: Has the Time Come to Vaccinate?

International audience

Efficacy and safety of direct-acting antiviral regimens in HIV/HCV-co-infected patients – French ANRS CO13 HEPAVIH cohort

International audience; Background & aims: There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported.Methods: HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined b…

Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation

International audience; Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid a…

Emergence of tularemia in France: paradigm of the Burgundy region

International audience; We report three consecutive cases of tularemia occurring in Burgundy, France, a region previously considered not endemic for tularemia. The patients presented with varied and unspecific clinical manifestations. The epidemiological circumstances, especially the mode of contamination, were not particularly suggestive of tularemia. Serological diagnosis was delayed in two cases because of the lack of significant antibody titers at the time of admission. In contrast, a diagnosis could readily be obtained in all three cases by detection of Francisella tularensis DNA from clinical samples using PCR-based methods. These cases highlight the increased incidence and geographic…

Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients

International audience; In hepatitis B “e” antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) u…

Determinants of high-grade anal intraepithelial lesions in HIV-positive MSM.

Objective - To assess determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive men who have sex with men (MSM), a population at high-risk of HPV-related anal cancer. Design - APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged at least 35 years in six centres across France. Methods - At baseline, participants underwent high-resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA. hHSIL diagnosis was established by histopathological review panel consensus, and determinants assessed by logistic regression. Results - B…

Rotavirus 2/6 virus-like particles administered intranasally in mice, with or without the mucosal adjuvants cholera toxin and Escherichia coli heat-labile toxin, induce a Th1/Th2-like immune response

ABSTRACTWe investigated the rotavirus-specific lymphocyte responses induced by intranasal immunization of adult BALB/c mice with rotavirus 2/6 virus-like particles (2/6-VLPs) of the bovine RF strain, by assessing the profile of cytokines produced after in vitro restimulation and serum and fecal antibody responses. The cytokines produced by splenic cells were first evaluated. Intranasal immunization with 50 μg of 2/6-VLPs induced a high serum antibody response, including immunoglobulin G1 (IgG1) and IgG2a, a weak fecal antibody response, and a mixed Th1/Th2-like profile of cytokines characterized by gamma interferon and interleukin 10 (IL-10) production and very low levels of IL-2, IL-4, and…

Factors associated with 12 week case-fatality in Staphylococcus aureus bacteraemia: a prospective cohort study

International audience; Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients …

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Background: The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in patients with COVID-19 requiring oxygen and/or ventilator support. Methods: In this European multicentre, open-label, parallel-group, randomised, controlled trial in adults hospitalised with COVID-19 (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care alone or in combination with intravenous remdesivir (200 mg on day 1, then 100 mg once-daily for 9 days or until discharge). Treatment assignation was performed via web-based randomisation stratified on illness severity and administrative European regio…

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Abstract Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admiss…

Direct-acting antiviral-based therapy for chronic hepatitis C virus in HIV-infected patients

The aim of this review was to detail the current therapies and treatments for chronic hepatitis C virus in coinfected patients, focusing on HCV antiviral agents currently used in practice today or scheduled to enter the open market soon. Several direct-acting antiviral (DAA) combinations show high sustained virologic response (SVR) rates in HIV/HCV-coinfected patients, which are often close to those observed in HCV-monoinfected patients. Most recommendations regarding treatment stem from trials with coinfected patients. However, data are lacking for some aspects of HCV-treatment in coinfection, so extrapolations must be made from data obtained predominately from monoinfected patients. HIV/H…

Specific Features of the Coagulopathy Signature in Severe COVID-19 Pneumonia

Rationale: COVID-19 displays distinct characteristics that suggest a unique pathogenesis. The objective of this study was to compare biomarkers of coagulopathy and outcomes in COVID-19 and non-COVID-19 patients with severe pneumonia.Methods: Thirty-six non-COVID-19 and 27 COVID-19 non-immunocompromised patients with severe pneumonia were prospectively enrolled, most requiring intensive care. Clinical and biological characteristics (including plasma biomarkers of coagulopathy) were compared.Results: At similar baseline severity, COVID-19 patients required mechanical ventilation (MV) for significantly longer than non-COVID-19 patients (p = 0.0049) and more frequently developed venous thrombot…

ITPA deficiency and ribavirin level are still predictive of anaemia in HCV–HIV-coinfected patients receiving ribavirin combined with a first-generation DAA (ANRS HC27 study)

Background We aimed to determine the impact of inosine triphosphatase (ITPA) deficiency on ribavirin (RBV)-induced anaemia in HIV–HCV-coinfected patients receiving a triple therapy including the haematotoxic direct-acting antiviral agent boceprevir (BOC). Methods Patients of the ANRS HC27 BocepreVIH study were genotyped for two ITPA single nucleotide polymorphisms involved in ITPA deficiency. RBV trough concentration (Ctrough) was determined at week (W)4 and W8. Impact of ITPA deficiency on anaemia, RBV Ctrough, response and haematotoxicity (grade 3/4 anaemia, erythropoietin [EPO] use, RBV dose reduction or transfusion between day [D]0 and W8) was evaluated. Impact of RBV Ctrough on anaemia…

Low 25-OH vitamin D serum levels correlate with severe fibrosis in HIV-HCV co-infected patients with chronic hepatitis.

