Changing profile of encephalitis: Results of a 4-year study in France.

CONTEXT: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson's Chi2 test, and means were compared using Student's t-test for continuous variables. RESULTS: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines.

COVID-19: The forgotten cases of hidden exiles.

PURPOSE OF THE RESEARCH: We describe two interventions to screen for SARS-CoV-2 in two squats of exiled persons in France following the diagnosis of symptomatic COVID-19 cases. PRINCIPAL RESULTS: In squat A, 50 (25%) persons were screened; 19 were found positive, and three accepted a transfer. In squat B, 65 (54%) persons were screened at three different times, and only two were found positive. MAJOR CONCLUSIONS: Discrepant outcomes may reflect different levels of sanitation, prevention, and acceptance of interventions. Refusal to be transferred to specific COVID-19 homes if tested positive underscores the importance of local sanitary solutions for all. Cross-curricular strategies addressed to exiled persons are essential means of providing medical and public health solutions designed to deter COVID-19 outbreaks in these populations.

Post-exposure prophylaxis completion and condom use in the context of potential sexual exposure to HIV.

OBJECTIVES: Post-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours. METHODS: A retrospective analysis was carried out on data from the French Dat'AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant). RESULTS: Overall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner's HIV status. CONCLUSIONS: We provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.

[How to reduce lung cancer mortality among people living with HIV?] / Comment réduire la mortalité par cancer du poumon chez les personnes vivant avec le VIH ? Du sevrage tabagique au dépistage radiologique.

Lung cancer is the leading cause of cancer related death among people living with HIV (PLHIV). Tobacco exposure is higher among PLHIV (38.5%) and mainly explains the increased risk of lung cancer. To reduce lung cancer mortality, two approaches need to be implemented: lung cancer screening with low-dose thoracic CT scan and smoking cessation. Low dose CT scan is feasible in PLHIV. The false positive rate is not higher than in the general population, except for cases with CD4 <200/mm3. The impact on survival remains to be assessed. Despite the high prevalence, smoking cessation research among PLHIV is scarce. Very low quality data from 11 studies showed that more intensive smoking cessation interventions were effective in achieving short-term abstinence. A single randomized phase 3 trial showed the superiority of varenicline compared to placebo in long-term smoking cessation. The maximum benefit of reducing lung cancer mortality should be obtained by combining smoking cessation and lung cancer screening.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

Implant retention and high rate of treatment failure in hematogenous acute knee and hip prosthetic joint infections.

OBJECTIVES: Only few studies evaluated hematogenous prosthetic joint infections. We aimed to describe the characteristics of these infections and factors associated with management failure. METHODS: We selected hematogenously-acquired infections, defined by the occurrence of infectious symptoms more than a year after implantation among records of patients treated for hip and knee prosthetic joint infections at Montpellier University Hospital between January 2004 and May 2015. Failure was defined by death due to prosthesis-related infection, need for prosthesis removal in case of conservative treatment, or recurrence of infectious signs on a new prosthesis. RESULTS: Forty-seven patients with hematogenous prosthetic joint infection were included (33 knee infections and 14 hip infections). Infectious agents were streptococci (43%), Staphylococcus aureus (43%), Gram-negative bacilli (13%), and Listeria monocytogenes (2%). Thirty-one patients were initially treated with debridement and implant retention and 15 with prosthesis removal (three with one-stage surgery, 10 with two-stage surgery). The median duration of antibiotic therapy was 66.5 days. The overall failure rate was 52% (24/48), 71% (22/31) with implant retention strategy, 13% (2/15) with prosthesis removal, and 63% (12/19) in case of Staphylococcus aureus infection. Conservative treatment was appropriate (arthrotomy on a well-implanted prosthesis without sinus tract and symptom onset <21 days) in 13/31 patients (42%) with a failure rate still high at 69% (9/13). The only factor associated with failure was conservative surgical treatment. CONCLUSION: The high risk of failure of conservative treatment for hematogenous prosthetic joint infections should lead to considering prosthesis replacement as the optimal strategy, particularly with Staphylococcus aureus.

Potential lung cancer screening outcomes using different age and smoking thresholds in the ANRS-CO4 French Hospital Database on HIV cohort.

OBJECTIVES: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility. METHODS: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer. RESULTS: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer. CONCLUSIONS: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Missed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT'AIDS cohort.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat'AIDS cohort in 2016. METHODS: Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area. RESULTS: Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%). CONCLUSION: With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access.

