Dominique Salmon

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (183)728.79 Total impact

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    ABSTRACT: Background & AimsThe efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon-alfa and ribavirin (PegIFN/RBV) has rarely been investigated in HIV/HCV genotype 1-coinfected patients with cirrhosis.Methods We conducted a European (France, Italy, Germany, Netherlands) multicenter study of triple therapy in cirrhotic HIV/HCV GT1-coinfected patients.ResultsFifty-nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 [293-578] /mm3, and HIV viral load was <50 copies/ml in 93% of patients. The HCV genotype was GT1a (78%) or GT1b (13%). Previous PegIFN/RBV therapy had resulted in non-response (73%) or relapse (12%), and 15% of patients were treatment-naïve. The sustained virological response rate at week 12 (SVR12) was 53% overall (57% with TVR, 36% with BOC). A baseline HCV-RNA level <800 000 IU/ml tended to be associated with SVR12 (65% vs 42%, P=0.11). In multivariate analysis, a virological response at week 4 after BOC or TVR initiation was significantly associated with SVR12 (P=0.040). Early discontinuation of triple therapy was frequent (n=26, 44%), because of non-response/breakthrough (65%) or adverse events (AEs) (35%). Three patients died. Severe anemia (<9 g/dl) occurred in 14 patients (25%), leading to ribavirin dose reduction (22%), EPO use (56%) or blood transfusion (14%). In multivariate analysis, lack of ribavirin dose reduction was significantly associated with severe AEs (P=0.006).Conclusions More than half of HIV/HCV GT1-coinfected patients with cirrhosis achieved a SVR12. To avoid unnecessary adverse effects, therapy should be discontinued if no response is obtained at week 4.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 02/2015; DOI:10.1111/liv.12799 · 4.41 Impact Factor
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    ABSTRACT: Objective To compare the management of chronic hepatitis B (CHB) and its evolution over time in currently-followed HIV-positive and HIV-negative patients.Methods709 consecutive patients with past or present positive HBs antigenemia seen in October 2012 in 19 French participating centers were included. The data were retrospectively collected from the first visit onwards through standardized questionnaires.ResultsCHB was less often assessed in the 299 HIV-positive patients, who were older, more likely to be male, excessive alcohol drinkers and HBe antigen-, HCV- and HDV-positive. They were also followed for a longer time (11.3+/-8.8 vs. 8.6+/-6.9 years, p<10-3) and were more frequently treated for HBV (95.3% vs. 56.8%, p<10-3). HBV was undetectable at the last visit in 80.8% of HIV-positive vs. 55.1% of HIV-negative patients (p<10-3).In multivariate analyses, undetectable HBV was significantly associated with older age, lower baseline HBV DNA, longer HBV therapy and no previous lamivudine monotherapy, but not with HIV.Cirrhosis was associated with age, male gender, Asian origin, alcoholism, HCV, HDV but not with HIV infection. Hepatocellular carcinoma, less frequently observed in HIV-positive patients (0.7% vs 4.7%, p=0.002), was positively associated with age, male gender, cirrhosis, and negatively associated with HIV infection (OR 0.15, 95%CI 0.03-0.67, p=0.01).Conclusions Though the assessment of CHB still has to be improved in HIV-positive patients, the negative impact of HIV on the virological, histological and clinical evolution of CHB seems to be disappearing, probably because of the immunovirological impact of HAART and the more frequent and longer use of HBV therapy.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 01/2015; DOI:10.1111/liv.12777 · 4.41 Impact Factor
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    ABSTRACT: A majority of HIV-1-infected patients present a severe deficit in vitamin D, which predicts short-term mortality. Vitamin D is a naturally synthesized hormone, with important immunomodulatory functions. In the general population, its deficit has been associated with increased markers of inflammation. Vitamin D deficit may therefore play a role in the establishment of elevated systemic immune activation, which persists despite suppressive antiretroviral therapy (ART) in HIV-infected patients, and is predictive of disease progression; and vitamin D supplementation may be beneficial in this context. We performed both a cross-sectional study (vitamin D deficit versus normal level) and a longitudinal study (upon vitamin D supplementation for 6 to 12 months) of HIV-1-infected patients receiving suppressive ART. The primary outcome measure was the percentage of activated memory CD8 T cells in blood, which is a robust marker associated with disease progression. Secondary outcomes included general T-lymphocyte and B-lymphocyte phenotype. Although vitamin D deficiency had no influence on T-cell and B-cell subset distribution, we found an association between vitamin D and immune activation levels in HIV-1-infected patients. Vitamin D supplementation in vitamin D-deficient patients resulted in reduced immune activation levels. The present data support the rationale of vitamin D supplementation in the routine clinical management of HIV-1-infected patients, in order to decrease immune activation levels and possibly improve long-term survival.
