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Deroux A.,Service de medecine interne | Brion J.P.,Service de maladies infectieuses | Hyerle L.,Service de maladies infectieuses | Belbezier A.,Service de medecine interne | And 5 more authors.
Journal of Clinical Virology | Year: 2014

Hepatitis E (HEV) is an emerging disease in our developed countries, but is not routinely tested for in case of liver cytolysis. However, a growing number of extra-hepatic manifestations of HEV infection associated with acute hepatitis are reported. In this article, we discuss two cases of HEV with neurological symptoms, one with encephalitis, and the other with Parsonage Turner syndrome. All these disorders appeared concomitantly with liver cytolysis and disappeared quickly, following the viral kinetics. Only twenty cases of neurological manifestation of HEV have been described before. The use of HEV serology in patients with concurrent liver cytolysis and neurological symptoms has to be improved. © 2014 Elsevier B.V.


Goujard C.,Service de Medecine Interne | Goujard C.,University Paris - Sud | Emilie D.,University Paris - Sud | Roussillon C.,French Institute of Health and Medical Research | And 11 more authors.
AIDS | Year: 2012

OBJECTIVES: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI). DESIGN AND METHODS: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption. RESULTS: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups. CONCLUSION: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Maylin S.,Laboratoire Of Virologie | Maylin S.,French Institute of Health and Medical Research | Maylin S.,University Paris Diderot | Boyd A.,French Institute of Health and Medical Research | And 14 more authors.
AIDS | Year: 2012

Objective: Hepatitis B surface (HBs-Ag) and envelope (HBeAg) antigen loss are the primary goals of treating chronic hepatitis B virus (HBV). Although their quantification is useful for other antivirals, such has not been the case with tenofovir disoproxil fumarate (TDF), particularly in HIV infection. DESIGN:: Prospective, multicenter, cohort study in 143 antiretroviral- experienced HIV-HBV-co-infected patients initiating TDF. Methods: HBsAg (IU/ml) and HBeAg levels (S/CO) were measured every 6 months. HBsAg and HBeAg decline (Δ) were assessed by mixed-effect linear models. Quantification criteria were used to assess predictability of antigen loss with time-dependent receiver operating characteristic curves. Results: After a median follow-up of 30.3 months, cumulative incidence rate of HBsAg loss was 4.0% (n=4) in the entire study population and HBeAg loss was 21.0% (n=17) in the 96 HBeAg-positive patients. ΔHBsAg was steady during follow-up (HBeAg-positive: -0.027; HBeAg-negative: -0.017log10IU/ml per month), whereas ΔHBeAg ratio was strongly biphasic (-27.1S/CO per month before and -6.5S/CO per month after 18 months). Baseline HBeAg and ΔHBeAg were significantly different in patients harboring precore mutations (P<0.01), whereas both ΔHBsAg and ΔHBeAg were significantly slower among HBeAg-positive patients with CD4 + T-cell count less than 350 cells/μl (P< 0.05). HBeAg-ratio of 10S/CO or less at 12 months of therapy was the optimal marker of HBeAg loss, with high sensitivity (0.82) and specificity (0.84) at 36 months. In patients with HBsAg loss, three of four (75.0%) patients had a baseline level of HBsAg of 400 IU/ml or less. Conclusion: During TDF treatment, HIV-induced immunosuppression and HBV genetic variability are associated with differences in HBsAg and HBeAg decline among antiretroviral-experienced, co-infected patients. Considering the decline of HBsAg level is slow, further evaluation is needed to determine its role as a marker of therapeutic efficacy. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Lanoy E.,U943 | Lanoy E.,University Pierre and Marie Curie | Guiguet M.,U943 | Guiguet M.,University Pierre and Marie Curie | And 8 more authors.
Neurology | Year: 2011

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. Copyright © 2011 by AAN Enterprises, Inc. All rights reserved.


