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1. Existing Data Sources in Clinical Epidemiology:The Danish COVID-19 Cohort

Author

Pottegård, Anton, Kristensen, Kasper Bruun, Reilev, Mette, Lund, Lars Christian, Ernst, Martin Thomsen, Hallas, Jesper, Thomsen, Reimar Wernich, Christiansen, Christian Fynbo, Sørensen, Henrik Toft, Johansen, Nanna Borup, Støvring, Henrik, Christensen, Steffen, Kragh Thomsen, Marianne, Husby, Anders, Voldstedlund, Marianne, Kjær, Jesper, and Brun, Nikolai C

Subjects
Epidemiology, SARS-CoV-2, Follow-up, prospective cohort, Prognosis, Database, follow-up, epidemiology, Clinical Epidemiology, prognosis, HEALTH, Covid-19, database, SYSTEM, Original Research
Abstract

Anton Pottegård,1 Kasper Bruun Kristensen,1 Mette Reilev,1 Lars Christian Lund,1 Martin Thomsen Ernst,1 Jesper Hallas,1,2 Reimar Wernich Thomsen,3 Christian Fynbo Christiansen,3 Henrik Toft Sørensen,3,4 Nanna Borup Johansen,5 Henrik Støvring,1,6 Steffen Christensen,7 Marianne Kragh Thomsen,8 Anders Husby,9 Marianne Voldstedlund,10 Jesper Kjær,11 Nikolai C Brun5 1Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark; 2Department of Clinical Biochemistry and Clinical Pharmacology, Odense University Hospital, Odense, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; 5Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen, Denmark; 6Department of Public Health – Biostatistics, Aarhus University, Aarhus, Denmark; 7Department of Anesthesia and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark; 8Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark; 9Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; 10Infection Preparedness, Statens Serum Institut, Copenhagen, Denmark; 11Data Analytics Center, Danish Medicines Agency, Copenhagen, DenmarkCorrespondence: Anton PottegårdClinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, JB Winsløws Vej 19, 2, Odense DK-5000, DenmarkTel +45 28913340Email apottegaard@health.sdu.dkBackground: To facilitate research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a prospective cohort of all Danish residents tested for SARS-CoV-2 in Denmark is established.Data Structure: All Danish residents tested by reverse transcriptase polymerase chain reactions (RT-PCR) for SARS-CoV-2 in Denmark are included. The cohort is identified using the Danish Microbiology Database. Individual-level record linkage between administrative and health-care registries is facilitated by the Danish Civil Registration System. Information on outcomes related to SARS-CoV-2 infection includes hospital admission, intensive care unit admission, mechanical ventilation, and death and is retrieved from the five administrative Danish regions, the Danish National Patient Registry, and the Danish Register of Causes of Death. The Patient Registry further provides a complete hospital contact history of somatic and psychiatric conditions and procedures. Data on all prescriptions filled at community pharmacies are available from the Danish National Prescription Registry. Health-care authorization status is obtained from the Danish Register of Healthcare Professionals. Finally, selected laboratory values are obtained from the Register of Laboratory Results for Research. The cohort is governed by a steering committee with representatives from the Danish Medicines Agency, Statens Serum Institut, the Danish Health Authority, the Danish Health Data Authority, Danish Patients, the Faculties of Health Sciences at the Danish universities, and Danish regions. The steering committee welcomes suggestions for research studies and collaborations. Research proposals will be prioritized based on timeliness and potential clinical and public health implications. All research protocols assessing specific hypotheses for medicines will be made publicly available using the European Union electronic Register of Post-Authorisation Studies.Conclusion: The Danish COVID-19 cohort includes all Danish residents with an RT-PCR test for SARS-CoV-2. Through individual-level linkage with existing Danish health and administrative registries, this is a valuable data source for epidemiological research on SARS-CoV-2.Keywords: Covid-19, SARS-CoV-2, epidemiology, follow-up, database, prognosis, prospective cohort

Published
2020

2. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

Author

Judd, A, Lodwick, R, Noguera‐Julian, A, Gibb, DM, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi‐Lepri, A, García, F, Brockmeyer, NH, Warszawski, J, Gonzalez‐Tome, MI, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, MA, Chene, G, Phillips, A, Mary Krause, Murielle, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Amo, Julia Del, Thorne, Claire, Kirk, Ole, Pérez‐Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Rojo, Pablo, Soriano‐Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Teira, Ramon, Garrido, Myriam, Haerry, David, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Frederiksen, Casper M., Friis‐Møller, Nina, Kjaer, Jesper, Salbøl Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Davies, Mary‐Anne, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, van der Valk, Marc, Wyss, Natasha, The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, AII - Infectious diseases, APH - Aging & Later Life, Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, APH - Global Health, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord., [Judd,A, Gibb,DM] MRC Clinical Trials Unit, University College London, London, UK. [ Lodwick,R, Sabin,C, Mocroft,A, Cozzi-Lepri,A, Phillips,A] Department of Infection and Population Health, University College London, London, UK. [Noguera-Julian,A] Institut de Recerca Pedi atrica Hospital Sant Joan de Deu, Barcelona, Spain. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiologıa y Salud Publica Ciberesp, Barcelona, Spain. [Butler,K] Department of Infectious Diseases and Immunology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland. [Costagliola,D] INSERM, UPMC Univ Paris 06, Institut Pierre Louis d’epidemiologie et de Sante Publique (IPLESP UMRS 1136), Sorbonne Universites, Paris, France. [van Sighem,A] Stichting HIV Monitoring, Amsterdam, The Netherlands. [Ledergerber,B] Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland. [Torti,C] Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy. [Podzamczer,D[ HUV and STD Unit, Infectious Diseases Service, Hospital Universitari de Bellvitge. L’Hospitalet, Barcelona, Spain. [Dorrucci,M] Istituto Superiore di Sanit a, Rome, Italy. [De Wit,S] Departement of Infectious Diseases, Centre Hospitalier Saint-Pierre, Universite Libre de Bruxelles, Brussels, Belgium. [Obel,N] Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. [Dabis,F, Chene,D] NSERM U1219 – Centre Inserm Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. ISPED, Centre INSERM U1219-Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. [Garcia,F] Clinical Microbiology Department, Complejo Hospitalario Universitario Granada, Instituto de Investigacion Biosanitaria ibs.Granada, Granada, Spain. [Brockmeyer,NH] Department of Dermatology, Venerology and Allergology, Center for Sexual Health and Medicine, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany. [Warszawski,J] INSERM CESP U1018, AP-HP Public Health Department, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre Paris, France. [Gonzalez-Tome,MI] HIV and Paeds Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain. [Mussini,C] Infectious Diseases Clinics, University Hospital, Modena, Italy. [Touloumi,G] Department Hygiene, Epidemiology & Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece. [Zangerle,R] Medical University Innsbruck, Innsbruck, Austria. [Ghosn,J] EA 7327, Faculté de Médecine site Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France. [Castagna,A] San Raffaele Scientific Institute, Vita-SaLute University, Milan, Italy. [Fätkenheuer,G] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. [Stephan,C] Second Medical Department, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany. [Meyer,L] NSERM CESP U1018, Université Paris-Sud, Université Paris-Saclay, Paris, France. AP-HP Public Health Department, Le Kremlin-Bicêtre, Paris, France. [Campbell,MA] Centre for Health and Infectious Disease Research, University of Copenhagen, Copenhagen, Denmark. [Chene,G]. CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux, France., Financial disclosure: The PLATO II project is funded by the UK Medical Research Council (award G0700832). The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS), France, the HIV Monitoring Foundation, The Netherlands, and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. The group has also received project-specific funding from the UK Medical Research Council and the Swiss Bridge Foundation., Judd, A, Lodwick, R, Noguera-Julian, A, Gibb, D, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi-Lepri, A, García, F, Brockmeyer, N, Warszawski, J, Gonzalez-Tome, M, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, M, Chene, G, Phillips, A, Puoti, M, Goethe-Universität Frankfurt am Main, Sexualité et soins (Genre, Sexualité, Santé) (CESP - INSERM U1018 - Equipe 7), 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-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 Copenhagen = Københavns Universitet (UCPH), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, University College of London [London] (UCL), Universitat Autònoma de Barcelona (UAB), Hospital Sant Joan de Déu [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), Our Lady's Children's Hospital Crumlin (OLCHC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University hospital of Zurich [Zurich], Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Istituto Superiore di Sanita [Rome], Université libre de Bruxelles (ULB), Copenhagen University Hospital, Universidad de Granada = University of Granada (UGR), Ruhr-Universität Bochum [Bochum], Hospital Universitario 12 de Octubre [Madrid], Azienda Ospedaleria Universitaria di Modena, National and Kapodistrian University of Athens (NKUA), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University Hospital of Cologne [Cologne], HAL-SU, Gestionnaire, and The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord

