Factors associated with influenza vaccination of general medicine interns in Nancy, France, in 2017.

Winter flu is an epidemic infectious disease which sometimes causes serious complications in vulnerable people treated in general practice. Currently, the most effective means of prevention is influenza vaccination, which is recommended for healthcare professionals, including general medicine interns. The target of 75% coverage set by WHO for healthcare professional is rarely reached. Our survey provides an assessment of reported influenza vaccination of general medicine interns (GMI) and evaluates factors influencing their vaccination status. A cross-sectional survey was conducted from 27 September to 2 November 2017 in the Faculty of Medicine at the University of Lorraine in France. An anonymous self-administered questionnaire was distributed electronically (SurveyMonkey software) to all GMI. It collected data on their vaccination status and on levers and barriers to influenza vaccination. The data were analysed using SAS 9.4 software. Multivariate analysis helped identify factors associated with their influenza vaccination status. Of the 595 GMI invited, 269 participated in the survey, with a response rate of 45.2%. During the 2015, 2016, and 2017 winters, overall self-declared vaccine coverage was 37.9, 49.4, and 56.5%, respectively. Being at the end of training (p = 0.008, OR = 3.2), the presence of a mobile vaccination team (p = 0.019, OR = 3.1), and recommending vaccination to one's relatives and friends (p < 0.0001, OR = 5.4) were the three factors independently associated with influenza vaccination. The two main reasons which had a strong influence on non-vaccination were forgetting to do so (30.5%) and lack of time (24.8%). Influenza vaccination coverage of GMI in Nancy falls well short of WHO targets. Vaccination campaigns and facilitated access to vaccination at study and work placement locations should be considered.

Impact of baseline plasma HIV-1 RNA and time to virological suppression on virological rebound according to first-line antiretroviral regimen.

OBJECTIVES: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. PATIENTS AND METHODS: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound. RESULTS: During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens. CONCLUSIONS: In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy.

Tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients treated for tuberculosis: the ANRS 129 BKVIR trial.

BACKGROUND: HIV-infected patients with TB need simplified, effective and well-tolerated antiretroviral regimens. METHODS: The French ANRS 129 BKVIR open trial evaluated the once-daily tenofovir DF/emtricitabine and efavirenz combination, started within 12 weeks after TB treatment initiation, in antiretroviral-naive HIV-1-infected patients. Success was defined as an HIV-1 RNA <50 copies/mL and TB cure at 48 weeks. RESULTS: TB was confirmed microbiologically (90%) or histologically (10%) in 69 patients (71% male; median age 43 years; 54% born in Africa). The median time between TB treatment initiation and antiretroviral therapy was 8 weeks (range 1-22 weeks). At baseline, median HIV-1 RNA was 5.4 log10 copies/mL and median CD4 cell count 74 cells/mm(3). In the ITT analysis, combined success at week 48 was achieved in 57/69 patients (83%, 95% CI 74-92). Twelve patients did not achieve virological success, and TB was not cured in one of them. Among the 47 patients who fully adhered to the strategy, the success rate was 96% (95% CI 90-100) and was not affected by low rifampicin and isoniazid serum concentrations. Forty-nine serious adverse events were reported in 31 patients (45%), and 11 led to antiretroviral drug interruption. All adverse events resolved. The immune reconstitution inflammatory syndrome occurred in 23 patients (33%, 95% CI 22-44), and was associated with a low baseline BMI (P = 0.03) and a low haemoglobin level (P = 0.02). CONCLUSION: These results support the use of tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients with TB.

Primary cerebral alveolar echinococcosis: mycology to the rescue.

A case of primary cerebral alveolar echinococcosis with a favorable outcome is reported. A universal fungal PCR enabled this diagnosis, while the initial serological analysis remained noncontributive.

[Assessing the implementation of the 2010-2014 National Plan against HIV in the Regional Coordination Centers for the Fight against HIV (COREVIHs)]. / Déclinaison du plan national de lutte contre le VIH 2010/2014 au sein des COREVIH.