    AIDS (London, England) 11/2014; 28(18):2677-2682. DOI:10.1097/QAD.0000000000000472 · 6.56 Impact Factor
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    ABSTRACT: Objective: The Mortalite 2010 survey aimed at describing the causes of death among HIV-infected patients in France in 2010 and their evolution since 2000. Design and methods: A national sample of clinical sites, providing HIV care and treatment, notified and documented deaths using a standardized questionnaire. Results: The 90 participating wards notified 728 deaths. Median age at death was 50 years (interquartile range 45-58) and 75% were men. The main underlying causes of death were AIDS-related (25% in 2010 vs. 36% in 2005 and 47% in 2000), non-AIDS non-viral hepatitis-related malignancy (22 vs. 17 and 11%), liver-related (11 vs. 15 and 13%), cardiovascular diseases (10 vs. 8 and 7%) and non-AIDS-related infections (9 vs. 4 and 7%). Malignancies (AIDS and non-AIDS-related) accounted for a third of all causes of death. AIDS accounted for 33% of all causes of death among patients mono-infected with HIV vs. only 13% among those co-infected with hepatitis B virus or hepatitis C virus. Conclusion: In 2010, 25% of the causes of death among HIV-infected patients remained AIDS-related. Improved screening and earlier HIV treatment should lead to a smaller proportion of deaths due to AIDS. The majority of patients died of various causes, whereas their HIV infection was well controlled under treatment. Improving case management of HIV-infected patients should include a multidisciplinary approach (prevention, screening, treatment), especially in oncology. Smoking cessation should be a priority goal.
    AIDS (London, England) 05/2014; 28(8):1181-1191. DOI:10.1097/QAD.0000000000000222 · 6.56 Impact Factor
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    ABSTRACT: The impact of hepatitis C virus (HCV)-related characteristics such as genotype, viral load or liver fibrosis on the chances of achieving sustained HIV suppression in coinfected patients is not fully documented. We examined the relationship between both HIV/HCV-related and sociobehavioural characteristics and HIV sustained viral suppression (SVS) in 897 patients included in the ANRS CO13 HEPAVIH cohort. The main outcome variable was HIV SVS, defined as at least two consecutive undetectable HIV viral loads. Among the 897 HIV/HCV-coinfected patients, 419 (47%) had received HCV therapy at least once, and 103 patients (25%) had experienced an HCV sustained virologic response (SVR). In multivariate analysis, older age [odds ratio (OR) 1.23 for each period of 5 years of age, 95% confidence interval (CI) 1.02-1.49; P = 0.03], a higher level of school education (OR 1.92, 95% CI 1.04-3.56; P = 0.04), good adherence to HIV therapy (OR 2.05, 95% CI 1.23-3.43; P = 0.006) and HCV SVR (OR 1.81, 95% CI 1.01-3.26; P = 0.04) remained significantly associated with HIV SVS. In contrast, triple nucleoside reverse transcriptase inhibitor (NRTI) regimens were associated with failure to achieve HIV SVS (OR 0.50, 95% CI 0.27-0.94; P = 0.03). Our results show that HCV SVR is associated with a higher likelihood of achieving HIV SVS. With the advent of direct-acting anti-HCV drugs, a marked increase in the rate of virologic response is observed in coinfected patients. So, further research is needed to determine whether suppression of HCV replication could be associated with a higher efficacy of antiretroviral therapy.
