Search

BackgroundLopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a and hydroxychloroquine efficacy for COVID-19 have been evaluated, but detailed evaluation is lacking.ObjectiveTo determine the efficacy of lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a, hydroxychloroquine or remdesivir for improving the clinical, virological outcomes in COVID-19 inpatients.DesignOpen-label, randomized, adaptive, controlled trial.SettingMulti-center trial with patients from France.Participants583 COVID-19 inpatients requiring oxygen and/or ventilatory supportInterventionStandard of care (SoC, control), SoC plus lopinavir/ritonavir (400 mg lopinavir and 100 mg ritonavir every 12h for 14 days), SoC plus lopinavir/ritonavir plus IFN-ß-1a (44 μg of subcutaneous IFN-ß-1a on days 1, 3, and 6), SoC plus hydroxychloroquine (400 mg twice on day 1 then 400 mg once daily for 9 days) or SoC plus remdesivir (200 mg intravenously on day 1 then 100 mg once-daily for hospitalization duration or 10 days).MeasurementsThe primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens and safety analyses.ResultsAdjusted Odds Ratio (aOR) for the WHO 7-point ordinal scale were not in favor of investigational treatments: lopinavir/ritonavirversuscontrol, aOR 0.83, 95%CI, 0.55 to 1.26, P=0.39; lopinavir/ritonavir-IFN-β-1aversuscontrol, aOR 0.69, 95%CI, 0.45 to 1.04, P=0.08; hydroxychloroquineversuscontrol, aOR 0.93, 95%CI, 0.62 to 1.41, P=0.75. No significant effect on SARS-CoV-2 RNA clearance in respiratory tract was evidenced. Lopinavir/ritonavir-containing treatments were significantly associated with more SAE.LimitationsNot a placebo-controlled, no anti-inflammatory agents tested.ConclusionNo improvement of the clinical status at day 15 nor SARS-CoV-2 RNA clearance in respiratory tract specimens by studied drugs. This comforts the recent Solidarity findings.RegistrationNCT04315948.FundingPHRC 2020, Dim OneHealth, REACTing

Diagnosis of COVID-19 is essential to prevent the spread of SARS-CoV-2. Nasopharyngeal swabs (NPS) remain the gold standard in screening, although associated with false negative results (up to 30%). We developed a 3D simulator of the nasal and pharyngeal cavities for the learning and improvement of NPS collection.Simulator training sessions were carried out in 11 centers in France. A questionnaire assessing the simulator was administered at the end of the sessions. The study population included both healthcare workers (HCW) and volunteers from the general population.Out of 589 participants, overall satisfaction was scored 9.0 [8.9-9.1] on a scale of 0 to 10 with excellent results in the 16 evaluation items of each category (HCWs and general population, NPS novices and experienced). The simulator was considered very realistic (95%), easy to use (97%), useful to understand the anatomy (89%) and NPS sampling technique (93%). This educational tool was considered essential (93%). Participants felt their future NPS would be more reliable (72%), less painful (70%), easier to perform (88%) and that they would be carried out more serenely (90%). The mean number of NPS conducted on the simulator to feel at ease was two; technical fluency with the simulator can thus be acquired quickly.Our simulator, whose 3D printing can be reproduced freely using a permanent open access link, is an essential educational tool to standardize the learning and improvement of NPS collection. It should enhance virus detection and thus contribute to better pandemic control.

Exacerbation triggered by respiratory infection is an important cause of morbidity and mortality in Chronic Obstructive Pulmonary Disease (COPD) patients. Strategies aiming to preventing infection may have significant public health impact. Our previous study demonstrated decreased immunological response to seasonal flu vaccination in COPD patients, questioning the efficiency of other vaccines in this group of patients. We performed a prospective, monocenter, longitudinal study that evaluated the humoral and cellular responses upon pertussis vaccination. We included 13 patients with stable COPD and 8 healthy volunteers. No difference in circulating B and T cell subsets at baseline was noted. Both groups presented similar levels of TFH, plasmablasts and pertussis specific antibodies induction after vaccination. Moreover, monitoring T cell immunity after ex-vivo peptide stimulation revealed equivalent induction of functional and specific CD4 + T cells (IFNg, TNFa and IL-2-expressing T cells) in both groups. Our results highlight the immunological efficiency of pertussis vaccination in this particularly vulnerable population and challenge the concept that COPD patients are less responsive to all immunization strategies. Healthcare providers should stress the necessity of decennial Tdap booster vaccination in COPD patients.

Objectives Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Background Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. Methods In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies . Results Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N = 8), encephalopathy (N = 6), cerebrovascular events (ischemic strokes N = 4 and vein thromboses N = 2), other central nervous system (CNS) disorders (N = 4), and Guillain-Barre syndrome (N = 2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder , especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. Conclusions Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

Optimized antibiotic plasma predictor efficacy is essential in systemic infections. The uricosuric agent probenecid inhibits tubular excretion of antibiotics and may be used as β-lactam pharmacokinetic enhancer (BLPKE), even though few data are currently available for this purpose.We conducted a monocentric and retrospective observational study including all patients who received probenecid in combination with parenteral β-lactam antibiotics for systemic infections from Jan 1, 2014 to Dec 31, 2019. Demographics, infection characteristics, treatment and ATC (antibiotics trough concentration) were investigated.All in all, 38 patients were included. Eight patients had a history of sickle cell disease. Hyperfiltration (defined as eGFR130mL/min/1.73mProbenecid could be a BLPKE. Our data suggest this drug should be used more often to optimize β-lactam pharmacokinetics in clinical practice.

