[HIV prevention with PrEP: Challenges and prospects]. / Prévenir le VIH par la PrEP : enjeux et perspectives.

Pre-exposure prophlaxis (PrEP) is the use of antiretroviral drugs by uninfected people to prevent human immunodeficiency virus (HIV) infection. PrEP is used by people who are at substantial risk of being exposed to HIV. Numerous clinical trials have confirmed its effectiveness in reducing HIV acquisition and PrEP has been approved and allowed in several countries including France. However, PrEP uptake remains low as concerns about increase in sexual risk behaviour with PrEP use in the wake of a growing epidemic of sexually transmitted infections, and fear of drug resistance have been expressed. As a result, the difference between the proportion of people on PrEP and the proportion of people who would be very likely to use PrEP if they could access it -otherwise known as the PrEP gap- remains high. Nowadays, studies continue to explore long-term effects of PrEP as well as expand the array of available technologies and regimens.

[Cerebral infarction and tuberculosis: case report and literature review]. / Infarctus cérébral et tuberculose : rapport d'un cas et analyse de la littérature.

INTRODUCTION: Although tuberculous meningitis is an uncommon presentation of tuberculosis, it still remains one of the deadliest forms of this disease. In this context, the occurrence of a cerebral infarct is an aggravating factor. OBSERVATION: A 48-year-old Asian man presented himself in the emergency room for dysarthria and dysphagia of progressive onset. Cerebral CT showed a recent ischemic defect of the right internal capsule. Lumbar puncture showed meningitis with low sugar levels. Pulmonary micronodules on the thoracic CT suggested tuberculosis, which was confirmed by a broncho-alveolar lavage. Anti-tuberculosis treatment and early corticosteroid resulted in an improvement of the patient's state. CONCLUSION: Cerebral infarctions in patients with tuberculous meningitis are events that cannot be underestimated in terms of frequency or severity. Their poor prognosis is partly the result of insufficiently defined management, which combines anti-tuberculosis treatment and early corticosteroid therapy.

[Nasopharyngeal carriage of SARS-CoV-2 among health personnel with symptoms suggestive of COVID-19 in a University Hospital in the Paris suburbs]. / Évaluation par RT-PCR du portage nasopharyngé du SARS-Cov-2 chez les personnels de santé symptomatiques suspects de COVID-19 dans un CHU de la banlieue parisienne.

INTRODUCTION: A consultation dedicated to symptomatic health professionals was opened at the beginning of the COVID-19 epidemic in order to meet the specific needs of this population. The objective of this work was to estimate the frequency of SARS-Cov-2 nasopharyngeal carriage in symptomatic healthcare workers suspected of having COVID-19 and to determine the factors associated with this carriage. METHODS: Of the 522 consultants, 308 worked in the Hospital and 214 outside. They had mild forms of COVID-19 and non-specific clinical signs with the exception of agueusia/anosmia, which was significantly more common in those with positive RT-PCR. The rate of RT-PCR positivity was 38% overall, without significant difference according to profession. It was higher among external consultants (47% versus 31%). In the hospital, this rate was significantly lower for symptomatic staff in the care sectors, compared to staff in the technical platforms and laboratories (24%, versus 45%, p = 0.006 and 54%, respectively, p < 0.001), but did not differ between staff in COVID units and other care sectors (30% versus 28%). Among the external consultants, the positivity rates of nursing home and private practices staff (53% and 55% respectively) were more than double that of acute care hospital staff (24%, p < 0.001). CONCLUSIONS: These data confirm the strong impact of COVID-19 on health professionals. The higher positivity rates among symptomatic professionals working outside the hospital compared to those working in hospital may be explained in part by a shortage of protective equipment and by difficulties in accessing virological diagnosis, which were greater outside the hospital when the epidemic began.

[A tularemia mimicking lymphoma]. / Une tularémie mimant un lymphome.

INTRODUCTION: Adenopathies are a frequent cause of recourse in internal medicine. When histological analysis reveals the presence of granuloma, multiple infectious or non-infectious etiologies are considered. If diagnoses of lymphoma, sarcoidosis or tuberculosis are easily mentioned, tularemia should also be considered in the differential diagnosis. OBSERVATION: A 54-year-old patient had a fever at the evening with night sweats and a cough resistant to two lines of antibiotics. A thoraco-abdomino-pelvic CT scan revealed hilar and mediastinal adenopathies that appeared hypermetabolic with PET-TDM, as well as pulmonary nodules. A PCR performed on lymph node biopsy and serology allowed the diagnosis of tularemia. The evolution was favourable after antibiotic treatment. CONCLUSION: The association of fever, night sweats, altered general state and mediastinal adenopathies should be considered as a diagnosis of tularemia. Ganglionic biopsy, combined with molecular biology techniques and serology, can confirm the diagnosis.

