1HP safe, feasible for tuberculosis prevention in exposed individuals without HIV

Treatment with isoniazid and rifapentine (HP) either for 1 month daily (1HP) or 3 months weekly (3HP) results in high rates of treatment success among people with a positive latent tuberculosis infection test and without HIV infection, a study has shown. The 3HP regimen has slightly lower rates of adverse reactions, but neither exhibits superiority to the other.

“These data show that both regimens can be used by clinicians and public health programs as options for tuberculosis preventive therapy (TPT),” said the researchers, who conducted a phase IV randomized trial of 1HP vs 3HP in adolescents and adults without HIV infection with recent tuberculosis exposure and a positive latent tuberculosis test in two sites in Brazil.

Successful completion of >90 percent of medication via self-report, pill counts, and pharmacologic monitoring, and safety were the primary outcomes. Treatment safety was characterized by the occurrence of grade ≥2 targeted events or discontinuation of treatment for side effects.

Five hundred participants (median age 39 years, 307 females) were randomly allocated to receive either 1HP (n=249) or 3HP (n=251). Treatment completion rates between the two regimens were similarly high (89.6 percent vs 84.1 percent; site-adjusted risk difference, 5.2 percent, 95 percent confidence interval [CI], ‒0.1 to 11.2; p=0.10). [PLoS Med 2026;23:e1004758]

Of the participants, 16.1 percent in the 1HP arm and 10.4 percent in the 3HP arm experienced targeted grade ≥2 adverse safety events or discontinued treatment (site-adjusted risk difference, 6.1 percent, 95 percent CI, ‒0.04 to 12.3; p=0.05).

Treatment discontinuation rates for any side effects were 7.2 percent for 1 HP and 4.4 percent for 3HP, and the risk difference for the primary safety outcome adjusted for site and baseline demographic and clinical covariates was 3.4 percent (95 percent CI, ‒2.3 to 9.1; p=0.24). The trial, however, was not designed to establish efficacy.

Treatment duration

“The higher rate of completion of TPT with 1HP is consistent with findings over many years which have demonstrated that the key factor in treatment completion is the duration of treatment,” according to the researchers. [Int J Tuberc Lung Dis 2025;29:425-427]

“Adherence to treatment for an asymptomatic condition is notoriously challenging,” they added. Of note, studies of TPT for 1, 2, 3, and 4 months consistently found better completion rates for shorter regimens than for longer courses of isoniazid. [Eur Respir J 2019;53:1802396; Lancet 1998;351:786-792; N Engl J Med 2019;380:1001-1011; N Engl J Med 2011;365:11-20]

In the Prevent TB Trial, the pace of 3HP discontinuation for any reason was initially higher than that for isoniazid. However, since the 9-month course of isoniazid continued for a longer period, its overall rates of discontinuation were markedly higher than with 3HP. [N Engl J Med 2011;365:2155-2166]

“It is therefore no surprise that completion of a 1-month regimen should be higher than for a 3-month regimen, despite a slightly higher incidence of adverse safety reactions,” the researchers said.

The World Health Organization recommends 1HP as an alternative regimen for individuals without HIV infection, despite the lack of safety data. [J Pharm Biomed Anal 2023;228:115307]

“This trial now provides those data and allows clinicians, public health programs, and patients to make informed choices about which regimens to use,” the researchers said.