Tuberculosis (TB) is the world’s leading infectious disease killer; in 2024, 10.7 million people fell ill with TB and 1.23 million died. Prevention is crucial, and while promising vaccine candidates are in the pipeline, preventive therapy is the best course for people at risk of moving from infection to active disease. Current TB preventive therapy (TPT) regimens require taking antibiotics for one to six or more months, but not all are eligible for the existing one-month treatment option. For people with TB infection, it is challenging to sustain a long therapy course, especially because those without active disease do not have symptoms. It also challenges families and treatment programs to have to give different regimens depending on people’s health conditions — for example, pregnancy, HIV or exposure to drug-susceptible or drug-resistant TB. SMART4TB’s Bedaquiline Roll-out Evidence in Contacts and People Living with HIV to Prevent TB (BREACH-TB) trial is attempting to tackle some of these challenges with a simplified universal TPT of one month of bedaquiline.
The trial’s first site is in Tanzania, led by Dr. James Ngocho, a clinical research scientist at Kilimanjaro Clinical Research Institute and a senior lecturer at Kilimanjaro Christian Medical College University. Dr. Ngocho is inspired by the potential of a shorter treatment plan that has the potential to retain more people on treatment and lower costs for healthcare systems. “If this trial is successful, one-month preventive therapy for all would be sustainable for our communities, physicians and systems. We know from experience that as time goes on, we lose people who do not want to take medication when they are not experiencing an active infection. We would have a much easier time keeping them on treatment for one month.”
U.S.-based trial co-investigator, Dr. Eric Nuermberger, a professor of medicine at Johns Hopkins University School of Medicine, believes prevention is key to managing TB worldwide and a one-month regimen will help people who have been exposed to drug-resistant TB or who must manage complex drug-drug interactions, as the only existing one-month TPT regimen can interact with drugs, including some antiretrovirals used to treat HIV. “It has become clear over the last decade or two, the easier that we can make regimens for people to both tolerate and complete, the more effective they can be. Because this regimen is based on just one drug for one month, and has fewer drug-drug interactions, it reduces pill burden and is easier to take with other medications.”
Both Dr. Ngocho and Dr. Nuermberger were drawn to working on TB by the potential to make a real-world impact on a disease that they had seen historically and contemporaneously ravage societies. “I started my career working with people living with HIV, and TB was a common co-infection, so I wanted to learn more about it and help improve the lives of people living with HIV. I have seen children, families and relatives struggle with TB, and I know that if we can stop it from moving through a household, it will make a big difference,” said Dr. Ngocho.
If the trial is successful, it paves the way for a long-acting injectable, a form of treatment that Dr. Nuermberger describes as an efficient “one and done” solution. However, that will work for some, but not all, people who need preventive treatment. “We know from experience that it is important to have options. Oral treatment will always play a role, so having this potential in our arsenal to help end TB is vital.”
BREACH-TB plans to open sites in Mongolia, Peru and Uganda later this year.