The HIV-CAUSAL Collaboration
Writing Committee: Lauren E. Cain, PhD; Roger Logan, PhD; James M. Robins, MD; Jonathan A.C. Sterne, PhD; Caroline Sabin, PhD; Loveleen Bansi, MSc; Amy Justice, MD, PhD; Joseph Goulet, PhD; Ard van Sighem, PhD; Frank de Wolf, MD; Heiner C. Bucher, MD; Viktor von Wyl, PhD; Anna Esteve, PhD; Jordi Casabona, MD, MPH; Julia del Amo, MD, PhD; Santiago Moreno, MD; Rémonie Seng, MD; Laurence Meyer, PhD; Santiago Pérez-Hoyos, PhD; Roberto Muga, MD, PhD; Sara Lodi, PhD; Emilie Lanoy, PhD; Dominique Costagliola, PhD; and Miguel A. Hernán, MD, DrPH.
Grant Support: By the National Institutes of Health (grants R01-AI073127 and U10-AA013566) and the Medical Research Council (grant G0700820).
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2963.
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Cain (e-mail, email@example.com).
Requests for Single Reprints: Lauren E. Cain, PhD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Cain, Logan, Robins, and Hernán: Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115.
Dr. Sterne: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, United Kingdom.
Dr. Sabin and Ms. Bansi: Research Department of Infection and Population Health, University College London Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom.
Drs. Justice and Goulet: Veterans Affairs Connecticut Healthcare System and Yale University School of Medicine, Department of Internal Medicine, 950 Campbell Avenue, 11-ACSLG, Building 35A, 2nd Floor, Room 212, New Haven, CT 06516.
Drs. van Sighem and de Wolf: Stichting HIV Monitoring, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Dr. Bucher: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, CH-4031 Basel, Switzerland.
Dr. von Wyl: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Räemistrasse 100, 8091 Zurich, Switzerland.
Drs. Esteve and Casabona: CEEISCAT, Hospital Universitari Germans Trias i Pujol, Carretera Canyet s/n, 08916 Badalona, Spain.
Dr. del Amo: National Center of Epidemiology, Instituto de Salud Carlos III, Sinesio Delgado 6, 28029 Madrid, Spain.
Dr. Moreno: Servicio de Enfermedades Infecciosas, Hospital Ramón y Cajal, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain.
Drs. Seng and Meyer: INSERM U1018, Hôpital de Bicêtre, 82 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.
Dr. Pérez-Hoyos: Methodological Support Unit on Biomedical Research (USMIB), Vall d'Hebron Hospital Research Institute (VHIR), Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Dr. Muga: Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain.
Dr. Lodi: Clinical Trials Unit, Medical Research Council, 222 Euston Road, London NW1 2DA, United Kingdom.
Dr. Lanoy: INSERM U943 and Université Pierre et Marie Curie, 56 boulevard V Auriol, BP 335, 75625 Paris Cedex 13, France.
Dr. Costagliola: INSERM U943, Université Pierre et Marie Curie and Hôpital Pitié-Salpétrière, 56 boulevard V Auriol, BP 335, 75625 Paris Cedex 13, France.
Author Contributions: Conception and design: L.E. Cain, J.A.C. Sterne, C. Sabin, J. Goulet, F. de Wolf, H.C. Bucher, J. Casabona, J. del Amo, D. Costagliola, M.A. Hernán.
Analysis and interpretation of the data: L.E. Cain, R. Logan, J.A.C. Sterne, C. Sabin, A. Justice, J. Goulet, F. de Wolf, J. del Amo, L. Meyer, D. Costagliola, M.A. Hemán.
Drafting of the article: L.E. Cain, J.M. Robins, J.A.C. Sterne, A. Justice, J. Goulet, S. Moreno, S. Lodi, E. Lanoy, D. Costagliola, M.A. Hernán.
Critical revision of the article for important intellectual content: L.E. Cain, J.M. Robins, J.A.C. Sterne, C. Sabin, A. Justice, J. Goulet, F. de Wolf, H.C. Bucher, V. von Wyl, J. Casabona, J. del Amo, S. Moreno, L. Meyer, S. Lodi, E. Lanoy, D. Costagliola, M.A. Hernán.
Final approval of the article: L.E. Cain, J.A.C. Sterne, C. Sabin, L. Bansi, A. Justice, J. Goulet, A. van Sighem, F. de Wolf, H.C. Bucher, V. von Wyl, A. Esteve, J. Casabona, J. del Amo, S. Moreno, R. Seng, L. Meyer, S. Pérez-Hoyos, S. Lodi, E. Lanoy, D. Costagliola, M.A. Hernán.
Provision of study materials or patients: C. Sabin, A. van Sighem, H.C. Bucher, A. Esteve, J. Casabona, J. del Amo, S. Moreno, L. Meyer, S. Pérez-Hoyos, D. Costagliola.
Statistical expertise: L.E. Cain, R. Logan, J.M. Robins, J.A.C. Sterne, J. Goulet, J. Casabona, D. Costagliola, M.A. Hernán.
Obtaining of funding: J.A.C. Sterne, J. del Amo, M.A. Hernán.
Administrative, technical, or logistic support: R. Logan, J. Casabona, M.A. Hernán.
Collection and assembly of data: I.E. Cain, C. Sabin, L. Bansi, A. Justice, J. Goulet, A. van Sighem, F. de Wolf, H.C. Bucher, V. von Wyl, A. Esteve, J. Casabona, J. del Amo, R. Seng, L. Meyer, S. Pérez-Hoyos, S. Lodi, D. Costagliola, M.A. Hernán.
For a list of Writing Committee members, see end of article; for a list of the contributors to the HIV-CAUSAL Collaboration, see Appendix 1.
. When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries: An Observational Study. Ann Intern Med. 2011;154:509-515. doi: 10.7326/0003-4819-154-8-201104190-00001
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Published: Ann Intern Med. 2011;154(8):509-515.
Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 109 cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.
To identify the optimal CD4 cell count at which cART should be initiated.
Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 109 cells/L.
HIV clinics in Europe and the Veterans Health Administration system in the United States.
20 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 109 cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 109 cells/L and were included in the analysis.
Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.
Compared with initiating cART at the CD4 cell count threshold of 0.500 × 109 cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.
CD4 cell count at cART initiation was not randomized. Residual confounding may exist.
Initiation of cART at a threshold CD4 count of 0.500 × 109 cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 109 cells/L.
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Hospital Medicine, Infectious Disease, HIV.
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