LOW ANTITUBERCULOSIS DRUG CONCENTRATIONS IN PATIENTS WITH AIDS

OBJECTIVE: To determine the frequency and magnitude of below normal ap parent peak serum concentrations for antituberculosis drugs in patient s with AIDS and CD4 cell counts less than 200 cells/mm(3). We also exp lored the data for potential relationships between response variables and patient characteristics. DESIGN: Prospective study of consecutive patients seen in tuberculosis clinics. SETTING: Five urban tuberculosi s clinics in four major metropolitan areas. PARTICIPANTS: Twenty-six p atients diagnosed with HIV infection and receiving treatment for activ e tuberculosis were eligible. MAIN OUTCOME MEASURES: After 2 weeks or more of therapy, blood was collected 2 hours after observed doses of t he antituberculosis drugs. Serum samples were frozen, shipped to Natio nal Jewish Center in Denver, and analyzed by HPLC or GC. Serum concent rations were compared with the proposed normal ranges. Data were analy zed to determine correlations between antituberculosis drug serum conc entrations and patient characteristics. RESULTS: LOW 2-hour serum conc entrations were common for antituberculosis drugs, particularly rifamp in and ethambutol. Absorption of isoniazid was generally high. Potenti al drug-drug interactions were found between rifampin and fluconazole (fluconazole appears to increase rifampin concentrations) and between pyrazinamide and zidovudine (zidovudine may lower pyrazinamide concent rations). Patients receiving pyrazinamide had lower rifampin concentra tions than those not receiving pyrazinamide. CONCLUSIONS: Low antitube rculosis drug serum concentrations occur frequently during the treatme nt of tuberculosis in patients with AIDS. Additional research is requi red for patients with drug-resistant tuberculosis, and to clarify the nature of the potential drug-drug interactions.