OBJECTIVE: To compare two reduced dose indinavir (IDV) + ritonavir (RTV) combinations guided by therapeutic drug monitoring (TDM) in treatment-naive HIV1-infected patients. METHODS: HIV1-infected treatment naive patients were prospectively randomized to treatment with IDV 600 mg or 400 mg BID each in combination with RTV 100 mg BID. Boosted IDV was combined with 2 NRTI, and patients were followed for 48 weeks. IDV-trough levels and initially also peak levels (C2h) were performed to allow dose modification of IDV following a specified protocol. RESULTS: 14 patients were randomized (age 38 +/- 10.4 years; mean +/- SD; 3 female, 11 male). 8 were treated with 600 mg (group 1), 6 with 400 mg IDV BID (group 2). Efficacy of treatment was good: CD4-cell count increased from 198/microl (14-523; median, range) to 371/microl (214-927) after 48 weeks (p<0.01). All but one patient with adherence problems achieved a viral load below the limit of detection. At the beginning two patients had plasma levels below 0.1 mg/l, most likely due to adherence problems. However, in the course of the observation period all patients had adequate plasma levels. 3 patients in group 1 could further reduce their IDV dose to 400 mg BID due to high plasma (peak and trough) levels. Rate of discontinuation was high (1: 4 pat., 2: 2 pat.), but only one discontinuation was possibly associated with IDV (alopecia; group 2). There were no significant changes in laboratory parameters (bilirubin, triglycerides, cholesterol) or suspicious urine results. Incidence and severity of adverse events was lower than in previous studies. CONCLUSION: Despite the low number of patients it seems reasonable to state, that boosted IDV may be used in significantly reduced dose. Efficacy seemed not to be altered, whereas tolerability was improved.