Search

Your search keyword '"Grarup, Jesper"' showing total 77 results
Start Over Author "Grarup, Jesper"
77 results on '"Grarup, Jesper"'

51. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population:evidence from a large European observational cohort collaboration

Author

Lewden, Charlotte, Bouteloup, Vincent, De Wit, Stéphane, Sabin, Caroline, Mocroft, Amanda, Wasmuth, Jan Christian, van Sighem, Ard, Kirk, Ole, Obel, Niels, Panos, George, Ghosn, Jade, Dabis, François, Mary-Krause, Murielle, Leport, Catherine, Perez-Hoyos, Santiago, Sobrino-Vegas, Paz, Stephan, Christoph, Castagna, Antonella, Antinori, Andrea, d'Arminio Monforte, Antonella, Torti, Carlo, Mussini, Cristina, Isern, Virginia, Calmy, Alexandra, Teira, Ramón, Egger, Matthias, Grarup, Jesper, Chêne, Geneviève, Lewden, Charlotte, Bouteloup, Vincent, De Wit, Stéphane, Sabin, Caroline, Mocroft, Amanda, Wasmuth, Jan Christian, van Sighem, Ard, Kirk, Ole, Obel, Niels, Panos, George, Ghosn, Jade, Dabis, François, Mary-Krause, Murielle, Leport, Catherine, Perez-Hoyos, Santiago, Sobrino-Vegas, Paz, Stephan, Christoph, Castagna, Antonella, Antinori, Andrea, d'Arminio Monforte, Antonella, Torti, Carlo, Mussini, Cristina, Isern, Virginia, Calmy, Alexandra, Teira, Ramón, Egger, Matthias, Grarup, Jesper, and Chêne, Geneviève

Abstract

Using data from a large European collaborative study, we aimed to identify the circumstances in which treated HIV-infected individuals will experience similar mortality rates to those of the general population.

Published
2012

52. 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

Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord, Young, Jim, Psichogiou, Mina, Meyer, Laurence, Ayayi, Sylvie, Grabar, Sophie, Raffi, François, Reiss, Peter, Gazzard, Brian, Sharland, Mike, Gutiérrez, Félix, Obel, Niels, Kirk, Ole, Miró, José María, Furrer, Hansjakob, Castagna, Antonella, De Wit, Stéphane, Muñoz, Josefa, Kjaer, Jesper, Grarup, Jesper, Chêne, Geneviève, Bucher, Heiner H.C., Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord, Young, Jim, Psichogiou, Mina, Meyer, Laurence, Ayayi, Sylvie, Grabar, Sophie, Raffi, François, Reiss, Peter, Gazzard, Brian, Sharland, Mike, Gutiérrez, Félix, Obel, Niels, Kirk, Ole, Miró, José María, Furrer, Hansjakob, Castagna, Antonella, De Wit, Stéphane, Muñoz, Josefa, Kjaer, Jesper, Grarup, Jesper, Chêne, Geneviève, and Bucher, Heiner H.C.

Abstract

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., info:eu-repo/semantics/published

Published
2012

53. 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

Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Observational HIV Epidemiological Research Europe (COHERE) Group, Costagliola, Dominique, Lodwick, Rebecca, Ledergerber, Bruno, Torti, Carlo, van Sighem, Ard, Podzamczer, Daniel, Mocroft, Amanda, Dorrucci, Maria, Masquelier, Bernard, De Luca, Andrea, Jansen, Klaus, De Wit, Stéphane, Obel, Niels, Fätkenheuer, Gerd, Touoloumi, Giota, Mussini, Cristina, Castagna, Antonella, Stephan, Christoph, Garcia Colominas, Federico, Zangerle, Robert, Duval, Xavier, Pérez-Hoyos, Santiago, Meyer, Laurence, Ghosn, Jade, Fabre-Colin, Céline, Kjaer, Jesper, Chêne, Geneviève, Grarup, Jesper, Phillips, Andrew, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Observational HIV Epidemiological Research Europe (COHERE) Group, Costagliola, Dominique, Lodwick, Rebecca, Ledergerber, Bruno, Torti, Carlo, van Sighem, Ard, Podzamczer, Daniel, Mocroft, Amanda, Dorrucci, Maria, Masquelier, Bernard, De Luca, Andrea, Jansen, Klaus, De Wit, Stéphane, Obel, Niels, Fätkenheuer, Gerd, Touoloumi, Giota, Mussini, Cristina, Castagna, Antonella, Stephan, Christoph, Garcia Colominas, Federico, Zangerle, Robert, Duval, Xavier, Pérez-Hoyos, Santiago, Meyer, Laurence, Ghosn, Jade, Fabre-Colin, Céline, Kjaer, Jesper, Chêne, Geneviève, Grarup, Jesper, and Phillips, Andrew

