Molecular Medicine Israel

Easier cure for resistant TB

A new treatment strategy has had astonishing success against extensively drug-resistant tuberculosis (XDR TB), which kills more than 70% of patients. XDR and other drug-resistant forms of TB are burgeoning among people with HIV, and current treatments are so prolonged and toxic that many patients fail to adhere to them. But a small study now shows that a simpler, safer regimen can cure the disease. That “may represent an enormous breakthrough,” says Richard Chaisson, who directs the Johns Hopkins University Center for Tuberculosis Research in Baltimore, Maryland, and was not involved in the trial.

Called Nix-TB, the trial has had 34 people in South Africa with XDR on three antibiotics that have never been combined before to treat TB: bedaquiline, pretomanid, and linezolid. Bedaquiline, which was designed for TB but has not been used much, came to market in 2012. Pretomanid is also designed for TB but is still experimental. Linezolid is mainly used for skin infections and pneumonia.

After 6 months, the TB bacillus could not be cultured from anyone’s sputum, a sign that they had cleared the infection, Francesca Conradie of the University of the Witwatersrand in Johannesburg, South Africa, reported this week at the Conference on Retroviruses and Opportunistic Infections in Seattle, Washington. More impressive, 20 people stopped taking the drugs at that point and none relapsed. “I didn’t in my wildest dreams expect the results to be this successful,” Conradie says.

In 2015, the World Health Organization estimates, there were 480,000 new cases of multidrug-resistant (MDR) TB, and 7234 people were treated for XDR TB, which is even more drug resistant. Standard treatment takes up to 2.5 years, often requires hospitalization, and includes painful injections. In addition, “The toxicities are almost worse than the disease,” says Melvin Spigelman, who heads the TB Alliance, a nonprofit in New York City that sponsored the Nix-TB study.

The drugs in Nix-TB are all pills, and they have been used sparingly for TB before, which minimizes the chance that people will be resistant to the combination. Though they also have toxicities, no one withdrew from the study. Early on, however, four people died from advanced TB.

The Nix-TB protocol is tailored for XDR TB, but it could be used for MDR TB if future studies show that lower, less toxic doses of linezolid can work, Spigelman says. “This really gives us a window on how to truly transform TB therapy.” Cost remains another big unknown. For example, Janssen Therapeutics of Titusville, New Jersey, which makes bedaquiline, has promised to donate 30,000 doses to poor countries, which also can buy it for $900 for a 6-month course. The same course sells for $30,000 in high-income countries.

It’s unclear how quickly the treatment can be put into widespread use, as pretomanid has not yet been approved. “We’re discussing with regulatory authorities whether Nix-TB is sufficient for approval,” Spigelman says.

Nesri Padayatchi, a TB doctor at the Centre for the AIDS Programme of Research in South Africa in Durban, is enthusiastic about the new findings. But she cautions that because many MDR and XDR TB patients are coinfected with HIV, studies must carefully evaluate interactions between antiretrovirals and the new TB drug combination.

Sign up for our Newsletter