New regimen prevents TB in 12 weekly doses

A large trial has shown that a 12-week course of combination treatment for latent tuberculosis is just as effective as a nine-month course of isoniazid in countries with a low to moderate burden of TB, with the additional advantage that the new regimen can be dosed once a week.

The findings, from the Prevent TB study, were presented this week at the American Thoracic Society’s International Conference in Denver.

However, the applicability of the findings for people with HIV and for settings with a high burden of TB is unclear, and more research will be needed.

Latent tuberculosis (TB) is an infection with TB that has been contained by the immune system, does not cause symptoms and cannot be passed on to other people. Latent TB may develop into active TB if the immune system weakens due to malnutrition or HIV infection, for example.

Preventive treatment with a six- to nine-month course of the antibiotic isoniazid reduces the risk of developing active TB by between 30 and 60%, but the six- to nine-month course of daily isoniazid may be difficult for patients to take.

As a result there has been interest in determining whether it is possible to shorten the course of TB preventive treatment.

The Prevent TB trial was designed more than ten years ago, to compare:

• 12 weeks of treatment with a once-weekly regimen that combined isoniazid (900mg tablet) with a new anti-TB drug rifapentine (900mg in six 150mg tablets), given as directly observed treatment.
• Standard TB preventive TB treatment with nine months of self-administered isoniazid (300mg once daily), the recommended preventive regimen in the United States.

The trial recruited 8053 participants in the United States, Canada, Brazil and Spain, but excluded participants with HIV infection who were taking antiretroviral drugs, due to drug interactions between rifapentine and HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

Participants were randomised to the experimental regimen or to standard treatment, and followed for 33 months after enrolment to assess the effect on development of active TB and survival, as well as adherence and side-effects.

The new regimen was associated with fewer cases of active TB (7 versus 15 in the standard treatment arm) and better adherence (82 vs 69% completed the course of treatment).

“Although the standard regimen is very effective in treating latent TB infection, ensuring that those who need treatment both begin and complete the lengthy, cumbersome isoniazid regimen is challenging,” said CDC Director Thomas R Frieden, MD.  “New, simpler ways to prevent TB disease are urgently needed, and this breakthrough represents one of the biggest developments in TB treatment in decades.”

In the light of these results, new US guidelines on TB preventive treatment are expected before the end of the year.

Further research will be needed in countries with a high burden of TB, and in people with HIV.