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1. Risk of Severe Bacterial Infection in People Living Human Immunodeficiency Virus Infection in the Combined Antiretroviral Therapy Era

Author

Murielle Mary-Krause, Sébastien Gallien, Martin Siguier, Dominique Costagliola, Hugues Melliez, Patricia Enel, Patrizia Carrieri, Juliette Pavie, Xavier Duval, Pierre Tattevin, Marguerite Guiguet, Claudine Duvivier, Anaenza Freire-Maresca, Sophie Abgrall, Dupuis, Christine, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département des Maladies Infectieuses [CH Tourcoing] (Hôpital Gustave Dron), Centre Hospitalier Gustave Dron [Tourcoing]-Centre Hospitalier de Tourcoing, Hôpital de la Région de Saint-Omer [Helfaut], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique et information médicale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'Immunologie Clinique et Maladies Infectieuses [AP-HP Hôpital H. Mondor-A. Chenevier, Paris], Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-AP-HP Hôpital A. Chenevier [Créteil], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Service d'Immunologie Clinique [Hôpital Européen Georges Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de médecine interne [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], France Recherche Nord&Sud Sida-hiv Hépatites, Institut National de la Santé et de la Recherche Médicale, French Ministry of Health, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Antoine Béclère [Clamart], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-AP-HP Hôpital A. Chenevier [Créteil], Institut Pasteur [Paris], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Paris (UP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Médical de l'Institut Pasteur, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service des maladies infectieuses et réanimation médicale [Rennes], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou

Subjects
Male, 0301 basic medicine, Databases, Factual, Neutrophils, [SDV]Life Sciences [q-bio], HIV Infections, Comorbidity, Leukocyte Count, Liver disease, 0302 clinical medicine, Risk Factors, Immunology and Allergy, Prospective Studies, 030212 general & internal medicine, diabetes, Incidence, Incidence (epidemiology), Hazard ratio, Bacterial Infections, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Alcoholism, Infectious Diseases, Anti-Retroviral Agents, Drug Therapy, Combination, Female, France, liver disease, Adult, medicine.medical_specialty, Neutropenia, Malignancy, Risk Assessment, AIDS-defining malignancy, End Stage Liver Disease, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Renal Insufficiency, Chronic, Aged, business.industry, HIV, medicine.disease, Confidence interval, 030104 developmental biology, HIV-1, business, chronic kidney disease, Kidney disease
Abstract

BackgroundSevere bacterial infections are the first cause of morbidity in people with human immunodeficiency virus (PWH). We aimed to assess their incidence and to analyze their determinants.MethodsWe studied human immunodeficiency virus (HIV)-1-infected individuals aged at least 15 years and prospectively followed between 2006 and 2015 in the French Hospital Database on HIV. The Andersen and Gill model was used to calculate the adjusted hazard ratios (HRs), focusing on heavy alcohol use and neutrophil function-altering comorbidities.ResultsOf 25 795 participants, 1414 developed 1883 severe bacterial infections. Between 2006 and 2009 and 2013 and 2015, the incidence fell from 13.2 (95% confidence interval [CI], 12.3–14.1) to 7.1 (95% CI, 6.3–7.8) per 1000 person-years. Heavy alcohol use was associated with an increased risk of severe bacterial infection (HR = 1.3, 95% CI = 1.1–1.7 for 40–80 g/day and HR = 1.6, 95% CI = 1.2–2.1 for >80 g/day), as were diabetes, chronic kidney disease, and end-stage liver disease (HR = 1.2, 95% CI = 1.0–1.4 when 1 comorbidity; HR = 2.3, 95% CI = 1.6–3.4 when more than 1 comorbidity), and nonacquired immune deficiency syndrome-defining malignancy (HR = 2.0; 95% CI, 1.6–2.4).ConclusionsHeavy alcohol use was associated with an increased risk of severe bacterial infection, as were neutrophil function-altering comorbidities. Controlled-drinking approaches should be promoted and comorbidity management should be strengthened in PWH.

Published
2020

2. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

Author

Lauren E. Cain, Dominique Costagliola, Valdilea G. Veloso, Heiner C. Bucher, Janet P. Tate, James M. Robins, Rémonie Seng, Daniel R. Drozd, Matthias Egger, Ellen C. Caniglia, George R. Seage, José M. Miró, Michael J. Mugavero, Kholoud Porter, Sophie Abgrall, Andrew N. Phillips, Jonathan A C Sterne, Michael S. Saag, Sonia Napravnik, William C. Mathews, Steven G. Deeks, Hansjakob Furrer, Peter Reiss, Giota Touloumi, Roger Logan, John Gill, Roberto Muga, Elena Ferrer, Heidi M. Crane, Laurence Meyer, François Dabis, Amy C. Justice, Joseph J. Eron, Stephen L. Boswell, Santiago Moreno, Ard van Sighem, Fabrice Bonnet, Sophie Jose, Caroline A. Sabin, Richard D. Moore, Sonia Hernandez-Diaz, Antonio G. Pacheco, Julia del Amo, Miguel A. Hernán, AII - Infectious diseases, APH - Aging & Later Life, Global Health, Amsterdam institute for Infection and Immunity, Gestionnaire, Hal Sorbonne Université, Harvard T.H. Chan School of Public Health, University College of London [London] (UCL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Alabama at Birmingham [ Birmingham] (UAB), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Washington [Seattle], Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University (JHU), Amsterdam UMC - Amsterdam University Medical Center, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Amsterdam Institute for Global Health and Development, Institute of Health Carlos III, Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Fenway Health Institute, Boston, MA, USA., Hospitalet de Llobregat, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Yale School of Medicine [New Haven, Connecticut] (YSM), VA Connecticut Healthcare System, University of Calgary, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University Hospital Basel [Basel], University of Cape Town, University of Bern, Bern University Hospital [Berne] (Inselspital), University of Athens Medical School [Athens], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), School of Social and Community Medicine [Bristol], and University of Bristol [Bristol]

