Continued lamivudine versus delavirdine in combination with indinavir and zidovudine or stavudine in lamivudine-experienced patients: results of Adult AIDS Clinical Trials Group protocol 370

Objective: To compare the virologic activity of continued lamivudine (3TC) versus a switch to delavirdine (DLV) when initiating protease inhibitor therapy in nucleoside-experienced patients. Design: Randomized, open-label, multi-center study. Setting: Adult AIDS clinical trials units. Patients: Protease and non-nucleoside reverse transcriptase inhibitor-naive patients who had received 3TC plus zidovudine (ZDV), stavudine (d4T), or didanosine (ddl) for at least 24 weeks. Interventions: Patients with plasma HIV-1 RNA levels > 500 copies/mi who previously received d4T + 3TC or ddl + 3TC were randomized to ZDV + 3TC + indinavir (IDV) or ZDV + DLV + IDV. Main outcome measures: Primary endpoints were the proportion of patients with plasma HIV-1 RNA levels less than or equal to 200 copies/ml at 24 weeks, and occurrence of serious adverse events. The proportion of patients with plasma HIV-1 RNA levels less than or equal to 200 copies/ml at week 48 was a secondary endpoint. Results: At week 24, 58% of subjects in the ZDV + 3TC + IDV arm and 73% in the ZDV + DLV + IDV arm had plasma HIV-1 RNA levels less than or equal to 200 copies/ml (P = 0.29). At week 48, plasma HIV-1 RNA levels were less than or equal to 200 copies/ml in 48% and 83%, respectively (P = 0.007). Rash and hyperbilirubinemia occurred more frequently in DLV arm than in the 3TC arm. Steady-state plasma IDV levels were higher among patients in the DLV arm as compared with the 3TC arm. Conclusions: Substituting DLV for 3TC when adding IDV improved virologic outcome in nucleoside-experienced patients. This result might be explained, in part, by the positive effect of DLV on IDV pharmacokinetics. (C) 2000 Lippincott Williams & Wilkins.