Tuberculosis (TB) disease has rarely been reported in patients with sickle cell disease, but it is associated with an increased risk of bacterial infections. In France, sickle cell disease is frequent in populations with the highest prevalence of TB disease. We aimed to highlight clinical aspects of TB disease in patients with sickle cell disease.Over a 10-year period, we retrospectively included all adults with sickle cell disease who had a positive culture for Mycobacterium tuberculosis managed in the adult sickle cell center of Henri-Mondor hospital. Sickle cell patients with TB disease were matched for comparison to adults without hemoglobinopathy and with documented TB disease in a 1:2 ratio. Logistic regression mixed models were performed.Twelve patients with sickle cell disease and documented TB disease (median age: 29years; IQR [25-34]) were compared to 24 non-sickle cell patients (median age: 33years; IQR [27.5-38.5]). Baseline characteristics were similar between groups except for sickle cell disease. Ten of the 12 patients with sickle cell disease had pulmonary TB. TB disease characteristics were similar between sickle cell and non-sickle cell patients although sickle cell patients had fewer positive sputum smears for acid-fast bacilli (P=0.003) and fewer lung cavitations (P=0.03).TB disease in sickle cell patients was globally similar to non-sickle cell patients, even though less infectious. Regular follow-up in specialized centers might allow for earlier TB disease diagnosis in sickle cell patients.

SummaryHow a previous SARS-CoV-2 infection may amplify and model the memory B cell (MBC) response elicited by mRNA vaccines was addressed by a comparative longitudinal study of two cohorts, naive individuals and disease-recovered patients, up to 2 months after vaccination. The quality of the memory response was assessed by analysis of the VDJ repertoire, affinity and neutralization against variants of concerns (VOC), using unbiased cultures of 2452 MBCs. Upon boost, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOC. Maturation of the MBC response in naive individuals was much less pronounced. Nevertheless, and as opposed to their weaker neutralizing serum response, half of their RBD-specific MBCs displayed high affinity towards multiple VOC and one-third retained neutralizing potency against B.1.351. Thus, repeated vaccine challenges could reduce these differences by recall of affinity-matured MBCs and allow naive vaccinees to cope efficiently with VOC.

International audience; Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely.Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.

Bacterial infective endocarditis (IE) is rarely suspected in patients with a low C-reactive protein (CRP) concentration.To address the incidence, characteristics and outcome of left-sided valvular IE with low CRP concentration.This was a retrospective analysis of cases of IE discharged from our institution between January 2009 and May 2017. The 10% lowest CRP concentration (20mg/L) was used to define low CRP concentration. Right-sided cardiac device-related IE, non-bacterial IE, sequelar IE and IE previously treated by antibiotics were excluded.Of the 469 patients, 13 (2.8%; median age 68 [61-76] years) had definite (n=8) or possible (n=5) left-sided valvular IE with CRP20mg/L (median 9.3 [4.7-14.2] mg/L). The median white blood cell count was 6.3 (5.3-7.5) G/L. The main presentations were heart failure (n=7; 54%) and stroke (n=3; 23%). Transthoracic echocardiography (TTE) showed vegetations (n=5) or isolated valvular regurgitation (n=4). Overall, eight patients (62%) had severe valvular lesions on transoesophageal echocardiography (TOE), and nine patients (69%) underwent cardiac surgery. All patients survived at 1-year follow-up. Bacterial pathogens were documented in eight patients (streptococci, coagulase-negative Staphylococcus, Corynebacteriumjeikeium, HACEK group, Coxiella burnetii, Bartonella henselae) using blood cultures, serology or valve culture and/or polymerase chain reaction analysis.Left-sided valvular IE with limited or no biological syndrome is rare, but is often associated with severe valvular and paravalvular lesions. TOE should be performed in presence of unexplained heart failure, new valvular regurgitation or cardioembolic stroke when TTE is insufficient to rule out endocarditis, even in patients with a low CRP concentration.

Background In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher’s exact test, multivariate logistic regression and Cox proportional hazards models. Results Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0–113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13–4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97–12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients. Conclusions Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS. Trial registration The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1850-2) contains supplementary material, which is available to authorized users.

Background Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce. Materials/methods A retrospective monocentric study was conducted on all patients who underwent simultaneous PKT from January 2007 to December 2016. Deep sites positive cultures for fungi during the first post-transplantation year were collected. Clinical, radiological, and microbiological data of proven and probable invasive fungal infections were analysed. Results Among sixteen PKT patients, 15 were included. Seven patients (47%) developed an invasive fungal infection, exclusively IAFI (six proven, one probable). The proven IAFI included four peritonitis, one pancreatic necrosis with infected hematoma, and one patient with positive preservation fluid only (PF). Candida albicans (n = 4) was the most prevalent species (associated with Galactomyces candidus in one case), C glabrata, C dubliniensis, and C krusei were found in one case each. Three patients had either a positive direct examination and/or culture for renal or pancreatic PF and the culture of PF was positive for the same species that caused IAFI. IAFIs were significantly associated with pancreatic graft arterial thrombosis (5/7 vs 0/8, P = .007) and fungal contamination of PF (3/7 vs 0/8, P = .008). Among patients with IAFI, all required an early surgical revision post-transplantation [1-18 days] and six had early or delayed pancreatic graft removal. One patient died in the first post-transplant year. Conclusion IAFI is a common complication in PKT, associated with pancreatic graft thrombosis or fungal contamination of the graft PF, and can sometimes lead to pancreatic detransplantation.

BackgroundTreatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies.MethodsWe used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting.ResultsThis study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47–1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13–2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65–2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation.InterpretationThese results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.