    AIDS (London, England) 02/2014; 28(8). DOI:10.1097/QAD.0000000000000218 · 6.56 Impact Factor
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    ABSTRACT: Background & Aims We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. Methods Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (⩾3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N = 990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. Results After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR = 0.65; p = 0.04 and OR = 0.57; p = 0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p = 0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p = 0.003 for AST; p = 0.002 for ALT). Conclusions Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.
    Journal of Hepatology 01/2014; 60(1):46–53. DOI:10.1016/j.jhep.2013.08.014 · 9.86 Impact Factor
  • La Revue de Médecine Interne 12/2013; 34:A60-A61. DOI:10.1016/j.revmed.2013.10.089 · 1.32 Impact Factor
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    ABSTRACT: Objective TNF-alpha antagonists have changed the outcome of various chronic inflammatory diseases. Their use has spread widely and many patients receive those treatments for years. Previous reports found that the use of TNF-alpha antagonists may be associated with an increased risk of serious bacterial infections. We report 47 prospective bacteremia cases from the RATIO registry. Methods A national prospective study was conducted in France between 2004 and 2007 to collect severe bacterial infections in patients receiving TNF-alpha antagonists. All reported cases of bacteremia were validated by an expert committee. Results Forty-seven bacteremic episodes were reported. Staphylococcus aureus represented the most frequent causative pathogen (40%) and was mostly associated with bones and/or joints infections (68%) and with a worse outcome compared to that observed with other bacterial pathogens. Conclusions Patients receiving TNF-alpha antagonists may develop bacteremia and S. aureus has to be included in the spectrum of the initial empiric antimicrobial therapy.
    Journal of Infection 12/2013; 67(6):524–528. DOI:10.1016/j.jinf.2013.07.027 · 4.02 Impact Factor
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    ABSTRACT: Differentiation marker, multifunctionality and magnitude analyses of specific-CD8(+) memory T cells are crucial to improve development of HIV vaccines designed to generate cell-mediated immunity. Therefore, we fully characterized the HIV-specific CD8(+) T cell responses induced in volunteers vaccinated with HIV lipopeptide vaccines for phenotypic markers, tetramer staining, cytokine secretion, and cytotoxic activities. The frequency of ex vivo CD8(+) T cells elicited by lipopeptide vaccines is very rare and central-memory phenotype and functions of these cells were been shown to be important in AIDS immunity. So, we expanded them using specific peptides to compare the memory T cell responses induced in volunteers by HIV vaccines with responses to influenza (FLU) or Epstein Barr virus (EBV). By analyzing the differentiation state of IFN-γ-secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile (>85%) belonging to a subset of intermediate-differentiated effector T cells for HIV, FLU, and EBV. We then assessed the quality of the response by measuring various T cell functions. The percentage of single IFN-γ T cell producers in response to HIV was 62% of the total of secreting T cells compared with 35% for FLU and EBV, dual and triple (IFN-γ/IL-2/CD107a) T cell producers could also be detected but at lower levels (8% compared with 37%). Finally, HIV-specific T cells secreted IFN-γ and TNF-α, but not the dual combination like FLU- and EBV-specific T cells. Thus, we found that the functional profile and magnitude of expanded HIV-specific CD8(+) T precursors were more limited than those of to FLU- and EBV-specific CD8(+) T cells. These data show that CD8(+) T cells induced by these HIV vaccines have a similar differentiation profile to FLU and EBV CD8(+) T cells, but that the vaccine potency to induce multifunctional T cells needs to be increased in order to improve vaccination strategies.
