Michel Duong

Does hepatitis C virus co-infection accelerate clinical and immunological evolution of Hiv-infected patients?

Objective:To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. Design:A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. Methods:One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 × 106 cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Petos tests) and multivariate methods (Coxs model). Results:In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log–rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06–2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09–109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16–4.62; P < 0.02) for patients with an initial CD4 count above 600 × 106 cells/l. Conclusions:Clinical progression is more rapid in HIV–HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 × 106 cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.

Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients.

Objectives:To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients.Design:Prospective cross-sectional study.Setting:Tertiary care clinic at Bocage Hospital, Dijon, France.Patients:HIV-infected patients with and without oral candidiasis.Interventions:Clinical examination, oral swab for mycologic investigations.Main outcome measures:Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count.Results:Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P<0.05); the mean T-helper cell counts were 200, 135, 210 and 238×106/l cells, respectively (P <0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (1 3.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 1 7.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P= 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6mg/l, respectively (P=0.06).Conclusions:Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.

Couverture vaccinale des professionnels de santé dans un service d’infectiologie

OBJECTIVESnThe studys objective was to evaluate with a standardized questionnaire the knowledge of healthcare workers (HCWs) regarding occupational vaccinations and their vaccination coverage.nnnPOPULATION AND METHODSnThis cross-sectional survey was conducted in the department of infectious diseases of a 1796 bed-teaching hospital in Dijon, France.nnnRESULTSnFifty-seven (93%) out of 61 HCPs completed the questionnaire. Vaccination against HVB was the most frequently mentioned vaccination (79%), followed by BCG (66%), and combine vaccine against diphtheria, tetanus, and polio (DTP) (66 %). Influenza was the most often quoted among recommended vaccinations (70%), followed by measles (61%), pertussis (39%), and varicella (14%). The number of correct answers was significantly correlated with age of participants, being a physician, and having had courses on vaccination. Almost all HCPs were up to date for mandatory vaccinations. In 2009 to 2010, vaccination rates against seasonal flu and H1N1 flu reached 88%. Only 52% of HCPs knew about their pertussis immunization and only a third of those born before 1980 had been tested for measles.nnnCONCLUSIONSnHCPs knowledge of mandatory vaccinations is adequate but more limited for recommended vaccinations. Information on influenza vaccination has significantly improved its perception among HCPs resulting in a better adhesion to vaccination.

Response to anti-HCV therapy in HIV-HCV-coinfected patients: does the lipid profile really have an effect?

BACKGROUNDnBecause high serum low-density lipoprotein (LDL) and total cholesterol concentrations before treatment have been found to be significant positive prognostic factors for a sustained virological response to HCV therapy in monoinfected patients, the aim of this study was to assess this relationship in HIV-HCV-coinfected patients.nnnMETHODSnPretreatment fasting lipid parameters (in particular total cholesterol, LDL, high-density lipoprotein [HDL], apolipoprotein B [apoB] and triglycerides [TG]) were assessed in 315 patients from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) HC02-Ribavic therapeutic trial.nnnRESULTSnThere was a significant correlation between pretreatment lipid parameters and steatosis (total cholesterol r=-0.23, P<0.0001; LDL r=-0.23, P<0.0001; HDL r=-0.28, P<0.0001; and TG r=0.18, P=0.002), but not with fibrosis. None of these lipid parameters were significant predictors of a sustained virological response to HCV therapy, even after adjustment for the type of interferon treatment and for the main known prognostic factors for a response to HCV therapy.nnnCONCLUSIONSnThe possible effect of lipid metabolism on virological response is outweighed by other prognostic factors that affect response to HCV therapy in the ANRS HC02-Ribavic study.

Modifications de la sensibilité des Candida au fluconazole chez les patients VIH après suppression de la prophylaxie secondaire systématique de la candidose orale

Resume Lefficacite et la bonne toleance du fluconazole ont incie a proposer ce medicament comme prophylaxie secondaire des rechutes de candidose oropharyngee chez les patients VIH. Cependant des resistances cliniques et mycologiques de Candida sont apparues. Les resultats de deux etudes transversales de la sensibilite de Candida, faites a un an dintervalle, la premiere alors que la prophylaxie secondaire par fluconazole etait systematique, la deuxieme sans prophylaxie systematique, sont rapportes. La sensibilite au fluconazole a ete mesuree sur les souches de Candida isolees du prelevement buccal des 154 et 146 patients inclus. La proportion Candida albicans vs “non-albicans” a diminue avec larret de la prophylaxie (88/17 vs 98/8, p = 0,02). Par contre les repartitions des niveaux de sensibilite de C. albicans etaient similaires pour les deux periodes (souches resistantes = 5,6 % vs 6,7 %, p = 0,71). En analyse multivariee, la resistance de C.albicans etait significativement associee a la dose cumulee de fluconazole (R2 = 0,23, p = 0,0054). En outre, le delai sans prise de fluconazole etait plus court chez les patients hebergeant une souche resistante que chez ceux ayant une souche sensible (1,7 mois vs 3,7 mois, Log rank test, p = 0,01) indiquant le long portage des souches. Ces resultats indiquent la necessite de trouver de nouvelles strategies therapeutiques reposant sur la decouverte dautres molecules antifongiques ne partageant pas les mecanismes de resistance des azoles.

Pancréatite aiguë et infection à Campylobacter jejuni

Summary Acute enteritis is the most common presentation of Campylobacter jejuni infection. However, extraintestinal manifestations have been occasionnaly reported. There have been rare cases of C. jejuni infection concurrent with clinical pancreatitis. We present a case of pancreatitis associated with C. jejuni enteritis.