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Le Touquet – Paris-Plage, France

Assoumou L.,Paris-Sorbonne University | Assoumou L.,Institute Pierre Louis Depidemiologie Et Of Sante Publique | Assoumou L.,French Institute of Health and Medical Research | Weiss L.,AP HP Hopital Europeen Georges Pompidou | And 9 more authors.
AIDS | Year: 2015

Objective: The main aim of this study was to determine whether HIV replication can be controlled following interruption of treatment started early in the course of infection (CD4+ >350cells/μl and viral load <50000copies/ml), but not during the primary infection. Methods: Patients enrolled in a multicenter trial of treatment interruption (ANRS 116 SALTO) with CD4+ above 450cells/μl and viral load below 400copies/ml at treatment interruption were selected for this second analysis. We determined the proportion of patients whose plasma HIV-RNA load remained below 400copies/ml during the first 12 months of treatment interruption, and baseline factors predictive of time to loss of viral control. Viral load rebound was defined as two successive values above 400copies/ml, or as one value above 400copies/ml, followed by treatment resumption. Results: We studied 95 patients with a median CD4+ nadir of 382cells/μl (340-492). At treatment interruption, the median CD4+ cell count and HIV-DNA load were 813/μl (695-988) and 206copies/106 peripheral blood mononuclear cells (PBMCs) (53-556). Twelve months after treatment interruption, seven patients still had viral load below 400copies/ml (Kaplan-Meier estimate 7.5%, 95% confidence interval 3.7-14.6), and four of them still had viral load below 400copies/ml at 36 months. A multivariable Cox proportional-hazards model showed that time to loss of viral control was more shorter in patients with HIV-DNA at least 150copies/106 PBMCs at treatment interruption (hazard ratio 2.1, 95% confidence interval 1.3-3.3, P=0.002) than in those with HIV-DNA below 150copies/106 PBMCs. Conclusion: Patients who have low HIV-DNA levels at antiretroviral treatment interruption are more likely to maintain viral control for long periods. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Weiss L.,University of Paris Descartes | Weiss L.,Institute Pasteur Paris | Chevalier M.F.,Institute Pasteur Paris | Chevalier M.F.,University Paris Diderot | And 9 more authors.
AIDS | Year: 2014

We investigated the relationship between the size of blood HIV reservoirs and T-cell activation in patients with primary HIV infection (PHI) and chronic HIV infection (CHI) before and after antiretroviral therapy (ART) interruption. Levels of T-cell activation strongly positively correlated with HIV-DNA levels in viremic PHI and CHI patients. In ART-treated CHI patients, residual immune activationwas not associated with HIV-DNA levels. Interestingly, early levels of HIV-DNA in PHI predicted the extent of residual T-cell proliferation under ART. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Weiss L.,AP HP Hopital Europeen Georges Pompidou | Weiss L.,University of Paris Descartes | Weiss L.,Institute Pasteur Paris | Chevalier M.F.,Institute Pasteur Paris | And 15 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2016

Objective: The aim of the trial was to evaluate in patients under antiretroviral therapy (ART) the effect of rosuvastatin on cellular and soluble markers of immune activation/inflammation, as well as to identify patients who better benefit from statin administration. Methods: IMEA-043-CESAR was a phase II open-label pilot trial that enrolled patients under suppressive ART and CD4 <500/mm3. Patients received rosuvastatin (20 mg/d) for 12 weeks. The primary outcome was the variation at week 12 (W12) in the proportion of CD38+HLA-DR+CD8+ T lymphocytes. Secondary outcomes included evolution of other markers of T-cell activation and of inflammatory biomarkers between baseline, W12, and W24. Results: Fifty patients were enrolled; end points were available for 43 patients. When considering all patients, the proportion of CD38+HLA-DR+CD8+ T cells did not significantly decline throughout the follow-up. However, the proportion of CD38+CD8+T cells significantly decreased at W12 [median percentage change of 222.2% (232.3; +1.4)]. Principal component analysis allowed identification of 3 groups of patients based on their baseline activation/inflammation profiles, 1 group with elevated levels of CD8 T-cell activation, and a small group with high levels of systemic inflammation and low levels of T-cell activation. Half of the patients exhibited relatively low levels of inflammation and activation. The proportion of activated CD8 T cells significantly decreased only in the particular group of patients with high baseline CD8 T-cell activation. Conclusions: This study shows that combining rosuvastatin with effective ART can result in a sustained decrease in CD8 T-cell activation and highlights the importance of identifying patients who can benefit from specific immunotherapeutic strategies. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Champenois K.,French Institute of Health and Medical Research | Champenois K.,University of Lille Nord de France | Cousien A.,French Institute of Health and Medical Research | Cousien A.,University of Lille Nord de France | And 15 more authors.
BMC Infectious Diseases | Year: 2013

Background: In France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients.Methods: Cross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions.Results: 1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing.Conclusions: Under current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities. © 2013 Champenois et al.; licensee BioMed Central Ltd.

Chalastanis A.,French Institute of Health and Medical Research | Penard-Lacronique V.,University Pierre and Marie Curie | Penard-Lacronique V.,French Institute of Health and Medical Research | Penard-Lacronique V.,University of Paris Descartes | And 12 more authors.
Journal of the National Cancer Institute | Year: 2010

Background The thiopurine prodrug azathioprine is used extensively in cancer therapy. Exposure to this drug results in the selection of DNA mismatch repair-deficient cell clones in vitro. It has also been suggested that thiopurine drugs might constitute a risk factor for the emergence of human neoplasms displaying microsatellite instability (MSI) because of deficient DNA mismatch repair. Methods Azathioprine was administered via drinking water (6-20 mg/kg body weight per day) to mice that were null (Msh2-/-; n = 27), heterozygous (Msh2+/-; n = 22), or wild type (Msh2 WT; n = 18) for the DNA mismatch repair gene Msh2. Control mice (45 Msh2-/-, 38 Msh2+/-, and 12 Msh2WT) received drinking water lacking azathioprine. The effect of azathioprine on tumorigenesis and survival of the mice was evaluated by Kaplan-Meier curves using log-rank and Gehan-Breslow-Wilcoxon tests. Mouse tumor samples were characterized by histology and immunophenotyping, and their MSI status was determined by polymerase chain reaction analysis of three noncoding microsatellite markers and by immunohistochemistry. Msh2 status of tumor samples was assessed by loss of heterozygosity analyses and sequencing after reverse transcription-polymerase chain reaction of the entire Msh2 coding sequence. All statistical tests were two-sided. Results Most untreated Msh2WT and Msh2+/- mice remained asymptomatic and alive at 250 days of age, whereas azathioprine-treated Msh2WT and Msh2+/- mice developed lymphomas and died prematurely (median survival of 71 and 165 days of age, respectively). Azathioprine-treated Msh2+/- mice developed diffuse lymphomas lacking Msh2 expression and displaying MSI due to somatic inactivation of the functional Msh2 allele by loss of heterozygosity or mutation. By contrast, azathioprine-treated Msh2WT mice displayed no obvious tumor phenotype, but histological examination showed microscopic splenic foci of neoplastic lymphoid cells that retained Msh2 expression and did not display MSI. Both untreated and azathioprine-treated Msh2-/- mice had a reduced lifespan compared with untreated Msh2WT mice (median survival of 127 and 107 days of age, respectively) and developed lymphomas with MSI. Conclusion Azathioprine-induced carcinogenesis in mice depends on the number of functional copies of the Msh2 gene. The Author 2010. Published by Oxford University Press.2010 © The Author 2010. Published by Oxford University Press. © 2010 The Author. Published by Oxford University Press. All rights reserved.

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