    Vaccine 11/2013; DOI:10.1016/j.vaccine.2013.11.052 · 3.49 Impact Factor
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    ABSTRACT: In HCV genotype 1-infected patients with HIV co-infection, tritherapy [HCV protease inhibitors (PIs) plus peg-interferon and ribavirin] has been shown to have an increased rate of sustained virological response. However, complex drug-to-drug interactions and tolerability issues remain a concern. Under the auspices of four French scientific societies of medicine, a committee was charged of establishing guidelines on the use of first-generation HCV PIs in these patients. This scientific committee based its work on preliminary results from tritherapy clinical trials in co-infected patients and, since data on these patients are still scarce, on the statements already made by the French Association for the Study of the Liver (AFEF) on the use of tritherapy in HCV mono-infected patients, written in May 2011 and updated in 2012. Each AFEF guideline concerning HCV mono infection was examined in order to determine whether it could be used in the context of HIV/HCV coinfection. These guidelines are addressed for the treatment of coinfected patients with various profiles, including treatment-naïve or patients with failure to previous bitherapy and mention those patients for whom tritherapy should start or those for whom it should be delayed. Preliminary results of triple therapy as well as factors associated to virological response are also discussed. Other issues include virological monitoring, clinical and virological criteria to stop therapy, practical treatment management, treatment adherence and the management of side effects and interactions with antiretroviral drugs. These guidelines were submitted for critical review to independent experts. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 10/2013; 34(6). DOI:10.1111/liv.12363 · 4.41 Impact Factor
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    ABSTRACT: BACKGROUND: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. METHODS: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. RESULTS: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL. DISCUSSION: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.
    Clinical Infectious Diseases 10/2013; 57(7):1038-1047. · 9.42 Impact Factor
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    ABSTRACT: Our main objective was to improve non-invasive fibrosis staging accuracy by resolving the limits of previous methods via new test combinations. Our secondary objectives were to improve staging precision, by developing a detailed fibrosis classification, and reliability (personalized accuracy) determination. All patients (729) included in the derivation population had chronic hepatitis C, liver biopsy, 6 blood tests and Fibroscan. Validation populations included 1584 patients. The most accurate combination was provided by using most markers of FibroMeter and Fibroscan result targeted for significant fibrosis, i.e., "E-FibroMeter". Its classification accuracy (91.7%) and precision (assessed by F difference with Metavir: 0.62±0.57) were better than those of FibroMeter (84.1%, p<0.001; 0.72±0.57, p<0.001), Fibroscan (88.2%, p=0.011; 0.68±0.57, p=0.020), and a previous CSF-SF classification of FibroMeter + Fibroscan (86.7%, p<0.001; 0.65±0.57, p=0.044). The accuracy for fibrosis absence (F0) was increased, e.g., from 16.0% with Fibroscan to 75.0% with E-FibroMeter (p<0.001). Cirrhosis sensitivity was improved, e.g., E-FibroMeter: 92.7% vs. Fibroscan: 83.3%, p=0.004. The combination improved reliability by deleting unreliable results (accuracy <50%) observed with a single test (1.2% of patients) and increasing optimal reliability (accuracy ≥85%) from 80.4% of patients with Fibroscan (accuracy: 90.9%) to 94.2% of patients with E-FibroMeter (accuracy: 92.9%), p<0.001. The patient rate with 100% predictive values for cirrhosis by the best combination was twice (36.2%) that of the best single test (FibroMeter: 16.2%, p<0.001). the new test combination increased: accuracy, globally and especially in patients without fibrosis, staging precision, cirrhosis prediction, and even reliability, thus offering improved fibrosis staging. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 09/2013; 34(6). DOI:10.1111/liv.12327 · 4.41 Impact Factor