Haim-Boukobza S.,Groupe Hospitalier Pitie Salpetriere | Morand-Joubert L.,Laboratoire Of Virologie | Morand-Joubert L.,University Pierre and Marie Curie | Flandre P.,Groupe Hospitalier Pitie Salpetriere | And 10 more authors.
AIDS | Year: 2011

Objectives: To compare the level of HIV-1 residual viremia, defined by a viral load below 50 copies/ml in patients receiving a tenofovir/emtricitabine and nevirapine (NVP) or efavirenz (EFV)-containing regimen. Design: One hundred and sixty-five HIV-1-infected patients were retrospectively included since they achieved virological suppression (viral load <50 copies/ml) for at least 6 months with a tenofovir/emtricitabine and non-nucleoside reverse transcriptase inhibitor-containing regimen (NVP, n = 75 and EFV, n = 90). Methods: Residual plasma viremia was measured using an ultrasensitive assay with a limit of quantification of 1 copy/ml. A Fisher's exact test was used to compare the percentage of patients with HIV-1 RNA below 1 copy/ml between the two treatment groups. Logistic regression was used to search for factors associated with a viral load below 1 copy/ml among the different patient characteristics. Results: Patients in the NVP group had more frequently a viral load below 1 copy/ml than patients in the EFV group (81.3 vs. 55.6%, P < 0.001). In multivariate analysis, only NVP vs EFV (P = 0.005) and duration of viral suppression under antiretroviral treatment (P = 0.005) were independently associated with viral load below 1 copy/ml. Conclusions: It is well known that NVP has a good penetration in anatomic compartments that could explain a deep control of virus replication in some compartments and consequently decrease the residual level of viral load. The clinical relevance of having a viral load below 1 copy/ml has now to be studied for example on systemic inflammatory or immune activation markers. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Pulcini C.,Nancy University Hospital Center | Pulcini C.,University of Lorraine | Botelho-Nevers E.,Service de Maladies Infectieuses | Botelho-Nevers E.,Jean Monnet University | And 2 more authors.
Clinical Microbiology and Infection | Year: 2014

Given the current bacterial resistance crisis, antimicrobial stewardship programmes are of the utmost importance. We present a narrative review of the impact of infectious disease specialists (IDSs) on the quality and quantity of antibiotic use in acute-care hospitals, and discuss the main factors that could limit the efficacy of IDS recommendations. A total of 31 studies were included in this review, with a wide range of infections, hospital settings, and types of antibiotic prescription. Seven of 31 studies were randomized controlled trials, before/after controlled studies, or before/after uncontrolled studies with interrupted time-series analysis. In almost all studies, IDS intervention was associated with a significant improvement in the appropriateness of antibiotic prescribing as compared with prescriptions without any IDS input, and with decreased antibiotic consumption. Variability in the antibiotic prescribing practices of IDSs, informal (curbside) consultations and the involvement of junior IDSs are among the factors that could have an impact on the efficacy of IDS recommendations and on compliance rates, and deserve further investigation. We also discuss possible drawbacks of IDSs in acute-care hospitals that are rarely reported in the published literature. Overall, IDSs are valuable to antimicrobial stewardship programmes in hospitals, but their impact depends on many human and organizational factors. © 2014 European Society of Clinical Microbiology and Infectious Diseases.


Fardet L.,Service de Medecine Interne | Lambotte O.,Service de Medecine Interne | Meynard J.-L.,Service de Maladies Infectieuses | Kamouh W.,Service de Medecine Interne | And 8 more authors.
AIDS | Year: 2010