Highlights • Less than 20% of febrile acute chest syndromes are microbiologically documented in adults presenting with sickle cell disease. • Molecular testing for respiratory pathogens slightly improves the microbiological diagnosis for viral detection but allows for reducing the antibiotic therapy duration. • Beyond the technical limits of microbiological molecular testing in standard clinical settings, our findings suggest the limited role of infections in the pathophysiology of acute chest syndrome., Background Differentiating acute chest syndrome (ACS) from community-acquired pneumonia (CAP) is challenging in adults presenting with major sickle cell disease (SCD) (semiological similarity, rare microbiological documentation). We aimed to assess the usefulness of nucleic acid amplification test (NAAT) for respiratory pathogens, in combination with standard bacteriological investigations, in febrile ACS adult patients presenting with major SCD. Methods We performed a prospective, monocentric, observational study of 61 SCD adults presenting with febrile ACS from February 2015 to April 2016. Systematic blood, urine, and respiratory specimens were collected, before antibiotic initiation, for culture, urinary antigen tests, serology, and NAAT for respiratory pathogens. Results A pathogen was detected in 12 febrile ACS (19.7%): four viruses (6.6%) (Rhinovirus; Influenza A/B), seven bacteria (11.4%) (S. aureus, S. pneumoniae, K. pneumoniae, L. pneumophila, M. pneumoniae), one mixed infection (1.6%) (S. aureus and Influenza B). NAAT only detected L. pneumophila in one case (serogroup 2). Apart from a significantly shorter antibiotic therapy duration (6.1 vs. 7.8 days, P = 0.045), no difference was observed between undocumented and microbiologically-documented febrile ACS. Conclusion Using NAAT for the detection of respiratory pathogens in adults presenting with SCD slightly improved the microbiological diagnostic of febrile ACS, although respiratory infections are not the main etiological factor.

Background Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring. Objectives To analyse available data on these unconventional LB diagnostic assays through a systematic literature review. Methods We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983–2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale. Results Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-α); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-γ, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57+ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses). Discussion QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters. The development of active infection biomarkers would greatly advance LB diagnosis and monitoring.

Introduction L’optimisation des concentrations plasmatiques des antibiotiques est essentielle dans le traitement des infections systemiques pour repondre aux objectifs PK/PD d’autant plus en cas de modifications du volume de distribution ou de la clairance renale. Le probenecide inhibe l’excretion tubulaire des antibiotiques, specifiquement des penicillines et augmente donc leur concentration plasmatique. Cependant, utilise comme potentialisateur pharmacocinetique des β-lactamines, ce medicament a ete peu etudie alors meme qu’il a ete initialement developpe dans ce but. L’objectif de notre etude est d’analyser de maniere retrospective l’utilisation du probenecide comme potentialisateur des β-lactamines. Materiels et methodes Nous avons mene une etude observationnelle retrospective et monocentrique, incluant les patients ayant recu du probenecide en association a des β-lactamines pour traiter une infection systemique, de 2014 a 2019. Les caracteristiques des patients, des pathologies, de la prescription de probenecide ainsi que les dosages des antibiotiques ont ete recueillis. Une analyse descriptive et statistique des variables continues et categoriques a ete menee. Resultats Au total, 38 patients ont ete inclus avec un âge median de 45 ans, et une clairance renale moyenne de 128,7 mL/min/1,73 m2 (CKD-EPI). Huit patients avaient comme antecedent une drepanocytose et 16 patients une hyperclairance renale (c.-a-d. DFG > 130 mL/min/1,73 m2). Les infections traitees etaient cerebrales (n = 14), pulmonaires (n = 9), osteoarticulaires (n = 6), de la peau et des tissus mous (n = 3), cardiaques (n = 3), urinaires (n = 2), une bacteriemie sans porte d’entree retrouvee, un abces hepatique et un syndrome de Lemierre. Vingt patients ont recu une penicilline, 16 une cephalosporine, et 2 une carbapeneme. Sur le plan microbiologique, 34 infections etaient documentees. Le probenecide (2 g/jour per os) etait ajoute dans un delai median de 7 jours (4–16) apres le debut des antibiotiques, et ce pour une duree mediane de 13 jours (6,75–21,75). Le probenecide a ete prescrit en raison d’un sous-dosage de l’antibiotique pour 29 patients, pour une hyperclairance renale chez 5 patients, et pour la persistance de la fievre malgre l’antibiotherapie chez 4 patients. Vingt-quatre patients ont eu un nouveau dosage plasmatique d’antibiotique apres introduction du probenecide dans un delai median de 3 jours (2–5). Le probenecide a permis une augmentation de la concentration plasmatique de l’antibiotique chez 91,7 % des patients (22/24) avec une variation mediane de +356 % (IQR : 46,6–673). Pour 8 infections documentees dont la CMI avait ete determinee, la variation de la mediane du taux plasmatique d’antibiotiques/CMI calculee etait de +547 % (IQR : 149–868,9). Aucun effet secondaire lie a l’utilisation de probenecide n’a ete decrit. Conclusion Le probenecide est un potentialisateur sur et efficace des β-lactamines, probablement sous-utilise. Nos donnees suggerent de l’utiliser plus souvent pour optimiser la pharmacocinetique des β-lactamines dans les infections bacteriennes systemiques.

Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, is the recognized standard of care (SOC), which has helped extend life expectancy in people living with HIV. In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTIs, "NRTI-reducing" regimens have been investigated. This descriptive review assessing the results of NRTI-reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity. The review considers efficacy across various NRTI-sparing strategies, for example an integrase strand transfer inhibitor (INSTI) plus a ritonavir-boosted protease inhibitor (PI/r) or PI/r + lamivudine (3TC), in both naïve and switch regimes. Of 10 key studies in treatment-naïve adults assessing five NRTI-reducing strategies, only four studies demonstrated noninferiority vs. SOC [GARDEL, NEAT 001, AIDS Clinical Trials Group 5142 and PROGRESS]. In switch settings, 17 studies (10 randomized) were reviewed that used four strategies, including three studies assessing an INSTI plus a nonnucleoside reverse transcriptase inhibitor . Noninferiority of the NRTI-reducing arm was shown in six of 10 studies (ATLAS-M, SALT, DUAL, OLE, LATTE-2 and SWORD). In general, NRTI-reducing therapy did not always result in an improvement in short- or long-term adverse events; however, in many cases, these endpoints were not reported. Some of these studies reported higher virological failure rates with more frequent emergence of resistance mutations. None of these NRTI-reducing strategies has been compared against a single-pill regimen, including those containing tenofovir alafenamide. Only strategies demonstrating noninferior efficacy, a benefit in safety/tolerability, and a favourable cost-efficacy ratio, preferably in a single pill, will eventually match the current SOC of triple ARV therapy.