Background & Aims Recent findings in hepatitis C virus (HCV)-monoinfected patients have shown a correlation between low serum levels of 25-OH vitamin D3 [25(OH)D3] and severe liver fibrosis and low sustained virologic response to therapy. Data are lacking in HIV-HCV coinfected patients. Methods One hundred and eighty nine HIV-HCV coinfected patients, who received ⩾80% of interferon (IFN) plus ribavirin therapy, were analyzed for baseline serum 25(OH)D3 levels. Correlations between serum 25(OH)D3 levels, chronic hepatitis C features, HCV virologic response to antiviral therapy, and HIV infection characteristics were analyzed. Results Mean serum 25(OH)D3 level was 18.5±9.8ng/ml, including 162…

Staphylococcus aureus Bloodstream Infection and Endocarditis―A Prospective Cohort Study

Equipe CHU UB (EA) Pôle MERS CT3 Hors Enjeu The VIRSTA Study Group : Clinical centres: Besançon: Catherine Chirouze, Elodie Curlier, Cécile Descottes-Genon, Bruno Hoen, Isabelle Patry, Lucie Vettoretti. Dijon: Pascal Chavanet, Jean-Christophe Eicher, Sandrine Gohier-Treuvelot, Marie-Christine Greusard, Catherine Neuwirth, André Péchinot, Lionel Piroth. Lyon: Marie Célard, Catherine Cornu, François Delahaye, Malika Hadid, Pascale Rausch. Montpellier: Audrey Coma, Florence Galtier, Philippe Géraud, Hélène Jean-Pierre, Vincent Le Moing, Catherine Sportouch, Jacques Reynes. Nancy: Nejla Aissa, Thanh Doco- Lecompte, François Goehringer, Nathalie Keil, Lorraine Letranchant, Hepher Malela, Thierry…

Prevalence and incidence of kidney diseases leading to hospital admission in people living with HIV in France: an observational nationwide study.

ObjectivesTo describe hospitalisations for kidney disease (KD) among people living with HIV (PLHIV) in France and to identify the factors associated with such hospitalisations since data on the epidemiology of KD leading to hospitalisation are globally scarce.DesignObservational nationwide study using the French Programme de Médicalisation des Systèmes d’Information database.SettingFrance 2008–2013.ParticipantsAround 10 862 PLHIV out of a mean of 5 210 856 patients hospitalised each year. All hospital admissions with a main diagnosis code indicating KD (International Classification of Diseases, 10th revision codes, N00 to –N39) were collected.Main outcome measuresThe prevalence and incidenc…

Association of country income level with the characteristics and outcomes of critically ill patients hospitalized with acute kidney injury and COVID-19

Introduction Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results Among patients with COVID-19 ad…

The value of open-source clinical science in pandemic response

International audience

Raltegravir Pharmacokinetics in Patients on Asunaprevir-Daclatasvir.

ABSTRACT Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV) quadritherapy, including pegylated-interferon–ribavirin and asunaprevir plus daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether administered on or off anti-HCV therapy. In addition, concentrations of raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis. These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected patients, whether cirrhotic or not, asunaprevir and daclatasvir could be administered safely with raltegravir.

The usefulness of NEWS2 at day 7 of hospitalization in predicting COVID-19 evolution and as an early endpoint in therapeutic trials

Highlights • There is a need for reliable tools to predict the evolution of hospitalized patients suffering from COVID-19 • The likelihood of unfavourable evolution for patients hospitalized for COVID-19 with a National • Early Warning Score 2 (NEWS2) below 7 at Day 7 of hospitalization is nearly non-existent • Such a score could thus be used to allow earlier discharge of the patients and as a judgement criterion in therapeutic trials

Burden of HIV and hepatitis C co-infection: the changing epidemiology of hepatitis C in HIV-infected patients in France.

Équipe UB/CHU (EA) Pôle MERS CT3 Hors Enjeu; International audience; Background & AimsTo better evaluate the HIV-HCV co-infection burden in the context of new effective HCV treatment. MethodsWe reviewed all the epidemiological data available on HCV-related disease in HIV-infected patients in France. Sources of data have been selected using the following criteria: (i) prospective cohorts or cross-sectional surveys; (ii) conducted at a national level; (iii) in the HIV-infected population; (iv) able to identify HCV co-infection and chronic active hepatitis C (HCV RNA positive); and (v) conducted during the period 2003-2012. ResultsThe overall prevalence of HIV-HCV co-infection has decreased fr…

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients

Abstract Background Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. Methods A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone…

Is there a need to widely prescribe antibiotics in patients hospitalized with COVID-19?

Highlights • Antibiotics were a main part of COVID-19 treatments during the first epidemic peak. • Bacterial coinfections seem to be rare, especially if no ICU transfer needed. • We studied the place of antibiotics and the impact on prognosis of patients. • Antibiotics were prescribed if more severe infection and has no impact on prognosis. • We think that antibiotic therapy must be not widely prescribed.

Time to blood culture positivity: An independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia

International audience; Objectives - Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia. Methods - VIRSTA is a multicenter prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009-2011). We analyzed data from four centers which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria)…

Evolving epidemiology and antimicrobial resistance in spontaneous bacterial peritonitis: a two-year observational study.

Background Current recommendations for empirical antimicrobial therapy in spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since microbial epidemiology and the management of patients have changed, whether these recommendations are still appropriate must be confirmed. Methods An observational study that exhaustively collected the clinical and biological data associated with positive ascitic fluid cultures was conducted in four French university hospitals in 2010–2011. Results Two hundred and sixty-eight documented positive cultures were observed in 190 cirrhotic patients (median age 61.5 years, 58.5% Child score C). Of these, 57 were classified as confirmed SBP and 140 …