Implementing screening, brief intervention and referral to treatment in a French cohort of people living with HIV: a pilot study.

OBJECTIVES: Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based practice used to identify, reduce and prevent problematic use and abuse of, and dependence on, tobacco, alcohol and psychoactive substances. To date, the pertinence of this practice among people living with HIV (PLHIV) is unknown. In this pilot study, we aimed to assess the acceptability of SBIRT in a cohort of HIV-infected out-patients who were asked about their consumption of alcohol, tobacco and psychoactive substances. METHODS: A monocentric study was performed at the University Hospital of Montpellier. In a 6-month period, 20 trained physicians screened for the consumption of alcohol [using the Alcohol Use Disorders Identification Test (AUDIT)], tobacco (using the Short Fagerstrom Test) and psychoactive substances [using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) V3.0] via an auto-questionnaire and proposed a brief intervention to patients with misusage. RESULTS: One thousand and eighteen PLHIV completed the questionnaire, and 861 [84.6%; 95% confidence interval (CI) 82.2-86.7%] PLHIV returned it to the physician. Among the latter, 650 patients wished to discuss the answers with their physician (75.5%; 95% CI 72.5-78.3%), and brief interventions were realized in 405 patients (62.3%). CONCLUSIONS: SBIRT is a simple screening and harm reduction tool that is well accepted by PLHIV in out-patient clinics. This method could be implemented in routine HIV care to screen and manage patients systematically for harmful substance use.

Staging of recent HIV-1 infection using Geenius rapid confirmatory assay compared to INNO-LIA, New Lav and Blot 2.2 assays.

BACKGROUND: Besides confirmation of HIV seropositivity, Western Blot (WB) assays play an important role for identification of recent infection based on incomplete antibody reactivity and lack of p31 band. OBJECTIVES: We evaluated the capacities of the Geenius™ HIV1/2 Confirmatory Assay (Bio-Rad), a new generation rapid confirmatory assay based on immune-chromatography and automated reading, for staging of HIV-1 infection. STUDY DESIGN: Sixteen samples collected during early HIV-1 infections (Fiebig stage III-VI) were tested using the Geenius assay, and compared to HIV Blot 2.2 WB assay (MP Diagnostics), New Lav Blot I WB assay (Bio-Rad) and INNO-LIA™ HIV I/II Score Dot Blot assay (Fujirebio). Results obtained with Geenius and INNO LIA in 47 newly diagnosed chronic HIV-1 infections were also compared. RESULTS: The p24 band was less frequently detected in early HIV-1 infections using the Geenius (3/16) compared to the New Lav (15/16, p<0.0001), INNO-LIA (13/16, p=0.0011), and Blot 2.2 (13/16, p=0.0011). Testing samples collected during chronic infection allowed to confirm that p31 band and complete Gag, Pol, Env profiles were less frequently observed using the Geenius assay compared to the INNO LIA assay (p=0.027 for p31, and p=0.0015 for complete profile). CONCLUSIONS: The Geenius assay is a simple and rapid test showing a high sensitivity to detect Env bands and to confirm HIV-1 seropositivity during the early phases of infection. However, this test is less suitable for distinguishing between later stages of acute and chronic infections because of a reduced sensitivity to detect the p31 and p24 bands compared to INNO LIA and New Lav assays.

Impact of T cell activation, HIV replication and hepatitis C virus infection on neutrophil CD64 expression.

BACKGROUND: Overexpression of the Fc receptor CD64 on neutrophils is associated with innate immune response and bacterial infections. During HIV infection a large set of immune disorders including T-lymphocyte over-activation, microbial translocation, impairment of neutrophil functions, and immunodeficiency may interplay with neutrophil CD64 expression. METHODS: Associations of neutrophil CD64 expression with CD8+ T cell activation, CD4+ T cells number, HIV, and HCV replications were investigated in HIV infected patients using a standardized method. RESULTS: Higher neutrophil CD64 expression was observed in HIV infected subjects compared to healthy controls (0.91 vs. 0.75, P < 0.001). Among 115 HIV infected patients, nine (8.8%) had a CD64 expression over the clinical threshold as calculated against bead standard (i.e., 1.5). HIV viremic patients were more likely to have an index above 1.5 (OR: 6.68, P values: 0.01). A trend for correlation between CD64 expression and CD8 T cell activation was observed (P values: 0.08). Blood CD4+ T lymphocyte depletion and HCV replication did not affect neutrophil CD64 expression. CONCLUSIONS: HIV infection and HIV replication are associated with up-regulation of neutrophil CD64. CD64 overexpression above the clinical threshold was observed in a minor proportion of HIV infected individuals treated by antiretroviral therapy and may be a marker of neutrophil activation related to non-AIDS-linked comorbidities. © 2016 International Clinical Cytometry Society.

