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Antimicrobial Agents and Chemotherapy, October 2001, p. 2733-2739, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2733-2739.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Phase I/II Trial of the Pharmacokinetics, Safety, and Antiretroviral Activity of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Adults

Patricia Barditch-Crovo,1,* Steven G. Deeks,2 Ann Collier,3 Sharon Safrin,4 Dion F. Coakley,5 Michael Miller,5 Brian P. Kearney,5 Rebecca L. Coleman,5 Patrick D. Lamy,5 James O. Kahn,2 Ian McGowan,5 and Paul S. Lietman1

The Johns Hopkins University School of Medicine, Baltimore, Maryland1; San Francisco General Hospital AIDS Program, University of California, San Francisco,2 and Gilead Sciences, Inc.,5 Foster City,4 California; and University of Washington, Seattle, Washington3

Received 25 January 2001/Returned for modification 26 April 2001/Accepted 11 July 2001

Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period. Thereafter, subjects received their assigned study drug once daily for 28 days. Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing. Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg, but there was no increase in virus suppression between the 300- and 600-mg dose cohorts, despite dose-proportional increases in drug exposure. Grade III or IV adverse events were limited to laboratory abnormalities, including elevated creatine phosphokinase and liver function tests, which resolved with or without drug discontinuation and without sequelae. No patients developed detectable sequence changes in the reverse transcriptase gene.

* Corresponding author. Mailing address: Harvey 502, The Johns Hopkins Hospital, 600 N. Wolfe St. Baltimore, MD 21287. Phone: (410) 614-1147. Fax: (410) 955-9708. E-mail: pbarditc{at}jhmi.edu.

Antimicrobial Agents and Chemotherapy, October 2001, p. 2733-2739, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2733-2739.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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