Shorter treatment found for latent tuberculosis

In what is being hailed as the biggest breakthrough since the 1960s in treatment for latent tuberculosis — noninfectious TB without symptoms — researchers said Monday that weekly doses of a cocktail of antibiotics can cure the infection in only three months as effectively as the standard treatment of daily drugs for nine months.

By reducing the number of pills and shortening the time required for therapy, the new regimen increased the proportion of patients who completed treatment from 69% to 82%. By increasing the success rate of therapy, the regimen should reduce spread of the disease and the risk of inducing resistance to TB drugs, experts said.

“It’s very clear that, in this country, if we are going to get rid of TB, we have to do so by preventing people at risk from going on to develop the disease,” said Dr. Richard Chaisson of the Johns Hopkins University School of Medicine, the senior author of the study. That can only be accomplished by curing latent TB, he said.

Latent TB refers to infection by the TB bacterium in people who do not have symptoms and cannot infect others. But that latent infection can be converted into an active one by many different factors — at which point the patient becomes infectious.

Although TB control measures in the United States have brought the incidence of the disease to an all-time low of 11,181 cases in 2010, it is estimated that at least 11 million Americans have latent TB.


“The 11 million Americans with latent TB represent a ticking time bomb,” Dr. Kenneth Castro, director of the Centers for Disease Control and Prevention’s division of tuberculosis elimination, said at a news conference Monday. “They’re the source of future TB cases.”

Daily doses of the antibiotic isoniazid have been the standard of care for TB for nearly 60 years. But a newer, more potent drug, rifapentine, marketed under the brand name Priftin by Sanofi-Aventis, persists in the body for long periods.

In the study, begun 10 years ago, researchers enrolled 8,053 people with latent TB, most living in the U.S. and Canada, though some were in Brazil and Spain. Half were selected to receive conventional daily isoniazid treatment for nine months and half received a combination of isoniazid and rifapentine weekly for 12 weeks.

In the 33 months of follow-up, seven of those receiving the combination therapy developed TB, compared with 15 of those receiving isoniazid alone, coauthor Dr. Timothy Sterling of Vanderbilt University reported at the American Thoracic Society International Conference in Denver.

The combination “works certainly as well as isoniazid, and actually a little bit better,” Chaisson said.

One complication is that the treatment cannot be given simultaneously with drugs for HIV infections, a significant drawback because many patients in the developing world have both diseases. Rifapentine stimulates the production of liver enzymes that break down many drugs, including protease inhibitors used for HIV treatment. The enzymes reduce levels of the drugs by as much as 95%, making use of the drugs at the same time pointless.

Chaisson said the team was now testing a regimen in which protease inhibitor treatment is halted for a month and rifapentine given daily. Normal HIV treatment is then resumed. Results from that study should be published soon.

The trial was sponsored by the CDC, and results have been submitted for publication.