Several dose-finding studies of boosted protease inhibitors have demonstrated that doses lower than those recommended in Caucasian populations exhibit in the Thai population similar pharmacokinetic (PK) properties with sustained virological suppression but reduced toxicity. We therefore evaluated the PK profiles of lower than the standard doses of atazanavir/ritonavir (ATV/RTV) in 22 adult Thai patients with well-suppressed human immunodeficiency virus 1 (HIV-1) infection. The PK parameters of ATV/RTV at a dosage of 200/100 mg once daily, plus two nucleoside reverse transcriptase inhibitors, were significantly lower than those associated with a dosage of 300/100 mg once daily in the same patients. In addition, the PK parameters for the lower dosage in these Thai patients were comparable to historical data from Caucasian cohorts who received the standard dose of ATV/RTV (300/100 mg). None of the patients showed subtherapeutic values of <0.15 mg/l at any time point. Bilirubin concentration decreased significantly after dose reduction, and viral load remained at <50 copies/ml in all subjects. Therefore, ATV/RTV at a dose of 200/100 mg once daily (plus appropriate backbone medication) warrants further long-term efficacy studies, particularly in patients of Thai and other Asian ethnicities.

Methods HIV-infected adults (viral load < 50) on atazanavir/ritonavir 300/100 mg once-daily plus two NRTIs for at least 2 weeks were enrolled. Two 24-hour intensive PK were studied at baseline and 14 days after switching to atazanavir/ ritonavir 200/100 mg once-daily regimen plus two NRTIs. Atazanavir plasma concentrations were calculated using non-compartmental methods. A repeated measures GEE/ random effect model was used to compare the two dose levels. Comparison between the different subgroups were made using the Mann-Whitney U model.