First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine.

BACKGROUND: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. METHODS: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. RESULTS: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35-2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84-2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. CONCLUSIONS: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

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.

Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study.

Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1-24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.

Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.

Community-acquired pneumonia: impact of empirical antibiotic therapy without respiratory fluoroquinolones nor third-generation cephalosporins.

Guidelines for inpatients with community-acquired pneumonia (CAP) propose to use respiratory fluoroquinolone (RFQ) and/or third-generation cephalosporins (Ceph-3). However, broad-spectrum antibiotic therapy is associated with the emergence of drug-resistant bacteria. We established a guideline in which RFQ and Ceph-3 were excluded as a first course. Our aim was to evaluate the impact of our therapeutic choices for CAP on the length of hospital stay (LOS) and patient outcome. This was a cohort study of patients with CAP from July 2005 to June 2014. We compared patients benefiting from our guideline established in 2008 to those receiving non-consensual antibiotics. Disease severity was evaluated through the Pneumonia Severity Index (PSI). The empirical treatment for PSI III to V was a combination therapy of amoxicillin-clavulanic acid (AMX-C) + roxithromycin (RX) or AMX + ofloxacin. Adherence to guidelines was defined by the prescription of one of these antibiotic agents. Requirement for intensive care or death defined unfavorable outcome. Among 1,370 patients, 847 were treated according to our guideline (61.8 %, group 1) and 523 without concordant therapy (38.2 %, group 2). The mean PSI was similar: 82 vs. 83, p > 0.5. The mean LOS was lower in group 1: 7.6 days vs. 9.1 days, p < 0.001. An unfavorable outcome was less frequent in group 1: 5.4 % vs. 9.9 %, p = 0.001. In logistic regression models, concordant therapy was associated with a favorable outcome: adjusted odds ratio (AOR) [95 % confidence interval (CI)] 1.85 [1.20-2.88], p = 0.005. CAP therapy without RFQ and Ceph-3 use was associated with a shorter LOS and fewer unfavorable outcomes.

Preexposure prophylaxis (PrEP) of HIV infection in France: a nationwide cross-sectional study (PREVIC study).

Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.

Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study.

Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.

Antibiotic therapy in necrotising external otitis: case series of 32 patients and review of the literature.

Necrotising external otitis (NEO) is a rare but severe bone infection, usually due to Pseudomonas aeruginosa, the management of which is not standardised. Systemic antibiotic therapy is usually prescribed for at least 6 weeks, but no review has been published on this topic. We report our experience and have reviewed the literature regarding antibiotic therapy in NEO. Here we describe a case-series of consecutive NEO cases seen over an 8-year period (2004-2011) in a French tertiary-care teaching hospital. Since 2009 we have shortened the duration of antibiotic therapy to 6 weeks. We also present a review of the literature regarding antibiotic therapy in NEO. We include 32 NEO cases, with positive microbiological cultures in 30 cases. Among the 30 patients with suspected or proven P. aeruginosa infections, 27 received an initial combination therapy of ceftazidime and ciprofloxacin. The duration of antibiotic therapy and length of hospital stay were significantly reduced after 2009 (9.4 ± 3.2 weeks versus 5.8 ± 0.7, P < .0.001; and 18.2 ± 8.7 days versus 11.6 ± 6.9, P = .0.03, respectively). Patient outcomes were favorable in all cases, with a 14-month median duration of follow-up. Our literature review (30 case series) shows that initial combination therapy is associated with better outcomes as compared with single therapy (97 % versus 83 %, P < .0.001). We suggest 3 weeks of initial combination therapy (ceftazidime + ciprofloxacin, high doses) followed by 3 weeks single therapy with ciprofloxacin in susceptible P. aeruginosa NEO. A close collaboration between ear, nose and throat and infectious diseases specialists is needed.

Increased time exposure to tenofovir is associated with a greater decrease in estimated glomerular filtration rate in HIV patients with kidney function of less than 60 ml/min/1.73 m2.

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m(2)) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m(2)/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, -0.07 ± 0.08 and -0.87 ± 0.06 ml/min/1.73 m(2)/year for no time exposure, <34, 34-67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.

Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort.

OBJECTIVES: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). METHODS: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed. RESULTS: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/µL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001). CONCLUSIONS: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. CLINICALTRIAL: Gov identification number: NCT01730690.

Botulism and hot-smoked whitefish: a family cluster of type E botulism in France, September 2009.