[Tuberculosis and healthcare workers: Risk reduction and disease prevention in health care settings]. / Tuberculose et personnel soignant : prévention du risque en milieu de soins.

Tuberculosis is a human disease caused by Mycobacteriumtuberculosis, and transmitted by airborne pathway. Documented cases of tuberculosis infection in healthcare workers have been reported in both developed and developing countries. Early recognition of potentially infectious cases, immediate implementation of airborne precautions and prompt medical treatment of cases, are required to lower the risk of disease transmission. Molecular biology techniques allow earlier diagnosis. In the event of non-compliance with airborne precautions, the investigation will further have to establish exhaustive lists of potentially exposed healthcare workers and patients, looking for cases of latent tuberculosis infections whose treatment should help avoid active tuberculosis disease.

[Occupational and non occupational exposure to viral risk]. / Exposition à risque de transmission virale (AES).

The transmission of an infectious disease can occur through exposure to blood or other potentially infectious body fluids, particularly in the event of skin-puncture injuries for healthcare workers, and during sexual intercourse. These situations are known as accidental blood exposures and sexual exposures respectively. Combined actions carried out have allowed to significantly reduce risks, either to healthcare professionals (by standard precautions, provision of safety devices, Hepatitis B vaccination made compulsory in the 1990s, antiretroviral post-exposure prophylaxis that should be initiated as soon as possible after exposure), or to people engaging in unprotected sex (by prevention messages, condom promotion, and antiretroviral post-exposure prophylaxis). In any case, treatment of people infected by chronic diseases such as HBV or HIV, as well as possible drug eradication of HCV, are key for decreasing post-exposure risk of disease transmission. Post-exposure prophylaxis should be initiated as early as possible and intended for use only in patients with high-risk exposures. Knowledge of source person serostatus, information of exposed person on prevention, benefits and risks of treatment, and follow-up procedure are key points. Procedures to be followed in the event of an exposure must be known by all. Arrangements set up to allow risk assessment and management of exposed people rely on hospital services operating on a permanent basis.

Non-typhi Salmonella enterica urinary tract infections.

OBJECTIVE: Non-typhi Salmonella enterica urinary tract infections (UTIs) are not frequent and rarely reported in the literature. We aimed to characterize clinical presentations and risk factors for the infection. PATIENTS AND METHODS: We performed a retrospective study of non-typhi Salmonella enterica strains isolated from urine cytobacteriological examinations (UCBE) collected between January 1, 1996 and October 30, 2014 and analyzed by the microbiology laboratories of the university hospitals of the western part of Île-de-France and of Paris, France. RESULTS: Twenty UCBEs positive for non-typhi Salmonella enterica were analyzed. The sex ratio was 0.53 and the average age of patients was 57 years. Clinical presentations were acute pyelonephritis, acute cystitis, and prostatitis. Eight cases of bacteremia were identified. Diarrhea was observed in half of patients, either before the UTI or simultaneously. No patient required to be transferred to the intensive care unit. Immunodeficiency and/or diabetes were observed in eight patients. Three patients presented with a uropathy. Prescribed antibiotics were third generation cephalosporins and fluoroquinolones. The average treatment duration was 20 days. A spondylitis and a purulent pleurisy were observed and deemed related to the UTI. Patient outcome was always favorable following treatment prescription. CONCLUSION: Non-typhi Salmonella enterica UTIs are rare. They are mainly observed in elderly patients presenting with immunodeficiency or an underlying urological disorder.

[Splenic abscesses: From diagnosis to therapy]. / Abcès de la rate : du diagnostic au traitement.

Splenic abscess is septic collection which occurs after haematogenous spread or local dissemination. Splenic abscess is an uncommon and rare condition, more frequently affecting male and immunocompromised patients. There are no guidelines regarding its diagnosis and management. Computed tomography (CT) scan is highly sensitive and specific (95% and 92%, respectively) in the diagnosis of splenic abscess. Diagnosis is based on blood cultures which are positive in 24 to 80% of cases. Bacterial growth culture of abscess after drainage is more efficient (50-80%) and can be performed after surgery or percutaneous drainage under imaging, including CT scan. Microorganisms involved are frequently enterobacteriaceae, gram-positive cocci and anaerobes. This particular ecology leads to an empiric broad-spectrum antibiotic therapy, with a variable duration, from 10days to more than one month. Management remains very close to the one applied in case of liver abscesses. The role of splenectomy in the prevention of recurrence remains controversial. We reviewed the literature regarding splenic abscesses, from diagnosis to therapy.

[Choice of initial regimen for antiretroviral-naïve HIV patients: Analysis of motivation]. / Analyse des motivations du choix des antirétroviraux (ARV) prescrits chez des patients infectés par le VIH (PVVIH) naïfs.