INTRODUCTION: In France, 50,000 people are unaware of their HIV status because they have not been screened. Every year, there are nearly 7,000 new HIVinfections. To address this issue, the French Ministry of Health and Sport published the 2010-2014 National Plan against HIV/AIDS and other sexually transmitted diseases. A national survey was conducted among the Regional Coordination Centers for the Fight against HIV (COREVIHs) to assess their views of the National Plan and their current funding levels. METHOD: A questionnaire was sent to the presidents and coordinators of the 28 COREVIHs. RESULTS: After two reminders, 19 of the 28 COREVIHs responded. The National Plan was the original impetus for an assessmentofcurrent practices, accompanied by the implementation ofnew measures and new working groups. There is evidence that the COREVIHs are committed to developing incentive measures to promote screening and that they are also working to coordinate regional training programs in the area of screening and testing. The assessment also found that 11 COREVIHs were considering a reorganization of the CDAG/CIDDIST centers (CDAG: Free Anonymous Testing Center/ CIDDIST: STI Information, Testing and Diagnosis Center). Some COREVIHs have been involved in coordinating therapeutic education at a regional level. Most COREVIHs are also actively involved in the fight against discrimination. However, a number of obstacles to the implementation of the plan were identified. DISCUSSION: The purpose of this study was to examine the involvement of the COREVIHs in the implementation of the 2010-2014 National Plan against HIV The results indicate that implementing a system involving a specific form ofregionalcoordination of a public health problem is possible and should provide a basis for the decentralized implementation of public health plans.

Relevance of fluoroquinolone use in hospitals in the Lorraine region of France before and after corrective measures: an investigation by the Antibiolor Network.

OBJECTIVES: This study of fluoroquinolone use was carried out before and after an educational intervention run by Antibiolor, a regional network to all hospitals in the Lorraine region of France. METHODS: The relevance of fluoroquinolone prescription according to regional guidelines was assessed using a standard card filled out by physicians and pharmacists at the voluntarily participating hospitals. A therapeutic index of adequacy was established for each card. The initial survey took place in January 2008, with feedback and proposals for corrective measures in January 2009. The second survey was organized in June 2009. The results of the 2 surveys were compared. RESULTS: Twenty-four hospitals completed a total of 1336 cards in the first survey (S1) and 944 cards in the second (S2). The appropriateness of indications for fluoroquinolone use improved by 57% between the 2 surveys. All the criteria analyzed (choice of drug, dosage, treatment duration) were significantly improved in S2 compared to S1, as was the adequacy index (70% improvement). CONCLUSIONS: In view of the consequences of fluoroquinolone use, many hospitals in Lorraine were keen to participate in this study, confirming its feasibility over a large area. In view of the study results, the book of guidelines was re-examined and republished at the conclusion of S2. Greater adherence to guidelines was noted in S2, demonstrating the benefit of assessing the situation thoroughly before proposing corrective measures and evaluating their impact.

Fatal Histoplasma capsulatum mitral endocarditis in a French patient treated for rheumatoid arthritis.

Histoplasmosis is an infectious disease caused by the inhalation of Histoplasma capsulatum spores, a fungus encountered in many diverse areas around the world. Although this infection is often asymptomatic, it may become dramatic in immunocompromised patients. In November 2005, an endocarditis due to Histoplasma capsulatum was diagnosed in a French woman treated for rheumatoid arthritis and who had traveled to South America 2 years earlier. We confirmed the biological diagnosis by mycological, serological, and histological methods. In spite of receiving the appropriate treatment, the patient died 3 months later of cardiac insufficiency. We report here this additional case of Histoplasma endocarditis, by hoping to help rapid and accurate diagnosis of such infections in their early stages of development, in non-endemic areas.

Efficacy and safety of raltegravir in treatment-experienced HIV-1-infected patients switching from enfuvirtide-based regimens: 48 week results of the randomized EASIER ANRS 138 trial.