Subjects
Male, 0301 basic medicine, Pediatrics, Epidemiology, [SDV]Life Sciences [q-bio], HIV Infections, Medical and Health Sciences, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Prospective Studies, 030212 general & internal medicine, 610 Medicine & health, Prospective cohort study, Hazard ratio, Confounding, virus diseases, Viral Load, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Europe, Infectious Diseases, 6.1 Pharmaceuticals, HIV/AIDS, Female, Drug Monitoring, Infection, Viral load, 360 Social problems & social services, psychological phenomena and processes, Adult, medicine.medical_specialty, Adolescent, Anti-HIV Agents, Immunology, HIV-CAUSAL Collaboration, Young Adult, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Virology, mental disorders, Humans, Centers for AIDS Research Network of Integrated Clinical Systems, business.industry, Developed Countries, Prevention, Evaluation of treatments and therapeutic interventions, medicine.disease, 030112 virology, CD4 Lymphocyte Count, Regimen, Good Health and Well Being, Relative risk, HIV-1, business
Abstract

Summary Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86–1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95–1·22) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.

Published
2017

3. RE: 'EFFECT ESTIMATES IN RANDOMIZED TRIALS AND OBSERVATIONAL STUDIES: COMPARING APPLES WITH APPLES'

Author

Miguel A. Hernán, John Gill, Sophie Abgrall, Antonio G. Pacheco, Linda Wittkop, Alexandra Montoliu Giménez, James D. Neaton, Stephen R. Cole, Sara Lodi, Abdel Babiker, Haitao Chu, Giota Touloumi, Amy C. Justice, Inmaculada Jarrín, Laurence Meyer, Ard van Sighem, Jens D Lundgren, Andrzej Horban, Caroline A. Sabin, Andrew N. Phillips, Shweta Sharma, Santiago Pérez-Hoyos, Kholoud Porter, Heiner C. Bucher, Dominique Costagliola, Dana Byrne, Peter Reiss, Roger Logan, Matthew Law, Jonathan A C Sterne, Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), University College of London [London] (UCL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Copenhagen = Københavns Universitet (KU), Harvard T.H. Chan School of Public Health, University of Minnesota Medical School, University of Minnesota System, The Kirby Institute for Infection and Immunity in Society (UNSW), University of New South Wales [Sydney] (UNSW), Cooper Medical School of Rowan University [Camden] (CMSRU), Medical University of Warsaw - Poland, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Bristol [Bristol], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Calgary, University of Athens Medical School [Athens], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), VU University Medical Center [Amsterdam], Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], University Hospital Basel [Basel], University of Basel (Unibas), Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Instituto de Salud Carlos III [Madrid] (ISC), Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], Institut de Recherche Interdisciplinaire sur les enjeux Sociaux - sciences sociales, politique, santé (IRIS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-École des hautes études en sciences sociales (EHESS), Université Paris-Sud - Paris 11 (UP11), and Yale University School of Medicine

Subjects
Adult, Male, medicine.medical_specialty, Randomization, target trial, Practice of Epidemiology, Epidemiology, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, 030204 cardiovascular system & hematology, medicine.disease_cause, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, antiretroviral initiation, Humans, Medicine, 030212 general & internal medicine, causal inference, Intensive care medicine, Randomized Controlled Trials as Topic, Intention-to-treat analysis, business.industry, Causal effect, Middle Aged, 3. Good health, Observational Studies as Topic, Anti-Retroviral Agents, Research Design, Causal inference, Malus, Female, Observational study, Epidemiologic Methods, per-protocol effect, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

