Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland (G.E.P.)

Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland (T.B., K.R.)

Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and Brooke Army Medical Center, Joint Base San Antonio-Fort Sam Houston, Texas (D.A.L.)

University of Maryland Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland (R.R.R.)

Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, California (S.B.D.)

National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, and Lee Kong Chian School of Medicine, Singapore (D.C.L.)

Department of Pulmonary and Critical Care Medicine, Northwest Permanente PC, and Kaiser Permanente Northwest Center for Health Research, Portland, Oregon (R.A.M.)

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (N.A.H.)

Department of Medicine, Division of Infectious Diseases and International Medicine, University of Minnesota Medical School, Minneapolis, Minnesota (S.K.)

Division of Infectious Diseases, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania (C.I.P.)

Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina (C.R.W.)

Department of Medicine, Denver Health Hospital Authority, Denver, Colorado, and University of Colorado School of Medicine, Aurora, Colorado (M.G.F.)

Hope Clinic, Emory Vaccine Center, Infectious Diseases Division, Atlanta, Georgia (N.G.R.)

Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (G.A.D., S.U.N., K.M.T.)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, California (D.A.S.)

Madigan Army Medical Center, Tacoma, Washington, Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland (R.E.C.)

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (R.T.D.)

Division of Infectious Diseases, Emory University School of Medicine, and National Emerging Special Pathogens Training and Education Center, Atlanta, Georgia (A.K.M.)

Departments of Molecular Virology and Microbiology and Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas (J.A.W.)

Division of Infectious Diseases, University of Miami, Miami, Florida (J.G.C.)

Department of Medicine, University of California, Irvine, Irvine, California (A.N.A.)

Madigan Army Medical Center, Tacoma, Washington, and Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland (C.J.C.)

Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, Texas (C.B.L.)

Department of Internal Medicine, Division of Infectious Disease and Geographic Medicine, UT Southwestern Medical Center, and Parkland Health & Hospital System, Dallas, Texas (M.K.J.)

Wake Forest University School of Medicine, Winston-Salem, North Carolina, and Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland (R.C.M.)

Emory University School of Medicine, Rollins School of Public Health, and Atlanta Veterans Affairs Medical Center, Atlanta, Georgia (V.C.M.)

Department of Medicine, Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York (R.G.)

Department of Medicine, Division of Hospital Medicine, University of Minnesota, Minneapolis, Minnesota (S.H.)

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland (T.H.B.)

Department of Medicine, Baylor College of Medicine, Houston, Texas (R.L.A.)

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and Walter Reed National Military Medical Center, Bethesda, Maryland (A.G.)

Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska (C.A.G.)

Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, California (C.A.B.)

Division of Infectious Diseases, Evergreen Health Medical Center, Kirkland, Washington (D.L.)

Department of Internal Medicine, Stanford University Medical Center, Palo Alto, California (N.A.)

Saint Louis University and St. Louis VA Medical Center, Saint Louis, Missouri (S.L.G.)

Division of Infectious Diseases, University of California, Davis, Sacramento, California (S.H.C.)

Naval Medical Center Portsmouth, Portsmouth, Virginia, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland (T.L.)

Department of Medicine, Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania (W.R.S.)

Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama (N.E.)

Division of Infectious Diseases/Clinical Trials Unit, University of Pennsylvania, Philadelphia, Pennsylvania (P.T.).

Disclaimer: The content of this article does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services; the Uniformed Services University of the Health Sciences; the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; the Departments of the Army, Navy, or Air Force; the Defense Health Agency; the Department of Defense; or the Department of Veterans Affairs, nor does any mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

Acknowledgment: The authors thank Lori Dodd for the initial idea for this manuscript and Alyssa La Regina for outstanding administrative support. This work utilized the computational resources of the National Institutes of Health (NIH) high-performance computing Biowulf cluster (http://hpc.nih.gov).

Financial Support: This work was supported with funds from the NIAID Division of Intramural Research and from the National Cancer Institute of the NIH under contract no. 75N91019D00024. The analysis used data from ACTT-1 (14), ACTT-2 (16), ACTT-3 (15), and ACTT-4 (17). The ACTT trials were sponsored and primarily funded by the NIAID of the NIH, Bethesda, Maryland. These trials have been funded in part with federal funds from NIAID and the National Cancer Institute of the NIH under contract HHSN261200800001E 75N910D00024, task order number 75N91019F00130/75N91020F00010, and by the Department of Defense, Defense Health Program. These trials have been supported in part by the NIAID of the NIH under award numbers UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689. These trials have also been funded in part by the governments of Denmark, Japan, Mexico, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council (MRC_UU_12023/23).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-2116.

Data Sharing Statement: The following data will be made available with publication: deidentified participant data and data dictionary (https://accessclinicaldata.niaid.nih.gov). The following supporting documents will be made available with publication: statistical/analytical code (https://github.com/gepotter/actt1234). To access the data, a data access request (DAR) is required to be submitted to NIAID by the requester using the electronic DAR form as part of the process for requesting access found on the [email protected] data platform. The DAR will be reviewed by the NIAID Clinical Trials Data Access Committee. Upon approval of the DAR by NIAID and before accessing the data set, the primary requester and their institutional official will be notified and will be required to agree to and sign an NIAID Data Use Agreement. The agreement outlines the terms of use of the data and can be found on the [email protected] data platform.

