333   GW433908, a Novel Prodrug of the HIV Protease Inhibitor (PI) Amprenavir (APV): Safety, Efficacy, and Pharmacokinetics (PK) (APV20001).

R. Wood*¹, K. Arasteh², R. Pollard³, P. Kaur⁴, O. Nadarer⁴, and M. B. Wire⁴.
¹Somerset Hosp., Cape Town, South Africa;²Auguste-Victoria-Krankenhaus, Berlin, Germany;³Univ. of Texas Medical Branch, Galveston; and⁴Glaxo Wellcome, Res. Triangle Park, NC.

Background:GW433908 is the prodrug of APV and was developed to improve the Agenerase (AGN) formulation, by reducing pill size and count.

Methods:Eighty-fivetreatment naive HIV infected adults were randomized to either 1395 mg (3 tabs) bid or 1860 mg (4 tabs) bid GW433908, or 1200 mg bid AGN for 28 days. After day 28 AGN subjects crossed over to one of the GW433908 doses, and both GW433908 groups crossed over to AGN until Day 42. All dosing groups received abacavir (300 mg bid) + lamivudine (150 mg bid).

Results:Efficacy and PK are summarized in the table below. Baseline HIV-1 RNA and CD4+ counts ranged from (4.52-4.75 log₁₀c/mL) and (177-348 cells/mm³), respectively, between the three groups.

Drug related AEs seen with both doses of GW433908 were similar and included nausea, diarrhea, and headache. AGN drug related AEs included nausea, diarrhea and abdominal pain. Although, C_maxdiffered between both GW433908 doses and APV, overall drug exposure as measured by AUC_{0<RIGHTARROW>12}was similar between all arms.

Conclusions:Treatment with GW433908 resulted in significant reductions in HIV-1 RNA with comparable safety and PK. This new formulation represents a significant advance in the simplification of PI therapy.