Published
2019

4. Lack of ADCC breadth of human non-neutralizing anti-HIV-1 antibodies

Author

Olivier Schwartz, Hugues Lortat-Jacob, Timothée Bruel, Hugo Mouquet, Françoise Baleux, Katia Bourdic, Florence Guivel-Benhassine, Olivier Lambotte, Nicolas Noel, Valérie Lorin, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Réponse humorale aux pathogènes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Chimie des Biomolécules - Chemistry of Biomolecules, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), O.S. was supported by grants from the Vaccine Research Institute (ANR-10-LABX-77), the Agence Nationale de Recherche sur le SIDA et les Hepatitis (ANRS) (AO 2015-2 CSS-2), the Labex Integrative Biology of Emerging Infectious Diseases program (ANR-10-LABX-62-IBEID), the FP7 program Hit Hidden HIV (Health-F3-2012-305762), and the Institut Pasteur. H.M. was supported by the European Research Council-Seventh Frame-Work Program (ERC-2013-StG 337146), the ANRS, the G5 Institut Pasteur Program, and The Milieu Intérieur Program (ANR1-101LABX-69-01), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), AP-HP - Hôpital Antoine Béclère [Clamart], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, reservoir, medicine.drug_class, Immunology, HIV Antibodies, HIV Envelope Protein gp120, Biology, Monoclonal antibody, Microbiology, Epitope, 03 medical and health sciences, 0302 clinical medicine, Immune system, Virology, Vaccines and Antiviral Agents, Bystander effect, medicine, Humans, neutralizing antibodies, Cells, Cultured, Antibody-dependent cell-mediated cytotoxicity, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], nonneutralizing antibodies, Antibody-Dependent Cell Cytotoxicity, Antibodies, Monoclonal, virus diseases, Fragment crystallizable region, HIV Envelope Protein gp41, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Insect Science, Monoclonal, biology.protein, HIV-1, monoclonal antibodies, Antibody, ADCC
Abstract

Anti-human immunodeficiency virus type 1 (HIV-1) nonneutralizing antibodies (nnAbs) capable of antibody-dependent cellular cytotoxicity (ADCC) have been identified as a protective immune correlate in the RV144 vaccine efficacy trial. Broadly neutralizing antibodies (bNAbs) also mediate ADCC in cell culture and rely on their Fc region for optimal efficacy in animal models. Here, we selected 9 monoclonal nnAbs and 5 potent bNAbs targeting various epitopes and conformations of the gp120/41 complex and analyzed the potency of the two types of antibodies to bind and eliminate HIV-1-infected cells in culture. Regardless of their neutralizing activity, most of the selected antibodies recognized and killed cells infected with two laboratory-adapted HIV-1 strains. Some nnAbs also bound bystander cells that may have captured viral proteins. However, in contrast to the bNAbs, the nnAbs bound poorly to reactivated infected cells from 8 HIV-positive individuals and did not mediate effective ADCC against these cells. The nnAbs also inefficiently recognize cells infected with 8 different transmitted-founder (T/F) isolates. The addition of a synthetic CD4 mimetic enhanced the binding and killing efficacy of some of the nnAbs in an epitope-dependent manner without reaching the levels achieved by the most potent bNAbs. Overall, our data reveal important qualitative and quantitative differences between nnAbs and bNAbs in their ADCC capacity and strongly suggest that the breadth of recognition of HIV-1 by nnAbs is narrow. IMPORTANCE Most of the anti-HIV antibodies generated by infected individuals do not display potent neutralizing activities. These nonneutralizing antibodies (nnAbs) with antibody-dependent cellular cytotoxicity (ADCC) have been identified as a protective immune correlate in the RV144 vaccine efficacy trial. However, in primate models, the nnAbs do not protect against simian-human immunodeficiency virus (SHIV) acquisition. Thus, the role of nnAbs with ADCC activity in protection from infection remains debatable. In contrast, broadly neutralizing antibodies (bNAbs) neutralize a large array of viral strains and mediate ADCC in cell culture. We analyzed the capacities of 9 nnAbs and 5 bNAbs to eliminate infected cells. We selected 18 HIV-1 strains, including virus reactivated from the reservoir of HIV-positive individuals and transmitted-founder isolates. We report that the nnAbs bind poorly to cells infected with primary HIV-1 strains and do not mediate potent ADCC. Overall, our data show that the breadth of recognition of HIV-1 by nnAbs is narrow.

Published
2017

5. All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus–coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13–HEPAVIH Cohort

Author

Daniel Vittecoq, David Zucman, Laurent Alric, Hugues Aumaitre, Firouzé Bani-Sadr, Julie Chas, Isabelle Poizot-Martin, Anne Simon, Philippe Sogni, Karine Lacombe, Didier Neau, Linda Wittkop, Laure Esterle, François Boué, Stéphanie Dominguez, Cécile Goujard, Camille Gilbert, Anne Gervais, Marc-Antoine Valantin, Caroline Lascoux-Combe, Dominique Salmon, François Dabis, Lionel Piroth, Philippe Morlat, Olivier Bouchaud, Eric Billaud, Eric Rosenthal, Patrick Miailhes, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dynamiques des Réponses immunes - Dynamics of Immune Responses, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Hôpital l'Archet, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CHU Tenon [AP-HP], Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Université de Bordeaux (UB), Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Foch [Suresnes], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Saint Jean de Perpignan, Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], French National Agency for Research on AIDS and Viral Hepatitis (ANRS). Roche, Schering-Plough, GSK, BMS, and Merck-Serono., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Service des maladies infectieuses et tropicales [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Immunologie [CHU Pitié-Salpétrière], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), AP-HP - Hôpital Antoine Béclère [Clamart], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Lissalde, Claire, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Simeprevir, Liver Cirrhosis, Male, Sofosbuvir, Sustained Virologic Response, HIV Infections, Hepacivirus, medicine.disease_cause, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, Prospective Studies, Middle Aged, virologic response, Hepatitis C, 3. Good health, Infectious Diseases, Treatment Outcome, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, Viral hepatitis, medicine.drug, Microbiology (medical), Ledipasvir, medicine.medical_specialty, Daclatasvir, [SDV.IMM] Life Sciences [q-bio]/Immunology, Hepatitis C virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, direct-acting antiviral treatment, Antiviral Agents, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Ribavirin, medicine, Humans, business.industry, cirrhosis, medicine.disease, Virology, human immunodficiency virus (HIV), Regimen, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, hepatitis C virus (HCV)
Abstract