Introduction Les infections bacteriennes severes sont la premiere cause de morbidite chez les personnes vivant avec le VIH (PVVIH). Nous avons cherche a evaluer leur incidence et a analyser leurs determinants. Materiels et methodes La population d’etude etait celle des PVVIH âgees d’au moins 15 ans suivies dans une cohorte prospective nationale multicentrique entre 2006 et 2015. Le modele d’Andersen et Gill a ete utilise pour estimer le risque d’infection bacterienne severe, y compris recidivante, en particulier en cas de consommation elevee d’alcool ou en presence d’une comorbidite alterant la fonction neutrophile (diabete, maladie renale chronique, cirrhose, cancers). Resultats Parmi 25 795 participants, 1414 ont developpe 1883 infections bacteriennes severes, incluant 1132 pneumonies, 154 infections des voies urinaires, 136 infections de la peau et des tissus mous, 70 colites, 6 meningites, 14 endocardites, 94 infections intra-abdominales, 33 arthrites, osteomyelites ou osteites, 3 myosites, 236 bacteriemies ou sepsis d’autre origine et 3 chocs septiques d’autre origine. Entre 2006–2009 et 2013–2015, l’incidence a diminue de 13,2 (IC95 %: 12,3–14,1) a 7,1 (IC95 %: 6,3–7,8) pour 1000 personne-annees (ratio du taux d’incidence 0,54, IC95 %: 0,47–0,60). Une consommation elevee d’alcool etait associee a un risque accru d’infection bacterienne severe, avec un risque relatif ajuste (RRa) a 1,4 (IC95 %: 1,1–1,7) pour 40–80 g/jour et 1,6 (IC95 %: 1,3–2,1) pour > 80 g/jour. C’etait le cas egalement pour le diabete, la maladie renale chronique et la cirrhose, avec un RRa a 1,2 (IC95 %: 1,0–1,4) pour une seule comorbidite et 2,3 (IC95 %: 1,6–3,4) lorsque deux comorbidites etaient presentes, ainsi que pour les cancers non classants et classants, avec un RRa respectivement a 2,0 (IC95 %: 1,6–2,4) et 1,4 (IC95 %: 1,2–1,7). Conclusion Sur une periode de 10 ans, l’incidence des infections bacteriennes severes a diminue de moitie. Une consommation elevee d’alcool et les comorbidites alterant la fonction neutrophile etaient associees a un risque accru. Le controle de la consommation d’alcool et la prise en charge des comorbidites doivent etre renforcees chez les PVVIH.

Introduction Les infections sont la principale cause de mortalite non cardiovasculaire apres transplantation renale (TR). Malgre l’existence de recommandations de prevention avant TR, celles-ci restent peu appliquees. Nous decrivons l’interet d’une consultation d’infectiologie avant la TR comme outil pour ameliorer la prevention anti-infectieuse dans ce contexte. Materiels et methodes Il s’agit d’une etude mono centrique prospective de cohorte ayant interesse tous les patients adultes en liste d’attente de TR entre janvier 2014 et decembre 2018. A l’inclusion, les donnees demographiques et nephrologiques des patients etaient recueillies, ainsi que celles relatives aux vaccinations recues avant la consultation d’infectiologie. Les serologies suivantes etaient realisees : hepatites A et B, fievre jaune (si prealablement vaccines), rougeole, VZV. Chez tous les patients, une imagerie pulmonaire etait realisee ainsi qu’un test de depistage de l’infection tuberculose latente (ITL) par detection de production d’interferon gamma (IGRA). Resultats Parmi les 994 patients sur liste de transplantation, 467 (47 %) ont eu une consultation d’infectiologie pre-greffe. Parmi eux, 302 (65 %) etaient des hommes (sex ratio 1,83), l’âge median etait de 58 ans (46–66), 333 (71 %) etaient dialyses. Une immunosuppression (greffe anterieure, traitement immunosuppresseur) etait presente chez 107 (23 %) patients. Pour l’etat vaccinal a l’inclusion : 109 (24 %) et 27 (6 %) patients avaient une vaccination diphterie-tetanos-polio-coqueluche (dTPc) et anti-pneumocoque a jour respectivement, 51 % des patients (228) avaient ete vaccines contre la grippe l’annee precedente. Les patients non dialyses etaient significativement moins vaccines contre l’hepatite B que ceux dialyses (46 % vs. 57 %, p = 0,0001), mais leur vaccination contre dTPc etait plus frequemment a jour (33 % vs. 20 %, p = 0,005). Les patients vaccines contre le pneumocoque etaient plus immunodeprimes (33 % vs 17 %, p = 0,028), avaient plus de vaccinations a jour contre dTPc (41 % vs 23 %, p = 0,040) et grippe (70 % vs 50 % p = 0,038) que les patients non vaccines contre le pneumocoque. Soixante-quinze patients (16 %) avaient un IGRA positif et 26 avaient des lesions pulmonaires sequellaires (6 %). Un traitement de l’ITL (INH ou INH/RMP) a ete initie chez 78 (16 %) patients, complique d’effets secondaires chez 9 (11 %), dont une neurotoxicite centrale a l’INH. L’acceptabilite de la mise a jour vaccinale et du traitement de la TL, proposes au cours la consultation, etait excellente (2 refus de vaccinations sur 467). Conclusion Une consultation d’infectiologie avant TR optimise l’application des mesures recommandees de prevention anti-infectieuse.

