For both adults and children, a 4-month rifampin regimen is safer and less expensive than a 9-month isoniazid regimen for the treatment of latent tuberculosis infection, according to a study published in the Annals of Internal Medicine.

Globally, it is estimated that 1.7 billion people, or one-quarter of the population, have latent tuberculosis infection and serve as a reservoir for new active tuberculosis cases. It is estimated that 10% of these people will develop active tuberculosis if left untreated. In order to achieve the goal set by the End TB Strategy — reducing the incidence of tuberculosis by 90% by 2035 — the prevention of latent tuberculosis infection via treatment among those who are high-risk is needed.

The 9-month isoniazid regimen has been available since the 1960s, although the long treatment duration and a fear of adverse events limited acceptance and compliance. A newer 4-month rifampin regimen has demonstrated superior treatment completion and better tolerance. However, the daily costs of the rifampin regimen are higher than the isoniazid regimen. Therefore, researchers compared healthcare use and associated cost data of 4 months of rifampin with 9 months of isoniazid from 2 randomized clinical trials ( identifiers NCT00931736 and NCT00170209).

Continue Reading

The 2 clinical trials included a total of 6012 adults and 829 children from high-income (Australia, Canada, Saudi Arabia, and South Korea), middle-income (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). All participants had an increased risk of developing tuberculosis that warranted treatment for latent tuberculosis infection. The primary outcome was health system cost per participant.

Results demonstrated that the 9-month isoniazid regimen had greater health system use and higher costs in both adults and children across all settings. The mean ratio of costs of the 4-month rifampin regimen compared with the 9-month isoniazid regimen in adults was 0.76 (95% CI, 0.70-0.82) in high-income countries, 0.90 (95% CI, 0.85-0.96) in middle-income countries, and 0.80 (95% CI, 0.78-0.81) in African countries. Similar findings were observed in the pediatric population.

The most frequent costs components included visits during routine follow-up, blood tests, adverse events, and latent tuberculosis infection drugs. In the middle- and high-income countries, routine follow-up visits accounted for 30% to 50% of costs in both regimens; in the African countries, these visits accounted for 15% of costs in the rifampin group and 21% of costs in the isoniazid group. Participants in the African sites had more follow-up visits compared with participants at other sites, and participants in high-income country sites had more blood tests compared with participants at other sites.

One limitation of this comparison study was that regimen-associated costs may have been overestimated due to the required minimum follow-up visits in the protocols, since fewer visits are recommended by many authoritative guidelines.

“Tuberculosis programs in all countries should consider adoption of the 4-month rifampin regimen as first-line therapy for latent tuberculosis infection,” the researchers concluded.


Bastos ML, Campbell JR, Oxlade O, et al. Health system costs of treating latent tuberculosis infection with four months of rifampin versus nine months of isoniazid in different settings [published online June 16, 2020]. Ann Intern Med. doi:10.7326/M19-3741