International audience; BACKGROUND:Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce.METHODS:Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome.RESULTS:We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA

Published
2016

6. Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group

Author

Amélie Guihot, Guislaine Carcelain, Brigitte Autran, Dominique Costagliola, Caroline Solas, Olivier Rosmorduc, Sylvain Choquet, Christine Katlama, M-A Valantin, Veronique Leblond, Jean-Philippe Spano, Armelle Lavolé, Pierre-Etienne Heudel, Laurent Quero, Isabelle Poizot-Martin, Jean Gabarre, François Boué, Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de médecine interne, immunologie clinique [Béclère], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Faculté de médecine de l'Université Paris-Sud [Kremlin Bicêtre, Paris], UPMC - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'hépatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Service d'oncologie médicale (Centre Léon Bérard), Centre Léon Bérard [Lyon], Service d'Immunologie [CHU Pitié-Salpétrière], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Cytosquelette et Intégration des Signaux du Micro-Environnement Tumoral - UMR 6032 (CISMET), Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Université de la Méditerranée - Aix-Marseille 2, Pharmacocinétique Toxicocinétique - [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Service de cancérologie et radiothérapie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Lissalde, Claire

Subjects
Risk, Drug, medicine.medical_specialty, Consensus, media_common.quotation_subject, Human immunodeficiency virus (HIV), review, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Acquired immunodeficiency syndrome (AIDS), Multidisciplinary approach, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, medicine, Humans, cancer, 030212 general & internal medicine, Intensive care medicine, Expert Testimony, Sarcoma, Kaposi, media_common, Acquired Immunodeficiency Syndrome, treatment, business.industry, Incidence (epidemiology), Cancer, virus diseases, HIV, Hematology, Prognosis, medicine.disease, Hodgkin Disease, 3. Good health, Lymphoma, AIDS, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sarcoma, business
Abstract

International audience; Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti-HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals.

Published
2016

7. Burden of HIV disease and comorbidities on the chances of maintaining employment in the era of sustained combined antiretoviral therapies use.: HIV disease, comorbidityand employment

Author

Rosemary, Dray-Spira, Camille, Legeai, Mariette, Le Den, François, Boué, Caroline, Lascoux-Combe, Anne, Simon, Thierry, May, Cécile, Goujard, Laurence, Meyer, Isabelle, Suaud, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de médecine interne, immunologie clinique [Béclère], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and ANRS COPANA Cohort Study Group

Subjects
Male, Gerontology, Health Status, HIV Infections, Kaplan-Meier Estimate, Comorbidity, Cohort Studies, 0302 clinical medicine, Cost of Illness, Employment status, Immunology and Allergy, Prospective Studies, 030212 general & internal medicine, 10. No inequality, Prospective cohort study, Depression (differential diagnoses), education.field_of_study, Depression, Hazard ratio, 1. No poverty, Middle Aged, 3. Good health, Infectious Diseases, Cardiovascular Diseases, Cohort, Female, France, HIV-related discrimination, 0305 other medical science, Cohort study, Adult, Employment, Anti-HIV Agents, Immunology, Population, Socioeconomic factors, Truth Disclosure, Article, 03 medical and health sciences, Diabetes Mellitus, medicine, Humans, education, Occupational Health, Proportional Hazards Models, 030505 public health, business.industry, Proportional hazards model, medicine.disease, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract

International audience; OBJECTIVES: Employment status is a major predictor of health status and living conditions, especially among HIV-infected people, a predominantly working-aged population. We aimed to quantify the risk of work cessation following HIV diagnosis in France in 2004-2010 and to measure the respective burden of HIV-related characteristics and of associated comorbidities on this risk. DESIGN: We used data from a multicenter cohort made of a diversified sample of recently diagnosed HIV-1-infected adults, antiretroviral treatment-naive at baseline in 2004-2008 (ANRS-COPANA cohort). Detailed information on living conditions and clinical and biological characteristics were collected prospectively. METHODS: The risk of work cessation among the 376 working-aged participants employed at baseline was estimated using the Kaplan-Meier method. Characteristics associated with the risk of work cessation were identified using multivariate Cox models. RESULTS: The cumulative probability of work cessation reached 14.1% after 2 years and 34.7% after 5 years. Diabetes, hypertension and, to a lesser extent, signs of depression were associated with increased risks of work cessation after accounting for socio-occupational characteristics [adjusted hazard ratios (95% confidence interval): 5.7 (1.7-18.8), 3.1 (1.5-6.4) and 1.6 (0.9-2.9), respectively]. In contrast, HIV disease severity and treatment and experience of HIV-related discrimination were not statistically associated with the risk of work cessation. CONCLUSION: The risk of work cessation during the course of HIV disease has remained substantial in the most recent period in France. Comorbidities, but not characteristics of HIV disease itself, substantially affect chances of maintaining employment. This provides insights into strategies for limiting the burden of HIV disease for individuals and society.