Diagnosis of prosthetic valve infective endocarditis (IE) is challenging because sensitivity of Duke Criteria is low, ranging from 52% to 70% [(1)][1]. Therefore, fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was included in the modified Duke Criteria to improve

Introduction A l’ere de la prophylaxie anti-cytomegalovirus (CMV) systematique post transplantation (Tx), l’impact du statut serologique CMV du donneur et receveur sur la mortalite est debattu. L’objectif etait d’etudier la mortalite et la morbidite a 5 ans post-Tx chez des transplantes pulmonaires seronegatifs pour le CMV (R-) selon le statut serologique du donneur (D+ ou D-). Methodes Etude retrospective monocentrique realisee a l’Hopital Bichat (Paris). 42 patients R- recevant un greffon D+ (mismatch) entre 2007 et 2017 ont ete apparies sur l’âge, le sexe et la date de transplantation a 42 patients R- recevant un greffon D-. L’objectif principal etait de comparer la survie globale a 5 ans entre les deux groupes. Les objectifs secondaires etaient: rechercher des facteurs de risque de mortalite, decrire les infections/maladies a CMV et le taux de resistance, evaluer la tolerance des traitements prophylactiques systematiques anti-CMV dans le groupe D+/R-, comparer les rejets aigus, les dysfonctions chroniques du greffon, et la survenue de complications indirectes attribuables au CMV (analyse de survie par methode de Kaplan-Meier, comparaison par log-rank, modele de Cox pour estimer l’association entre statut D/R et survie). Resultats Les patients D+/R- et D-/R- avaient une survie a 5 ans post-Tx comparable, avec une tendance a une surmortalite de 15% dans le groupe D+/R- (49% vs 64% respectivement, p = 0,27). En analyse univariee, la dysfonction chronique du greffon et l’infection a CMV etaient des facteurs de risque de mortalite, non retrouves en analyse multivariee. Il y a eu plus d’infections (59%) et de maladies a CMV (21%) dans le groupe D+/R- que dans le groupe D-/R- (7% et 0 respectivement, p Conclusion Les patients D+/R- et D-/R- avaient une mortalite comparable, mais la morbidite notamment infectieuse etait plus importante dans le groupe D+/R-. Le statut D/R pour le CMV doit etre pris en compte dans le choix du donneur lors d’une Tx pulmonaire.

Introduction La bronchopneumopathie chronique obstructive (BPCO) represente la 3e cause de deces dans le monde. L’exacerbation aigue est la principale cause de morbi-mortalite. Elle est principalement d’origine infectieuse, impliquant en premier lieu le virus de la grippe. D’autres pathogenes comme Bordetella pertussis (BP) peuvent etre responsables de complications severes. Si la vaccination constitue un element determinant pour proteger le patient BPCO contre ces episodes infectieux, une moins bonne reponse a la vaccination antigrippale a ete observee chez les patients BPCO. L’objectif de notre etude etait d’analyser les reponses humorale et cellulaire apres vaccination anti-BP chez les patients BPCO ce qui a notre connaissance n’a jamais ete realisee. Materiels et methodes Une etude prospective interventionnelle monocentrique a ete mise en place afin d’analyser la reponse immunitaire post-vaccinale specifique contre BP apres une injection de rappel du vaccin tetravalent dTCaPolio (Repevax°). Les parametres etudies ont ete : – j0 : analyse des populations lymphocytaires Tfh, T regulatrices, lymphocytes B naifs et memoires et des anticorps anti-BP ; – j7 post-vaccination (PV) : analyse des populations de plasmablastes et Tfh ; – j15 PV : analyse de la reponse T (restimulation ex vivo avec pool de peptide comprenant FHA, PRN, PT, et Fim 2/3, marquage intracellulaire des cytokines [IL2, IFNg, TNFa]) ; – j30 PV dosage des anticorps anti-BP. Resultats Entre septembre 2018 et mai 2019, 23 patients ont ete inclus : 14 patients BPCO (VEMS/CV : 0,5 ± 0,14) et 9 temoins fumeurs non BPCO apparies sur l’âge et le sexe. A j0, une frequence plus elevee de lymphocytes T CD4+ exprimant PD1 a ete observee chez les patients BPCO (mediane 45,1 % [IQR : 33–55] versus 32,95 % [IQR : 28–40] chez les temoins [p = 0,0241]). On notait une augmentation significative des lymphocytes Tfh et des plasmablastes chez les patients BPCO 7 jours PV (mediane 1,5 %) (IQR : 0,5–2,4) a j0 et 5,2 % (IQR : 1,9–7,5) a j7 (p = 0,002) ; 0,41 % (IQR : 0,2–1,4) a j0 et 2,1 % (IQR : 1,1–5,9) a j7 (p = 0,0039), respectivement, sans difference avec le groupe temoin. A j15 PV, la frequence de LT CD4+ BP specifiques etait de 0,08 % (IQR : 0,06–0,45) chez les sujets temoins et de 0,15 % (IQR : 0,09–0,36) (somme de la production des 3 cytokines IL2, IFNg, TNFa) chez les patients BPCO sans difference significative entre les 2 groupes. A j0, la majorite des sujets presentait un taux faible d’IgG anti-BP. Une augmentation significative de ces anticorps etait observee a j30 (34,5 UI/mL IQR [20,75–139,5] [p = 0,03] vs 39 UI/mL IQR [31–53] [p = 0,002]), pour les groupes temoin et BPCO respectivement, sans difference significative entre les deux groupes. Conclusion Contrairement a ce qui a pu etre observe avec d’autres vaccins, et malgre l’augmentation de PD1 (marqueur d’immunosenescence) sur les lymphocytes T CD4, la reponse vaccinale anti-coquelucheuse tant cellulaire qu’humorale semble conservee chez les sujets avec BPCO, soulignant la pertinence de la revaccination dans cette population vulnerable.