Subjects
Male, HIV Infections, Pharmacologie, Santé publique, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Sexual Behavior::Sexuality::Heterosexuality [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pharmacology (medical), Inhibidores de proteasas, Young adult, Europe, perinatal HIV infection, virological failure, young people, Adolescent, Adult, Anti-Retroviral Agents, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Time Factors, Treatment Failure, Young Adult, Drug Resistance, Viral, Population Groups, Pathologie maladies infectieuses, ComputingMilieux_MISCELLANEOUS, Adolescente, ADN polimerasa dirigida por ADN, Original Research, Health Policy, Enfermedades transmisibles, 3. Good health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], G0700832, Young people, Viral load, Human, Factores de riesgo, medicine.medical_specialty, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], 03 medical and health sciences, Virological failure, Recién nacido, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings], Heterosexualidad, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Infection::Communicable Diseases [Medical Subject Headings], Perinatal HIV infection, RCUK, medicine.disease, Infecciones por VIH, Persons::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Observational study, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], 0301 basic medicine, Pediatrics, Science et gestion hospitalières, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Anti-Retroviral Agents/therapeutic use, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Interquartile range, Epidemiology, HIV Infection, 030212 general & internal medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adulto, MRC, Infectious Diseases, Niño, Europa, VIH-1, Population Group, Time Factor, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Acquired immunodeficiency syndrome (AIDS), medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections::Acquired Immunodeficiency Syndrome [Medical Subject Headings], Persons::Persons::Age Groups::Child [Medical Subject Headings], ddc:610, Intervalos de confianza, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Inhibidores de la transcriptasa inversa, Confidence interval, Carga viral, Fármacos anti-VIH, Anti-Retroviral Agent, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objectives: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. Methods: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. Results: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. Conclusions: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development., 0, SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published

Published
2017

3. Open-Scholarship-Strategy/indexed: Foundations for Open Scholarship Strategy Development: Second formal release

Author

Tennant, Jonathan, Dugan, Jonathan, Harding, Rachel, Ross-Hellauer, Tony, Khanal, Kshitiz, Pasquier, Thomas, Bosman, Jeroen, Enkhbayar, Asura, Clement, Gail, Eccles, David, Bradley, Fiona, Brembs, Bjoern, Szczesny, Pawel, Matthias, Lisa, Kjaer, Jesper Norgaard, Katz, Daniel S., Crick, Tom, Madan, Christopher R., Macklin, Paul, Havemann, Johanna, Beamer, Jennifer E., Schulte-Mecklenbeck, Michael, Sholler, Dan, Masuzzo, Paola, Steiner, Tobias, Koder, Tim, Nichols, David, Graziotin, Daniel, Dunning, Alastair, Turner, Andy, and Chung, Neo Christopher

Subjects
Open Scholarship, strategy
Abstract

For preprint version, please see: https://doi.org/10.31222/osf.io/b4v8p This version contains all indexed files in all formats as part of the second release for the Strategy. All content is openly licensed for re-use, including the website.

Published
2019
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5. Immunological and virological response to antiretroviral treatment in migrant and native men and women in Western Europe; is benefit equal for all?

Author

Monge, S., Mocroft, A., Sabin, A., Touloumi, G., Sighem, A., Abgrall, S., Dray-Spira, R., Spire, B., Castagna, A., Mussini, C., Zangerle, R., Hessamfar, M., Anderson, J., Hamouda, O., Ehren, K., Obel, N., Kirk, O., Antinori, A., Girardi, E., Saracino, A., Calmy, A., Wit, S., Wittkop, L., Bucher, C., Montoliu, A., Raben, D., Prins, M., Meyer, L., Chene, G., Burns, F., Amo, J., Judd, Ali, Zangerle, Robert, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Amo, Julia, Obel, Niels, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miró, Josem, Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Sabin, Caroline, Teira, Ramon, Garrido, Myriam, Haerry, David, Wit, Stéphane, Miró, M., Costagliola, Dominique, d'Arminio-Monforte, Antonella, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Miró, Jose, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Valk, Marc, Migrant Health Working Group for the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in, Eurocoord, Castagna, Antonella, AII - Infectious diseases, APH - Global Health, Infectious diseases, APH - Aging & Later Life, Global Health, Monge, S, Mocroft, A, Sabin, A, Touloumi, G, Sighem, A, Abgrall, S, Dray-Spira, R, Spire, B, Castagna, A, Mussini, C, Zangerle, R, Hessamfar, M, Anderson, J, Hamouda, O, Ehren, K, Obel, N, Kirk, O, Antinori, A, Girardi, E, Saracino, A, Calmy, A, Wit, S, Wittkop, L, Bucher, C, Montoliu, A, Raben, D, Prins, M, Meyer, L, Chene, G, Burns, F, Amo, J, Judd, A, Warszawski, J, Dabis, F, Krause, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Bucher, H, Gibb, D, Fatkenheuer, G, Thorne, C, Stephan, C, Perez-Hoyos, S, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Miro, J, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Miro, M, Costagliola, D, d'Arminio-Monforte, A, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, and Valk, M

Subjects
Male, 0301 basic medicine, Latin Americans, HIV Infections, migrants, Anti-Retroviral Agents/therapeutic use, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Epidemiology, Pharmacology (medical), 030212 general & internal medicine, Immunovirological response, Young adult, ddc:616, Transients and Migrants, Health Policy, virus diseases, Middle Aged, Viral Load, 3. Good health, Europe, combination antiretroviral therapy, HIV, immunovirological response, sex, Infectious Diseases, Treatment Outcome, Anti-Retroviral Agents, RNA, Viral, Female, Sex, Viral load, Cohort study, Adult, Cart, Combination antiretroviral therapy, medicine.medical_specialty, Adolescent, HIV Infections/drug therapy, Young Adult, 03 medical and health sciences, Population Groups, medicine, Humans, RNA, Viral/blood, Aged, business.industry, Migrant, 030112 virology, Confidence interval, CD4 Lymphocyte Count, migrant, Institutional repository, Immunology, business, Demography
Abstract

Objectives: The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy (cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004-2013. Methods: Migrants were defined as those with geographical origin (GO) different from the reporting country and were grouped as originating from Western Europe and Western Countries (WEWC), Eastern Europe (EE), North Africa and the Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), Caribbean (CRB) and Asia/Oceania (ASIA/OCE). Native (NAT) individuals were defined as those originating from the reporting country. CD4 cell counts were modelled using piecewise linear mixed-effects models with two slopes, whereas models to estimate subdistribution hazard ratios (sHRs) were used for time to virological response (VR) (i.e. time from cART initiation to the first of two successive HIV RNA measurements < 400 HIV-1 RNA copies/ml). Results: Of 32 817 individuals, 25 799 (78.6%) were men. The percentage of migrants was higher in women (48.9%) than in men (21.2%) and migrants from SSA accounted for the largest migrant group (29.9% in men and 63.3% in women). Migrant men and women from SSA started at lower CD4 cell counts than NAT individuals, which remained lower over time. VR was ≥ 85% at 12 months for all groups except CRB women (77.7%). Compared with NAT men and women, lower VR was experienced by NAME [sHR 0.91; 95% confidence interval (CI) 0.86-0.97] and SSA (sHR 0.88; 95% CI 0.82-0.95) men and CRB (sHR 0.77; 85% CI 0.67-0.89) women, respectively. Conclusions: Immunovirological response to cART in Western Europe varies by GO and sex of patients. ART benefits are not equal for all, underlining the point that efforts need to prioritize those most in need.

