Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In a new study, 3 months of weekly isoniazid plus rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone.
Tuberculosis results in nearly 2 million deaths annually worldwide. Treatment of latent Mycobacterium tuberculosis infection among persons at highest risk for progression to active infection is an important strategy for tuberculosis control and elimination.
• What are the limitations of the current standard of care for the treatment of latent tuberculosis?
The current standard regimen for the treatment of latent M. tuberculosis infection is 9 months of daily isoniazid. However, the effectiveness of isoniazid is limited by treatment completion rates of 30 to 64%, owing in part to the long duration of the regimen. Toxic effects of the drug, especially hepatic, are also a concern.
• What new regimen is effective for the treatment of latent tuberculosis?
This study showed that for the treatment of latent M. tuberculosis, directly observed, once-weekly therapy with rifapentine plus isoniazid for 3 months was as effective as self-administered daily isoniazid for 9 months, with the rate of tuberculosis in the combination-therapy group approximately half that in the isoniazid-only group.
Morning Report Questions
Q: Which patients are at highest risk of conversion from latent M. tuberculosis infection to active disease?
A: Persons at high risk of conversion from latent tuberculosis to active disease include close contacts of a patient with culture-confirmed tuberculosis, a recent conversion to a positive tuberculin skin test (PPD), immunocompromised patients with a positive PPD, as well as patients with a positive PPD who have fibrotic changes on chest radiography consistent with previously untreated tuberculosis.
Q: What adverse effects were more common in the combination-therapy group (rifixamin plus isoniazid) than in the isoniazid-only group?
A: Among other adverse events attributed to study drug, the proportion of participants with possible hypersensitivity or other causes was higher in the combination-therapy group. The proportion of participants who permanently discontinued a study drug because of possible hypersensitivity was 2.9% in the combination-therapy group and 0.4% in the isoniazid-only group (P<0.001).