Published
2012

8. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

Author

Damouche, Abderaouf, Lazure, Thierry, Avettand-Fenoël, Véronique, Huot, Nicolas, Dejucq-Rainsford, Nathalie, Satie, Anne-Pascale, Mélard, Adeline, David, Ludivine, Gommet, Céline, Ghosn, Jade, Noel, Nicolas, Pourcher, Guillaume, Martinez, Valérie, Benoist, Stéphane, Béréziat, Véronique, Cosma, Antonio, Favier, Benoît, Vaslin, Bruno, Rouzioux, Christine, Capeau, Jacqueline, Müller-Trutwin, Michaela, Dereuddre-Bosquet, Nathalie, Le Grand, Roger, Lambotte, Olivier, Bourgeois, Christine, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service d'Anatomo-Pathologie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Assistance Publique-Hopitaux de Paris, Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), HIV, Inflammation et persistance, Institut Pasteur [Paris], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Infectious Diseases Models for Innovative Therapies (IDMIT), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Médecine Interne et Immunologie clinique, Hôpital Bicêtre, Service de Chirurgie Viscérale Minimale invasive, Hôpital Antoine-Béclère AP-HP, U972, Hôpital Paul Brousse, Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie générale et digestive [CHU Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Recherche en Hémato-Immunologie (SRHI - UMR_E 05), Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Neuro-Immuno-Virologie, Service de Neurovirologie EMI E-01 (UMR E01), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by the AgenceNationale de Recherche sur le Sida et les HépatitesVirales (ANRS, France)., Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Jonchère, Laurent, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université Paris-Sud - Paris 11 ( UP11 ) -Hôpital Bicêtre-Assistance Publique-Hopitaux de Paris, Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Institute for Emerging Diseases and Innovative Therapies (iMETI) ( IDMIT Center ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Recherche en Hémato-Immunologie ( SRHI - UMR E05 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Diderot - Paris 7 ( UPD7 ), Laboratoire de Neuro-Immuno-Virologie, Service de Neurovirologie EMI E-01 ( UMR E01 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Panniculitis, QH301-705.5, [SDV]Life Sciences [q-bio], Simian Acquired Immunodeficiency Syndrome, HIV Infections, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Animals, Humans, Biology (General), Cells, Cultured, Aged, Disease Reservoirs, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [ SDV ] Life Sciences [q-bio], Macrophages, HIV, RC581-607, Middle Aged, Coculture Techniques, Immunity, Innate, [SDV] Life Sciences [q-bio], Macaca fascicularis, Adipose Tissue, Host-Pathogen Interactions, Female, Simian Immunodeficiency Virus, Immunologic diseases. Allergy, Stromal Cells, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways., Author Summary Chronic immune activation/inflammation and viral persistence in reservoirs are important features of chronic HIV infection—even in patients receiving ART. We sought to evaluate the involvement of adipose tissue in chronic HIV/SIV infections. Adipose tissue accounts for 15 to 20% of the body weight, contains both adipocytes and (within the stromal vascular fraction) immune cells, and exerts crucial metabolic and immune activities. We postulated that adipose tissue might provide an ideal environment for HIV persistence and immune inflammation. We first showed that viremic SIV-infected macaques had elevated levels of immune activation and inflammation in adipose tissue, and that both resident CD4+ T cells and macrophages were infected. In similar experiments in ART-controlled HIV-infected patients, HIV DNA was detected in the stromal vascular fraction of adipose tissue (more specifically, in adipose tissue CD4+ T cells). Replication-competent HIV was detected in ex vivo- activated, sorted adipose tissue CD4+ T cells from six aviremic, ART-treated patients. Thus, adipose tissue may constitute a viral reservoir and be involved in long-term immune activation and inflammation—even in ART-suppressed patients. Given that adipose tissue is strongly regulated by both metabolic and immune pathways, modulating adipose tissue may constitute a valuable means of limiting both viral persistence and chronic inflammation in HIV-infected patients even ART-controlled.

Published
2015

9. Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort

Author

Hleyhel , Mira, Belot , Aurélien, Bouvier , Anne-Marie, Tattevin , Pierre, Pacanowski , Jérôme, Genet , Philippe, De Castro , Nathalie, Berger , Jean-Luc, Dupont , Caroline, Lavole , Armelle, Pradier , Christian, Salmon , Dominique, Simon , Anne, Martinez , Valérie, Spano , Jean-Philippe, Costagliola , Dominique, Grabar , Sophie, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), FHDH-ANRS CO4, Cancer Research UK, London Research Institute, Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Département des maladies chroniques et traumatismes, Institut de Veille Sanitaire (INVS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service des maladies infectieuses, CHU Pontchaillou [Rennes], Fonction, structure et inactivation d'ARN bactériens, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie SIDA, Centre Hospitalier Victor Dupouy, Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et de pathologie infectieuse, Centre Hospitalier Universitaire de Reims (CHU Reims), Service de médecine interne, Hôpital Ambroise Paré [AP-HP], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de santé publique, Hôpital l'Archet, Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne, immunologie clinique [Béclère], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de biostatistique et épidémiologie, Sorbonne Universités UPMC Paris Univ 06 (Doctoral contract for M.H.), Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS), INSERM and the French Ministry of Health (FHDH-ANRS CO4), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre Hospitalier d'Argenteuil, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Reims ( CHU Reims ), Hôpital Ambroise Paré, Service de pneumologie, CHU Tenon [APHP], Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], CHU Pitié-Salpêtrière [APHP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Administateur, HAL Sorbonne Université, and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Adult, Male, Lung Neoplasms, Anti-HIV Agents, HIV Infections, [SDV.CAN]Life Sciences [q-bio]/Cancer, survival, general population, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antiretroviral Therapy, Highly Active, Neoplasms, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Humans, cancer, Mortality, Sarcoma, Kaposi, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Lymphoma, Non-Hodgkin, Liver Neoplasms, HIV, Middle Aged, Anus Neoplasms, Hodgkin Disease, Survival Analysis, Female, France, calendar period, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan–Meier survival rates were estimated for four periods: 1992–1996, 1997–2000, 2001–2004 and 2005–2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001–2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992–1996) and early-cART (1997–2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005–2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001–2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future.