OBJECTIVES: To assess the sustainable efficacy and safety of a switch from enfuvirtide to raltegravir in patients with multidrug-resistant HIV infection. METHODS: One hundred and seventy patients with multidrug-resistant HIV infection and suppressed plasma HIV RNA levels < 400 copies/mL under an enfuvirtide-based regimen were randomized to maintain their regimen or to switch to a raltegravir-based regimen (immediate group) in a 48 week prospective, randomized, open-label trial. At week 24, patients in the maintenance arm also switched to raltegravir (deferred group). Baseline genotypic susceptibility scores (GSSs) were calculated using available historical resistance tests. Efficacy was assessed by the cumulative proportion of patients with virological failure, defined as a confirmed plasma HIV RNA ≥ 400 copies/mL up to week 48. The EASIER ANRS 138 trial is registered at ClinicalTrials.gov (NCT00454337). RESULTS: At baseline, 86% of patients had plasma HIV RNA levels <50 copies/mL and 86% had a GSS ≥ 1. Through to week 48, in the on-treatment analysis, only one patient in the immediate group, with a GSS of 0, developed virological failure. At week 48, 90% of patients in both the immediate and deferred groups had plasma HIV-1 RNA levels <50 copies/mL. Median CD4 cell counts remained stable during follow-up. Of note, 12 of 66 (18.2%) patients receiving a regimen combining raltegravir and ritonavir-boosted tipranavir experienced alanine aminotransferase elevations, which led to a switch from tipranavir to darunavir in 8 cases, without discontinuation of raltegravir. CONCLUSIONS: In well-suppressed patients with multidrug-resistant HIV infection, a switch from enfuvirtide to raltegravir is generally well tolerated and has sustained antiviral efficacy when combined with a potent background regimen.

Changes in cancer mortality among HIV-infected patients: the Mortalité 2005 Survey.

BACKGROUND: The goal of the current study was to describe the distribution and characteristics of malignancy related deaths among human immunodeficiency virus (HIV)-infected patients with use of data obtained from a national survey conducted in France in 2005 and to compare with results obtained from a similar survey conducted in 2000. METHOD: The underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards and networks that were involved in the treatment of HIV-infected patients. RESULTS: Among the 1042 deaths reported in 2005 (964 were reported in 2000), 344 were cancer related (34%), which represented a significant increase from 2000 (29% of deaths were cancer related) (P=.02); 134 of the cancer-related deaths were AIDS related and 210 were not AIDS related. Among the cancer-related causes of death, the proportion of hepatitis-related cancers (6% in 2000 vs. 11% in 2005) and non-AIDS/hepatitis-related cancers (38% in 2000 vs 50% in 2005) significantly increased from 2000 to 2005 (P=.03 and P=.01, respectively), compared with the proportion of cancer that was AIDS related and adjusting for age and sex. Among cases involving AIDS, the proportion of non-Hodgkin lymphoma-associated deaths did not change statistically significantly between 2000 and 2005 (11% and 10% of deaths, respectively). CONCLUSIONS: In this study, an increasing proportion of lethal non-AIDS-related cancers was demonstrated from 2000 to 2005; meanwhile, the proportion of lethal AIDS-related cancers remained stable among HIV-infected patients. Thus, cancer prophylaxis, early diagnosis, and improved management should be included in the routine long-term follow-up of HIV-infected patients.

Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalité 2005 study.