OBJECTIVE: Several therapeutic combination antiretroviral therapy regimen are available for initial treatment in naïve HIV infected patients. The choice of a particular regimen remains often subjective. The aim of this study was to determine factors associated with the choice of molecules in initial ARV prescriptions. METHODS: From 01/01 to 30/10/2014, every initial cART prescription was analyzed regarding patients and physicians characteristics. Then, prescriptions were evaluated by an independent committee of ART prescribers. RESULTS: One hundred and thirty two consecutive initial prescriptions by 34 physicians of 11 medical centers were included: 71 M, migrants: 57 %, MSM: 21 %, CD4<200/mm3: 26 %, HIV RNA>100 000 cp/mL (33 %). cART regimen were: NRTI/PI (43 %), NRTI/NNRTI (29.5 %), NRTI/integrase inhibitor (23 %). 75 % of initial cART regimen were consistent with expert guidelines recommendations. The choice of initial cART was not influenced by the type of HIV contamination risk group, patient's geographic origin, CD4 levels. In contrast, working or not (P=0.007), pregnancy wish (P=0.07), pregnancy (P=0.001), HIV RNA levels (P=0.02) and HIV primary infection (P=0.049) influenced the initial choice. Neither physician's age, nor physician's experience influenced this choice. The prescription's non accordance to 2013 French guidelines was mainly related to integrase inhibitor utilisation (P= 0.0001). CONCLUSION: Overall, cART initial choice is mostly consistent with guidelines. Primary HIV infection, procreation features and high viral load are the main factors influencing this choice. New regimen with better tolerability is prescribed even if it is not yet included in the guidelines.

HSV-2 meningoencephalitis in an immunocompetent young man: what is the pathogenesis and what is the treatment?

Herpes simplex encephalitis is rarely caused by herpes simplex virus type 2 (HSV-2) after the neonatal period. The pathogenesis of HSV-2 encephalitis is not known and its treatment has not been discussed. We report a case of mild meningoencephalitis secondary to HSV-2 primary infection after sexual risk behaviour in a healthy young man. The diagnosis was established upon clinical, biological and electroencephalographic criteria. Aciclovir treatment led to rapid clinical improvement. This case highlights HSV-2 as a rare cause of meningoencephalitis, and questions the management of this rare manifestation of HSV-2 infection.

Management of accidental exposure to HIV: the COREVIH 2011 activity report.

BACKGROUND: Post-exposure prophylaxis (PEP) relies on procedures allowing quick access to treatment in case of accidental exposure to viral risk (AEV). Occupational blood exposure (OBE) affects mainly caregivers; these accidents are monitored and assessed by the inter-regional center for nosocomial infections (C-CLIN), occupational physicians, and infection control units. They are classified apart from sexual exposure for which there is currently no monitoring. METHODS: Data was extracted from the COREVIH (steering committee for the prevention of HIV infection) 2011 activity reports (AR), available online. Data collection was performed using a standardized grid. RESULTS: Twenty-four out of 28 AR were available online. Nine thousand nine hundred and twenty AEV were reported, 44% of OBE, and 56% of sexual and other exposures. PEP was prescribed in 8% of OBE and in 77% of sexual exposures. The type of PEP was documented in 52% of the cases. Follow-up was poorly documented. CONCLUSION: AR provide an incomplete and heterogeneous review of exposure management without any standardized data collection. The difficulties encountered in data collection and monitoring are due to differences in care centers (complex patient circuits, multiple actors) and lack of common dedicated software. Sexual exposures account for 50% of AEV and most are treated; but they are incompletely reported and consequently not analyzed at the regional or national level. A typical AR collection grid is being studied in 2 COREVIH, with the objective to improve collection and obtain useful national data.

[Tubular renal acidosis]. / Les acidoses tubulaires rénales.

Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment.

[Low vaccination coverage against influenza in elderly hospitalized in France]. / Faible taux de couverture vaccinale contre la grippe des sujets âgés hospitalisés en France.

PURPOSE: Annual influenza epidemics is still a major cause of illness and mortality especially in the elderly. Annual vaccination is the most effective way to prevent disease and reduce hospitalizations and deaths related to influenza in the elderly population. In France, there are few data available about vaccination coverage of elderly at risk for influenza. The aim of the study was to measure the influenza vaccination coverage and assess traceability in the elderly (≥ 75 years old) admitted to hospital. METHODS: In participating French hospitals, each patient aged 75 years or more, hospitalized in acute units of internal medicine, geriatric and infectious disease, was included in a multicentric point prevalence survey. RESULTS: Between April and May 2011, 63 departments of 28 hospitals participated and 903 patients were included (mean age of included patients: 85 years): 82% were previously living at home and 13% were institutionalized. Most of them had multiple diseases (77%) and 21% were admitted for a respiratory disease: 58% were vaccinated against influenza. A back-up for traceability was identified in 53% of cases. Patient refusal may be a common determinant of non-vaccination, as well as non-proposal by the attending physician. The vaccination rate did not differ according to usual living place including accommodation facilities in geriatric. CONCLUSION: Coverage for influenza vaccination is low in hospitalized elderly patients and traceability is insufficient. This vaccine, noncompliance mostly linked to the refusal of patients, is a worrisome public health problem, on which physicians and hospital staff in charge, as well as institutions, should turn attention toward a multi-professional preventive strategy against the morbidity risk of this infectious disease.

