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Antimicrobial Agents and Chemotherapy, June 1999, p. 1373-1378, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

ACTG 260: a Randomized, Phase I-II, Dose-Ranging Trial of the Anti-Human Immunodeficiency Virus Activity of Delavirdine Monotherapy

Michael F. Para,^1,* Patricia Meehan,^2, Jeanne Holden-Wiltse,² Margaret Fischl,³ Gene Morse,⁴ Robert Shafer,⁵ Lisa M. Demeter,⁶ Kenneth Wood,⁷ Tom Nevin,⁸ Nzeera Virani-Ketter,^8, and William W. Freimuth⁹ For The Aids Clinical Trials Group Protocol 260 Team

Division of Infectious Disease, The Ohio State University, Columbus, Ohio¹; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts²; Department of Medicine, University of Miami School of Medicine, Miami, Florida³; Department of Pharmacy Practice, State University of New York at Buffalo, Buffalo, New York⁴; Frontier Science and Technology Research Foundation, Amherst, New York⁵; Department of Medicine, Stanford University, Palo Alto, California⁶; Infectious Disease Unit, University of Rochester, Rochester, New York⁷; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland⁸; and The Pharmacia & Upjohn Company, Kalamazoo, Michigan⁹

Received 17 September 1998/Returned for modification 20 January 1999/Accepted 16 March 1999

ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 µM). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV-1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log₁₀ for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log₁₀ reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log₁₀, respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance.

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^* Corresponding author. Mailing address: Ohio State University ACTU, Room 4725, University Hospitals Clinic, 456 West 10th Ave., Columbus, OH 43210. Phone: (614) 293-3870. Fax: (614) 293-5240. E-mail: para.1{at}osu.edu.

Present address: 30 Overbrook Dr., Wellesley, MA 02181.

Present address: VaxGen, Inc., Brisbane, CA 94005-1841.

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Antimicrobial Agents and Chemotherapy, June 1999, p. 1373-1378, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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