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Antimicrobial Agents and Chemotherapy, July 2005, p. 2828-2833, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2828-2833.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Safety, Pharmacokinetics, and Efficacy of (+/–)-ß-2',3'-Dideoxy-5-Fluoro-3'-Thiacytidine with Efavirenz and Stavudine in Antiretroviral-Naïve Human Immunodeficiency Virus-Infected Patients

EPIMED GmbH, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany,¹ Northwestern University, Chicago, Illinois,² Emory University School of Medicine and VA Medical Center, Decatur, Georgia,³ Pharmasset, Inc., Tucker, Georgia⁴

Received 27 July 2004/ Returned for modification 20 September 2004/ Accepted 18 March 2005

Racivir [RCV; (+/–)-ß-2',3'-dideoxy-5-fluoro-3'-thiacytidine], a 50:50 racemic mixture of the two ß nucleoside enantiomers, is currently in development for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. RCV was administered once a day orally for 14 days at doses of 200, 400, or 600 mg in combination with stavudine and efavirenz to HIV-1-infected treatment-naïve male volunteers in a phase Ib/IIa study. Six volunteers at each dose were monitored for a total of 35 days for tolerance, pharmacokinetics, and plasma HIV RNA levels. RCV in combination with stavudine and efavirenz was well tolerated at all doses tested. Pharmacokinetic parameters were dose proportional, and the maximum concentration of drug in serum at all doses exceeded the 90% effective concentration for wild-type HIV-1. Viral loads dropped as expected in all dosage groups, with mean reductions from 1.13 to 1.42 log₁₀ by day 4 and 2.02 to 2.43 log₁₀ by day 14. HIV RNA levels remained suppressed for more than 2 weeks in the absence of any additional therapy, with mean viral loads ranging from 2.1 to 2.6 log₁₀ below baseline through day 28. By day 35, HIV RNA levels began to increase but still remained >1 log₁₀ below baseline levels.