Interventions for Tuberculosis Control and Elimination
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The United States Public Health Service conducted a clinical trial to evaluate the usefulness of once-weekly rifapentine in the continuation phase. Both the control and experimental arm received the same four-drug intensive phase and were then randomized to receive either twice-weekly isoniazid plus rifampicin (control arm) or once-weekly isoniazid plus rifapentine. All patients had organisms that were fully susceptible to all study drugs at intake.
In the above article only the outcome among patients with HIV infection was reported. There were no failures in either arm. In the control arm there were three relapses, all fully susceptible. In the rifapentine arm there were five relapses, four of whom with acquired rifamycin resistance.
The problem is isoniazid which cannot be given only once per week (particularly rapid acetylators). Thus patients received effective rifamycin monotherapy. Although there might be problems specifically related to rifapentine, this study alerts very clearly that effective rifamycin monotherapy in the continuation phase in patients with HIV infection is a potential risk for the acquisition of multidrug-resistant tuberculosis that is not even recognized (no failures) during treatment.