BACKGROUND/AIMS: Longer exposure to hepatitis C (HCV) or B virus (HBV) and the increased use of hepatitis treatment might have an impact on liver-related deaths in patients co-infected with the Human Immunodeficiency Virus (HIV). We describe the proportion of liver-related deaths among HIV-infected patients in 2005 compared with 2000. METHODS: In a nationwide survey (341 hospital departments involved in HIV management), all deaths of HIV-infected patients were prospectively reported. Deaths from either cirrhosis, hepatocellular carcinoma or fulminant hepatitis were defined as liver-related deaths. RESULTS: Of the 898 deaths reported in 2005, liver-related causes accounted for 15.4%; this is compared to 13.4% in 2000. Among liver-related deaths, hepatocellular carcinoma increased from 15% to 25% (p=0.04). Among hepatocellular carcinoma-related deaths: in 2000, 10% were HCV-infected; in 2005, 25% were HCV-infected (p=0.03). Half of the HCV-related deaths had been treated for HCV but 98% remained HCV-RNA positive at time of death. The proportion of HBV-related deaths remained stable between 2000 and 2005. CONCLUSIONS: Liver-related deaths, mainly liver cancers, have increased in HIV-infected patients in France despite wide access to HCV treatment. The stability of HBV-related deaths might be explained by the use of dually active antiretroviral drugs in co-infected patients.

A case report of Guillain Barré syndrome revealing underlying infective endocarditis due to Cardiobacterium hominis.

RATIONALE: Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy presumed to result from an infection-triggered autoimmune reaction. PATIENT CONCERNS: This paper describes a 53-year-old man admitted to hospital for deterioration of his general condition. DIAGNOSIS: He developed GBS, confirmed by lumbar puncture and electromyogram, which recovered after intravenous immunoglobulins. A grade 2 aortic regurgitation was detected by transthoracic echocardiography upon diagnosis of GBS, but in the absence of fever, no further investigations were conducted. A few weeks later, the patient presented with fever and infective endocarditis (IE) was diagnosed after the identification of vegetation on the aortic valve with transesophageal echocardiography. The etiologic agent was identified as Cardiobacterium hominis based on 3 positive blood cultures and DNA detection in valvular material. INTERVENTIONS: IE was cured with a 6-week course of antibiotics and aortic valve replacement. OUTCOMES: The patient completely recovered from Guillain-Baré syndrome and IE. LESSONS: This case of GBS associated with C hominis endocarditis, emphasizes the importance of blood cultures and transesophageal echocardiography for the detection of IE and highlights the insidious nature of C hominis endocarditis which is often diagnosed late.

Vaccination for influenza and pneumococcus in patients with gastrointestinal cancer or inflammatory bowel disease: A prospective cohort study of methods for improving coverage.

BACKGROUND: Although influenza and pneumococcal vaccinations for high-risk populations are recommended by current guidelines, vaccination coverage is low in patients with gastrointestinal cancer (GC) or inflammatory bowel disease (IBD). AIM: To evaluate the impact of a specialised infectious disease consultation on vaccination coverage rates in these patients. METHODS: Between December 2016 and April 2017, all patients with GC or IBD followed in the outpatient clinic of the Gastroenterology department at the Nancy University Hospital enrolled in a 3-phase vaccination programme. Phase 1: Initial questionnaire (vaccination status, knowledge about vaccines and possible barriers to vaccination); Phase 2: Infectious disease consultation; Phase 3: Subsequent questionnaire (evolution of patients' knowledge about vaccination). RESULTS: A total of 366 patients were included (GC = 99, IBD = 267). Vaccination rate was 34.7% for influenza and 14.5% for pneumococcus. About 43% of the patients feared side effects of vaccines. After the initial questionnaire, 49.3% of the interested patients participated in a specialised vaccination consultation (n = 102). 87.3% (n = 89) received new vaccination, 41.2% changed their mind about vaccination, and 92.2% would recommend this programme to other patients. Among vaccinated patients, 97.8% (n = 87) received pneumococcal vaccine, 40.4% received tetanus-diphtheria-polio vaccine, and 7.9% received influenza vaccine. In GC patients, anti-pneumococcal vaccination rate was 87.5% after the specialised consultation compared with 10.1% before. In IBD patients, corresponding rates were 85.7% and 16.1%. CONCLUSIONS: A specialised infectious disease consultation can improve GC and IBD patients' knowledge about vaccination and vaccination coverage. This approach could be applied to all high-risk populations.