Introduction Le phenotype du COVID-19 est tres variable. Identifier et caracteriser les populations a risque d’evolution defavorable est cruciale. L’objectif de cette etude est de decrire l’infection COVID-19 dans une population de transplantes renaux (TR). Materiels et methodes Il s’agit d’une etude retrospective monocentrique des TR atteints de COVID-19 de fevrier a mai 2020. Les cas confirmes par PCR et les cas possibles (clinique et lesions pulmonaires scanographiques compatibles) ont ete inclus. La mortalite a ete comparee avec celle de la population generale non transplantee dans le meme centre. Resultats Parmi 1004 TR, 34 dont 26 hommes ont ete atteints de COVID-19, avec un delai median de 6 ans [2,2–10,3] apres la transplantation. Deux patients avaient ete transplantes dans les 6 mois precedents. L’âge moyen etait de 61 ans [23–81]. Les principales comorbidites etaient une hypertension arterielle (31 cas, 94 %), une cardiopathie (16 cas, 47 %) et un diabete (14 cas, 41 %). Le traitement de maintenance associait les inhibiteurs de la calcineurine, les anti-metabolites et les corticoides chez 22 patients (65 %). Le debit de filtration glomerulaire estime etait de 40 mL/min/1,73 m2 [32–52]. Neuf patients (26,5 %) avaient deja presente des complications infectieuses pulmonaires apres la greffe. Trente patients (88 %) ont ete hospitalises avec un delai median de 7,7 jours [3–9,5] apres le debut des symptomes. Les signes cliniques initiaux principaux etaient une fievre (n = 28,82 %), une toux (n = 23, 68 %), une dyspnee (n = 16, 47 %) et une diarrhee (n = 12, 35 %). A l’admission on observait une lymphopenie chez 18 patients (53 %), une CRP mediane a 84 mg/L [31,2–99,8] et une PCT mediane a 0,25 μg/L [0,19–0,4]. Sept patients sur 18 (39 %) presentaient une atteinte parenchymateuse pulmonaire severe (plus de 50 %) au scanner. Les traitements specifiques comprenaient l’hydroxychloroquine (n = 6, 18 %), l’association lopinavir/ritonavir (n = 1, 3 %), les anti-IL6 (n = 2, 6 %). L’arret d’un des immunosuppresseurs a ete effectue chez 20 patients. Une forme clinique severe (admission en reanimation ou oxygenotherapie ≥ 9 L/min) est survenue chez 20 patients (61 %). Le delai d’admission en reanimation etait de 2,5 jours [0–6,5] depuis l’hospitalisation. Vingt patients (61 %) ont presente une insuffisance renale aigue dont 6 necessitant de l’hemodialyse. Quinze patients (44 %) sont decedes dans un delai de 11 jours [7–16] apres l’hospitalisation. Le taux de deces chez les patients hospitalises pour COVID-19 non TR etait de 15,4 %. Conclusion Les patients transplantes renaux sont une population a haut risque de forme severe de COVID-19 avec un taux de mortalite approchant 50 % dans cette etude. Le renforcement des strategies preventives et de depistage semble primordial chez ces patients immunodeprimes et a fort risque cardiovasculaire.

HIV-1 infection is associated with B cell dysregulation and dysfunction. In HIV-1–infected patients, we previously reported preservation of intestinal lymphoid structures and dendritic cell maturation pathways after early combination antiretroviral therapy (e-ART), started during the acute phase of the infection, compared with late combination antiretroviral therapy started during the chronic phase. In this study, we investigated whether the timing of combination antiretroviral therapy initiation was associated with the development of the HIV-1–specific humoral response in the gut. The results showed that e-ART was associated with higher frequencies of functional resting memory B cells in the gut. These frequencies correlated strongly with those of follicular Th cells in the gut. Importantly, frequencies of HIV-1 Env gp140–reactive B cells were higher in patients given e-ART, in whom gp140-reactive IgG production by mucosal B cells increased after stimulation. Moreover, IL-21 release by PBMCs stimulated with HIV-1 peptide pools was greater with e-ART than with late combination antiretroviral therapy. Thus, early treatment initiation helps to maintain HIV-1–reactive memory B cells in the gut as well as follicular Th cells, whose role is crucial in the development of potent affinity-matured and broadly neutralizing Abs.

OBJECTIVES To compare nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-sparing regimens with tenofovir alafenamide (TAF)-based combinations in HIV-1-infected adults, we performed a network meta-analysis (NMA) to provide estimates of relative efficacy for these two regimens. METHODS A systematic literature review (SLR) was performed to identify phase 3/4 randomized controlled clinical trials evaluating the efficacy of commonly used combination antiretroviral therapy (cART) including an NRTI backbone or that of commonly used NRTI-sparing regimens. A Bayesian random-effect model was used to compare virological suppression rates at 48 weeks for NRTI-sparing regimens and elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF). RESULTS Twenty-three studies in treatment-naive patients identified by the SLR were included in the NMA, including four studies assessing NRTI-sparing regimens. In treatment-naive patients, the probability of achieving virological suppression at 48 weeks was between 40% and 60% higher with E/C/F/TAF than with NRTI-sparing strategies. The credible interval vs. darunavir/ritonavir (DVR/r) + raltegravir (RAL) and LPV/r monotherapy did not include 1. In the subgroup of naive patients with viral load

The purpose of this review was to provide current data on clinical presentation, diagnosis, and treatment of primary HIV infection (PHI). In 65 to 95% of cases, PHI causes acute retroviral syndrome presenting with unspecific flu-like symptoms. Symptomatic PHI was associated with a faster clinical and immunological progression of HIV infection. Point-of-care tests remain less sensitive than fourth-generation immunoassays (IA) in PHI, especially after tenofovir-based prophylaxis use. Early antiretroviral treatment (ART) started during PHI prevents HIV transmission and decreases viral and immunological reservoir constitution. Recommended ART regimens in PHI are combinations of tenofovir and emtricitabine with either darunavir/ritonavir, or dolutegravir. Starting ART the earliest is highly recommended for clinical, virological, immunological, and public health benefits. Reducing HIV reservoir constitution in PHI may optimize potential opportunities for future functional cure.

