The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of human immunodeficiency virus (HIV)-infected, indinavir-experienced patients, was designed to study the durability of "salvage" treatment regimens. Patients received saquinavir in combination with either ritonavir or nelfinavir and, in addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic response at weeks 12-16 were eligible to continue therapy in the extension through week 48. Of the 105 eligible subjects who were enrolled in the extension, 86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels ≤500 copies/mL at week 48. For these 86 subjects who completed 48 weeks, the median change in CD4 cell count from baseline was +72 cells/mm3. Greater body weight, higher CD4 cell count, and greater degree of phenotypic susceptibility to indinavir and saquinavir at baseline were significantly associated with durable virologic suppression. These results show that some patients who experience treatment failure can demonstrate durable virologic and immunologic responses with salvage antiretroviral regimens.