Abstract

Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09., info:eu-repo/semantics/published

Published
2012

54. Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe.

Author

Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Group, Nakagawa, Fumiyo, Lodwick, Rebecca, Costagliola, Dominique, van Sighem, Ard, Torti, Carlo, Podzamczer, Daniel, Mocroft, Amanda, Ledergerber, Bruno, Dorrucci, Maria, Cozzi-Lepri, Alessandra, Jansen, Klaus, Masquelier, Bernard, Garcia Colominas, Federico, De Wit, Stéphane, Stephan, Christoph, Obel, Niels, Fätkenhaeuer, Gerd, Castagna, Antonella, Sambatakou, Hellen, Mussini, Cristina, Ghosn, Jade, Zangerle, Robert, Duval, Xavier, Meyer, Laurence, Pérez-Hoyos, Santiago, Fabre-Colin, Céline, Kjaer, Jesper, Chêne, Geneviève, Grarup, Jesper, Phillips, Andrew, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Group, Nakagawa, Fumiyo, Lodwick, Rebecca, Costagliola, Dominique, van Sighem, Ard, Torti, Carlo, Podzamczer, Daniel, Mocroft, Amanda, Ledergerber, Bruno, Dorrucci, Maria, Cozzi-Lepri, Alessandra, Jansen, Klaus, Masquelier, Bernard, Garcia Colominas, Federico, De Wit, Stéphane, Stephan, Christoph, Obel, Niels, Fätkenhaeuer, Gerd, Castagna, Antonella, Sambatakou, Hellen, Mussini, Cristina, Ghosn, Jade, Zangerle, Robert, Duval, Xavier, Meyer, Laurence, Pérez-Hoyos, Santiago, Fabre-Colin, Céline, Kjaer, Jesper, Chêne, Geneviève, Grarup, Jesper, and Phillips, Andrew

Abstract

Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years., info:eu-repo/semantics/published

Published
2012

55. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial

Author

Jensen, Jens U, Hein, Lars, Lundgren, Bettina, Bestle, Morten H, Mohr, Thomas T, Andersen, Mads H, Thornberg, Klaus J, Løken, Jesper, Steensen, Morten, Fox, Zoe, Tousi, Hamid, Søe-Jensen, Peter, Lauritsen, Anne Ø, Strange, Ditte, Petersen, Pernille L, Reiter, Nanna, Hestad, Søren, Thormar, Katrin, Fjeldborg, Paul, Larsen, Kim M, Drenck, Niels E, Ostergaard, Christian, Kjær, Jesper, Grarup, Jesper, Lundgren, Jens D, Jensen, Jens U, Hein, Lars, Lundgren, Bettina, Bestle, Morten H, Mohr, Thomas T, Andersen, Mads H, Thornberg, Klaus J, Løken, Jesper, Steensen, Morten, Fox, Zoe, Tousi, Hamid, Søe-Jensen, Peter, Lauritsen, Anne Ø, Strange, Ditte, Petersen, Pernille L, Reiter, Nanna, Hestad, Søren, Thormar, Katrin, Fjeldborg, Paul, Larsen, Kim M, Drenck, Niels E, Ostergaard, Christian, Kjær, Jesper, Grarup, Jesper, and Lundgren, Jens D

Abstract

For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival.

