REDUCED PLASMA-CONCENTRATIONS OF ANTITUBERCULOSIS DRUGS IN PATIENTS WITH HIV-INFECTION

Background: Reports suggest that antituberculosis drugs are malabsorbe d in patients with advanced HIV disease, Objective: To evaluate the ph armacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease, Design: Parallel study. Setting: Two hospital outpatient clinics. Participants: 12 healthy volunteers, 12 p atients with asymptomatic HIV disease, 12 patients with symptomatic HI V disease, and 12 patients with symptomatic HIV disease and diarrhea. Measurements: Drug plasma concentrations were measured over 24 hours o n day 4 of concurrent therapy. Intervention: Oral isoniazid (300 mg/d) , rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d). Results: Reduced total drug exposure to rifampin and pyrazinami de was associated with D-xylose malabsorption in persons with HIV infe ction or AIDS. Peak drug exposure to isoniazid was lower in patients w ith diarrhea. Conclusions: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.