Clinical experience with adding delavirdine to combination therapy in patients in whom multiple antiretroviral treatment including protease inhibitors has failed

To determine the effectiveness and safety of adding delavirdine mesylate to a treatment regimen that included indinavir and nucleoside analog reverse transcriptase inhibitors in patients in whom combination therapy had failed. Observational study. Private practice. HIV-1-positive patients with peripheral blood CD4+ lymphocyte counts < 300 x 10(6)/l in whom antiretroviral therapy had failed or whose condition was deteriorating. Of the 53 patients who were eligible for the study, 47 took part; for the majority of these patients indinavir combination therapy had been unsuccessful. the majority of the patients were male (98%), white (92%) and homo/bisexuals (96%). Delavirdine added to current therapy (usually zidovudine, indinavir and lamivudine); in approximately half of the patients zidovudine was replaced with stavudine. Plasma HIV-1 RNA levels; peripheral blood CD4+ and CD8+ lymphocyte counts. Safety of the therapy was assessed by monitoring side-effects. Mean baseline CD4+ lymphocyte count was 127 x 10(6)/l and mean baseline HIV-1 plasma RNA was 5 log10 copies/ml. Adding delavirdine to the therapeutic regimen produced a rapid and sustained decrease in the mean plasma HIV-1 RNA of 1.1 log10 copies/ml over 6 months; 18-21% of patients showed decreases of 2-3 log10 copies/ml. Viral burden in 33% of subjects declined below the assay's limit of detection (2.6 log10 copies/ml) after 6 months. CD4+ lymphocyte counts increased by 66-90% in each group between 1 and 9 months (mean increase approximately 60 x 10(6)/l after 6 months). Adding delavirdine to current therapy was well tolerated. Side-effects reported were: skin rash, 28%; nausea, 9%; kidney stones, 9%; diarrhea, 6%; flank pain, 2%; proteinuria, 2%. Three patients reported serious medical events all of which resolved and none of which were attributed to delavirdine. Adding delavirdine to the combination regimen of patients in whom protease inhibitor therapy had failed often resulted in a rapid and remarkable decrease in viral load, sustained improvement in CD4+ lymphocyte counts and viral load, and clinical improvement with minimal toxicity.