Published
2011

56. Risk of triple-class virological failure in children with HIV: a retrospective cohort study

Author

Castro, Hannah, Judd, Ali, Gibb, Diana M, Butler, Karina, Lodwick, Rebecca K, van Sighem, Ard, Ramos, Jose T, Warsawski, Josiane, Thorne, Claire, Noguera-Julian, Antoni, Obel, Niels, Costagliola, Dominique, Tookey, Pat A, Colin, Céline, Kjaer, Jesper, Grarup, Jesper, Chene, Genevieve, Phillips, Andrew, Castro, Hannah, Judd, Ali, Gibb, Diana M, Butler, Karina, Lodwick, Rebecca K, van Sighem, Ard, Ramos, Jose T, Warsawski, Josiane, Thorne, Claire, Noguera-Julian, Antoni, Obel, Niels, Costagliola, Dominique, Tookey, Pat A, Colin, Céline, Kjaer, Jesper, Grarup, Jesper, Chene, Genevieve, and Phillips, Andrew

Abstract

In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children.

Published
2011

57. Regulatory impediments jeopardizing the conduct of clinical trials in Europe funded by the National Institutes of Health

Author

Neaton, James D, Babiker, Abdel, Bohnhorst, Mark, Darbyshire, Janet, Denning, Eileen, Frishman, Arnie, Grarup, Jesper, Larson, Gregg, Lundgren, Jens, Neaton, James D, Babiker, Abdel, Bohnhorst, Mark, Darbyshire, Janet, Denning, Eileen, Frishman, Arnie, Grarup, Jesper, Larson, Gregg, and Lundgren, Jens

Abstract

A number of reports have highlighted problems of conducting publicly funded trials in Europe as a consequence of the European Union (EU) Clinical Trials Directive. The impact of the EU Directive on multi-national trials, which include sites in Europe that are funded by the US National Institutes of Health (NIH) have not been described.

Published
2010

58. Notification of suspected and unexpected serious adverse reactions according to the Clinical Trials Directive - A descriptive analysis of the legislation and the requirements in a European context

Author

Larsen, Ellen Frøsig Moseholm, Grarup, Jesper, Gey, Daniela Christine, Jensen, Majken Karoline, Kirk, Ole, Larsen, Ellen Frøsig Moseholm, Grarup, Jesper, Gey, Daniela Christine, Jensen, Majken Karoline, and Kirk, Ole

Abstract

The European Clinical Trials Directive (CTD) came into force on May 1st 2004. The CTD provides the legal basis for monitoring the safety of clinical trials and covers the requirements for notification of SUSAR. Implementation of the CTD into national legislation in each Member State has resulted in various interpretations of CTD requirements. The objective of this paper is to investigate how the European Member States administer the safety reporting requirements of the CTD and to clarify the requirements for SUSAR notification in the different Member States. Data was collected through publicly available sources and questionnaires sent to the Competent Authorities and Ethics Committees in 30 European countries. The results document that Competent Authorities and Ethics Committees in the different Member States administer the legislation very differently. This has resulted in different requirements for notification of SUSARs in the Member States, as well as different requirements between the Competent Authorities and Ethics Committees in the same Member State. These requirements have not previously been described and the present overview of the legislation and the requirements of SUSAR reporting is of immediate practical use to especially non-commercial sponsors when conducting clinical trials in Europe.

Published
2010

59. 605Clinically Applied Variation in Replication Kinetics During Episodes of Post-Transplant Cytomegalovirus (CMV) Infections

Author

Lodding, Isabelle, primary, Da Cunha-Bang, Caspar, additional, Frederiksen, Casper Møller, additional, Gustafsson, Finn, additional, Iversen, Martin, additional, Kirkby, Nikolai, additional, Rasmussen, Allan, additional, Sørensen, Søren Schwartz, additional, Sengeløv, Henrik, additional, Vindeløv, Lars, additional, Grarup, Jesper, additional, and Lundgren, Jens, additional

