Session 66Poster Presentations New Antiretrovirals Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall A
552 Sustained Anti-HIV-1 Effect of Racivir Combined with D4T and Sustiva Following a 14-day Treatment of Infected Volunteers M. J. Otto*1, K. Arastèh2, P. Kreckel2, D. Drauz2, A. Beard1, L. Cartee1, S.J. Hurwitz3, D.C. Liotta4, R.F. Schinazi3, R. L. Murphy5 1Pharmasset, Inc, Tucker, GA; 2Epimed GmbH, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany; 3Emory Univ Sch Med, and Veterans Affairs Med Ctr, Atlanta, GA; 4Emory Univ, Atlanta, GA; and 5Northwestern Univ, Chicago, IL
Background: Racivir (RCV, [±]-2-hydroxymethyl-5-[5-fluorocytosine-1-yl]-1,3-oxathiolane) is a nucleoside analog with potent and selective activity against both HIV and HBV in cell culture and in animal models. It is well tolerated in preclinical safety assessment studies in dogs (> 100 mg/kg/day for 28 days) and rats (> 1 g/kg/day for 28 days) with excellent oral bioavailability in animals and humans. It is being developed under a U.S. IND for the treatment of HIV-1.
Methods: RCV was administered once a day orally for 14 days at doses of 200, 400, or 600 mg in combination with D4T and Sustiva to HIV-1 infected treatment naïve male volunteers in a Phase Ib/IIa study. Entry criteria included HIV RNA levels > 5,000 copies/ml and CD4 cells > 50 cells/ml. Six (6) volunteers at each dose were monitored for a total of 35 days for tolerance, pharmacokinetics, and plasma HIV RNA levels. The volunteers received no antiretroviral therapy from day 15 to day 35.
Results: Oral administration of 200, 400, or 600 mg of RCV in combination with D4T and Sustiva resulted in an expected rapid initial drop in viral load, with mean reductions ranging from 1.13-1.42 logs by day 4. Mean HIV RNA levels continued to drop more slowly through the end of treatment on day 14 with mean drops in viral load ranging from 2.02-2.43 logs. Surprisingly, upon cessation of therapy HIV RNA levels remained suppressed at all dose levels for more than 2 wks. Mean viral loads ranged from 2.1-2.6 logs below baseline through day 28. By day 35, HIV RNA levels began to increase, but still remained more than 1 log below baseline levels. RCV in combination with D4T and Sustiva was well tolerated at all doses tested.
Conclusions: Racivir in combination with D4T and Sustiva exhibited a significant post-antibiotic effect in HIV-1 infected antiretroviral therapy naïve individuals with HIV RNA levels remaining suppressed for up to 2 wks after cessation of therapy. These data strongly suggest that Racivir will be useful as a once-a-day component of treatment regimens for HIV-1 infected individuals.