Treatment as prevention enrolling at least 75% of individuals on ART will be needed to significantly reduce HIV prevalence in a HIV cohort.

BACKGROUND: "Treatment as Prevention" (TasP) aims to reduce new HIV infections through higher enrolment on suppressive antiretroviral therapy (ART). OBJECTIVES: We studied the current epidemic and possible impact of TasP in a French HIV cohort including MSM and migrant subjects. STUDY DESIGN: Socio-demographic, clinical and laboratory variables were collected during the follow-up of 6995 HIV-infected patients. The numbers of individuals living with HIV in each year were estimated from diagnoses up to that year minus recorded deaths. Patients were classified according to gender, transmission mode, country of birth and treatment status. RESULTS: The cohort includes 6995 individuals diagnosed from 1985 to 2015, of whom 72% were men. Unprotected sexual intercourse was the main mode of transmission. Women were more likely to be migrants (45% versus 13%), whereas men were more likely to have been born in France (52% versus 27%). Diagnoses were more correlated with untreated than treated prevalence in each group. MSM diagnoses was strongly correlated to untreated prevalence whatever the country of birth (p < 0.0001). However, heterosexual diagnoses were better correlated with prevalence within individual country groups (b = 0.29 female diagnoses/year per untreated male born in France, compared to b = 0.73 for foreigners). Using these transmission rates, mathematical modelling estimated that enrolling 75% of untreated individuals per year would decrease diagnoses ten-fold by 2021. CONCLUSIONS: Enrolling at least 75% of individuals on ART is necessary to substantially impact numbers of new HIV infections in this cohort. Treatment as prevention will actually be effective to reduce HIV prevalence.

Antiretroviral exposure and comorbidities in an aging HIV-infected population: The challenge of geriatric patients.

As HIV-infected adults on successful antiretroviral therapy (ART) are expected to have close to normal lifespans, they will increasingly develop age-related comorbidities. The objective of this cross-sectional study was to compare in the French Dat'AIDS cohort, the HIV geriatric population, aged 75 years and over, to the elderly one, aged from 50 to 74 years. As of Dec 2015, 16,436 subjects (43.8% of the French Dat'AIDS cohort) were aged from 50 to 74 (elderly group) and 572 subjects (1.5%) were aged 75 and over (geriatric group). Durations of HIV infection and of ART were slightly but significantly different, median at 19 and 18 years, and 15 and 16 years in the elderly and geriatric group, respectively. The geriatric group was more frequently at CDC stage C and had a lower nadir CD4. This group had been more exposed to first generation protease inhibitors and thymidine analogues. Despite similar virologic suppression, type of ART at the last visit significantly differed between the 2 groups: triple ART in 74% versus 68.2%, ART ≥ 4 drugs in 4.7% versus 2.7%; dual therapy in 11.6% versus 16.4% in the elderly group and the geriatric group, respectively. In the geriatric group all co-morbidities were significantly more frequent, except dyslipidemia, 4.3% of the elderly group had ≥4 co-morbidities versus18.4% in the geriatric group. Despite more co-morbidities and more advanced HIV infection the geriatric population achieve similar high rate of virologic suppression than the elderly population. A multidisciplinary approach should be developed to face the incoming challenge of aging HIV population.

Intermittent antiretroviral therapy in patients with controlled HIV infection.