A family cluster of three cases of type E botulism were identified in south-east France in September 2009. The suspected food source of infection was a vacuum packed hot-smoked whitefish of Canadian origin purchased by the family during a visit to Finland and consumed several weeks later in France on the day prior to symptom onset. No leftover fish was available to confirm this hypothesis. Vacuum packed hot-smoked whitefish has previously been associated with cases of type E botulism in multiple countries, including Finland, Germany, the United States and Israel.

[Usefulness of C-reactive protein in the therapeutic follow-up of infected patients]. / Utilité de la C-reactive protein dans le suivi thérapeutique des patients infectés.

UNLABELLED: Monitoring of body temperature, but also of C-reactive protein (CRP) level is performed in infected patients treated with antibiotics. These two parameters having low specificity for any diagnosis, our aim was to evaluate the usefulness of CRP in this context. PATIENTS AND METHOD: A representative sample of patients was randomly extracted from our medical computerized tables. All patients presented community-acquired infections and had at least two CRP level assessments. Kinetics of body temperature and CRP allowed to quantify clinical and biological discrepancy while the patient's chart was studied to determine the etiologies. RESULTS: Three hundred and ninety-two patients over 942 (42%) were admitted in our department over 2 years, including 147 cases of respiratory infections (37%), 91 of urinary infections (23%), 65 of cellulitis (17%), 70 of primary bacteremia (18%), 19 of digestive infections (5%). Ninety-four percent of the patients had been prescribed antibiotic therapy. We observed a correlation between temperature and CRP in 83% of the patients. Forty-seven percent of patients presented with normalized body temperature and persistently high levels of CRP, which was most of the time related to comorbid conditions. Twenty patients (5%) presented with unexplained persistent fever despite CRP normalization. Therapeutic modifications were mostly observed in the presence of clinicobiological discrepancy: 21% versus 6%, p<0.001. DISCUSSION: Body temperature and CRP are two parameters leading to comparable information in more than 80% of infected patients receiving specific antibiotic therapy. These clinical and biological discrepancies are associated to a modified antibiotherapy with inconclusive results.

Adverse effects of parenteral antimicrobial therapy for chronic bone infections.

Responsible pathogens of chronic bone infections (CBI) are frequently resistant, requiring parenteral antimicrobial therapy. Therefore, adverse effects may be observed. We have determined the rate of adverse effects of antimicrobial therapy for CBI in a retrospective study of all patients receiving parenteral drugs via an implantable port. Patients from one medical ward (n = 89) and from one surgical ward (n = 40) between January 1995 and December 2005 were included in this study. The CBI included were 85 osteomyelitis (66%) and 44 prosthetic joint infections (34%). The main group of pathogens was gram positive cocci (n = 144; 65%). The total duration of antibiotic treatment was 205 +/- 200 days, including 133 +/- 100 days for parenteral therapy. Thirty-three catheter-related complications were observed in 27 patients (21%). All complications led to hospitalization but none led to death. Twenty-one antibiotic-related complications occurred in 18 patients (16%), and one allergic reaction led to death. The mean duration of follow-up was 290 days. Remission was observed in 84 patients (65%). In multivariate analysis, adverse effects were mostly observed in the medical department. Adverse effects affect at least one third of the patients treated for CBI with parenteral antimicrobial therapy and are related to both the implantable port and the antibiotic compounds.

[Computerized management of a medical department, disease-related group management, clinical research and evaluations]. / Gestion de services, tarification à l'activité, recherche clinique et évaluation des pratiques professionnelles: un même outil informatique.

The current French hospital reform is based on the disease-related group (DRG) approach and the constitution of bigger units pooling several departments of different specialties. This reform needed an efficient assessment of various medical activities. We report our experience of a medical table of our hospital activities used for 27 months. This medical table was made with a basic software integrating 24 parameters. The original concept was the translation of the specific final diagnosis for DRG defined by the site of infection. To create this medical table, we first simplified the conclusions of the patient's chart using a consensual and systematic plan. The number of patients per DRG and their evolution were therefore specifically determined. The medical table helped us in the daily management of our department, to identify the area of recruitment, the potential for heterogeneous care, allowing the implementation of protocols and their applications. Moreover, the table quantified morbidity and mortality, indicating our need for cooperation with other departments. All this data used medical-lexical terms, allowing other than economic analyses, even if this table identifies hospitalization-related costs, namely duration of hospital-stay, nosocomial infections and iatrogenic events. Finally, our table supports medical research and evaluation of practice. Our future goals are to introduce this table in several infectious-diseases units, and create specific tables for the main RDG, including economic parameters.

