Rifampin is the cornerstone of antituberculosis therapy, but induction of hepatic cytochrome P4503A by rifampin markedly lowers HIV protease inhibitor plasma concentrations.This phase 1, open-label, one-arm study was designed to assess pharmacokinetic interactions and safety of atazanavir, ritonavir, and rifampin among 14 evaluable HIV-seronegative volunteers. The study included 3 sequential periods of study drug dosing, with plasma sampling for pharmacokinetic analyses to occur on the last day of each period. During period 1, participants received rifampin 600 mg every 24 hours for 8 days. During period 2, participants continued rifampin 600 mg every 24 hours, and added atazanavir 300 mg and ritonavir 100 mg every 12 hours, to continue for at least 11 days. During period 3, atazanavir was to be increased to 400 mg every 12 hours.Upon adding atazanavir and ritonavir, the first 3 subjects developed vomiting and transaminase elevations resulting in study drug discontinuation. The study was therefore terminated.Coadministration of rifampin with HIV protease inhibitors may not be a viable treatment option if rifampin administration precedes protease inhibitor initiation. Future studies, which explore concomitant HIV protease inhibitors with rifampin must carefully consider the sequence in which drugs are initiated.
View details for Web of Science ID 000263920800007
View details for PubMedID 19194314