ObjectiveTo determine the impact of prior nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy, genotypic resistance, and other variables on response to efavirenz (EFV)- and adefovir dipivoxil (ADV)-based salvage therapy.DesignRetrospective clinical cohort study.SettingOne university and one community-based HIV clinic.Study subjectsAll 33 patients who were coenrolled in both the EFV and ADV expanded access programs.InterventionsPatients received EFV 600 mg/day and ADV 120 mg/day in addition to other antiretroviral agents.Outcome measureHIV viral load (<500 copies/ml) at 12 and 24 weeks.Results10 of 33 (30%) patients at 12 weeks and 8 of 33 (24%) patients at 24 weeks had viral loads <500 copies/ml. Prior NNRTI use and a history of any NNRTI-associated mutations predicted failure. Patients with Y181C or G190A single mutations had an initial greater magnitude of viral load suppression than those with K103N, but this advantage was short lived. No one with any NNRTI mutations responded with a viral load <500 copies/ml at 12 or 24 weeks.ConclusionsEFV/ADV-based salvage yielded viral load suppression at 24 weeks in 42% (8 of 19) of patients who were highly NRTI and protease inhibitor experienced but NNRTI naive. NNRTI-experienced study subjects had a poor response regardless of the specific NNRTI resistance mutation they harbored.