Summary of Work: Protease inhibitors are potent anti-retroviral agents that delay the progression of HIV disease, yet clinical failures due to retroviral resistance are becoming more common. In this protocol the genotypic and phenotypic correlates of protease failure are being explored, as are other causes of drug failure, such as drug interactions and poor absorption. The activity in vivo of an experimental nucleoside and an experimental protease inhibitor are being examined. Patients who fail a licensed protease inhibitor will be randomized to a combination regimen consisting of GW1592, Vl41, and DMP-226. Frequency and durability of response will be assessed and correlated with pre- regimen markers such as CD4 count and HIV RNA level.