Background Few data on bariatric surgery are available regarding obese human immunodeficiency virus (HIV)-infected patients. Settings Antoine Beclere hospital, Clamart, Paris-sud University, France Methods Prospective observational follow-up study recruited HIV-infected patients who underwent bariatric surgery from 2009 to 2015. Baseline demographic characteristics, surgery characteristics, perioperative outcomes, changes in weight loss, HIV markers, antiretroviral drug plasma levels are described. Results There were 10 patients followed before and after sleeve gastrectomy: 2 men and 8 women; 50% of African origin; median age, 48.5 years, median time since HIV infection, 7.5 years; median body mass index, 48.5 kg/m 2 . Of patients, 8 had co-morbidities. All except 2 patients received antiretroviral drugs at the time of surgery with a median CD4 cell count at 709/mm 3 . There was no death or postoperative infectious complications. The median follow-up was 18 months (range, 15–55). The median postoperative weight loss was 43 kg (range, 17–83). Median percentage of excess weight loss was 82.5% (range, 35–119) at the latest visit after surgery. All co-morbidities were resolutive with weight loss. We observed no significant modification of CD4 cell count before and after surgery. Pharmacokinetics of antiretroviral drugs remains adequate and efficacious. Conclusion Our prospective series is the largest one on sleeve gastrectomy procedures performed on obese-treated HIV-infected patients. The sleeve generates good results in weight loss, with no significant impact on HIV infection, and with improvement of obesity-associated co-morbidities. Optimal management of HIV-infected patients with morbid obesity may include classical surgical procedures.

Due to the differences between bioavailability of efavirenz (EFV) and tenofovir (TDF), the single-tablet regimen of EFV/emtricitabine (FTC)/TDF is not approved as initial antiretroviral therapy (ART) in Europe by the European Medical Agency. To compare clinical, immunological, and virological outcomes between co-formulated TDF/FTC+EFV and the co-formulated EFV/FTC/TDF single-tablet regimen in patients infected with HIV-1 naive to ART, the data of patients (n = 231) who initiated either TDF/FTC+EFV (n = 155) or EFV/FTC/TDF (n = 76) between January 1, 2007 and June 1, 2010 were analyzed. Changes from baseline to week 48 (TDF/FTC+EFV vs. EFV/FTC/TDF) in HIV plasma load (− 3.25 log vs. −3.32 log) and CD4+ T cell count (+180 vs. +138 cells/mm3) were similar in the two groups. Treatment discontinuation was recorded in 50 (22%) patients (40 on TDF/FTC+EFV and 10 on EFV/FTC/TDF, P = 0.03) but time to discontinuation did not differ between the two groups. Only patients on TDF/FTC+EFV discontinued treatment because of neurological symptoms. Virological failure occurred in 11 (4.7%) patients (seven on TDF/FTC+EFV and four on EFV/FTC/TDF, P = 0.75) with new resistance-associated mutations in five among the six with successful resistance genotype tests. Only baseline resistance-associated mutations was a risk factor for virological failure (P = 0.0146). These data show comparable outcomes between TDF/FTC+EFV or EFV/FTC/TDF used in patients infected with HIV-1 and not treated previously, consistent with a low rate of virological failure in the absence of pretreatment resistance. This would suggest that the European Medical Agency should approve co-formulated EFV/FTC/TDF single-tablet regimen for patients naive to ART. J. Med. Virol. 87:187–191, 2015. © 2014 Wiley Periodicals, Inc.

We report the neuropathological findings in 10 HIV-infected patients treated by combination antiretroviral therapy who developed subacute encephalopathy of rapidly progressive onset. Brain biopsy showed encephalitic lesions variably associated with myelin loss and slight axonal damage. There was inconstant, weak expression of HIV protein p24; tests for other pathogens were negative. The most striking feature was diffuse, perivascular and intraparenchymal infiltration by CD8+ T-lymphocytes. Six patients improved after the treatment. Four had an unfavorable outcome and died within a year. Post-mortem in one case confirmed HIV leukoencephalitis with p24-positive multinucleated giant cells, associated with acute demyelinating encephalomyelitis (ADEM) in the cerebellum. There was diffuse infiltration by CD8+ lymphocytes; CD4+ cells were virtually absent. These cases may represent a specific clinicopathological entity, of which a few comparable cases have been already described. They can be included in the wide framework of immune reconstitution disease. Such syndromes have been described with opportunistic infections, but only seldom with HIV infection of the central nervous system (CNS). Our findings support the hypothesis that CD8+ cytotoxic lymphocytes can be harmful in immune reconstitution disease, particularly in the absence of CD4+ lymphocytes. CD8 cytotoxicity produces an acutization of a smoldering infection and/or an immunopathological reaction similar to ADEM.

OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. METHODS: HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. RESULTS: A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. CONCLUSIONS: HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype.

