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Lopinavir/ritonavir plus indinavir was administered once daily as directly observed protease inhibitor-only therapy in 12 heavily pretreated HIV-1-infected patients with multiple virological failures and advanced immunosuppression (CD4 cell count 95 × 106 cells/μl). The treatment was well tolerated. At weeks 12, 24 and 48, most patients on treatment achieved viral suppression of less than 400 copies/ml and a corresponding median CD4 T-cell count increase. Pharmacokinetic data indicated therapeutic concentrations for both protease inhibitors in most patients.