Published
2018

6. The Incidence of AIDS-Defining Illnesses at a Current CD4 Count ≥200 Cells/µL in the Post-Combination Antiretroviral Therapy Era

Author

Mocroft, A., Furrer, H. J., Miro, J. M., Reiss, P., Mussini, C., Kirk, O., Abgrall, S., Ayayi, S., Bartmeyer, B., Braun, D., Castagna, A., d'Arminio Monforte, A., Gazzard, B., Gutierrez, F., Hurtado, I., Jansen, K., Meyer, L., Muñoz, P., Obel, N., Soler-Palacin, P., Papadopoulos, A., Raffi, F., Ramos, J. T., Rockstroh, J. K., Salmon, D., Torti, C., Warszawski, J., de Wit, S., Zangerle, R., Fabre-Colin, C., Kjaer, J., Chene, G., Grarup, J., Lundgren, J. D., Mocroft, Amanda, Furrer, Hansjakob, Miro, Jose M., Reiss, Peter, Mussini, Cristina, Kirk, Ole, Abgrall, Sophie, Ayayi, Sylvie, Bartmeyer, Barbara, Braun, Dominique, Castagna, Antonella, d'Arminio Monforte, Antonella, Gazzard, Brian, Gutierrez, Félix, Hurtado, Isabel, Jansen, Klaus, Meyer, Laurence, Muñoz, Pepa, Obel, Niels, Soler-Palacin, Pere, Papadopoulos, Antonios, Raffi, François, Ramos, Jose T., Rockstroh, Jürgen, Salmon, Dominique, Torti, Carlo, Warszawski, Josianne, de Wit, Stephane, Zangerle, Robert, Fabre-Colin, Céline, Kjaer, Jesper, Chene, Genevieve, Grarup, Jesper, Lundgren, Jens D., Lundgren, Jens, Miiro, Jose, Palacin, Pere Soler, Torti, Carolo, Warszawski, Josiane, Rockstroh, Jurgen, Ramos, José, Miró, Jose M., Munoz, Pepa, Judd, Ali, Haerry, David, Weller, Ian, Casabona, Jordi, Costagliola, Dominique, d'Arminio-Monforte, Antonella, Battegay, Manuel, Prins, Maria, de Wolf, Frank, Colin, Céline, Schwimmer, Christine, Touzeau, Guillaume, Campbell, Maria, Bohlius, Julia, Bouteloup, Vincent, Bucher, Heiner, Cozzi-Lepri, Alessandro, Dabis, François, Dorrucci, Maria, Egger, Matthias, Engsig, Frederik, Lambotte, Olivier, Lewden, Charlotte, Lodwick, Rebecca, Matheron, Sophie, Miro, Jose, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Reekie, Joanne, Sabin, Caroline, Scherrer, Alexandra, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Thorne, Claire, von Wyl, Viktor, Wittkop, Linda, and Young, Jim

Abstract

The incidence of AIDS was higher in patients with a current CD4 count of 500-749 cells/µL compared to 750-999 cells/µL, but did not decrease further at higher CD4 levels. Results were similar in those virologically suppressed on combination antiretroviral therapy, suggesting immune reconstitution is incomplete until CD4 >750/µL

Published
2017

7. Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Author

Engsig, Frederik N., Zangerle, Robert, Katsarou, Olga, Dabis, Francois, Reiss, Peter, Gill, John, Porter, Kholoud, Sabin, Caroline, Riordan, Andrew, Fätkenheuer, Gerd, Gutiérrez, Félix, Raffi, Francois, Kirk, Ole, Mary-Krause, Murielle, Stephan, Christoph, de Olalla, Patricia Garcia, Guest, Jodie, Samji, Hasina, Castagna, Antonella, d'Arminio Monforte, Antonella, Skaletz-Rorowski, Adriane, Ramos, Jose, Lapadula, Giuseppe, Mussini, Cristina, Force, Lluís, Meyer, Laurence, Lampe, Fiona, Boufassa, Faroudy, Bucher, Heiner C., De Wit, Stéphane, Burkholder, Greer A., Teira, Ramon, Justice, Amy C., Sterling, Tim R., M. Crane, Heidi, Gerstoft, Jan, Grarup, Jesper, May, Margaret, Chêne, Geneviève, Ingle, Suzanne M., Sterne, Jonathan, Obel, Niels, Burkholder, Greer, Justice, Amy, R Sterling, Tim, Crane, Heidi M., Boulle, Andrew, Brodt, Hans-Reinhard, Casabona, Jordi, Cavassini, Matthias, Costagliola, Dominique, Dabis, François, D'Arminio Monforte, Antonella, del Amo, Julia, Van Sighem, Ard, Hans-Ulrich Haerry, David, Hogg, Robert, Mocroft, Amanda, Kitahata, Mari, Saag, Michael, Williams, Matthew, Ingle, Suzanne, Touloumi, Giota, Warszawski, Josiane, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wit, Ferdinand, Prins, Maria, Gibb, Diana, Del Amo, Julia, Thorne, Claire, Pérez-Hoyos, Santiago, Hamouda, Osamah, Gussenheimer-Bartmeyer, Barbara, Noguera-Julian, Antoni, Antinori, Andrea, Brockmeyer, Norbert, Ramos, José, Battegay, Manuel, Rauch, Andri, Tookey, Pat, Miró, Jose M., de Wit, Stephane, Goetghebuer, Tessa, Torti, Carlo, Garrido, Myriam, Judd, Ali, Conejo, Pablo Rojo, Haerry, David, Weller, Ian, d'Arminio-Monforte, Antonella, Colin, Céline, Schwimmer, Christine, Termote, Monique, Kjaer, Jesper, Campbell, Maria, Raben, Dorthe, Bohlius, Julia, Bouteloup, Vincent, Bucher, Heiner, Cozzi-Lepri, Alessandro, Dorrucci, Maria, Egger, Matthias, Engsig, Frederik, Furrer, Hansjakob, Lambotte, Olivier, Lewden, Charlotte, Lodi, Sara, Lodwick, Rebbeca, Matheron, Sophie, Miro, Jose, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Reekie, Joanne, Scherrer, Alexandra, Smit, Colette, Thiebaut, Rodolphe, and Wittkop, Linda

Abstract

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of death

Published
2017

8. A multi-disciplinary perspective on emergent and future innovations in peer review [version 1; referees: 2 approved with reservations]

Author

Tennant, Jonathan P., Dugan, Jonathan M., Graziotin, Daniel, Jacques, Damien C., Waldner, François, Mietchen, Daniel, Elkhatib, Yehia, Collister, Lauren B., Pikas, Christina K., Crick, Tom, Masuzzo, Paola, Caravaggi, Anthony, Berg, Devin R., Niemeyer, Kyle E., Ross-Hellauer, Tony, Mannheimer, Sara, Rigling, Lillian, Katz, Daniel S., Tzovaras, Bastian Greshake, Pacheco-Mendoza, Josmel, Fatima, Nazeefa, Poblet, Marta, Isaakidis, Marios, Irawan, Dasapta Erwin, Renaut, Sébastien, Madan, Christopher R., Matthias, Lisa, Kjær, Jesper Nørgaard, O'Donnell, Daniel Paul, Neylon, Cameron, Kearns, Sarah, Selvaraju, Manojkumar, and Colomb, Julien

Subjects
ddc:570
Abstract

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of Web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform current models while avoiding as many of the biases of existing systems as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that, at least partially, resolves many of the technical and social issues associated with peer review, and can potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments.

