A scourge for at least the past 6,000 years, tuberculosis (TB) continues to pose a significant global health challenge. The World Health Organization (WHO) estimates that TB is a latent infection in one quarter of the world’s population, approximately 2 billion people. In 2024 alone, more than 10 million people worldwide developed active TB disease, with 1.2 million deaths recorded, making TB the leading cause of death from an infectious disease.
One of the current stalwarts in the fight against TB has been the treatment of its latent form with a combination of two drugs, isoniazid and rifapentine, in a three-month, weekly regimen known as 3HP. Meanwhile, a second regimen, 1HP, requires the drugs to be taken daily for just one month. Previously recommended for people living with both TB and HIV, and those over age 13 in contact with infected individuals, the efficacy of 1HP for broader populations was uncertain.
New Findings from the Ultra Curto Trial
In a groundbreaking study published today in PLOS Medicine, researchers from Johns Hopkins Medicine and organizations in Brazil have demonstrated that the 1HP regimen is safe and effective for patients with latent TB infection and without HIV. This finding comes from the Ultra Curto randomized clinical trial, which was designed to assess the safety and efficacy of 1HP compared to the established 3HP regimen.
“What hasn’t been known previously is whether 1HP also would be safe and effective for patients with latent TB infection and without HIV, for whom current practice would advise a 3HP regimen,” says Richard Chaisson, M.D., director of the Johns Hopkins University Center for Tuberculosis Research and leader of the trial.
“We randomized 500 adolescents and adults in the two Brazilian cities to get either 1HP [249 participants] or 3HP [251 participants], with the 193 males and 307 females all having positive tests for TB infection but not HIV, and with a median age of 39 years,” says Chaisson.
Comparative Results and Implications
The study found that treatment completion was 89.6% for 1HP recipients and 84.1% for those on the 3HP regimen. Adverse safety effects or discontinuation due to side effects occurred in 16.1% of the 1HP recipients and in 10.4% of the 3HP group. Despite slightly higher adverse events in the 1HP group, these were considered minor and did not prevent the majority of patients from completing the treatment.
Before the introduction of 1HP and 3HP, Tuberculosis Preventive Therapy (TPT) required 6-9 months of treatment with isoniazid alone, which often resulted in greater toxicity and lower completion rates. The two shorter regimens have proven to be more effective and easier for patients to complete. The Ultra Curto trial’s findings now provide clinicians and public health programs with validated options for TPT.
“Now that we’ve done that with the Ultra Curto trial, the data show both regimens can be used by clinicians and public health programs as options for TPT,” says Chaisson.
Research Team and Funding
The research team from Johns Hopkins Medicine included Abiye Berihum, Silvia Cohn, Beatriz Kohler, Mark Marzinke, and Lawrence Moulton. Collaborators from Brazil included Betina Durovni, Solange Cavalcante, Jamile Garcia, and Valeria Saraceni from the Secreteria Municipal de Saúde do Rio de Janeiro, as well as Alexandra Brito da Souza, Marcelo Cordeiro-Santos, and Renate Spener-Gomes from the Fundação de Medicina Tropical in Manaus.
Federal funding for the study was provided by the National Institutes of Health’s National Institute of Allergies and Infectious Diseases through two grants: U01AI152961 and P30AI18436, the latter via the Johns Hopkins Tuberculosis Research Advancement Center.
Chaisson disclosed ownership of stock in Merck and consulting fees from Johnson & Johnson, while no other authors reported conflicts of interest.
Looking Forward
The validation of the 1HP regimen for a broader patient population marks a significant advancement in TB treatment strategies. As public health officials and clinicians consider these findings, the potential for more accessible and efficient TB prevention methods becomes increasingly tangible. The ongoing challenge will be to implement these findings into global health strategies effectively, ensuring that the benefits of shorter, more manageable treatment regimens reach those in need.