Use of quantitative susceptibility mapping (QSM) in progressive multifocal leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic demyelinating encephalopathy related to JC virus. Its characteristics on conventional brain MRI are well known and are important for the diagnosis. OBJECTIVE: To analyze SWI hypointensities recently described in U-fibers and cortex adjacent to the white matter lesions of PML. METHODS: Prospective study including four patients with an history of definite diagnosis of PML. Clinical data were collected retrospectively. Brain MRI exams were done on a 3T magnet, including FLAIR, T2 GRE sequences and SWI. RESULTS: Four males were included (mean age: 47 years, mean PML duration: 24.2 months). Immunosuppression was related to AIDS (n=2), natalizumab for multiple sclerosis (n=1), B-cell lymphoma treated by chemotherapeutic agents and rituximab (n=1). All patients had SWI hypointensities in cortex and/or U-fibers adjacent to the white matter lesions. QSM always suggested a paramagnetic effect. CONCLUSION: SWI and T2 GRE hypointensities in cortex and U-fibers adjacent to the white matter lesions seem highly prevalent in PML, irrespective of the delay between PML onset and the MRI. QSM data suggest a paramagnetic effect.

Infectious chest complications in haematological malignancies.

The management of infections in haematology is dictated by the patient's type of acquired or induced immune deficiency (neutropenia, deficiency in cell-mediated or antibody-mediated immunity), and findings from clinical examination, laboratory studies, or morphologic investigations. The CT scan dominates in the initial management and follow-up of these patients, since clinical features very often appear to be non-specific. The radiologist's role is to guide the clinician towards a specific diagnosis such as aspergillosis or pneumocystosis, or to point them towards a non-infectious cause: tumour localisation, hypervolaemia, bronchiolitis obliterans suggestive of GVH disease, drug toxicity, or embolism.

'Active chronic visceral leishmaniasis' in HIV-1-infected patients demonstrated by biological and clinical long-term follow-up of 10 patients.

OBJECTIVES: The aim of the study was to describe a new evolutionary form of visceral leishmaniasis observed in immunocompromised patients. METHODS: We carried out long-term clinical and biological follow-up of 10 HIV-1/Leishmania-coinfected patients presenting numerous secondary visceral leishmaniasis episodes despite treatment, with the follow-up time ranging from 0.5 to 10 years. RESULTS: Analysis of polymerase chain reaction (PCR) and blood culture results demonstrated continuous multiplication and circulation of parasites despite treatment, both during asymptomatic periods and during secondary visceral leishmaniasis episodes. This condition may be termed 'chronic' because of the presence of relapses over a period of several years and 'active' because of the continuous blood circulation of the parasite. CONCLUSION: We wish to define 'active chronic visceral leishmaniasis' as a novel nosological entity observed in HIV-1/Leishmania-coinfected patients.

[Adherence to antibiotherapy guidelines for acute community-acquired pneumonia in adults, in a teaching hospital]. / Audit des prescriptions d'antibiotiques dans les pneumonies aiguës communautaires de l'adulte dans un centre hospitalier universitaire.

OBJECTIVE: The authors had for aim to assess the conformity of antibiotic prescription with guidelines, for the management of community-acquired pneumonia, in a French University Hospital. DESIGN: This prospective study included adults patients hospitalized for pneumonia over a period of six months. The attending physician estimated the severity of pneumonia. The adequacy to guidelines focused on: first antibiotic choice and prescription modality, antibiotic choice in case of treatment modification at 48 to 72 hours, and duration of antibiotherapy. RESULTS: A hundred and nine cases of pneumonia were included in 106 patients. The mean age was 66 years, the mortality rate was 17 %. Bacterial documentation was recorded in 40.4 % of cases. The first antibiotics used were in accordance with guidelines in 52.3 % of cases. The non conformity rate was minor in 55.8 % of cases. Antibiotherapies putting the patient at risk were used in less than 10 % of the cases. The rate of antibiotic modification at 48 to 72 hours was 46.8 %, primarily for bacteriological purposes (35.3 %) or initial treatment failure (27.4 %). The treatment duration was inappropriate in 52.7 % of cases and generally too long in case of non conformity. CONCLUSION: It seems important to support guideline information, training of prescribers, and to consult an antibiotic expert.