Published
2017

10. Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study

Author

Wang, Qing, De Luca, Andrea, Smith, Colette, Zangerle, Robert, Sambatakou, Helen, Bonnet, Fabrice, Smit, Colette, Schommers, Philipp, Thornton, Alicia, Berenguer, Juan, Peters, Lars, Spagnuolo, Vincenzo, Ammassari, Adriana, Antinori, Andrea, Roldan, Eugenia Quiros, Mussini, Cristina, Miro, Jose M., Konopnicki, Deborah, Fehr, Jan, Campbell, Maria A., Termote, Monique, Bucher, Heiner C., De Wit, Stéphane, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Castagna, Antonella, Del Amo, Julia, Mocroft, Amanda, Raben, Dorthe, Chêne, Geneviève, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Sabin, Caroline, Gibb, Diana, Fätkenheuer, Gerd, Obel, Niels, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, D'Arminio Monforte, Antonella, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Rauch, Andri, Tookey, Pat, Casabona, Jordi, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Judd, Ali, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Schomaker, Michael, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Wyss, Natasha, Barger, Diana, Schwimmer, Christine, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Wang, Q, De Luca, A, Smith, C, Zangerle, R, Sambatakou, H, Bonnet, F, Smit, C, Schommers, P, Thornton, A, Berenguer, J, Peters, L, Spagnuolo, V, Ammassari, A, Antinori, A, Roldan, E, Mussini, C, Miro, J, Konopnicki, D, Fehr, J, Campbell, M, Termote, M, Bucher, H, Puoti, M, University of Zurich, Bucher, Heiner C, Quiros Roldan, E, Miro, Jm, Campbell, Ma, Bucher, Hc, on behalf of The Hepatitis Coinfection and Non Hodgkin Lymphoma project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, and Castagna, Antonella

Subjects
Male, Lymphoma, Hepatitis B Surface Antigen, HIV Infections, medicine.disease_cause, Cohort Studies, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Risk Factors, HIV Infection, 030212 general & internal medicine, Viral, Chronic, media_common, Incidence (epidemiology), Hepatitis B Core Antigen, Lymphoma, Non-Hodgkin, Hazard ratio, virus diseases, General Medicine, Hepatitis C, Hepatitis B, Hepatitis B Core Antigens, Hepatitis Antibodie, 030220 oncology & carcinogenesis, RNA, Viral, Female, hepatitis c and b, Cohort study, Human, Adult, medicine.medical_specialty, Anti-HIV Agents, Biomarkers, Hepatitis Antibodies, Hepatitis B Surface Antigens, Hepatitis B, Chronic, Hepatitis C, Chronic, Humans, Immunoglobulin G, Hepatitis C virus, Non-Hodgkin, 610 Medicine & health, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, Internal medicine, Internal Medicine, medicine, media_common.cataloged_instance, HIV HCV NHL HBV, European union, Hepatitis B virus, business.industry, Risk Factor, Anti-HIV Agent, Biomarker, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), medicine.disease, digestive system diseases, 2724 Internal Medicine, Immunology, RNA, Cohort Studie, business
Abstract

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.

Published
2017

11. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Author

Chereau, Fanny, Madec, Yoann, Sabin, Caroline, Obel, Niels, Ruiz-Mateos, Ezequiel, Chrysos, Georgios, Fidler, Sarah, Lehmann, Clara, Zangerle, Robert, Wittkop, Linda, Reiss, Peter, Hamouda, Osamah, Perez, Vicente Estrada, Leal, Manuel, Mocroft, Amanda, De Olalla, Patricia Garcia, Ammassari, Adriana, Monforte, Antonella D'Arminio, Mussini, Cristina, Segura, Ferran, Castagna, Antonella, Cavassini, Matthias, Grabar, Sophie, Morlat, Philippe, De Wit, Stéphane, Lambotte, Olivier, Meyer, Laurence, Judd, Ali, Touloumi, Giota, Warszawski, Josiane, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Del Amo, Julia, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Miró, Jose Ma, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M., Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Fanny, C, Yoann, M, Caroline, S, Niels, O, Ezequiel, R, Georgios, C, Sarah, F, Clara, L, Robert, Z, Linda, W, Peter, R, Osamah, H, Vicente Estrada, P, Manuel, L, Amanda, M, Patricia Garcia De, O, Adriana, A, Antonella D’Arminio, M, Cristina, M, Ferran, S, Antonella, C, Matthias, C, Sophie, G, Philippe, M, Stéphane De, W, Olivier, L, Laurence, M, Puoti, M, Chereau, F, Madec, Y, Sabin, C, Obel, N, Ruiz-Mateos, E, Chrysos, G, Fidler, S, Lehmann, C, Zangerle, R, Wittkop, L, Reiss, P, Hamouda, O, Perez, Ve, Leal, M, Mocroft, A, De Olalla, Pg, Ammassari, A, Monforte, Ada, Mussini, C, Segura, F, Castagna, A, Cavassini, M, Grabar, S, Morlat, P, De Wit, S, Lambotte, O, Meyer, L, The HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), HIV Monitoring Foundation, Augustinus Foundation, European Commission, 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), 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), University College London Hospitals (UCLH), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Hospital Universitario Virgen del Rocío [Sevilla], Tzaneio General Hospital, Imperial College London, German Center for Infection Research - Partner Site Bonn-Cologne (DZIF), Universität Innsbruck [Innsbruck], Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Robert Koch Institute [Berlin] (RKI), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), CIBER de Epidemiología y Salud Pública (CIBERESP), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), University of Milan, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Hospital Universitari Parc Taulí of Sabadell, Barcelona, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Université de Lausanne (UNIL), 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), 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 libre de Bruxelles (ULB), 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), 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), 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), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université de Lausanne = University of Lausanne (UNIL), 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), HAL UPMC, Gestionnaire, AII - Infectious diseases, APH - Aging & Later Life, Global Health, Amsterdam institute for Infection and Immunity, HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCOORD, Imperial College Healthcare NHS Trust- BRC Funding, and Medical Research Council (MRC)

Subjects
Male, HIV Infections, CD8-Positive T-Lymphocytes, Pathology and Laboratory Medicine, Immunodeficiency Viruses, HIV-1/immunology, Public and Occupational Health, lcsh:Science, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV-1, Humans, Viral Load, Viremia, Virus Replication, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), virus diseases, CD8-Positive T-Lymphocytes/drug effects, Antiretroviral Therapy, Highly Active/methods, Medical Microbiology, Viral Pathogens, Science & Technology - Other Topics, Human, Blood cells, Immunology, HIV Infections/drug therapy, Virus Replication/immunology, Men WHO Have Sex with Men, Cytotoxic T cells, Microbiology, Viremia/drug therapy, Microbial Pathogens, Science & Technology, lcsh:R, Organisms, Biology and Life Sciences, Anti-HIV Agent, NATURAL-HISTORY, CD8-Positive T-Lymphocyte, Anti-HIV Agents/therapeutic use, HIV CD4 AIDS, T-CELLS, Population Groupings, lcsh:Q, Preventive Medicine, Sexuality Groupings, RNA viruses, RNA LEVELS, lcsh:Medicine, PROGRESSION, ACTIVATION, INFECTION, Cellular types, Medicine and Health Sciences, HIV Infection, Medicine (all), Immune cells, HIV diagnosis and management, ABSENCE, Vaccination and Immunization, Multidisciplinary Sciences, Infectious Diseases, CD4-Positive T-Lymphocyte, Viruses, White blood cells, Pathogens, Research Article, Cell biology, Evolutionary Immunology, Infectious Disease Control, General Science & Technology, T cells, Antiretroviral Therapy, CD4-Positive T-Lymphocytes/drug effects, CD4 Lymphocyte Count/methods, Viral Evolution, Antiviral Therapy, Virology, MD Multidisciplinary, Retroviruses, Evolutionary Biology, Lentivirus, HIV, Viral Load/drug effects, Diagnostic medicine, Organismal Evolution, Animal cells, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, REPLICATION, People and Places, Microbial Evolution, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, CD8-Positive T-Lymphocytes/immunology, HIV Infections/immunology, HIV Infections/virology, Viral Load/immunology, Viremia/immunology, Viremia/virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, INVERSE PROBABILITY
Abstract

[Objective] HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control., [Methods] HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models., [Results] We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds., [Discussion] Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs., The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement n° 260694.

