No abstract

Lower plasma concentrations of rifabutin and, perhaps, isoniazid were associated with ARR failure or relapse in patients with tuberculosis and HIV infection treated with twice-weekly therapy.

To understand why once-weekly isoniazid/rifapentine therapy for than rifampin (14-15 hours versus 2-5 hours, respectively) tuberculosis was less effective than twice-weekly isoniazid/rifampin, was undertaken with the hope that it would allow highly we studied human immunodeficiency virus-seronegative patients active once-weekly therapy. However, in three large randomwith either failure (n ϭ 4), relapse (n ϭ 35), or cure (n ϭ 94), reized trials (1-3), once-weekly isoniazid/rifapentine was less cruited from a comparative treatment trial. In multivariate analyses effective than twice-or thrice-weekly isoniazid/rifampin in that were adjusted for severity of disease, low plasma concentrathe last 4 months of treatment of active tuberculosis.tions of isoniazid were associated with failure/relapse with onceTwo problems were identified in the randomized trials weekly isoniazid/rifapentine (median isoniazid area under the conof once-weekly isoniazid/rifapentine: a higher rate of drug- cin-monoresistance suggests that the activity of the compantion-time curve than isoniazid may be needed to achieve highly ion drug, in this case isoniazid, was inadequate to prevent the active once-weekly therapy with rifapentine.selection of rifamycin-resistant Mycobacterium tuberculosis. These two theories lead to substantially different interven-