Author Contributions: Dr Swindells had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Swindells, DiRienzo, Wilkin, Fletcher, Margolis, Thal, Godfrey, Bastow, McKinnon, Mellors.
Acquisition of data: Swindells, Wilkin, Margolis, Bastow, Ray, Combs, McKinnon.
Analysis and interpretation of data: Swindells, DiRienzo, Wilkin, Fletcher, Margolis, Thal, Godfrey, Wang, McKinnon, Mellors.
Drafting of the manuscript: Swindells, DiRienzo, Fletcher, Margolis, Wang, McKinnon, Mellors.
Critical revision of the manuscript for important intellectual content: Swindells, DiRienzo, Wilkin, Fletcher, Margolis, Thal, Godfrey, Bastow, Ray, Combs, McKinnon, Mellors.
Statistical analysis: Swindells, DiRienzo, Fletcher, Wang.
Obtained funding: Swindells, Wilkin, Margolis.
Administrative, technical, or material support: Swindells, Wilkin, Fletcher, Margolis, Thal, Godfrey, Bastow, Ray, Combs, McKinnon.
Study supervision: Swindells, Wilkin, Fletcher, Margolis, Mellors.
Financial Disclosures: Dr Swindells reports receiving research grants or contracts from or was a consultant for Abbott Pharmaceuticals, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, and Pfizer; Dr Wilkin reports serving as a consultant for Bristol-Myers Squibb and receiving an honorarium from Abbott Laboratories; Dr Fletcher reports participating on ad hoc advisory boards for Bristol-Myers Squibb, Glaxo Inc, Roche Inc, and Tibotec Inc, and has received honoraria for this participation; Dr Margolis reports financial affiliations with Gilead Sciences, Monogram Biosciences, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Abbott, Boehringer-Ingelheim, Pfizer, Biotron Ltd, Hoffman-La Roche, and Trimeris; Dr Thal reports that he was an employee of and held stock in Bristol-Myers Squibb; Ms Ray reports that she has received honoraria for speaking engagements for GlaxoSmithKline in the past year; Dr McKinnon reports receiving a research grant from the BMS Foundation; and Dr Mellors reports that during the past 5 years, he has been a consultant to Abbott Laboratories, Bristol-Myers-Squibb, Agouron Pharmaceuticals, Boehringer-Ingelheim, Gilead Sciences, GlaxoSmithKline, Intelligent Therapeutic Solutions, Merck, Noviro/Idenix, Pharmasset, Trimeris, and Visible Genetics, and that he currently is a consultant for Abbott Laboratories, Gilead Sciences, and Merck. He also reports that during the past 5 years, he has owned stock or stock options in Achillion Pharmaceuticals, Novirio/Idenix, Intelligent Therapeutic Solutions, Pharmasset, Triangle Pharmaceuticals, and Virco-Tibotec, and that he currently owns stock options in Achillion Pharmaceuticals and Pharmasset. He also reports that he has filed patents for High Efficiency Single Genome Sequencing of HIV, for Novel HIV-1 Drug Resistance Mutations, and for Multigenome Sequencing Methods. Drs Godfrey and Coombs, and Mss Bastow and Wang reported no disclosures.
Funding/Support: This work was supported by NIH grants AI38858, AI38855, AI27666, AI46383, AI27661, AI39156, AI25897, AI25868, AI46376, AI34853, AI34832, AI32770, and AI46386 and a Virology Support Laboratory subcontract of the ACTG Central Group Grant (U01 AI38858). Industry support from Bristol-Myers Squibb and Abbott Laboratories was in the form of supplying study drugs and participation on the protocol team.
Role of the Sponsor: The study was designed and conducted by investigators of the AIDS Clinical Trials Group (ACTG). Pharmaceutical company representatives on the protocol team had an opportunity to comment on the study design, but all final design decisions were made by the investigators. The National Institute of Allergy and Infectious Disease (NIAID) provided final approval of the study prior to implementation. Conduct of the study was entirely the responsibility of the investigators, with regulatory oversight by the NIAID. Data collection, management, and interpretation were entirely the responsibility of the ACTG investigators. Statistical analysis was conducted by A. Gregory DiRienzo, PhD, and Hongying Wang, MS, of the Statistical and Data Analysis Center (SDAC) at Harvard School of Public Health, Boston, Mass. All members of the protocol team, including pharmaceutical company representatives and the NIAID, had an opportunity to comment on interpretation of the data, but final decisions regarding data interpretation were the prerogative of the ACTG investigators. The manuscript was prepared by a writing team comprising Drs Swindells, DiRienzo, Fletcher, and Mellors and circulated to coauthors for review, comment, and approval. Once all of the authors had granted approval, the manuscript was circulated to protocol team members, including the pharmaceutical company representatives and the NIAID, for review and comment. The manuscript also received internal review by the ACTG scientific leadership and by the ACTG Statistics and Data Analysis Center prior to submission. Final responsibility for approval of the manuscript rests with the authors.