Published
2017

12. The clinical trajectory of patients with borderline personality disorder

Author

Kjaer, Jesper Nørgaard, Biskin, Robert, Vestergaard, Claus, Gustafsson, Lea Nørgreen, and Munk-Jørgensen, Povl

Subjects
Adult, Male, Young Adult, Borderline Personality Disorder, Journal Article, Humans, Female, Registries
Abstract

OBJECTIVE: The epidemiological data on the diagnostic course of patients with borderline personality disorder (BPD) is limited. We used a nationwide register to investigate the diagnostic stability and changes over time.METHOD: The Danish nationwide registers were used to follow all patients with a diagnosis of BPD and investigate their first-ever psychiatric diagnosis and their latest diagnosis in the time period of 1995-2012. From this, we found the diagnostic stability and described the diagnostic changes.RESULTS: A total of 10 786 patients diagnosed with BPD were identified. The prospective diagnostic stabilities were 37% for females and 25% for males, and retrospective stabilities were 20% for females and 22% for males. More than 60% of patients received other diagnoses than BPD as their first-ever diagnosis. Stress-related (17%) and depressive disorders (14%) were most frequent as first-ever diagnosis. The latest diagnosis remained BPD in nearly half of females and one third of males, followed by schizophrenia, notably for those with longer follow-up and males.CONCLUSION: This study gives a detailed display of complicated clinical trajectories. The low diagnostic stabilities demonstrate a heterogenous patient group diagnosed with many other psychiatric diagnoses over time. Copyright © 2016 John Wiley & Sons, Ltd.

Published
2016

13. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Author

Mocroft, Amanda, Lundgren, Jens D., Sabin, Miriam Lewis, D'arminio Monforte, Antonella, Brockmeyer, Norbert, Casabona, Jordi, Costagliola, Dominique, Dabis, Francois, De Wit, Stã©phane, Fã¤tkenheuer, Gerd, Furrer, Hansjakob, Johnson, Anne M., Lazanas, Marios K., Leport, Catherine, Moreno, Santiago, Obel, Niels, Post, Frank A., Reekie, Joanne, Reiss, Peter, Sabin, Caroline, Skaletz rorowski, Adriane, Suarez lozano, Ignacio, Torti, Carlo, Warszawski, Josiane, Zangerle, Robert, Fabre colin, Cã©line, Kjaer, Jesper, Chene, Genevieve, Grarup, Jesper, Kirk, Ole, Lundgren, Jens, Sabin, Miriam, Castagna, Antonella, Johnson, Anne, Lazanas, Mario, Suarez loano, Ignacio, Post, Frank, Touloumi, Giota, Meyer, Laurence, Dabis, Franã§ois, Krause, Murielle Mary, Ghosn, Jade, De Wolf, Frank, Prins, Maria, Bucher, Heiner, Gibb, Diana, Hamouda, Osamah, Bartmeyer, Barbara, Del Amo, Julia, Thorne, Claire, Stephan, Christoph, Pã©rez hoyos, Santiago, Noguera julian, Antoni, Antinori, Andrea, Ramos, Josã©, Battegay, Manuel, Rauch, Andri, Mussini, Cristina, Tookey, Pat, Mirã³, Jose M., De Wit, Stephane, Goetghebuer, Tessa, Teira, Ramon, Garrido, Myriam, Judd, Ali, Haerry, David, Weller, Ian, D'arminio monforte, Antonella, Schwimmer, Christine, Termote, Monique, Touzeau, Guillaume, Campbell, Maria, Friis mã¸ller, Nina, Bohlius, Julia, Bouteloup, Vincent, Cozzi lepri, Alessandro, Dorrucci, Maria, Egger, Matthias, Engsig, Frederik, Lambotte, Olivier, Lewden, Charlotte, Lodwick, Rebecca, Matheron, Sophie, Miro, Jose, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Scherrer, Alexandra, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Von Wyl, Viktor, Wittkop, Linda, CASTAGNA, ANTONELLA, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Mocroft, Amanda, Lundgren, Jens D., Sabin, Miriam Lewi, D'arminio Monforte, Antonella, Brockmeyer, Norbert, Casabona, Jordi, Castagna, Antonella, Costagliola, Dominique, Dabis, Francoi, De Wit, Stã©phane, Fã¤tkenheuer, Gerd, Furrer, Hansjakob, Johnson, Anne M., Lazanas, Marios K., Leport, Catherine, Moreno, Santiago, Obel, Niel, Post, Frank A., Reekie, Joanne, Reiss, Peter, Sabin, Caroline, Skaletz rorowski, Adriane, Suarez lozano, Ignacio, Torti, Carlo, Warszawski, Josiane, Zangerle, Robert, Fabre colin, Cã©line, Kjaer, Jesper, Chene, Genevieve, Grarup, Jesper, Kirk, Ole, Lundgren, Jen, Sabin, Miriam, Johnson, Anne, Lazanas, Mario, Suarez loano, Ignacio, Post, Frank, Touloumi, Giota, Meyer, Laurence, Dabis, Franã§oi, Krause, Murielle Mary, Ghosn, Jade, De Wolf, Frank, Prins, Maria, Bucher, Heiner, Gibb, Diana, Hamouda, Osamah, Bartmeyer, Barbara, Del Amo, Julia, Thorne, Claire, Stephan, Christoph, Pã©rez hoyos, Santiago, Noguera julian, Antoni, Antinori, Andrea, Ramos, Josã©, Battegay, Manuel, Rauch, Andri, Mussini, Cristina, Tookey, Pat, Mirã³, Jose M., De Wit, Stephane, Goetghebuer, Tessa, Teira, Ramon, Garrido, Myriam, Judd, Ali, Haerry, David, Weller, Ian, D'arminio monforte, Antonella, Schwimmer, Christine, Termote, Monique, Touzeau, Guillaume, Campbell, Maria, Friis mã¸ller, Nina, Bohlius, Julia, Bouteloup, Vincent, Cozzi lepri, Alessandro, Dorrucci, Maria, Egger, Matthia, Engsig, Frederik, Lambotte, Olivier, Lewden, Charlotte, Lodwick, Rebecca, Matheron, Sophie, Miro, Jose, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Scherrer, Alexandra, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, Von Wyl, Viktor, and Wittkop, Linda

Subjects
Male, Time Factors, Epidemiology, HIV Infections, Substance Abuse, Intravenou, Logistic regression, Rate ratio, Biochemistry, 0302 clinical medicine, Risk Factors, HIV Seropositivity, HIV Infection, 030212 general & internal medicine, Cooperative Behavior, Substance Abuse, Intravenous, 10. No inequality, 0303 health sciences, Incidence, Incidence (epidemiology), General Medicine, Sciences bio-médicales et agricoles, 3. Good health, AIDS, Europe, Substance abuse, Infectious Diseases, Treatment Outcome, Disease Progression, symbols, Medicine, Female, Human, Biotechnology, HIV infections, Research Article, medicine.medical_specialty, Time Factor, Sexually Transmitted Diseases, 610 Medicine & health, Sensitivity and Specificity, 03 medical and health sciences, symbols.namesake, Acquired immunodeficiency syndrome (AIDS), 360 Social problems & social services, Mortalitat, medicine, Humans, Poisson regression, Mortality, Epidemiologia, Molecular Biology, 030306 microbiology, business.industry, Risk Factor, Cell Biology, Odds ratio, medicine.disease, CD4 Lymphocyte Count, Immunology, Infeccions per VIH, business, Demography
Abstract