Published
2014
Full Text
View/download PDF

60. The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

Author

Jensen, Jens-Ulrik, Lundgren, Bettina, Hein, Lars, Mohr, Thomas, Petersen, Pernille L, Andersen, Lasse H, Lauritsen, Anne Øberg, Hougaard, Sine, Mantoni, Teit, Bømler, Bonnie, Thornberg, Klaus Julius, Thormar, Katrin, Løken, Jesper, Steensen, Morten, Carl, Peder, Petersen, J Asger, Tousi, Hamid, Søe-Jensen, Peter, Bestle, Morten, Hestad, Søren, Andersen, Mads H, Fjeldborg, Paul, Larsen, Kim M, Rossau, Charlotte Dahl, Thomsen, Carsten B, Ostergaard, Christian, Kjaer, J, Grarup, Jesper, Lundgren, Jens, Jensen, Jens-Ulrik, Lundgren, Bettina, Hein, Lars, Mohr, Thomas, Petersen, Pernille L, Andersen, Lasse H, Lauritsen, Anne Øberg, Hougaard, Sine, Mantoni, Teit, Bømler, Bonnie, Thornberg, Klaus Julius, Thormar, Katrin, Løken, Jesper, Steensen, Morten, Carl, Peder, Petersen, J Asger, Tousi, Hamid, Søe-Jensen, Peter, Bestle, Morten, Hestad, Søren, Andersen, Mads H, Fjeldborg, Paul, Larsen, Kim M, Rossau, Charlotte Dahl, Thomsen, Carsten B, Ostergaard, Christian, Kjaer, J, Grarup, Jesper, and Lundgren, Jens

Abstract

Udgivelsesdato: 2008, BACKGROUND: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. METHODS: Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding.Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection.Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. DISCUSSION: For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically i

Published
2008

61. Grarup, Jesper

Author

Grarup, Jesper and Grarup, Jesper

Published
2008

62. Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials.

Author

Larson, Gregg S., Carey, Cate, Grarup, Jesper, Hudson, Fleur, Sachi, Karen, Vjecha, Michael J., and Gordin, Fred

Subjects
BUDGET, CLINICAL trials, EXPERIMENTAL design, HIV infections, HEALTH insurance reimbursement, FINANCIAL management, FEE for service (Medical fees)
Abstract

Background/aims: Randomized clinical trials are widely recognized as essential to address worldwide clinical and public health research questions. However, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost. We identify approaches and practices for large, publicly funded, international trials that reduce cost without compromising data integrity and recommend an approach to cost reporting that permits comparison of clinical trials. Methods: We describe the organizational and financial characteristics of The International Network for Strategic Initiatives in Global HIV Trials, an infectious disease research network that conducts multiple, large, long-term, international trials, and examine challenges associated with simple and streamlined governance and an infrastructure and financial management model that is based on performance, transparency, and accountability. Results: It is possible to reduce costs of participants’ follow-up and not compromise clinical trial quality or integrity. The International Network for Strategic Initiatives in Global HIV Trials network has successfully completed three large HIV trials using cost-efficient practices that have not adversely affected investigator enthusiasm, accrual rates, loss-to-follow-up, adherence to the protocol, and completion of data collection. This experience is relevant to the conduct of large, publicly funded trials in other disease areas, particularly trials dependent on international collaborations. Conclusion: New approaches, or creative adaption of traditional clinical trial infrastructure and financial management tools, can render large, international clinical trials more cost-efficient by emphasizing structural simplicity, minimal up-front costs, payments for performance, and uniform algorithms and fees-for-service, irrespective of location. However, challenges remain. They include institutional resistance to financial change, growing trial complexity, and the difficulty of sustaining network infrastructure absent stable research work. There is also a need for more central monitoring, improved and harmonized regulations, and a widely applied metric for measuring and comparing cost efficiency in clinical trials. ClinicalTrials.gov is recommended as a location where standardized trial cost information could be made publicly accessible. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

63. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: A randomized trial*

Author

Jensen, Jens U., primary, Hein, Lars, additional, Lundgren, Bettina, additional, Bestle, Morten H., additional, Mohr, Thomas T., additional, Andersen, Mads H., additional, Thornberg, Klaus J., additional, Løken, Jesper, additional, Steensen, Morten, additional, Fox, Zoe, additional, Tousi, Hamid, additional, Søe-Jensen, Peter, additional, Lauritsen, Anne Ø, additional, Strange, Ditte, additional, Petersen, Pernille L., additional, Reiter, Nanna, additional, Hestad, Søren, additional, Thormar, Katrin, additional, Fjeldborg, Paul, additional, Larsen, Kim M., additional, Drenck, Niels E., additional, Østergaard, Christian, additional, Kjær, Jesper, additional, Grarup, Jesper, additional, and Lundgren, Jens D., additional

Published
2011
Full Text
View/download PDF

66. The Procalcitonin And Survival Study (PASS) – A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitoninand pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

Author

Jensen, Jens-Ulrik, primary, Lundgren, Bettina, additional, Hein, Lars, additional, Mohr, Thomas, additional, Petersen, Pernille L, additional, Andersen, Lasse H, additional, Lauritsen, Anne Ø, additional, Hougaard, Sine, additional, Mantoni, Teit, additional, Bømler, Bonnie, additional, Thornberg, Klaus J, additional, Thormar, Katrin, additional, Løken, Jesper, additional, Steensen, Morten, additional, Carl, Peder, additional, Petersen, J Asger, additional, Tousi, Hamid, additional, Søe-Jensen, Peter, additional, Bestle, Morten, additional, Hestad, Søren, additional, Andersen, Mads H, additional, Fjeldborg, Paul, additional, Larsen, Kim M, additional, Rossau, Charlotte, additional, Thomsen, Carsten B, additional, Østergaard, Christian, additional, Kjær, Jesper, additional, Grarup, Jesper, additional, and Lundgren, Jens D, additional

Published
2008
Full Text
View/download PDF

67. Investigating the Efficacy of Clinical Trial Monitoring Strategies: Design and Implementation of the Cluster Randomized START Monitoring Substudy.

Author

Hullsiek, Katherine Huppler, Kagan, Jonathan M., Engen, Nicole, Grarup, Jesper, Hudson, Fleur, Denning, Eileen T., Carey, Catherine, Courtney-Rodgers, David, Finley, Elizabeth B., Jansson, Per O., Pearson, Mary T., Peavy, Dwight E., and Belloso, Waldo H.

Subjects
CLINICAL trials, EXPERIMENTAL design
Abstract

The article discusses the study Strategic Timing of Initiating AntiRetroviral Treatment (START) Monitoring Substudy (SMS) to determine whether the addition of on-site monitoring increases participant safety and integrity of clinical trial data. Topics discussed include the theory that the addition of annual on-site monitoring to central and local monitoring will improve site performance and the role of emerging capabilities for secure remote access in molding future monitoring strategies.

Published
2015
Full Text
View/download PDF

68. 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

69. 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, Young, Jim, 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

70. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population: evidence from a large European observational cohort collaboration

Author

Lewden, Charlotte, Bouteloup, Vincent, De Wit, Stéphane, Sabin, Caroline, Mocroft, Amanda, Wasmuth, Jan Christian, van Sighem, Ard, Kirk, Ole, Obel, Niels, Panos, George, Ghosn, Jade, Dabis, François, Mary-Krause, Murielle, Leport, Catherine, Perez-Hoyos, Santiago, Sobrino-Vegas, Paz, Stephan, Christoph, Castagna, Antonella, Antinori, Andrea, d'Arminio Monforte, Antonella, Torti, Carlo, Mussini, Cristina, Isern, Virginia, Calmy, Alexandra, Teira, Ramón, Egger, Matthias, Grarup, Jesper, Chêne, Geneviève, Lewden, Charlotte, Bouteloup, Vincent, De Wit, Stéphane, Sabin, Caroline, Mocroft, Amanda, Wasmuth, Jan Christian, van Sighem, Ard, Kirk, Ole, Obel, Niels, Panos, George, Ghosn, Jade, Dabis, François, Mary-Krause, Murielle, Leport, Catherine, Perez-Hoyos, Santiago, Sobrino-Vegas, Paz, Stephan, Christoph, Castagna, Antonella, Antinori, Andrea, d'Arminio Monforte, Antonella, Torti, Carlo, Mussini, Cristina, Isern, Virginia, Calmy, Alexandra, Teira, Ramón, Egger, Matthias, Grarup, Jesper, and Chêne, Geneviève