Published
2015

10. Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: A French multicenter study

Author

Adrien Lorleac'h, J.M. Brisseau, Olivier Decaux, Eric Hachulla, Fabrice Bonnet, Jacques Serratrice, Guillaume Moulis, Robin Dhote, Pierre-Jean Weiller, Pierre Pottier, Fabienne Closs-Prophette, Jean-Dominique de Korwin, Jean-Marie Berthelot, Renato Fior, Bernard Grosbois, Benoit Henry, Antoine Néel, Achille Aouba, Bérangère Cador, Thomas Dejoie, Amar Smail, Xavier Puéchal, F. Perrin, Agathe Masseau, Arnaud Hot, Claire Bernier, Xavier Kyndt, Sébastien Barbarot, Mohamed Hamidou, H. Jardel, Jacques Ninet, Pierre-Yves Hatron, Leonardo Astudillo, David Launay, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine interne et néphrologie, CH Valenciennes, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne, Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de rhumatologie [Nantes], Service de médecine polyvalente et de médecine interne [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne et Médecine Générale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Avicenne, Service de médecine interne, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Faculté de Médecine Henri Warembourg - Université de Lille, CH Bretagne Atlantique, Service de Médecine Interne et Maladies Infectieuses, CH Bretagne Sud, Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, AN received a grant from Groupama Loire Bretagne--Fondation Groupama pour la Santé., Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de médecine interne, hôpital Purpan, CHU Toulouse [Toulouse], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Faculté de Médecine, PRES Université Lille Nord de France, Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service de Médecine Interne [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine Polyvalente, CH du Mans, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Laboratoire d'Immunologie ( EA 2686 ), and CHU Amiens-Picardie-Hôpital Sud

Subjects
Male, medicine.medical_specialty, Autoinflammatory disease, IL-1 receptor antagonist, Urticaria, Anemia, [SDV]Life Sciences [q-bio], Immunology, Schnitzler's syndrome, Neutropenia, AA amyloidosis, Gammopathy, Internal medicine, medicine, Humans, Immunology and Allergy, Schnitzler Syndrome, Retrospective Studies, Anakinra, [ SDV ] Life Sciences [q-bio], business.industry, Remission Induction, Macroglobulinemia, medicine.disease, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Interleukin 1 Receptor Antagonist Protein, Schnitzler syndrome, Joint pain, Quality of Life, Female, medicine.symptom, business, medicine.drug
Abstract

Conflicts of interest: DL received a grant from Sobi (< 10,000 USD). EH received lecture fees from Sobi (< 10,000 USD). The other authors have no conflict of interest to disclose. Ethics approval: According to French legislation regarding retrospective observational studies using anonymous data, Ethics Committee approval was not required, which was confirmed by the chair of our Institutional Ethics Committee. The study was performed in accordance with the Declaration of Helsinki's guidelines for research in humans.; International audience; The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.

Published
2014

11. High eomesodermin expression among CD57+ CD8+ T cells identifies a CD8+ T cell subset associated with viral control during chronic human immunodeficiency virus infection

Author

Simonetta, Federico, Hua, Stéphane, Lecuroux, Camille, Gérard, Sandie, Boufassa, Faroudy, Saez-Cirion, Asier, Pancino, Gianfranco, Goujard, Cécile, Lambotte, Olivier, Venet, Alain, Bourgeois, Christine, Guibert, Marie-Genevieve, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the Agence Nationale de la recherche contre le SIDA et les hépatites virales (ANRS) and Fondation de France. Federico Simonetta was also supported by the Fondation pour la recherche médicale (FRM)., Hôpital Universitaire de Genève, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut Pasteur [Paris]

Subjects
ddc:616, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cellular Response to Infection, HIV Infections, CD8-Positive T-Lymphocytes, Middle Aged, HIV Infections/immunology/virology, CD57 Antigens, T-Box Domain Proteins/metabolism, CD8-Positive T-Lymphocytes/virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Antigens, T-Box Domain Proteins, CD57, Antigens, CD57/immunology
Abstract

