Use of Rifabutin with Protease Inhibitors for HIV-Infected Patients with Tuberculosis [M Narita, et al. CID 2000;30:779]: This is a study of the simultaneous treatment of tuberculosis and HIV with HAART to determine the clinical significance of the drug interaction between protease inhibitors and rifabutin at A. G. Holley State Tuberculosis Hospital in Florida. Of 25 participants, all became culture-negative for tuberculosis within two months of initiation of treatment, all remained negative throughout hospitalization for a median of six months, and there were no relapses with a follow-up for a median of thirteen months. The response to HAART was also impressive. The mean CD4 cell count at baseline was 124/mm³, and this increased to 218/mm³ at the time of discharge following an average of 17.5 weeks of HIV treatment. There were 20 (80%) patients who had viral load decreases to <500 copies/mL by the time of discharge. Pharmacokinetic studies of rifabutin and PIs were done during treatment with 300 mg rifabutin twice weekly and variable doses of indinavir and nelfinavir. The mean 2-hour post-dose level of rifabutin before HAART was 0.1 mcg/mL and after HAART was 0.23 mcg/mL. (The expected level is 0.3 - 0.9 mg/mL) The mean 2-hour post-dose level of indinavir with 1200 mg q8h was 5.92 mcg/mL. (The expected level with 800 mg q8h is 5 - 11 mcg/mL.) For nelfinavir, the two-hour post-dose level with 1250 mg q12h was 2.6 mcg/mL. (The expected mean level with 750 mg q8h is 2 - 5 mcg/mL.) The authors concluded that tuberculosis and HIV can be treated simultaneously with regimens that are highly effective against both pathogens.
Comment: This is a reassuring report regarding the simultaneous use of anti-tuberculosis treatment and HAART. The doses of rifabutin do not conform to the current recommendations, which is a dose of 150 mg daily when combined with nelfinavir or indinavir; by contrast, the authors here used 300 mg rifabutin twice weekly. There was also a substantial variation in the doses of indinavir and nelfinavir, which the authors justified as reflecting variations in guidelines during the course of the study as well as dose modifications based on the pharmacokinetic study results. The pharmacokinetic data in the study seem to justify the current recommendations for dose modification, and the study as a whole is highly encouraging in terms of demonstrating that effective therapy of both pathogens can be achieved. posted 6/29/2000