[MR Features of hepatic macronodular mycobacteriosis]. / IRM des atteintes macronodulaires hépatiques à mycobactéries.

Hepatic macronodular mycobacteriosis is rare. Its diagnosis is challenging and is most often proposed on the basis of histological analysis. Final diagnosis, except for germ-proven cases, is made in conjunction with clinical, biological, and radiological arguments. We retrospectively report the MR features of ten hepatic lesions discovered on five patients. MRI is sensitive but has a low specificity in demonstrating pseudotumoral lesions most often exhibiting hypointensity on the T1-weighted sequence, hyperintensity on the T2-weighted sequence, and a slight rim enhancement after gadolinium-enhanced T1-weighted sequences.

Medical table: A major tool for antimicrobial stewardship policy.

Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.

Pre-exposure prophylaxis: a useful tool to prevent human immunodeficiency virus infection?

The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030.

Effect of diabetes and Sorbinil treatment on phospholipid metabolism in rat glomeruli.

To explore the hypothesis that changes in membrane phospholipids accompany tissue myo-inositol depletion and reduced (Na+ + K+)-ATPase activity in diabetes, we examined phospholipid concentrations in glomeruli isolated from control and streptozotocin-diabetic rats and the effect of diabetes on myo-[3H]inositol incorporation in vitro into glomerular phosphatidylinositol. Since the aldose reductase inhibitor, Sorbinil, prevents the fall in myo-inositol and the decrease in (Na+ + K+)-ATPase activity associated with diabetes, phospholipid and phosphatidylinositol content were also examined in glomeruli isolated from Sorbinil-treated diabetic rats. Total phospholipids (microgram phosphorus/mg dry weight) did not differ in the three groups of animals. The concentration of phosphatidylcholine was elevated in preparations from diabetic rats, both untreated and Sorbinil-treated. Phosphatidylethanolamine was reduced in glomeruli from Sorbinil-treated rats. Neither acute experimental diabetes nor Sorbinil treatment produced detectable changes in the glomerular concentration of phosphatidylinositol. In vitro incubations with glomeruli isolated from control and diabetic animals resulted in increased levels of incorporation of myo-[3H]inositol into phospholipids of diabetic glomeruli. The specific activity of [3H]phosphatidylinositol in glomeruli from diabetic rats was significantly greater than that in control samples. The findings do not support the postulate invoking correspondent changes in myo-inositol and phosphatidylinositol contents as contributory to diminished glomerular (Na+ + K+)-ATPase activity in diabetes, but are compatible with depletion of glomerular intracellular myo-inositol in diabetes.

[Gnathostomiasis: an emerging parasitic disease?]. / La gnathostomose, une parasitose émergente?

INTRODUCTION: Human gnathostomiasis is a parasitic disease caused by the ingestion of foods contaminated with the larvae of various species of Gnathostoma. This zoonosis is currently endemic in Asia and Central America. CASE REPORT: A 46-year-old French woman resident in Vietnam presented with intermittent pruritic swelling of the hand, present for one year, coupled with eosinophilia. The patient's history and serological testing confirmed the suspected diagnosis of gnathostomiasis. A favorable outcome was attained on treatment with albendazole. DISCUSSION: This case, together with several others recently reported in France and Europe, underlines the need to inform travelers and migrants to endemic regions of the risks associated with eating raw or marinated fish.

Variable virological outcomes according to the center providing antiretroviral therapy within the PharmAdapt clinical trial.

PURPOSE: Differences in virological response between HIV-infected patients at different study centers were analyzed as a substudy of PharmAdapt, a multicenter prospective randomized study to evaluate the utility of therapeutic drug monitoring after a genotypic-based treatment adaptation. RESULTS: After 12 weeks, the percentage of patients participating in PharmAdapt with HIV RNA < 200 copies/mL ranged from 17% to 69% between centers providing antiretroviral care. In a multivariate analysis, independent factors predictive of viral load <200 HIV RNA copies/mL at Week 12 included: lower baseline viral load, lower nonnucleoside reverse transcriptase inhibitor resistance, lower protease inhibitor resistance, and the center providing antiretroviral therapy. To evaluate the final factor, study sites were divided into two groups based on Week 12 HIV RNA values above or below the median. CONCLUSION: Using this definition, observed differences between centers included the use of stavudine, abacavir-, and/or efavirenz-based regimens and use of online expert advice.