Abstract

Background Using data from a large European collaborative study, we aimed to identify the circumstances in which treated HIV-infected individuals will experience similar mortality rates to those of the general population. Methods Adults were eligible if they initiated combination anti-retroviral treatment (cART) between 1998 and 2008 and had one prior CD4 measurement within 6 months. Standardized mortality ratios (SMRs) and excess mortality rates compared with the general population were estimated using Poisson regression. Periods of follow-up were classified according to the current CD4 count. Results Of the 80 642 individuals, 70% were men, 16% were injecting drug users (IDUs), the median age was 37 years, median CD4 count 225/mm3 at cART initiation and median follow-up was 3.5 years. The overall mortality rate was 1.2/100 person-years (PY) (men: 1.3, women: 0.9), 4.2 times as high as that in the general population (SMR for men: 3.8, for women: 7.4). Among 35 316 individuals with a CD4 count ≥500/mm3, the mortality rate was 0.37/100 PY (SMR 1.5); mortality rates were similar to those of the general population in non-IDU men [SMR 0.9, 95% confidence interval (95% CI) 0.7-1.3] and, after 3 years, in women (SMR 1.1, 95% CI 0.7-1.7). Mortality rates in IDUs remained elevated, though a trend to decrease with longer durations with high CD4 count was seen. A prior AIDS diagnosis was associated with higher mortality. Conclusions Mortality patterns in most non-IDU HIV-infected individuals with high CD4 counts on cART are similar to those in the general population. The persistent role of a prior AIDS diagnosis underlines the importance of early diagnosis of HIV infection

71. 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, Wittkop, Linda, 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

72. Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial

Author

Michal Odermarsky, Andrea Antinori, Nina Friis-Moller, Jean-michel Molina, Manuel Marquez, Magnus Gisslen, Mili Estee Torok, Clifford Leen, CARLO FEDERICO PERNO, Vicente Soriano, Mark Boyd, Pythia Nieuwkerk, Linos Vandekerckhove, Anne-Laure Knellwolf, Juan González-García, MAURIZIO MASSELLA, Elizabeth C George, STEFANO VELLA, André Cabié, Laura Richert, Juan Berenguer, Hernando Knobel, Jose Arribas, Julie Fox, Joaquín Portilla, Maladies infectieuses et tropicales, Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Inserm, Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Development and Differentiation, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Stockholm University Library (SUB), Stockholm University, Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Aménagement, Développement, Environnement, Santé et Sociétés (ADES), Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne, 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), DARMIGNY, Sandrine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), Raffi, Franã§oi, Babiker, Abdel G., Richert, Laura, Molina, Jean michel, George, Elizabeth C., Antinori, Andrea, Arribas, Jose R., Grarup, Jesper, Hudson, Fleur, Schwimmer, Christine, Saillard, Juliette, Wallet, Cã©drick, Jansson, Per O., Allavena, Clotilde, Van Leeuwen, Remko, Delfraissy, Jean franã§oi, Vella, Stefano, Chãªne, Geneviãve, Pozniak, Anton, Neat001/anrs143 Study, Group, Castagna, Antonella, Global Health, Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam Public Health, Medical Psychology, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], MESH: Sulfonamides, Lopinavir/ritonavir, HIV Infections, Kaplan-Meier Estimate, Pharmacology, Deoxycytidine, MESH: HIV-1, Emtricitabine, MESH: Anti-HIV Agents, MESH: Treatment Outcome, Darunavir, media_common, Sulfonamides, MESH: Middle Aged, MESH: Drug Resistance, Viral, Medicine (all), Standard treatment, MESH: HIV Infections, General Medicine, Middle Aged, Pyrrolidinones, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Drug Therapy, Combination, Female, MESH: Cholesterol, HDL, MESH: Organophosphonates, MESH: Cholesterol, LDL, medicine.drug, Adult, medicine.medical_specialty, MESH: Adenine, Anti-HIV Agents, Organophosphonates, MESH: Pyrrolidinones, Raltegravir Potassium, Internal medicine, Drug Resistance, Viral, medicine, Humans, media_common.cataloged_instance, European union, Tenofovir, MESH: Kaplan-Meier Estimate, MESH: Humans, Ritonavir, business.industry, Adenine, MESH: Deoxycytidine, Cholesterol, HDL, MESH: Adult, Cholesterol, LDL, Raltegravir, MESH: Male, CD4 Lymphocyte Count, MESH: Drug Therapy, Combination, Regimen, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, MESH: Ritonavir, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract

Summary Background Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Methods Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir–emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962. Findings Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112–133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI −0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively). Interpretation Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. Funding European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.

Published
2014
Full Text
View/download PDF

73. Predictors of CD4(+) T-cell counts of HIV type 1-infected persons after virologic failure of all 3 original antiretroviral drug classes.

Author

Costagliola D, Ledergerber B, Torti C, van Sighem A, Podzamczer D, Mocroft A, Dorrucci M, Masquelier B, de Luca A, Jansen K, De Wit S, Obel N, Fätkenheuer G, Touloumi G, Mussini C, Castagna A, Stephan C, García F, Zangerle R, Duval X, Perez-Hoyos S, Meyer L, Ghosn J, Fabre-Colin C, Kjaer J, Chêne G, Grarup J, Phillips A, Lodwick R, Torti C, Dorrucci M, Günthard HF, Michalik C, Chrysos G, and Castagna A

Subjects
Adult, CD4 Lymphocyte Count, Female, Humans, Male, Middle Aged, Treatment Failure, Viral Load, Anti-Retroviral Agents administration & dosage, HIV Infections drug therapy, HIV Infections immunology
Abstract

Background: Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure., Methods: We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4(+) T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations., Results: The analyses included 2424 individuals with a total of 23 922 CD4(+) T-cell count measurements. In adjusted models (excluding current viral load and year), CD4(+) T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/µL [95% confidence interval {CI}, 3.9-41]; P = .017) or drugs from the new classes (increase, 39 cells/µL [95% CI, 15-62]; P = .001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log(10) copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log(10) copies/mL were associated with CD4(+) T-cell count decreases of 51, 84, 137, and 186 cells/µL, respectively (P < .001)., Conclusions: The approximately linear inverse relationship between log(10) viral load and CD4(+) T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4(+) T-cell counts and few drug options.

Published
2013
Full Text
View/download PDF

74. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial.

Author

Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr T, Andersen MH, Thornberg KJ, Løken J, Steensen M, Fox Z, Tousi H, Søe-Jensen P, Lauritsen AØ, Strange DG, Reiter N, Thormar K, Fjeldborg PC, Larsen KM, Drenck NE, Johansen ME, Nielsen LR, Ostergaard C, Kjær J, Grarup J, and Lundgren JD

Abstract

Objectives: To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients., Design: Secondary analysis from a randomised antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis., Setting: Nine mixed surgical/medical intensive care units across Denmark., Participants: 1200 adult intensive care patients, 18+ years, expected to stay +24 h., Exclusion Criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients., Interventions: Patients were randomised to guideline-based therapy ('standard-exposure' arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements ('high-exposure' arm)., Main Outcome Measures: Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk 'R', Injury 'I' and Failure 'F'. Analysis was by intention to treat., Results: 28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the high-exposure versus 3016/6949 (43.4%) in the 'standard-exposure arm were spent with eGFR <60 ml/min/1.73 m(2), p<0.001. In a multiple effects model, 3 piperacillin/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used: 1.0 ml/min/1.73 m(2)/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m(2)/24 h) vs meropenem: 2.9 ml/min/1.73 m(2)/24 h (2.5 to 3.3 ml/min/1.73 m(2)/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m(2)/24 h (2.3 to 3.1 ml/min/1.73 m(2) /24 h)). eGFR <60 ml/min/1.73 m(2) in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively., Conclusions: Piperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics., Trial Registration: ClinicalTrials.gov identifier: NCT00271752.

