Patients with latent tuberulosis infection are those patients who are infected with Mycobacterium tuberculosis, do not have active tuberculosis disease and are non-infectious. The treatment however of latent M. tuberculosis infection in subjects at highest risk for progression to active disease remains an important health strategy.1-3 The current standard regimen is isoniazid (INH) for 9 months which despite having an efficacy of 69 to 93% in 1982, its efficacy has been limited by the treatment completion rates of 30 to 64%.3,4 This is partly due to the long duration of the regimen and the hepatotoxic effects of the drug.
Other regimens, for example, the combination of rifampin and pyrazinamide has been shown to be as effective as INH but is not often recommended due to the high rates of severe hepatotoxicity. Rifapentine, a drug with higher potency against M. tuberculosis and longer half-life when compared to rifampin, has been shown to be effective for the treatment of latent tuberculosis in animal models.5-7 In addition, it has been shown to be effective in combination with INH for the treatment of tuberculosis in the continuation phase as a weekly regimen for a certain subset of patients.
Sterling8 and colleagues in a recent non-inferiority trial published in the New England Journal of Medicine compared the efficacy of a 3-month therapy containing the combination of INH (900mg) plus rifapentine (900 mg), given once weekly under supervision, to the efficacy of a 9-month therapy with daily, self-administered INH (300mg). The main question was whether the efficacy and effectiveness of the combination therapy would be at least as good as INH alone. During the 33-month follow up in a total of 7731 subjects, the effectiveness analysis counted only 7 cases of tuberculosis in the combination-therapy group compared to 15 cases in the INH-only group (HR=0.38 (95% CI, 0.15 to 0.99)). Better adherence and fewer episodes of hepatotoxicity were observed in the shorter, supervised combination therapy than the INH alone therapy. Hypersensitivity however was more commonly associated with the combination of INH plus rifapentine. This trial suggests that the combination of rifapentin and INH could be used when the use of INH is not recommended.
Given that the study evaluated high-efficacy treatments in four low-incidence countries (Brazil, Canada, Spain, and the United States) for only 33 months, there were few cases in either of the two groups in the trial, therefore, a long-term study in a high-incidence setting is still needed to confirm these findings.
1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-S247.
2. Institute of Medicine. Ending neglect: the elimination of tuberculosis in the United States. Washington, DC: National Academy Press, 2000.
3. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in ...