Reduced Plasma Concentrations of Antituberculosis Drugs in Patients with HIV Infection

Abstract

Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease. To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease. Parallel study. Two hospital outpatient clinics. 12 healthy volunteers, 12 patients with asymptomatic HIV disease, 12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV disease and diarrhea. Drug plasma concentrations were measured over 24 hours on day 4 of concurrent therapy. Oral isoniazid (300 mg/d), rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d). Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug exposure to isoniazid was lower in patients with diarrhea. Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.