Amanda Mocroft and colleagues investigate risk factors and health outcomes associated with diagnosis at a late stage of infection in individuals across Europe. Please see later in the article for the Editors' Summary, Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count, Editors' Summary Background Every year about 2.5 million people become newly infected with HIV, the virus that causes AIDS. HIV can be transmitted through unprotected sex with an infected partner, from an HIV-positive mother to her unborn baby, or through injection of drugs. Most people do not become ill immediately after infection with HIV although some develop a short influenza-like illness. The next stage of the HIV infection, which may last up to 10 years, also has no major symptoms but, during this stage, HIV slowly destroys immune system cells, including CD4 cells, a type of lymphocyte. Eventually, when the immune system is unable to fight off infections by other disease-causing organisms, HIV-positive people develop AIDS-defining conditions—unusual viral, bacterial, and fungal infections and unusual tumors. Progression to AIDS occurs when any severe AIDS-defining condition is diagnosed, when the CD4 count in the blood falls below 200 cells/mm3, or when CD4 cells account for fewer than 15% of lymphocytes. Why Was This Study Done? People need to know they are HIV positive as soon as possible after they become infected because antiretroviral therapy, which controls but does not cure HIV infection, works best if it is initiated when people still have a relatively high CD4 count. Early diagnosis also reduces the risk of onward HIV transmission. However, 40%–60% of HIV-positive individuals in developed countries are not diagnosed until they have a low CD4 count or an AIDS-defining illness. Reasons for such late presentation include fear of discrimination or stigmatization, limited knowledge about HIV risk factors, testing, and treatment together with missed opportunities to offer an HIV test. Policy makers involved in national and international HIV control programs need detailed information about patterns of late presentation before they can make informed decisions about how to reduce this problem. In this study, therefore, the researchers use data collected by the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) to analyze trends in late presentation over time across Europe and in different groups of people at risk of HIV infection and to investigate the clinical consequences of late presentation. What Did the Researchers Do and Find? The researchers analyzed data collected from 84,524 individuals participating in more than 20 observational studies that were undertaken in 35 European countries and that investigated outcomes among HIV-positive people. Nearly 54% of the participants were late presenters—individuals who had a CD4 count of less than 350 cells/mm3 or an AIDS-defining illness within 6 months of HIV diagnosis. Late presentation was highest among heterosexual males, in Southern European countries, and among people originating in Africa. Overall, late presentation decreased from 57.3% in 2000 to 51.7% in 2010/11. However, whereas late presentation decreased over time among men having sex with men in Central and Northern Europe, for example, it increased over time among female heterosexuals in Southern Europe. Finally, among the 8,000 individuals who developed a new AIDS-defining illness or died during follow-up, compared to non-late presentation, late presentation was associated with an increased incidence of AIDS/death in all regions of Europe during the first and second year after HIV diagnosis (but not in later years); the largest increase in incidence (13-fold) occurred during the first year after diagnosis in Southern Europe. What Do These Findings Mean? These findings indicate that, although late presentation with HIV infection has decreased in recent years, it remains an important issue across Europe and in all groups of people at risk of HIV infection. They also show that individuals presenting late have a worse clinical outlook, particularly in the first and second year after diagnosis compared to non-late presenters. Several aspects of the study design may affect the accuracy and usefulness of these findings, however. For example, some of the study participants recorded as late presenters may have been people who were aware of their HIV status but who chose not to seek care for HIV infection, or may have been seen in the health care system prior to HIV diagnosis without being offered an HIV test. Delayed entry into care and late presentation are likely to have different risk factors, a possibility that needs to be studied further. Despite this and other study limitations, these findings nevertheless suggest that HIV testing strategies that encourage early testing in all populations at risk, that ensure timely referrals, and that improve retention in care are required to further reduce the incidence of late presentation with HIV infection in Europe. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001510. Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including detailed information on the stages of HIV infection and on HIV and AIDS in Europe (in English and Spanish) The HIV in Europe Initiative has information about strategies to improve earlier diagnosis and access to care in Europe Information about COHERE, which was established in 2005 to conduct epidemiological research on the prognosis and outcome of HIV-infected people from across Europe, is available; more information on the consensus definition of late presentation used in this study is available through the HIV in Europe initiative Patient stories about living with HIV/AIDS are available through Avert and through the nonprofit website Healthtalkonline

Published
2013

14. Clinical Psychiatric Research School

Author

Okkels, Niels, Ahlers, Frederik Spangsberg, Harboe, Louise Feldvoss, Kjær, Jesper Nørgaard, Mogensen, Rasmus Beyer, Okkels, Anna Sophie, Østergaard, Pernille Jul, and Lundberg, Anne Sofie

Published
2013

15. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE

Author

The Opportunistic Infections Project Team of the Collaboration o, Young, Jim, Psichogiou, Mina, Meyer, Laurence, Ayayi, Sylvie, Grabar, Sophie, Raffi, Francois, Reiss, Peter, Gazzard, Brian, Sharland, Mike, Gutierrez, Félix, Obel, Niels, Kirk, Ole, Miro, José M, Furrer, Hansjakob, Castagna, Antonella, De Wit, Stéphane, Muñoz, Josefa, Kjaer, Jesper, Grarup, Jesper, Chêne, Geneviève, Bucher, Heiner, Fisher, Martin, Young, Jim, Psichogiou, Mina, Meyer, Laurence, COHERE EuroCoord European AIDS Treatment, Grp, Castagna, Antonella, Universitat de Barcelona, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, and Infectious diseases

Subjects
Male, viruses, HIV Infections, Cohort Studies, 0302 clinical medicine, Epidemiology, Medicine, Viral Load -- drug effects, 030212 general & internal medicine, Longitudinal Studies, Pathologie maladies infectieuses, 0303 health sciences, Anti-Retroviral Agents -- therapeutic use, Mortality rate, Hazard ratio, virus diseases, General Medicine, Viral Load, Sciences bio-médicales et agricoles, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, Acquired Immunodeficiency Syndrome -- etiology, Drug Therapy, Combination, Female, Viral load, Research Article, HIV infections, Cohort study, Cart, Adult, medicine.medical_specialty, HIV Infections -- complications -- drug therapy -- mortality, Sexually Transmitted Diseases, RA0644.A25, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Mortalitat, Humans, Mortality, Acquired Immunodeficiency Syndrome, 030306 microbiology, business.industry, Proportional hazards model, medicine.disease, CD4 Lymphocyte Count, Immunology, Infeccions per VIH, business
Abstract

