The Centers for Disease Control and Prevention unveiled new guidelines Thursday for the treatment of latent tuberculosis infection in the U.S. with a 12-dose regimen, administered once-weekly under directly observed therapy. The current regimen requires daily drug administration over nine months, making the new treatment simpler and easier for patients.
People with LTBI are infected with mycobacterium tuberculosis but do not have active TB disease. While not infectious, about five to ten percent of people with LTBI who do not receive treatment will develop active disease in their lifetime – half of whom will do so within the first two years of infection. This risk is considerably higher for those with compromised immune systems, such as people living with HIV.
Three large clinical trials informed this decision, the largest of which had its results published this week in an article in The New England Journal of Medicine: “Three Months of Rifapentine and Isoniazid for Latent Tuberculosis Infection.” The study concluded that the combination three-month regimen was as effective as the standard nine-month isoniazid regimen in preventing TB and had a higher completion rate. The new regimen will not replace other regimens but rather supplement LTBI treatment choices. The feasibility of DOT, availability of drugs, and the patient’s likelihood to complete the treatment regimen are considerations for health experts when determining which regimen is best.
The CDC cautioned that additional studies are needed to explore treatment safety and efficacy in young children and people living with HIV who are on antiretroviral therapy, and that these populations should stick to existing treatment regimens for the time being. People who are presumed to be infected with isoniazid-resistant or rifampin-resistant M. tuberculosis also should not take this regimen.
While just more than 11,000 cases of active TB were reported in the U.S. in 2010, it is estimated that 11 million or four percent of Americans are infected with LTBI. Worldwide, about one third of the population is infected.
“If we are going to achieve our goal of TB elimination in the United States, we must ensure that those with latent TB infection receive appropriate evaluation and treatment to prevent their infection from progressing to TB disease and possibly spreading to others,” said Kevin Fenton, MD, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention in a press release. “It is critical that we accelerate progress against TB in the United States in order to avoid a resurgence of the disease.”
Further studies are also needed to determine whether the 12-dose regimen can be successfully self-administered. As for use of the regimen outside of the United States, “Countries with a high incidence of TB, especially those with high HIV prevalence and where the risk of TB reinfection is greater, will likely require additional studies before considering whether to recommend this regimen,” according to the CDC release. They also noted that the 3-month regimen initially will be more expensive than the other recommended therapies due to drug costs and DOT costs, but that higher treatment completion rates with the 12-dose regimen will eventually off-set these costs and ultimately prove more cost effective.
The Infectious Diseases Society of America and the American Thoracic Society are working with the CDC to update full public health guidelines for the identification and treatment of LTBI. The recommendations were published in the most recent issue of the CDC’s Morbidity and Mortality Weekly Report.