BACKGROUND: To assess the safety of a drug-sparing treatment regimen in patients with high CD4 cell counts and controlled HIV replication under antiretroviral therapy. METHODS: An open-label, non-inferiority study involving 403 adults with CD4 cell counts of 450 x 10(6) cells/l or greater and plasma HIV-1-RNA levels less than 200 copies/ml, randomly assigned to switch to an 8-week off, 8-week on regimen or to continue their antiretroviral regimen. The primary endpoint was the proportion of patients reaching a confirmed CD4 cell count less than 300 x 10(6) cells/l. RESULTS: Over 96 weeks, the proportion of patients meeting this endpoint was non-inferior in the intermittent group (3.6 versus 1.5%, upper bound of the 95% confidence interval of the difference 5.6%). No AIDS-defining event and two non-HIV-related deaths (intermittent arm) were recorded. The median decrease from baseline in the CD4 cell count was greater in the intermittent arm (-155 versus -8 x 10(6) cells/l, P < 0.0001). Minor HIV-related events, mainly lymphadenopathy and mucosal candidiasis, were more frequent in the intermittent group (14 versus 7%, P = 0.04) as were thrombocytopenia. The incidence of grade 3-4 non-HIV-related events and laboratory abnormalities were not statistically different between the groups. At week 96, the proportion of patients with plasma HIV-1-RNA levels less than 400 copies/ml were 81 and 90% in the intermittent (8 weeks after treatment resumption) and continuous groups (P = 0.02), respectively, with similar patterns of HIV resistance genotypes. CONCLUSION: Despite some limitations, an 8-week off and on intermittent treatment regimen appeared clinically safe over 96 weeks while sparing half of the drug exposure.

Urolithiasis in HIV-positive patients treated with atazanavir.

Among protease inhibitors, atazanavir has not been associated with urolithiasis in clinical studies. We describe 11 cases of atazanavir-associated urolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients with low water intake, high urinary pH, and a prior history of urinary stones may have a higher risk of atazanavir-associated urine crystallization.

Five-year follow up of once-daily therapy with emtricitabine, didanosine and efavirenz (Montana ANRS 091 trial).

BACKGROUND: Once-daily combination therapy with emtricitabine, didanosine and efavirenz has been highly effective in clinical trials but its long-term efficacy and safety has not been previously reported. METHODS: This multicentre, single-arm, open-label trial enrolled 40 antiretroviral-naive HIV-1-infected patients who received a once-daily regimen of emtricitabine, didanosine and efavirenz. The objective was to assess the long-term effects of this combination on plasma HIV RNA levels, CD4+ T-cell counts, safety and tolerability. RESULTS: After 5 years, 73% and 68% of patients had plasma HIV RNA levels < 400 and < 50 copies/ml, respectively, in an intent-to-treat, missing-equals-failure analysis. Genotypic resistance on treatment emerged in six patients. There was a significant increase in CD4+ T-cell count of 294 x 10(6) cells/l. Only six patients discontinued study treatment, because of non-severe adverse events. Lipodystrophy was infrequent, and lipid and glucose profiles were favourable with a significant increase in high-density lipoprotein cholesterol. CONCLUSION: A convenient once-daily regimen of emtricitabine, didanosine and efavirenz provided durable antiretroviral response and was well tolerated through 5 years of therapy.

Vaccine Education of Medical Students: A Nationwide Cross-sectional Survey.

Physicians play a primary role in vaccination of the population. Strong initial training of medical students is therefore essential to enable them to fulfill this role. This cross-sectional nationwide online survey conducted between September 2015 and January 2016 obtained 2,118 completed surveys from 6,690 eligible respondents (response rate, 32%) at 27 of 32 medical schools in France regarding their education about vaccination. The data were analyzed in April-June 2016. The survey covered their knowledge, attitudes, practices, and perceptions, and assessed their level of perceived preparedness for their future practice as interns. Around a third of the students (n=708, 34%) felt insufficiently prepared for questions about vaccination, especially for communicating with patients on side effects (n=1,381, 66%) and strategies to respond to vaccine hesitancy (n=1,217, 58%). The mean knowledge score was 26/45 (SD=7.9). Lecture courses, which are the main education method used in French medical schools (1,891/5,660 responses, 33%), were considered effective by only 11% of students (693/6,155 responses), whereas practical training was significantly associated with better perceived preparedness (p<0.001). In conclusion, education about vaccination during medical school in France is not optimal. Methods based on practical learning methods (case-based learning, clinical placements, and other hands-on methods) appear to produce the best results and must be favored for improving students' preparedness.