E. Cua

Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge.

Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.

Antibiotic misuse: a prospective clinical audit in a French university hospital

The aim of the study presented here was to prospectively audit antibiotic prescriptions given to patients attending L’Archet Hospital in Nice, France, with details of the initial medical examination included in the audit procedure. A total of 122 antibiotic treatments were evaluated, i.e. 31% of all antibiotic therapies initiated in the eight participating departments over the 9-week study period. Forty-two (34%) treatments were found to be unnecessary due to misdiagnosis, and 36 (30%) other treatments were inappropriate. Misdiagnosis, due to the misinterpretation or lack of clinical, microbiological and/or imaging data is thus a major cause of antibiotic misuse. Improvement in the diagnostic process should become part of antibiotic policy.

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 patients 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.

Cutaneous complications of direct intra-arterial injections in drug addicts.

Pascal Del Giudice, Frederic Vandenbos, Christian Boissy, Eric Cua, Bertrand Marion, Evelyne Bernard, Pierre Dellamonica and Evelyne Counillon Unite de Maladies Infectieuses et Dermatologie, Hopital Bonnet, Avenue Andre Leotard, 83700 Frejus, Service des Maladies Infectieuses et Tropicales, Hopital l’Archet 1, CHU Nice, Services de Chirurgie, Hopital Bonnet, Frejus and Laboratoire de Pathologie, Saint Raphael, France. E-mail: del-giudice-p@chi-frejus-saint-raphael.fr Accepted January 19, 2005.

Early CD4+ T Cell Recovery in Human Immunodeficiency Virus-Infected Patients Receiving Effective Therapy Is Related to a Down-Regulation of Apoptosis and Not to Proliferation

This prospective study investigated the contributions of apoptosis and proliferation of CD4(+) T cells obtained by the introduction of a new antiretroviral treatment for human immunodeficiency virus infection. Virus load; T cell counts; apoptosis of T cell subsets, including naive cells; and proliferation were determined from treatment initiation to the third month in a cohort of patients. An increase in CD4(+) T cell count > or = 100 cells/microL over baseline was considered to be a satisfactory immune reconstitution. Sixty-nine patients completed the protocol, 22 of whom met our definition of a satisfactory immune reconstitution, showing a significantly more pronounced reduction in spontaneous CD4(+) T cell apoptosis at month 1 as well as month 3, compared with the other patients. In contrast, neither Fas-induced apoptosis down-regulation nor Fas-induced increased proliferation capacity was associated with a satisfactory immune reconstitution. Down-regulation of CD4(+) T cell apoptosis by antiretroviral treatment is the main mechanism associated with early CD4(+) T cell increase.

Audit of antibiotic therapy used in 66 cases of endocarditis

OBJECTIVES We wanted to assess the quality of antibiotic therapy prescribed for infective endocarditis in our ward. DESIGN We conducted a retrospective audit of all adult patients with endocarditis hospitalized over a 3-year period in the Infectious Diseases Unit of the Nice University Hospital, France. The quality of antibiotic therapy was assessed using the 2004 European Society of Cardiology guidelines as a reference. Antibiotic therapy was considered as appropriate only if the five following items complied with guidelines: antibiotic, dose, route, interval of administration, and duration of antibiotic treatment. RESULTS Sixty-six patients were included, 63years of age on average. Antibiotic therapy complied with guidelines in 14% of the cases. The most frequent causes of inappropriate therapy were: gentamicin prescribed as a single daily dose in 55% (27/49) of the cases, unnecessary prescriptions of rifampin in 72% (18/25) of the cases, and too long duration of gentamicin course for staphylococcal endocarditis in 32% (9/28) of the cases. Antibiotic therapy was switched from intravenous to oral route in 29% of the patients (n=19), 18±9 days after starting therapy on average. These endocarditis were mainly left-sided (n=12) and/or complicated (n=15). There was no significant association between mortality and inappropriate antibiotic therapy (14% if inappropriate vs. 22%, P=0.62) or between mortality and oral switch (0% if oral switch vs. 21%, P=0.052). CONCLUSIONS Infective endocarditis antibiotic treatment rarely complied with the 2004 European guidelines, but this did not have a negative impact on mortality. Switching antibiotic therapy from intravenous to oral route was common, even for complicated left-sided endocarditis, and was associated with a favorable outcome in all cases.

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 m2) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m2/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 m2/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.

Variable Virological Outcomes According to the Center Providing Antiretroviral Therapy Within the PharmAdapt Clinical Trial

Abstract 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.

COPD in HIV-Infected Patients: CD4 Cell Count Highly Correlated

Background COPD is a frequent and significant cause of respiratory morbidity in HIV-infected patients despite the control of HIV. We aimed to analyze the factors correlated with COPD in this population to evaluate the existence of specific indicators of vulnerability in this population. Methods and Findings 623 HIV-infected outpatients were enrolled during one year. This population was characterised by a dedicated questionnaire and electronic patient records. COPD screening was performed according to recommended spirometric criteria. The prevalence of COPD was 9.0%. Age and smoking were independently correlated with COPD (OR, 1.61 per 10 years increase, P = 0.007; OR, 1.28 per 10 pack-year increase, P = 0.003, respectively). Body mass index (BMI) and CD4 cell-count were independently and negatively correlated with COPD (OR, 0.78, P < 0.001; 0R, 0.77 per 100 cell/mm3 increase, P < 0.001, respectively). Among COPD patients, 77% did not know their diagnosis. Five COPD-patients never smoked and 44.2% did not have any respiratory symptoms and so were not eligible to perform a spirometry according to the guidelines. Conclusions In addition to known risk factors, immune defect through CD4 cell count was independently and strongly correlated with COPD. COPD is largely underdiagnosed and thus unmanaged. However, early management and urgent smoking cessation are essential to improve prognosis. Clinicians’ awareness on the particular vulnerability for COPD in HIV-infected patients is crucial. Moreover, indications to perform conventional spirometry to diagnose COPD may include more parameters than tobacco-smoking and respiratory complaints with a particular concern toward patients with a profound CD4 cell count defect.

Assessment of HIV Screening Tests for Use in Preexposure Prophylaxis Programs

Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.