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    ABSTRACT: Combining noninvasive tests increases diagnostic accuracy for staging liver fibrosis in hepatitis C virus (HCV)-infected patients, but this strategy remains to be validated in HIV/HCV coinfection. We compared the performances of transient elastography (TE), Fibrotest (FT), the aspartate aminotransferase-to-platelet ratio index (APRI) and two algorithms combining TE and FT (Castera) or APRI and FT (SAFE) in HIV/HCV coinfection. One hundred and sixteen HIV/HCV-coinfected patients (64% male; median age 44 years) enrolled in two French multicentre studies (the HEPAVIH cohort and FIBROSTIC) for whom TE, FT and APRI data were available were included in the study. Diagnostic accuracies for significant fibrosis (METAVIR F ≥ 2) and cirrhosis (F4) were evaluated by measuring the area under the receiver-operating characteristic curve (AUROC) and calculating percentages of correctly classified (CC) patients, taking liver biopsy as a reference. For F ≥ 2, both TE and FT (AUROC = 0.87 and 0.85, respectively) had a better diagnostic performance than APRI (AUROC = 0.71; P < 0.005). Although the percentage of CC patients was significantly higher with Castera's algorithm than with SAFE (61.2% vs. 31.9%, respectively; P < 0.0001), this percentage was lower than that for TE (80.2%; P < 0.0001) or FT (73.3%; P < 0.0001) taken separately. For F4, TE (AUROC = 0.92) had a better performance than FT (AUROC = 0.78; P = 0.005) or APRI (AUROC = 0.73; P = 0.025). Although the percentage of CC patients was significantly higher with the SAFE algorithm than with Castera's (76.7% vs. 68.1%, respectively; P < 0.050), it was still lower than that for TE (85.3%; P < 0.033). In HIV/HCV-coinfected patients, TE and FT have a similar diagnostic accuracy for significant fibrosis, whereas for cirrhosis TE has the best accuracy. The use of the SAFE and Castera algorithms does not seem to improve diagnostic performance.
    HIV Medicine 09/2013; 15(1). DOI:10.1111/hiv.12082 · 3.45 Impact Factor
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    ABSTRACT: Background. We examined trends in the incidence of the 3 AIDS-defining cancers (ADC) (Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and cervical cancer) among HIV-infected patients relative to the general population between 1992 and 2009 in France, focusing on age at ADC diagnosis and on patients with controlled viral load and restored immunity on combined antiretroviral therapy (cART). Methods. Age- and sex- standardized incidence rates were estimated in patients enrolled in the French hospital database on HIV, and in the general population in France during 4 calendar periods (1992-1996, 1997-2000, 2001-2004, and 2005-2009). Standardized incidence ratios (SIR) were calculated for all periods and separately for patients on cART, with CD4 cell counts ≥500/mm(3) for at least 2 years and viral load ≤500 copies/ml. Results. Although the incidence of ADC fell significantly across the calendar periods, the risk remained constantly higher in HIV-infected patients than in the general population. In patients with restored immunity, the relative risk remained significantly elevated for KS [SIR= 35.4 (95% CI; 18.3-61.9)], and was similar to that of the general population for NHL [SIR= 1.0 (95% CI; 0.4-1.8)]. ADC were diagnosed at a younger age in HIV-infected patients, with a particularly marked difference for NHL (-11.3 years, p<0.0001). Conclusions. The incidence of all ADC continued to fall, including cervical cancer, in the cART period, but the risk remained higher than in the general population in 2005-2009. In patients with stably restored immunity, KS remained significantly more frequent than in the general population.