Resume Introduction Malgre la nette diminution des infections opportunistes grâce aux traitements antiretroviraux tres efficaces, la pneumonie a Pneumocystis jirovecii reste la premiere infection revelatrice du sida en France. Etat des connaissances Le diagnostic clinique, radiologique et mycologique posent peu de problemes chez les patients infectes par le VIH. Le traitement de reference est l’association trimethoprime-sulfamethoxazole a fortes doses, en association a la corticotherapie en cas d’hypoxemie severe, ce qui a permis de diminuer la mortalite chez ces patients. Il est indispensable de debuter la prophylaxie pour la prevention des pneumonies a P. jirovecii chez des patients dont l’infection virale n’est pas controlee avec un deficit immunitaire important a moins de 200 CD4/mm 3 . Perspectives La place des outils de biologie moleculaire (PCR) reste a definir chez les patients infectes par le VIH, ainsi que la valeur de la colonisation chez ces patients. La meilleure alternative therapeutique en cas d’echec ou d’intolerance au trimethoprime-sulfamethoxazole n’est pas clairement definie. Conclusion Le depistage universel et les nouvelles recommandations de debuter le traitement antiretroviral a un stade plus precoce de l’infection VIH, avant l’installation d’un deficit immunitaire, devrait permettre de diminuer encore le risque de survenue de pneumonies a P. jirovecii en France.

Introduction L’utilisation de nouveaux agents immunosuppresseurs apres transplantation a permis de diminuer l’incidence des rejets et d’ameliorer la survie des greffons. Aucune etude recente du spectre et des consequences des infections opportunistes n’est disponible. Patients et methodes Nous avons realise une etude retrospective monocentrique de cohorte chez des patients transplantes renaux entre 01/2008 et 12/2013. Le groupe infection opportuniste a ete compare au reste de la cohorte. L’objectif principal etait l’evaluation de la survie des patients et des greffons. Les objectifs secondaires etaient le spectre des infections opportunistes apres transplantation renale et les facteurs predisposants a une infection opportuniste. Resultats Sur les 538 transplantes renaux inclus, nous avons recense 55 episodes d’infections opportunistes chez 51 (9 %) patients. Le groupe controle etait constitue de 487 patients. A la fin du suivi, la survie des greffons et des patients etaient comparables dans les deux groupes avec 6 (11 %) perte de greffon dans le groupe infection et 59 (12 %) dans le groupe controle (p = 1,00) et 8 (16 %) deces dans le groupe infection et 50 (10 %) dans le groupe controle (p = 0,23). Le delai median de l’infection opportuniste etait de 20 (6–35) mois et 20 (36 %) des episodes etaient diagnostiques dans la premiere annee postgreffe. Les etiologies etaient virales pour 28 (51 %) episodes, fongiques pour 15 (27 %), parasitaires pour 7 (13 %) et bacteriennes pour 5 (9 %). Le nombre moyen de lymphocytes totaux le jour de la transplantation etait significativement plus bas dans le groupe infection (1210/mm3 vs. 1420/mm3 ; p = 0,03). Le nombre absolu de CD4+ et CD8+ a 6 mois de la transplantation etait significativement plus bas dans le groupe infection opportuniste (p = 0,01 et p = 0,03 respectivement). Discussion Une modulation de l’immunosuppression selon le chiffre de lymphocytes totaux avant la transplantation peut etre discutee. Conclusion Apres transplantation renale, la survenue d’une infection opportuniste ne semble pas impacter la survie des patients et des greffons. L’analyse multivariee a la recherche de facteurs de risque independants d’infection opportuniste apres transplantation renale est en cours.

Les traitements antiretroviraux ont considerablement ameliore le pronostic de l’infection par le virus de l’immunodeficience humaine (VIH) et sont largement prescrits en France chez les patients suivis pour cette infection. L’admission frequente des patients infectes par le VIH en reanimation confronte regulierement le reanimateur a la gestion de ces medicaments, a cote des autres traitements de reanimation. Cette revue aborde les principes generaux du traitement antiretroviral dans l’infection par le VIH, puis plus specifiquement des conditions d’utilisation des medicaments antiretroviraux en reanimation, incluant leurs circonstances d’utilisation, leurs modalites d’administration, leur toxicite et leurs interactions medicamenteuses potentielles.

BACKGROUND once-daily combinations of efavirenz and two nucleoside analogues are recommended for the treatment of HIV infection. Long-term efficacy and safety data are scarce for the combination of efavirenz, emtricitabine and didanosine. METHODS the ALIZE ANRS 099 trial enrolled 355 adults with plasma HIV RNA levels of

Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case-control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS135% HIV(+) group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13or=5% HIV(+) group). HIV(+) patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS135% idiopathic group) or without (17 patients, ADAMTS13or=5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS135% HIV(+) patients had less AIDS-related complications than ADAMTS13or=5% HIV(+) patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4(+) T cell count was higher (P = 0.05). TMA-associated death rate was higher in ADAMTS13or=5% HIV(+) patients than in ADAMTS135% HIV(+) patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS135% patients, TMA-associated death rate was comparable between HIV(+) and idiopathic patients (15.5% in idiopathic patients, P-value was non-significant). By contrast, TMA-associated death rate in ADAMTS13or=5% HIV(+) patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV-associated TMA with severe ADAMTS13 deficiency have less AIDS-related complications and a higher CD4(+) T cell count. TMA prognosis is better and comparable to this of idiopathic forms.

Resume La maladie de Kikuchi-Fujimoto (MKF) ou lymphadenite histiocytaire necrosante est une maladie ganglionnaire inflammatoire, benigne, surtout cervicale, d’etiologie inconnue et dont le diagnostic est histologique. Elle s’associe parfois a une maladie auto-immune, en premier lieu le lupus erythemateux systemique (LES). Une atteinte ganglionnaire profonde, une hepatosplenomegalie et un syndrome general (amaigrissement, sueurs nocturnes) sont des manifestions rares de la MKF qui orientent avant tout vers une cause infectieuse. Nous rapportons ici une presentation infectieuse trompeuse pseudotuberculeuse d’un LES associe a une MKF chez un patient senegalais porteur d’une hepatite B chronique. Ce cas clinique illustre ainsi ces tableaux cliniques atypiques pseudo-infectieux que revetent parfois les maladies inflammatoires systemiques et auxquels sont regulierement confrontes les infectiologues.