OBJECTIVE: To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS. DESIGN AND SETTING: Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres. PATIENTS AND METHODS: Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method. RESULTS: Fifty-eight HIV-1-infected patients were diagnosed with RHS [certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%]. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/μl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/μl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68). CONCLUSION: In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Antuna-Puente B.,University Pierre and Marie Curie | Boutet E.,University Pierre and Marie Curie | Vigouroux C.,University Pierre and Marie Curie | Lascols O.,University Pierre and Marie Curie | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Human lipodystrophies are characterized by loss of adipose tissue, insulin resistance, and metabolic complications. The mechanisms linking fat loss to severe insulin resistance remain unclear. Adipokines may have important roles as intermediary players in metabolism. Objective: Wesought to determine the plasma concentrations of leptin and adiponectin in patients with Berardinelli-Seip congenital lipodystrophy (BSCL) harboring mutations in the genes encoding either 1-acylglycerol-3-phosphate-O-acyltransferase-2 (AGPAT2) or BSCL2/seipin, in comparison with patients with other forms of inherited or acquired lipodystrophies or insulin receptor alterations. Design: Leptin and total and high-molecular-weight adiponectin were measured in plasma of 16 BSCL1/AGPAT2 and 19 BSCL2/seipin patients and compared with heterozygous (n = 22) or nonmutated relatives (controls, n = 30); patients with Dunnigan-type partial lipodystrophy due to lamin A/C mutations (n = 23), HIV-related lipodystrophy (n = 124), and insulin receptor dysfunctions caused by mutations or autoantibodies (n = 17). Results: Leptin was dramatically decreased in BSCL patients as compared with other subgroups. Adiponectin was decreased in BSCL as compared with controls and patients with altered insulin receptor but was discrepant between the two BSCL subgroups. Whereas total and high-molecular-weight adiponectin levels were almost undetectable in BSCL1/AGPAT2 patients, higher levels were detected in BSCL2/seipin patients, comparable with those of patients with partial lipodystrophy. Adiponectin greater than 1.6 mg/liter had a100%negative predictive value for AGPAT2 mutations in inherited lipodystrophies. Conclusions: The presence of circulating adiponectin in BSCL2/seipin patients with near absence of adipose tissue outlines the complexity of adiponectin biology. Use of circulating adiponectin might be helpful to guide the genetic investigations in BSCL. Copyright © 2010 by The Endocrine Society.


PubMed | University Blaise Pascal, Service de Biostatistiques, Service de maladies infectieuses, Laboratoire Of Bacteriologie and 2 more.
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2016

Urinary tract infections, among the leading causes of antibiotic prescriptions in adult women, are complicated by increasing antibiotic resistance. Current recommendations propose a 7 day treatment with fluoroquinolones or a 10-14 day course of third-generation cephalosporins (3GC). Our aim was to study the efficiency and tolerance of a short 7 day treatment with 3GC in uncomplicated acute pyelonephritis in women aged between 18 and 65 years.This study was an open, prospective, non-comparative, monocentric pilot study with consecutive patients. We included women between 18 and 65 years old who had been admitted to the emergency department with a diagnosis of acute pyelonephritis. The treatment consisted of 1 g of ceftriaxone injection followed by 6 days of 400 mg of cefixime per day. The primary endpoint was negative urine cultures on day 9. We opted for Flemings multistage design for this trial. ClinicalTrials.gov number: NCT01390623.Thirty-seven patients were analysed. The bacteriological response consisted of negative urine cultures for all 37 patients on day 9. On day 9, 30 patients were completely asymptomatic, while 7 exhibited clinical improvement though persistence of bladder irritation or flank pain. On day 37, there were no remaining symptoms and no recurrences of urinary tract infection, as noted during the last follow-up visits.These results suggest that acute pyelonephritis in women could be successfully treated with a short-term course of 1 g of ceftriaxone on the first day followed by 400 mg of cefixime per day for 6 days. These positive results must be confirmed by a non-inferiority study.


Charpentier C.,University of Paris Pantheon Sorbonne | Joly V.,University of Paris Pantheon Sorbonne | Larrouy L.,University of Paris Pantheon Sorbonne | Fagard C.,French Institute of Health and Medical Research | And 5 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2013

Objectives: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. Methods: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. Results: At baseline the median CD4 cell count was 30 cells/mm3. Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistanceassociated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. Conclusions: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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