    Clinical Infectious Diseases 07/2013; DOI:10.1093/cid/cit497 · 9.42 Impact Factor
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    ABSTRACT: ABSTRACT RATIONALE: We described legionellosis emergence during tumor necrosis factor (TNF)-α antagonist therapy. OBJECTIVE: Our objective here was to describe the incidence and risk factors of legionellosis associated with TNF-α antagonist use. METHODS: From February 1, 2004 to January 31, 2007, we prospectively collected all cases of legionellosis among French patients receiving TNF-α antagonists in the Research Axed on Tolerance of bIOtherapies (RATIO) national registry. We conducted an incidence study with the French population as a reference and a case-control analysis with 4 controls receiving TNF-α antagonists per case of legionellosis. RESULTS: Twenty-seven cases of legionellosis were reported. The overall annual incidence rate of legionellosis for patients receiving TNF-α antagonists, adjusted for age and sex, was 46.7 (95% confidence interval [95% CI] 0.0-125.7) per 100,000 patient-years. The overall standardized incidence ratio (SIR) was 13.1 (95% CI 9.0-19.1; p<0.0001) and was higher for patients receiving infliximab (SIR 15.3 [95% CI 8.5-27.6; p<0.0001]) or adalimumab (SIR 37.7 [95% CI 21.9-64.9, p<0.0001]) than etanercept (SIR 3.0 [95% CI 1.00-9.2, p=0.06]). In the case-control analysis, exposure to adalimumab (odds ratio [OR] 8.7 [95% CI 2.1-35.1]) or infliximab (OR 9.2 [95% CI 1.9-45.4]) versus etanercept was an independent risk factor for legionellosis. CONCLUSION: The incidence rate of legionellosis for patients receiving TNF-α antagonists is high and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis.
    Chest 06/2013; 144(3). DOI:10.1378/chest.12-2820 · 7.13 Impact Factor
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    ABSTRACT: OBJECTIVE:: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN:: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS:: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS:: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-γ, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION:: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.
    AIDS (London, England) 06/2013; 27(9):1421-1431. DOI:10.1097/QAD.0b013e32835f5b60 · 6.56 Impact Factor
  • La Revue de Médecine Interne 06/2013; 34:A38–A39. DOI:10.1016/j.revmed.2013.03.238 · 1.32 Impact Factor
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    ABSTRACT: OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score > F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (< 800 000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P = 0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P = 0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P = 0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.
    HIV Medicine 03/2013; DOI:10.1111/hiv.12023 · 3.45 Impact Factor
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    ABSTRACT: AIMS: Studying alcohol abuse impact, as measured by physicians' perceptions and patients' self-reports, on HIV virological rebound among patients chronically co-infected with HIV and hepatitis C virus (HCV). DESIGN: Cohort study. SETTING: Seventeen French hospitals. PARTICIPANTS: 512 patients receiving antiretroviral therapy (ART) with an undetectable initial HIV viral load and at least two viral load measures during follow-up. MEASUREMENTS: Medical records and self-administered questionnaires. HIV virological rebound defined as HIV viral load above the limit of detection of the given hospital's laboratory test. Alcohol abuse defined as reporting to have drunk regularly at least 4 (for men) or 3 (for women) alcohol units per day during the previous six months. Correlates of time to HIV virological rebound identified using Cox proportional hazards models. FINDINGS: At enrolment, nine percent of patients reported alcohol abuse. Physicians considered 14.8% of all participants as alcohol abusers. Self-reported alcohol abuse was independently associated with HIV virological rebound (hazard ratio [95% confidence interval]: 2.04 [1.13-3.67]; p=0.02), after adjustment for CD4 count, time since ART initiation and hospital HIV caseload. No significant relationship was observed between physician-reported alcohol abuse and virological rebound (p=0.87). CONCLUSIONS: In France, the assessment of alcohol abuse in patients co-infected with HIV and hepatitis C virus should be based on patients' self-reports, rather than physicians' perceptions. Baseline screening of self-reported alcohol abuse may help identify co-infected patients at risk of subsequent HIV virological rebound.
    Addiction 02/2013; 108(7). DOI:10.1111/add.12149 · 4.60 Impact Factor

Publication Stats

4k Citations
728.79 Total Impact Points

Institutions

  • 1998–2015
    • Université René Descartes - Paris 5
      • • Faculté de Médecine
      • • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Université de Reims Champagne-Ardenne
      Rheims, Champagne-Ardenne, France
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2006–2012
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      • Service de Médecine Interne
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • Groupe Hospitalier Saint Vincent
      Strasburg, Alsace, France
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 1999–2008
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Bordeaux School of Public Health
      Burdeos, Aquitaine, France
  • 2005
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 2004
    • University of Florida
      Gainesville, Florida, United States
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France