Background: Although nine months of daily isoniazid therapy is routinely recommended to treat latent Mycobacterium tuberculosis infection, only 30 to 64 percent of patients complete the prolonged regimen. Rifapentine (Priftin) has shown promise for treating latent tuberculosis in animal studies. Sterling and colleagues investigated whether adding rifapentine to isoniazid therapy could eradicate tuberculosis with a shorter treatment duration.

The Study: Persons at high risk of developing active tuberculosis were randomized to receive nine months of daily isoniazid monotherapy (5 to 15 mg per kg per day; maximum daily dosage of 300 mg), or three months of once-weekly isoniazid (15 to 25 mg per kg; maximum weekly dosage of 900 mg) plus rifapentine (900 mg, with adjustments for persons weighing 50 kg [111 lb] or less). Participants were followed for a total of 33 months after treatment initiation. Eligible participants had a positive tuberculin skin test and had been in close contact with a patient with active tuberculosis, although patients with human immunodeficiency virus (HIV) could be enrolled with either of these criteria. Exclusion criteria included confirmed or suspected tuberculosis, pregnancy, breastfeeding, recent treatment with either study agent, HIV treatment within 90 days after enrollment, or an aspartate transaminase level five times the upper limit of normal. The primary end point was the development of active tuberculosis, with secondary end points including completion of study therapy or treatment discontinuation because of an adverse drug reaction.

Results: A total of 7,731 persons were randomized between the monotherapy and combination therapy groups, with 86 and 88 percent of patients completing 33 months of follow-up, respectively. Approximately twice as many patients in the isoniazid-only group developed tuberculosis compared with the combination therapy group (0.43 versus 0.19 percent of patients). Patients receiving combination therapy were significantly more likely to complete their treatment than those receiving monotherapy (82.1 versus 69.0 percent; P < .001). Although the combination therapy group experienced fewer adverse events than the monotherapy group (14.7 versus 17.6 percent; P < .001), they were more likely to stop treatment because of these events (4.9 versus 3.7 percent; P = .009). However, there were no differences between the groups in the likelihood of a severe adverse event. The proportion of participants with drug-related hepatotoxicity was significantly greater in the monotherapy group (2.7 versus 0.4 percent; P < .001).

Conclusion: Once-weekly rifapentine plus isoniazid for three months was as effective as daily isoniazid for nine months at preventing the development of active tuberculosis, with higher treatment completion rates and lower rates of adverse events and hepatotoxicity.