Corresponding Author: Gail E. Potter, PhD, National Institutes of Health, 5601 Fisher's Lane, MSC 9820, Rockville, MD 20892-9820; e-mail, gail.[email protected]gov.

Author Contributions: Conception and design: G.E. Potter, T. Bonnett, D.C. Lye, R.A. Mularski, N.A. Hynes, C.I. Paules, C.R. Wolfe, R.E. Colombo, J.A. Whitaker, C.J. Colombo, V.C. Marconi, R. Grossberg, S. Hozayen, C.A. Benson, S.U. Nayak, N. Erdmann, K.M. Tomashek, P. Tebas.

Analysis and interpretation of the data: G.E. Potter, T. Bonnett, K. Rubenstein, D.A. Lindholm, R.R. Rapaka, S.B. Doernberg, D.C. Lye, R.A. Mularski, N.A. Hynes, S. Kline, C.R. Wolfe, N.G. Rouphael, G.A. Deye, D.A. Sweeney, R.E. Colombo, R.T. Davey, J.A. Whitaker, J.G. Castro, A.N. Amin, C.B. Levine, M.K. Jain, R.C. Maves, V.C. Marconi, S. Hozayen, T.H. Burgess, R.L. Atmar, C.A. Benson, N. Ahuja, S.L. George, S.U. Nayak, S.H. Cohen, N. Erdmann, K.M. Tomashek, P. Tebas.

Drafting of the article: G.E. Potter, R.A. Mularski, N.A. Hynes, C.R. Wolfe, G.A. Deye, D.A. Sweeney, R.E. Colombo, J.G. Castro, A.N. Amin, C.J. Colombo, C.B. Levine, R.C. Maves, V.C. Marconi, S. Hozayen, R.L. Atmar, C.A. Benson, D. Lopez de Castilla, S.L. George, S.U. Nayak, N. Erdmann, K.M. Tomashek, P. Tebas.

Critical revision for important intellectual content: G.E. Potter, T. Bonnett, K. Rubenstein, D.A. Lindholm, R.R. Rapaka, S.B. Doernberg, D.C. Lye, R.A. Mularski, N.A. Hynes, S. Kline, C.I. Paules, C.R. Wolfe, M.G. Frank, N.G. Rouphael, G.A. Deye, D.A. Sweeney, R.E. Colombo, A.K. Mehta, J.A. Whitaker, J.G. Castro, A.N. Amin, C.J. Colombo, C.B. Levine, R.C. Maves, R. Grossberg, S. Hozayen, R.L. Atmar, A. Ganesan, C.A. Gomez, C.A. Benson, S.L. George, S.U. Nayak, T. Lalani, N. Erdmann, K.M. Tomashek, P. Tebas.

Final approval of the article: G.E. Potter, T. Bonnett, K. Rubenstein, D.A. Lindholm, R.R. Rapaka, S.B. Doernberg, D.C. Lye, R.A. Mularski, N.A. Hynes, S. Kline, C.I. Paules, C.R. Wolfe, M.G. Frank, N.G. Rouphael, G.A. Deye, D.A. Sweeney, R.E. Colombo, R.T. Davey, A.K. Mehta, J.A. Whitaker, J.G. Castro, A.N. Amin, C.J. Colombo, C.B. Levine, M.K. Jain, R.C. Maves, V.C. Marconi, R. Grossberg, S. Hozayen, T.H. Burgess, R.L. Atmar, A. Ganesan, C.A. Gomez, C.A. Benson, D. Lopez de Castilla, N. Ahuja, S.L. George, S.U. Nayak, S.H. Cohen, T. Lalani, W.R. Short, N. Erdmann, K.M. Tomashek, P. Tebas.

Provision of study materials or patients: D.A. Lindholm, R.R. Rapaka, D.C. Lye, R.A. Mularski, N.A. Hynes, S. Kline, M.G. Frank, N.G. Rouphael, R.E. Colombo, R.T. Davey, J.A. Whitaker, C.J. Colombo, R.C. Maves, R. Grossberg, R.L. Atmar, A. Ganesan, C.A. Benson, N. Ahuja, S.H. Cohen, T. Lalani, P. Tebas.

Statistical expertise: G.E. Potter, K. Rubenstein.

Obtaining of funding: D.C. Lye.

Administrative, technical, or logistic support: D.A. Lindholm, N.G. Rouphael, R.L. Atmar.

Collection and assembly of data: D.A. Lindholm, R.R. Rapaka, S.B. Doernberg, D.C. Lye, R.A. Mularski, S. Kline, N.G. Rouphael, R.E. Colombo, R.T. Davey, A.K. Mehta, J.A. Whitaker, A.N. Amin, R.C. Maves, A. Ganesan, C.A. Benson, D. Lopez de Castilla, S.U. Nayak, N. Erdmann, K.M. Tomashek, P. Tebas.

This article was published at Annals.org on 29 November 2022.

* Drs. Tomashek and Tebas contributed equally to this work.