International audience; During HIV infection, increased CD57 expression among CD8(+) T cells has been associated with immune senescence and defective immune responses. Interestingly, CD57-expressing CD8(+) T cells exhibit a dual profile, being simultaneously highly cytotoxic (terminally differentiated effectors) and poorly proliferative (replicative senescent). Recent publications point toward a positive role of CD57-expressing CD8(+) T cell subsets, presumably due to their high cytolytic activity. We further investigated the phenotype of CD57-expressing CD8(+) T cells in healthy donors and during HIV infection combining CD57 expression to Eomesodermin (EOMES), a T box transcription factor which determines, coordinately with T-bet, effector and memory CD8(+) T cell differentiation. We defined in healthy donors two functionally distinct CD57-expressing CD8(+) T cell subsets exhibiting different levels of EOMES expression: EOMES(hi) CD57(+) and EOMES(int) CD57(+) CD8(+) T cells. EOMES(hi) CD57(+) cells exhibited low cytotoxic activity but preserved proliferative capacity and interleukin 7 (IL-7) receptor expression, whereas EOMES(int) CD57(+) cells exhibited obvious cytotoxic functions and a more terminally differentiated phenotype. We next performed a similar analysis in different contexts of HIV infection: primary infected patients, long-term viremic patients, aviremic patients treated with antiretroviral therapy, and HIV controllers; we demonstrated a higher percentage of CD57-expressing cells in all HIV-infected patients regardless of virological status. When heterogeneity in EOMES expression among CD57 cells was taken into account, we detected significantly higher proportions of EOMES(hi) CD57(+) cells among HIV-specific and nonspecific CD8(+) T cells from HIV controllers than in aviremic antiretroviral-treated patients and viremic patients. Importantly, such a peculiar non-terminally differentiated EOMES(hi) CD57(+) phenotypic profile was associated with viral control. Importance: This study demonstrates that functional heterogeneity exists among CD57-expressing CD8 T cells, which include both terminally differentiated, highly cytotoxic EOMES(int) CD57(+) CD8(+) T cells and less differentiated EOMES(hi) CD57(+) CD8 T cells, which do not exhibit immediate cytotoxic functions but present high proliferative capacity. Interestingly, HIV controllers present a high proportion of EOMES(hi) CD57 cells among CD57-expressing HIV-specific CD8 T cells compared to both long-term viremic and aviremic antiretroviral therapy (ART)-treated patients, suggesting a beneficial role for this cell subset in viral control.

Published
2014

12. Burden of HIV disease and comorbidities on the chances of maintaining employment in the era of sustained combined antiretoviral therapies use

Author

Dray-Spira, Rosemary, Legeai, Camille, Le Den, Mariette, Boué, François, Lascoux-Combe, Caroline, Simon, Anne, May, Thierry, Goujard, Cécile, Meyer, Laurence, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de médecine interne, immunologie clinique [Béclère], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and ANRS COPANA Cohort Study Group

Subjects
Employment status, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Comorbidity, France, Socioeconomic factors, HIV-related discrimination
Abstract

International audience; OBJECTIVES: Employment status is a major predictor of health status and living conditions, especially among HIV-infected people, a predominantly working-aged population. We aimed to quantify the risk of work cessation following HIV diagnosis in France in 2004-2010 and to measure the respective burden of HIV-related characteristics and of associated comorbidities on this risk. DESIGN: We used data from a multicenter cohort made of a diversified sample of recently diagnosed HIV-1-infected adults, antiretroviral treatment-naive at baseline in 2004-2008 (ANRS-COPANA cohort). Detailed information on living conditions and clinical and biological characteristics were collected prospectively. METHODS: The risk of work cessation among the 376 working-aged participants employed at baseline was estimated using the Kaplan-Meier method. Characteristics associated with the risk of work cessation were identified using multivariate Cox models. RESULTS: The cumulative probability of work cessation reached 14.1% after 2 years and 34.7% after 5 years. Diabetes, hypertension and, to a lesser extent, signs of depression were associated with increased risks of work cessation after accounting for socio-occupational characteristics [adjusted hazard ratios (95% confidence interval): 5.7 (1.7-18.8), 3.1 (1.5-6.4) and 1.6 (0.9-2.9), respectively]. In contrast, HIV disease severity and treatment and experience of HIV-related discrimination were not statistically associated with the risk of work cessation. CONCLUSION: The risk of work cessation during the course of HIV disease has remained substantial in the most recent period in France. Comorbidities, but not characteristics of HIV disease itself, substantially affect chances of maintaining employment. This provides insights into strategies for limiting the burden of HIV disease for individuals and society.

