Research Offers Simpler, Effective Treatment
Option for Latent TB Infection

May 16, 2011 -- Results from one of the largest U.S. government clinical trials on tuberculosis preventive therapy to date suggest that treatment for latent tuberculosis (TB) infection -- normally a difficult and lengthy regimen -- may soon be easier than ever before in countries with low-to-medium incidence of TB. The trial results showed that a supervised once-weekly regimen of rifapentine and isoniazid taken for three months was just as effective as the standard self-administered nine-month daily regimen of isoniazid, and was completed by more participants.

The multi-country, CDC-sponsored trial tested the effectiveness of this new preventive TB treatment regimen (using currently available anti-TB drugs) among persons with latent TB infection who are at high risk for progression to TB disease. The results were presented today at the American Thoracic Society International Conference in Denver by principal investigator Timothy Sterling, MD, of Vanderbilt University.

"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."

Latent TB infection occurs when a person has TB bacteria in his or her body, but does not have symptoms and cannot transmit the bacteria to others. However, if the bacteria become active, the person will develop TB disease, become sick, and may spread the disease to others. Although not everyone with latent TB infection will develop TB disease, some people, such as those with weakened immune systems, are at higher risk of progression to TB disease.

The new regimen to treat latent TB reduces the doses required for treatment from 270 daily doses to 12 once-weekly doses, making it much easier for patients to take.

In the United States, the number of persons with TB disease is at an all-time low (11,181 total cases were reported in 2010); however, approximately 4 percent of the U.S. population, or 11 million people, are infected with the TB bacterium. TB continues to disproportionately affect racial/ethnic minorities and foreign-born individuals in this country.

"If we are to achieve TB elimination in the United States, we must address the large number of people in this country with latent TB infection," said Kevin Fenton, MD, director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. "By effectively treating latent TB infection, not only can we reduce the potentially deadly consequences among those individuals, but we can also prevent many others from ever becoming infected."

One of the largest TB prevention trials to date

The study lasted approximately 10 years and included 8,053 participants over the age of 2 who lived in countries with low or medium TB incidence, with the majority from the United States or Canada. Additional participants were located in Brazil and Spain. Because of a known drug interaction between some anti-HIV drugs and rifapentine, HIV-infected persons taking antiretrovirals were not eligible for enrollment in the study.

Participants were randomized to receive one of two preventive treatment options -- a regimen consisting of three months of once-weekly rifapentine 900 milligrams and isoniazid 900 milligrams given with supervision (that is, directly observed therapy), or the current standard regimen used to treat latent TB infection, consisting of nine months of daily isoniazid 300 milligrams, which was not supervised (that is, self-administered by the participant). Each participant was evaluated for treatment-related adverse events, adherence to treatment, survival, and development of TB disease for a total of 33 months after the date of their enrollment.

The new regimen was found to be safe and as effective as the standard regimen in preventing new cases of TB disease, with very few cases of TB disease developing in either study arm. Seven cases occurred among those receiving the new treatment regimen compared to 15 among those receiving the standard treatment. Additionally, the percentage of participants completing the new, shorter regimen was substantially higher (82 percent) than the percentage completing the standard regimen (69 percent).

Next steps in implementation

Given the promise of these results, CDC has already held an expert consultation to review the data and begin working on new guidelines for its use in the United States. Researchers caution that these results are only directly applicable to countries with low-to-medium incidence of TB. Additional studies will likely be needed before this new regimen can be recommended in countries with a high incidence of TB, especially those with high HIV prevalence and where the risk of TB re-infection is greater.

The research was conducted through the TB Trials Consortium (TBTC), a CDC-funded partnership of domestic and international clinical investigators who conduct research on the prevention and treatment of TB.