Streptococcus pneumoniae vaccinal coverage in hospitalized elderly patients in France.

BACKGROUND: In France, there is little data on vaccinal coverage in elderly people at risk for invasive pneumococcal infections (IPI). OBJECTIVE: The study objective was to assess the pneumococcal vaccination coverage and traceability in hospitalized elderly people (>75 years of age). METHOD: A multicentric point prevalence survey was made on volunteers over 75 years of age, hospitalized in internal medicine, geriatrics, and infectious diseases units. RESULTS: Nine hundred and three patients in 63 units of 28 hospitals were included (mean 85 years of age) in the study between April and May 2011. Ten percent (93/903) were vaccinated against the pneumococcus. Thirty-eight percent of the patients had at least one risk factor for IPI and 20.5% of these had been vaccinated. There was a traceability back-up in 59% of the cases. Vaccination was not considered by the hospital for 83% of patients with IPI risk factor but not vaccinated (task delegated to the family physician in 50% of the cases). CONCLUSION: Vaccination coverage against the pneumococcus in France is very low in hospitalized patients over 75 years of age even though more than one out of three presents at least one risk factor for IPI. The rate of traceability is also poor. Hospitalization should be an opportunity to offer pneumococcal vaccination to elderly patients at risk for IPI in France because of unclear recommendations for elderly individuals and lack of political will to improve vaccination coverage.

Comparative effectiveness of continuing a virologically effective first-line boosted protease inhibitor combination or of switching to a three-drug regimen containing either efavirenz, nevirapine or abacavir.

OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

Survival after neuroAIDS: association with antiretroviral CNS Penetration-Effectiveness score.

OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.

Factors predictive of successful darunavir/ritonavir-based therapy in highly antiretroviral-experienced HIV-1-infected patients (the DARWEST study).

BACKGROUND: Darunavir (DRV) is the latest protease inhibitor (PI) to be approved for antiretroviral-naive and -experienced HIV-infected patients. OBJECTIVES: We examined virologic and immunologic outcomes of highly antiretroviral-experienced patients with triple-class drug resistance receiving DRV/r-based regimens, and attempted to identify factors predictive of virologic success. STUDY DESIGN: We studied patients beginning a ritonavir-boosted DRV (DRV/r 600/100mg twice daily)-containing regimen. Virologic success was defined as plasma viral load (pVL)<50copies/ml at week 36. RESULTS: We studied 62 patients with very severe immunodeficiency (CDC stage C in 69% of cases; median CD4 cell nadir 12/mm(3)). They had previously received a median of four PI and had extensive PI resistance, with a median of three major PI and two DRV resistance mutations. The baseline median pVL and CD4 cell count values were 4.6log(10) and 150/mm(3). At week 36, pVL had fallen by 2.6log(10) and the CD4 cell count had risen by 123cells/mm(3). The virologic success rate was 55% overall, and was improved by concomitant first use of enfuvirtide (67%), raltegravir (69%) or etravirine (75%). Virologic success was independently associated with fewer major PI mutations, previous tipranavir exposure, and concomitant first use of enfuvirtide or raltegravir. CONCLUSIONS: In these highly antiretroviral-experienced patients with triple-class drug resistance, virologic success of DRV-containing regimens was mainly associated with the use of new drug classes and/or fully active drugs. Interestingly, previous tipranavir failure did not undermine the efficacy of DRV, confirming the low level of cross-resistance and, probably, distinct resistance profiles between DRV and tipranavir.

[Cushing's syndrome induced by combined treatment with inhaled fluticasone and oral ritonavir]. / Syndrome de Cushing induit par la prise concomitante de fluticasone et de ritonavir.

INTRODUCTION: Fluticasone is a corticosteroid drug which is used in inhaled and nasal formulations for the treatment of asthma and allergic rhinitis. It is metabolized in the liver by the cytochrome P450. Ritonavir, an inhibitor of the HIV protease, also acts as an inhibitor of several isoenzymes of the P450 cytochrome. This property explains the many drug interactions observed with this agent. CASE REPORT: We report two cases of Cushing's syndrome with adrenal insufficiency associated with the combined administration of oral low dose ritonavir and moderate to high dose inhaled fluticasone. CONCLUSION: These observations highlight the fact that the combined administration of fluticasone and ritonavir must be avoided as well as the combined administration of fluticasone and other inhibitors of the cytochrome P450.