Published
2012
Full Text
View/download PDF

75. Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe.

Author

Nakagawa F, Lodwick R, Costagliola D, van Sighem A, Torti C, Podzamczer D, Mocroft A, Ledergerber B, Dorrucci M, Cozzi-Lepri A, Jansen K, Masquelier B, García F, De Wit S, Stephan C, Obel N, Fätkenhaeuer G, Castagna A, Sambatakou H, Mussini C, Ghosn J, Zangerle R, Duval X, Meyer L, Perez-Hoyos S, Fabre Colin C, Kjaer J, Chene G, Grarup J, and Phillips A

Subjects
Adult, Europe epidemiology, Female, HIV genetics, HIV Infections blood, HIV Infections virology, Humans, Incidence, Male, Prevalence, RNA, Viral blood, Anti-HIV Agents therapeutic use, HIV isolation & purification, HIV Infections drug therapy, HIV Infections epidemiology
Abstract

Background: Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years., Methods: Calendar time trends in the incidence and prevalence of TCVF from 2000 to 2009 were assessed in patients who started ART from January 1, 1998, and were followed within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)., Results: Of 91,764 patients followed for a median (interquartile range) of 4.1 (2.0-7.1) years, 2722 (3.0%) developed TCVF. The incidence of TCVF increased from 3.9 per 1000 person-years of follow-up [95% confidence interval (CI): 3.7 to 4.1] in 2000 to 8.8 per 1000 person-years of follow-up (95% CI: 8.5 to 9.0) in 2005, but then declined to 5.8 per 1000 person-years of follow-up (95% CI: 5.6 to 6.1) by 2009. The prevalence of TCVF was 0.3% (95% CI: 0.27% to 0.42%) at December 31, 2000, and then increased to 2.4% (95% CI: 2.24% to 2.50%) by the end of 2005. However, since 2005, TCVF prevalence seems to have stabilized and has remained below 3%., Conclusions: The prevalence of TCVF in people who started ART after 1998 has stabilized since around 2005, which most likely results from the decline in incidence of TCVF from this date. The introduction of improved regimens and better overall HIV care is likely to have contributed to these trends. Despite this progress, calendar trends should continue to be monitored in the long term.

Published
2012
Full Text
View/download PDF

76. 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

Costagliola D, Lodwick R, Ledergerber B, Torti C, van Sighem A, Podzamczer D, Mocroft A, Dorrucci M, Masquelier B, de Luca A, Jansen K, De Wit S, Obel N, Fätkenheuer G, Touoloumi G, Mussini C, Castagna A, Stephan C, García F, Zangerle R, Duval X, Pérez-Hoyos S, Meyer L, Ghosn J, Fabre-Colin C, Kjaer J, Chene G, Grarup J, and Phillips A

Subjects
Adolescent, Adult, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections blood, HIV Infections virology, Humans, Male, Middle Aged, RNA, Viral blood, Regression Analysis, Retrospective Studies, Young Adult, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1
Abstract

Background: Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09., Methods: In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF., Findings: 28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000-02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend was not significant after adjustment (p=0·22)., Interpretation: A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
Full Text
View/download PDF

77. Risk of triple-class virological failure in children with HIV: a retrospective cohort study.

Author

Castro H, Judd A, Gibb DM, Butler K, Lodwick RK, van Sighem A, Ramos JT, Warsawski J, Thorne C, Noguera-Julian A, Obel N, Costagliola D, Tookey PA, Colin C, Kjaer J, Grarup J, Chene G, and Phillips A

Subjects
Adolescent, Anti-Retroviral Agents classification, Child, Child, Preschool, Cohort Studies, Female, HIV Infections transmission, HIV Infections virology, Humans, Infant, Infectious Disease Transmission, Vertical, Kaplan-Meier Estimate, Male, Proportional Hazards Models, Retrospective Studies, Risk, Treatment Failure, Viral Load, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy
Abstract

Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children., Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation., Findings: Of 1007 children followed up for a median of 4·2 (IQR 2·4-6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4-14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6-3·0, p<0·0001])., Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression., Funding: UK Medical Research Council award G0700832., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results