Published
2012

13. Burden of HIV disease and comorbidities on the chances of maintaining employment in the era of sustained combined antiretoviral therapies use

Author

Dray-Spira, Rosemary, Legeai, Camille, Le Den, Mariette, Boué, François, Lascoux-Combe, Caroline, Simon, Anne, May, Thierry, Goujard, Cécile, Meyer, Laurence, Schmaus, Annie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and ANRS COPANA Cohort Study Group

Subjects
Employment status, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Comorbidity, France, Socioeconomic factors, HIV-related discrimination
Abstract

International audience; OBJECTIVES: Employment status is a major predictor of health status and living conditions, especially among HIV-infected people, a predominantly working-aged population. We aimed to quantify the risk of work cessation following HIV diagnosis in France in 2004-2010 and to measure the respective burden of HIV-related characteristics and of associated comorbidities on this risk. DESIGN: We used data from a multicenter cohort made of a diversified sample of recently diagnosed HIV-1-infected adults, antiretroviral treatment-naive at baseline in 2004-2008 (ANRS-COPANA cohort). Detailed information on living conditions and clinical and biological characteristics were collected prospectively. METHODS: The risk of work cessation among the 376 working-aged participants employed at baseline was estimated using the Kaplan-Meier method. Characteristics associated with the risk of work cessation were identified using multivariate Cox models. RESULTS: The cumulative probability of work cessation reached 14.1% after 2 years and 34.7% after 5 years. Diabetes, hypertension and, to a lesser extent, signs of depression were associated with increased risks of work cessation after accounting for socio-occupational characteristics [adjusted hazard ratios (95% confidence interval): 5.7 (1.7-18.8), 3.1 (1.5-6.4) and 1.6 (0.9-2.9), respectively]. In contrast, HIV disease severity and treatment and experience of HIV-related discrimination were not statistically associated with the risk of work cessation. CONCLUSION: The risk of work cessation during the course of HIV disease has remained substantial in the most recent period in France. Comorbidities, but not characteristics of HIV disease itself, substantially affect chances of maintaining employment. This provides insights into strategies for limiting the burden of HIV disease for individuals and society.

Published
2012

14. Simplified Assessment of Antiretroviral Adherence and Prediction of Virological Efficacy in HIV-Infected Patients in Cambodia

Author

Anne Marie Taburet, Vara Ouk, Yoann Madec, Arnaud Fontanet, Olivier Segeral, Clotilde Le Tiec, Boroath Ban, Cécile Goujard, Chan Roeurn Hak, Eric Nerrienet, Jean François Delfraissy, Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Calmette Hospital [Phnom Penh], Service de pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Service de médecine interne, immunologie clinique [Béclère], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Multivariate analysis, Article Subject, Visual analogue scale, Dermatology, 03 medical and health sciences, Zidovudine, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Immunology and Allergy, Hiv infected patients, 030212 general & internal medicine, 0303 health sciences, 030306 microbiology, business.industry, Stavudine, Public Health, Environmental and Occupational Health, Drug assay, 3. Good health, Regimen, Infectious Diseases, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:RC581-607, business, Viral load, Research Article, medicine.drug
Abstract

Background. Adherence to antiviral therapy is important for HIV-infected people living in low- and middle-income countries, because of poor access to alternative regimens.Methods. We conducted a cross-sectional survey of adherence in Cambodian patients enrolled in the ESTHER program and treated with WHO first-line regimen for at least 6 months. The survey was based on a self-report questionnaire, drug assay, MCV measurement, visual analog scale, and viral load HIV RNA.Results. Two hundred fifty-nine patients treated for a median of 16 months participated in the survey. At inclusion in the program, 158 patients (61%) were ARV-naïve. The virological success rate was 71% overall and 81% in previously ARV-naive patients. Considered individually, the measures suggested perfect adherence in 71% to 93% of patients. In multivariate analysis adjusted for sex and therapeutic status before HAART initiation, only the biological markers were associated with virological efficacy. Self-funded treatment before entry to the program was highly predictive of virological failure.Conclusion. Adherence was excellent in these Cambodian patients. Biological markers were predictive of virological efficacy. MCV might thus serve as a simple alternative for assessing adherence and predicting virological efficacy among patients receiving AZT- or d4T-based regimens.

Published
2010

15. Lymphatic Vascularisation and Involvement of Lyve-1+ Macrophages in the Human Onchocerca Nodule

Author

Valérie Martinez, Achim Hoerauf, Odile Bain, Samuel Wanji, Ohene Adjei, Alexander Yaw Debrah, Gaelle Denece, Sabine Mand, Sabine Specht, Tarik Attout, Yeboah Marfo-Debrekyei, Michel Boussinesq, Coralie Martin, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), University Hospital Bonn, Antenne ORSTOM auprès du Centre Pasteur, ORSTOM, University of Buéa, Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Laboratory Animal Science, Vetsuisse Faculty, Universität Zürich [Zürich] = University of Zurich (UZH), Centre National de la Recherche Scientifique (CNRS), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Sorbonne Universités, and Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pathology, medicine.medical_specialty, Endothelium, Angiogenesis, government.form_of_government, 030231 tropical medicine, Vesicular Transport Proteins, lcsh:Medicine, Pathology/Immunology, Onchocerciasis, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Immunology/Immunity to Infections, parasitic diseases, medicine, Animals, Humans, Onchocerca, lcsh:Science, Microfilariae, Infectious Diseases/Helminth Infections, ComputingMilieux_MISCELLANEOUS, Lymphatic Vessels, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Macrophages, lcsh:R, Nodule (medicine), Dermis, biology.organism_classification, Onchocerca volvulus, 3. Good health, Lymphangiogenesis, Lymphatic Endothelium, Lymphatic system, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunology, government, Angiogenesis Inducing Agents, Female, lcsh:Q, Endothelium, Lymphatic, medicine.symptom, Research Article
Abstract

Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e. g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses.

Published
2009

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