Using data from the Collaboration of Observational HIV Epidemiological Research Europe, Jim Young and colleagues show that in successfully treated patients the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression., Background Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. Methods and Findings Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50–500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30–0.40) for counts, Editors' Summary Background Currently, about 34 million people are infected with HIV and every year nearly 3 million people are newly infected with this virus, which causes AIDS. Most people do not become ill immediately after infection with HIV although some develop a short, flu-like illness (a “seroconversion” illness). The next stage of HIV infection, which may last up to 10 years, also has no major symptoms but, during this stage, HIV slowly destroys immune system cells (including CD4 cells, a type of lymphocyte). Eventually, the immune system can no longer fight off infections by other disease-causing organisms and HIV-positive people then develop one or more AIDS-defining condition(s), including severe but unusual infections, Kaposi sarcoma (a skin cancer), and non-Hodgkin lymphoma (a cancer of the lymph nodes). Many of these AIDS-defining conditions are life-threatening and, in the past, HIV-positive people died on average within 10 years of infection. Nowadays, although there is still no cure for HIV infection, combination antiretroviral therapy (cART; a cocktail of powerful antiretroviral drugs) has turned HIV/AIDS into a chronic, treatable condition, at least in developed countries. Why Was This Study Done? Most HIV-positive adults achieve viral suppression within a year of starting cART. That is, the number of copies of the virus in their blood drops to below 50 copies/ml. But what is the likely clinical outcome for patients who achieve viral suppression and what is their risk of developing a new AIDS-defining condition or of dying? For people starting cART for the first time, the number of CD4 cells in the blood when cART is initiated provides a strong indication of an individual's likely clinical outcome. Specifically, people who start cART when they have a high CD4 cell count tend to do better than people who start treatment when they have a low CD4 cell count. In this study, the researchers use data collected by the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) to estimate the association between CD4 cell count and progression to a new AIDS-defining event or death among patients who have achieved viral suppression while on cART. What Did the Researchers Do and Find? The researchers identified more than 75,000 patients in the COHERE database who, between them, had had more than 104,000 episodes (periods) of viral suppression while on cART and who had had their CD4 cell count determined shortly before or during their viral suppression episodes. The researchers then used stratified multivariate Cox models (a type of statistical analysis method) to estimate the association between CD4 cell counts and the occurrence of a new AIDS-defining event or death. Among the patients included in the study, the mortality (death) rate was 4.8 per 1,000 years of viral suppression. The highest rates of new AIDS-defining events or death were seen in those patients with less than 50 CD4 cells/µl blood and a higher CD4 cell count was associated with a reduced risk of a new AIDS-defining event or death. Finally, among those patients with a CD4 cell count below 200 cells/µl, the risk of progression decreased over time for those patients with higher CD4 cell counts. What Do These Findings Mean? These findings suggest that, although new AIDS-defining events and death are uncommon among patients whose viral load is suppressed by cART, the risk of a new AIDS-defining event or death follows a CD4 cell count gradient with the patients with the highest CD4 cell counts having the lowest risk of a new AIDS-defining event or death. The findings also suggest that higher CD4 cell counts provide the greatest benefit for patients with a CD4 cell count below 200 cells/µl blood. These findings have two main clinical implications. First, they add to the evidence that suggests that, to facilitate immune system recovery, cART should be started when a patient's CD4 cell count is between 350 and 500 cells/µl blood, the current recommended range for cART initiation. Unfortunately, most patients in resource-limited settings only start cART when their CD4 cell count is below 200 cells/µl. Second, these findings suggest that patients with sustained viral suppression but low CD4 cell counts should be monitored regularly to ensure that any life-threatening AIDS-defining events are dealt with quickly and effectively. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001194. Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including detailed information on HIV treatment and care (in English and Spanish) The World Health Organization's 2010 antiretroviral therapy guidelines provide recommendations on when to initiate cART Information about COHERE is available Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline

Published
2012

16. Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study

Author

Castagliola, Dominique, Ledergerber, Bruno, Torti, Carlo, van Sighem, Ard, Podzamczer, Daniel, Mocroft, Amanda, Dorrucci, Maria, Masquelier, Bernard, de Luca, Andrea, Jansen, Klaus, De Wit, Stephane, Obel, Niels, Fätkenheuer, Gerd, Touloumi, Giota, Mussini, Cristina, Castagna, Antonella, Stephan, Cristoph, Garcia, Frederico, Zangerle, Robert, Duval, Xavier, Pérez-Hoyos, Santiago, Meyer, Laurence, Ghosn, Jade, Fabre-Colin, Céline, Kjaer, Jesper, Chene, Genevieve, Grarup, Jesper, Costagliola, Dominque, Lodwick, Rebecca, Phillips, Andrew, University of Zurich, and Costagliola, Dominque

Subjects
10234 Clinic for Infectious Diseases, 610 Medicine & health, 2725 Infectious Diseases
Published
2012

17. Eff ect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

Author

Wittkop, Linda, Huldrych, F. Günthard, De Wolf, Frank, Dunn, David, Cozzi Lepri, Alessandro, De Luca, Andrea, Kücherer, Claudia, Obel, Niels, Von Wyl, Viktor, Masquelier, Bernard, Stephan, Christoph, Torti, Carlo, Antinori, Andrea, Garcia, Federico, Judd, Ali, Porter, Kholoud, Thiébaut, Rodolphe, Castro, Hannah, Van Sighem, Ard I, Colin, Céline, Kjaer, Jesper, Lundgren, Jens D, Paredes, Roger, Pozniak, Anton, Clotet, Bonaventura, Phillips, Andrew, Pillay, Deenan, and Chêne, Geneviève

Subjects
trasmitted drug resistence, Settore MED/17 - MALATTIE INFETTIVE, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Published
2011

18. Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy

Author

Bohlius, Julia, Schmidlin, Kurt, Costagliola, Dominique, Fätkenheuer, Gerd, May, Margaret, Murillo, Ana Maria Caro, Mocroft, Amanda, Bonnet, Fabrice, Clifford, Gary, Touloumi, Giota, Miro, Jose M., Chene, Genevieve, Lundgren, Jens, Egger, Matthias, Antinori, Andrea, Boué, François, Brockmeyer, Norbert, Casabona, Jordi, Lopez-Guillermo, Armando, Ribera, Josep Maria, Dronda, Fernando, Obel, Niels, Fisher, Martin, Franceschi, Silvia, Gibb, Diana, Le Moing, Vincent, Nadal, David, Prins, Maria, Raffi, François, Roca, Bernardino, Verbon, Annelies, Wolf, Timo, Fortuny, Claudia, Chakraborty, Rana, Minder, Christoph, Sterne, Jonathan, Zwahlen, Marcel, Ellefson, Michelle, Kjaer, Jesper, Collin, Fidéline, Colin, Céline, Weller, Ian, Ledergerber, Bruno, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Goujard, Cecile, Leport, Catherine, de Wolf, Frank, Reiss, Peter, Porter, Kholoud, Dorrucci, Maria, Sabin, Caroline, Del Amo, Julia, Thorne, Claire, Kirk, Ole, Staszewski, Schlomo, Perez-Hoyos, Santiago, Almeda, Jesus, D'Arminio Monforte, Antonella, de Martino, Maurizio, Ramos, Jose, Battegay, Manuel, Mussini, Cristina, Tookey, Pat, Castagna, Antonella, de Wit, Stephane, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Dedes, Nikos, Phillips, Andrew, Furrer, Hansjakob, Newell, Marie Louise, Telenti, Amalio, Pantazis, Nikos, Lechenadec, Jérôme, Boufassa, Faroudy, Tran, Laurent, Balestre, Eric, Lanoy, Emilie, Couturier, Françoise, Rispens, Theo, Gras, Luuk A.J., Bhaskaran, Krishnan, Hill, Teresa, Judd, Ali, Duong, Trinh, Sobrino, Paz, Jennings, Beverley, Bonfigli, Sandro, Cozzi-Lepri, Alessandro, Corvasce, Stefano, Adorni, Fulvio, Ridolfo, Anna Lisa, Paraninfo, Giuseppe, Keiser, Olivia, Borghi, Vanni, Weller, Ian, Costagliola, Dominique, Ledergerber, Bruno, Lundgren, Jen, Chene, Genevieve, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, Francoi, Krause Murielle, Mary, Leport, Catherine, de Wolf, Frank, Reiss, Peter, Porter, Kholoud, Dorrucci, Maria, Sabin, Caroline, Gibb, Diana, Del Amo, Julia, Obel, Niel, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Staszewski, Schlomo, Perez Hoyos, Santiago, Almeda, Jesu, Antinori, Andrea, Monforte A., D'Arminio, de Martino, Maurizio, Brockmeyer, Norbert, Faetkenheuer, Gerd, Ramos, Jose, Battegay, Manuel, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miro Jose, M., Castagna, Antonella, de Wit, Stephane, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Dedes, Niko, Phillips, Andrew, Furrer, Hansjakob, Egger, Matthia, Newell Marie, Louise, Sterne, Jonathan, Telenti, Amalio, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Infectious diseases

Subjects
Cart, Adult, Male, medicine.medical_specialty, Adolescent, Immunology, AIDS-related lymphoma, Young Adult, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antiretroviral Therapy, Highly Active, Epidemiology, medicine, Immunology and Allergy, Humans, Young adult, Mortality, Prospective cohort study, Collaborative study, Immunodeficiency, Non-Hodgkin lymphoma, Lymphoma, AIDS-Related, business.industry, Lymphoma, Non-Hodgkin, Middle Aged, medicine.disease, Prognosis, Surgery, Lymphoma, Antiretroviral therapy, CD4 Lymphocyte Count, Europe, Infectious Diseases, Treatment Outcome, HIV-1, Cohort studies, Female, business, Epidemiologic Methods, Cohort study
Abstract