AIDS Clinical Trials Group 5201 Study Team:Protocol Chair: Susan Swindells, MD (University of Nebraska Medical Center, Omaha); Vice Chair: Timothy Wilkin, MD, MPH (Weill Medical College of Cornell University, New York, NY); Clinical Trials Specialist: Barbara Bastow, RN, BSN (Adult AIDS Clinical Trials Group Operations Center, Silver Spring, Md); Statisticians: Greg DiRienzo, PhD, Hongying Wang, MS (Statistical and Data Analysis Center/Harvard School of Public Health, Boston, Mass); Data Manager: Stéphannie Charles, BA (Frontier Science & Technology Research Foundation, Amherst, NY); Pharmacist: Elaine Ferguson, RPh, MS (Division of Acquired Immunodeficiency Syndrome, NIAID, NIH), Bethesda, Md; Virologist and Investigator: John W. Mellors, MD (University of Pittsburgh School of Medicine, Pittsburgh, Pa); Pharmacologist: Courtney V. Fletcher, PharmD (University of Colorado Health Science Center, Denver); Investigators: David M. Margolis, MD (University of Texas Southwestern Medical Center, Dallas, Tex), John McKinnon, MD (University of Pittsburgh Medical Center, Pittsburgh, Pa); Field Representative: Todd Stroberg, RN (Cornell Clinical Trials Unit-Chelsea, New York, NY); Laboratory Technologist: Lori Mong-Kryspin, BS, MT (Ohio State University, Columbus); Constituency Group Representative: Philip Anthony (O’Fallon, Ill); Industry Representatives: Gary D. Tahl, MD (Bristol-Myers Squibb Co, Plainsboro, NJ), William Chris Woodward, DO (Abbott Laboratories, Nicholasville, Ky); Laboratory Data Coordinator: Courtney Ashton, BS, MT (Frontier Science & Technology Research Foundation, Amherst, NY).
Sites and Contributors: Cathi J. Basler, RN, MSN, CANP, John Koeppe, MD (University of Colorado Health Sciences Center, Denver); Charles B. Hicks, MD, Robin L. May, RN, MSN (Duke University Medical Center, Durham); Debbie Slamowitz, RN, BSN, ACRN, Sylvia Stoudt, RN (Stanford University, Stanford, Calif); Jeffery Meier, MD, Barbara Ann Wiley, BSN, RN (University of Iowa Hospitals and Clinics, Iowa City); Chip Lohner, MA, Philip Keiser, MD (University of Texas, Southwestern Medical Center, Dallas); Kristine Patterson, MD, Susan Marie Richard, MSN (University of North Carolina, Chapel Hill); Nancy K. Mantz, MSN, CRNP, CCRC, Deborah McMahon, MD (University of Pittsburgh, Pittsburgh, Pa); Santiago Marrero, MD, Jorge L. Santana, MD (University of Puerto Rico, San Juan); Linda Hinds, RN, Judith Feinberg, MD (University of Cincinnati, Cincinnati, Ohio); Scott Souza, PharmD, Debra M. Ogata-Arakaki, RN (University of Hawaii at Manoa); Frances J. Van Meter, RN, ARNP, MSN, Sarah Elizabeth Roth, RN, BSN (University of Nebraska Medical Center, Omaha).
Previous Presentation: Presented in part at the 13th Conference on Retroviruses and Opportunistic Infections, February 5-8, 2006, Denver, Colo.
Acknowledgment: We thank William Chris Woodward, DO, Antiviral Global Project Team, Abbott Laboratories, for participation on the protocol team and provision of study drugs; Brian J. Sycks, BS, University of Washington, for assistance with analysis of HIV-1 RNA in seminal plasma; Erin M. Werner, MS, for assistance with pharmacokinetic analyses; Todd Stroberg, RN, BSN, Cornell Clinical Trials Unit, for participation as the field representative; Lori Mong-Kryspin, BS, MT(ASCP), Ohio State University, for participation as the laboratory technologist; Peter Bohlin, Harvard School of Public Health for assistance with data presentation; and especially the participants in this study. Elaine Ferguson, RPh, MS, Division of AIDS, was the Division of Acquired Immunodeficiency Syndrome (DAIDS) pharmacist; Stéphannie Charles, BA, Frontier Science & Technology Research Foundation was the data manager; Courtney Ashton, BS, MT, Frontier Science & Technology Research Foundation, was the laboratory data coordinator; and Philip Anthony, O’Fallon, Ill, was the Constituency Group Representative. Compensation was not received by any of these individuals.