A scourge for at least the past 6,000 years, tuberculosis (TB) is estimated by the World Health Organization (WHO) to be a latent infection in one quarter of the world's population, approximately 2 billion people. In 2024 alone, WHO reported that more than 10 million people worldwide developed active TB disease, with 1.2 million deaths recorded. This makes TB the leading cause of death from an infectious disease.
One of the current stalwarts in the fight against TB has been treatment of its latent form with a combination of two drugs, isoniazid and rifapentine, in a three-month, weekly regimen (12 doses) known as 3HP (H for isoniazid and P for rifapentine). A second regimen, 1HP, requires the drugs to be taken daily, but just for one month (30 doses). It has been recommended for people living with both TB and HIV, and for those over age 13 who have been in contact with people infected with TB.
"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, professor of medicine at the Johns Hopkins University School of Medicine and leader of the federally funded Ultra Curto randomized clinical trial designed to answer that question.
In a study published today in PLOS Medicine, the Ultra Curto trial researchers from Johns Hopkins Medicine and organizations in two Brazilian cities (Rio de Janeiro and Manaus) demonstrate that the 1HP regimen is safe, encourages patients to complete the course of therapy, and has a high rate of treatment success comparable to that seen with 3HP.
"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. "Our measures for success were greater than 90% completion of the drug regimens, low incidence of side effects or discontinuation of treatment because of side effects, and of course, prevention of the latent TB infection from progressing to the disease."
People with latent TB are infected with the bacillus that causes the disease, but the bacteria are dormant and cause no symptoms.
Chaisson says that treatment completion was 89.6% for 1HP recipients and 84.1% for those on the 3HP regimen. He reports that adverse safety effects or discontinuation of treatment because of side effects occurred in 16.1% of the 1HP recipients and in 10.4% of the 3HP group. Both regimens had high rates of positive treatment outcomes.
"While the 1HP participants did have slightly more adverse safety events than those in the 3HP group, they were considered minor and did not keep the majority of patients from completing the one-month course of treatment," says Chaisson.
Before 1HP and 3HP, Chaisson says that Tuberculosis Preventive Therapy (TPT) to reduce the incidence of TB required 6-9 months of treatment with isoniazid alone. Unfortunately, he adds, there was greater toxicity and less treatment completion with the longer regimen.
"The two shorter regimens, 1HP and 3HP, were shown to be effective and easier for patients to complete; however, 1HP had been studied only in people with HIV infection and the safety of the two regimens had not been compared in a head-to-head trial," says Chaisson. "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."
Along with Chaisson, the members of the research team from Johns Hopkins Medicine are Abiye Berihum, Silvia Cohn, Beatriz Kohler, Mark Marzinke and Lawrence Moulton.
Team members from other institutions are study lead author Betina Durovni, Solange Cavalcante, Jamile Garcia and Valeria Saraceni from the Secreteria Municipal de Saúde do Rio de Janeiro (Brazil); Alexandra Brito da Souza, Marcelo Cordeiro-Santos and Renate Spener-Gomes from the Fundação de Medicina Tropical (Manaus, Brazil); and the Ultra Curto Study Team.
Federal funding for the study came from two grants from the National Institutes of Health's National Institute of Allergies and Infectious Diseases: U01AI152961 and P30AI18436, the latter via the Johns Hopkins Tuberculosis Research Advancement Center.
Chaisson reports ownership of stock in Merck and consulting fees from Johnson&Johnson. None of the other authors had any conflict of interest disclosures to report.