Objective: We examined survival and prognostic factors of patients who developed HIV-associated non-Hodgkin lymphoma (NHL) in the era of combination antiretroviral therapy (cART). Design and setting: Multicohort collaboration of 33 European cohorts. Methods: We included all cART-naive patients enrolled in cohorts participating in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who were aged 16 years or older, started cART at some point after 1 January 1998 and developed NHL after 1 January 1998. Patients had to have a CD4 cell count after 1 January 1998 and one at diagnosis of the NHL. Survival and prognostic factors were estimated using Weibull models, with random effects accounting for heterogeneity between cohorts. Results: Of 67 659 patients who were followed up during 304 940 person-years, 1176 patients were diagnosed with NHL. Eight hundred and forty-seven patients (72%) from 22 cohorts met inclusion criteria. Survival at 1 year was 66% [95% confidence interval (CI) 63-70%] for systemic NHL (n = 763) and 54% (95% CI: 43-65%) for primary brain lymphoma (n = 84). Risk factors for death included low nadir CD4 cell counts and a history of injection drug use. Patients developing NHL on cART had an increased risk of death compared with patients who were cART naive at diagnosis. Conclusion: In the era of cART two-thirds of patients diagnosed with HIV-related systemic NHL survive for longer than 1 year after diagnosis. Survival is poorer in patients diagnosed with primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL.

Published
2009

19. Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Author

Mocroft, Amanda, Lundgren, Jens D., Sabin, Miriam Lewis, D'Arminio Monforte, Antonella, Brockmeyer, Norbert, Casabona, Jordi, Castagna, Antonella, Costagliola, Dominique, Dabis, Francois, De Wit, Stéphane, Fätkenheuer, Gerd, Furrer, Hansjakob, Johnson, Anne M., Lazanas, Marios K., Leport, Catherine, Moreno, Santiago, Obel, Niels, Post, Frank A., Reekie, Joanne, Reiss, Peter, Sabin, Caroline, Skaletz-Rorowski, Adriane, Suarez-Lozano, Ignacio, Torti, Carlo, Warszawski, Josiane, Zangerle, Robert, Fabre-Colin, Céline, Kjaer, Jesper, Chene, Genevieve, Grarup, Jesper, and Kirk, Ole

Subjects
10. No inequality, 610 Medicine & health, 360 Social problems & social services, 3. Good health
Abstract

Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count

22. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): A European multicohort study

Author

Rodolphe Thiébaut, Jens D Lundgren, Andrea De Luca, Christoph Stephan, Andrea Antinori, Ard van Sighem, Frank de Wolf, Andrew N. Phillips, Niels Obel, Alessandro Cozzi-Lepri, Roger Paredes, Kholoud Porter, Viktor von Wyl, Deenan Pillay, Huldrych F. Günthard, Bernard Masquelier, Ali Judd, Geneviève Chêne, Céline Colin, Anton Pozniak, Linda Wittkop, Claudia Kücherer, Bonaventura Clotet, Federico García, Carlo Torti, Jesper Kjaer, David Dunn, Hannah Castro, Wittkop, Linda, Gã¼nthard, Huldrych F, De Wolf, Frank, Dunn, David, Cozzi lepri, Alessandro, De Luca, Andrea, Kã¼cherer, Claudia, Obel, Niel, Von Wyl, Viktor, Masquelier, Bernard, Stephan, Christoph, Torti, Carlo, Antinori, Andrea, Garcã­a, Federico, Judd, Ali, Porter, Kholoud, Thiã©baut, Rodolphe, Castro, Hannah, Van Sighem, Ard I, Colin, Cã©line, Kjaer, Jesper, Lundgren, Jens D, Paredes, Roger, Pozniak, Anton, Clotet, Bonaventura, Phillips, Andrew, Pillay, Deenan, Chãªne, Geneviãve, Eurocoord chain Study, Group, Castagna, Antonella, University of Zurich, and Wittkop, L

Subjects
Cart, Drug, Adult, Male, medicine.medical_specialty, Adolescent, Anti-HIV Agents, media_common.quotation_subject, HIV Infections, 610 Medicine & health, Drug resistance, Cohort Studies, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Humans, 030212 general & internal medicine, Young adult, Child, media_common, 0303 health sciences, 030306 microbiology, business.industry, HIV, Infant, 2725 Infectious Diseases, Middle Aged, Viral Load, 3. Good health, Surgery, Clinical trial, Europe, Infectious Diseases, trasmitted drug resistence, Child, Preschool, Mutation, Drug Therapy, Combination, Female, business, Viral load, Cohort study
Abstract

Background: The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods: HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings: Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p

Published
2011

23. Triple-Class Virologic Failure in HIV-Infected Patients Undergoing Antiretroviral Therapy for Up to 10 Years

Author

Daniel Podzamczer, Cristina Mussini, Huldrych F. Günthard, Jade Ghosn, Peter Reiss, Xavier Duval, Ali Judd, Bernard Masquelier, Joan Masip, Pursuing Later Treatment Options, Alessandro Cozzi-Lepri, Laurence Meyer, Santiago Pérez-Hoyos, Giota Touloumi, Niels Obel, Rebecca Lodwick, Geneviève Chêne, Bruno Ledergerber, Antonella Castagna, Céline Fabre-Colin, Andrea Antinori, Federico García, Deenan Pillay, Jesper Kjaer, Maria Dorrucci, Roger Paredes, Sergio Lo Caputo, Claire Thorne, Josiane Warsawski, José Ramos, Dimitrios Paraskevis, Amanda Mocroft, Schlomo Staszewski, Stéphane De Wit, Ard van Sighem, Jens D Lundgren, Andrea De Luca, Ramón Teira, Andrew N. Phillips, Dominique Costagliola, Carlo Torti, Lodwick, Rebecca, Costagliola, Dominique, Reiss, Peter, Torti, Carlo, Teira, Ramon, Dorrucci, Maria, Ledergerber, Bruno, Mocroft, Amanda, Podzamczer, Daniel, Cozzi Lepri, Alessandro, Obel, Niel, Masquelier, Bernard, Staszewski, Schlomo, Garcia, Federico, De Wit, Stephane, Castagna, Antonella, Antinori, Andrea, Judd, Ali, Ghosn, Jade, Touloumi, Giota, Mussini, Cristina, Duval, Xavier, Ramos, Jose, Meyer, Laurence, Warsawski, Josiane, Thorne, Claire, Masip, Joan, Perez Hoyos, Santiago, Pillay, Deenan, van Sighem, Ard, Lo Caputo, Sergio, Guenthard, Huldrych, Paredes, Roger, De Luca, Andrea, Paraskevis, Dimitrio, Fabre Colin, Celine, Kjaer, Jesper, Chene, Genevieve, Lundgren Jens, D., Phillips Andrew, N., University of Zurich, Lodwick, R, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, and Infectious diseases

Subjects
Male, HAART, HIV Infections, Kaplan-Meier Estimate, 10234 Clinic for Infectious Diseases, Interquartile range, virologic failure, Treatment Failure, HIV, education.field_of_study, Incidence (epidemiology), Middle Aged, Viral Load, Europe, AIDS, Reverse Transcriptase Inhibitors, Female, Viral load, ART, medicine.drug, Adult, medicine.medical_specialty, COHERE, Adolescent, Anti-HIV Agents, Population, 610 Medicine & health, Article, Young Adult, Pharmacotherapy, Life Expectancy, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Internal Medicine, medicine, Humans, education, Proportional Hazards Models, Ritonavir, business.industry, HIV Protease Inhibitors, medicine.disease, Regimen, 2724 Internal Medicine, Immunology, business
Abstract

BACKGROUND: Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades. METHODS: We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed. RESULTS: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings

Published
2010

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