Treatment of Latent Tuberculosis in a Trice

It is projected that approximately 80% of active tuberculosis (TB) cases in the United States arise from patients with reactivated latent TB infection (LTBI).¹ Thus, the ability to screen for and treat LTBI is paramount to helping eliminate TB nationally. However, the current therapy options for the treatment of LTBI can be poorly tolerated and have lengthy durations.^2,3 In addition, other social determinants of health can limit patients’ ability to complete therapy, such as lower access to health care, affordable housing, and language barriers.⁴

Currently there are 3 oral evidence-based regimens for LTBI, including 3HP (isoniazid 15 mg/kg plus rifapentine up to 900 mg weekly for 3 months), 4R (rifampin 10 mg/kg daily, with a maximum of 600 mg, for 4 months), 3HR (isoniazid 5 mg/kg plus rifampin 10 mg/kg daily for 3 months), and 6-9H (isoniazid 5 mg/kg daily or 15 mg/kg twice weekly for 6-9 months).⁵ Recent literature has shown that novel oral regimen 1HP (isoniazid 300 mg daily plus rifapentine 300-600 mg, based on patient weight, for 1 month) is noninferior to 6-9H, with better rates of therapy completion.^6,7 This new regimen has not been widely used despite the World Health Organization’s support for it. With its short duration and comparable tolerability to other regimens, 1HP would be advantageous for patients with social determinants of health.

Starke and colleagues conducted a retrospective study reviewing the use of multiple LTBI regimens across 3 clinics overseen by the Cook County Department of Health (CCDPH) from January 2024 to May 2025. Adult and pediatric patients were referred to the CCDPH after a positive TB screen, either by interferon-γ release assay (IGRA) or tuberculin skin test (TST). All patients were required to have an initial visit between January 1 and October 31, 2024, and active disease was required to be ruled out by microbiological testing, radiographic testing, and symptom assessment.

Regimens were recommended based on comorbidities, drug interactions, and patient preference. Patients received follow-up via telehealth within 2 to 4 weeks of the start of treatment and monthly thereafter to monitor adherence, tolerance, provide support, and arrange medication refills.⁸ The primary study outcome was completion of therapy, verified by a documenting nurse through medication receipt and the patient’s self-reported medication intake. Medications were not given under directly observed therapy (DOT). Other outcomes included the number of patients who received the full course of therapy, patient adherence at the last nursing contact, adverse events, and early discontinuation rates.

Overall, 291 clients were screened for consultation, and 225 patients started treatment for LTBI. There were 22 patients assigned to 1HP, 58 to 3HP, 141 to 4R, and 4 to other regimens. Approximately 90% of patients were not born in the United States, and comorbidities were present in 30% to 45% of each group. Approximately 95% of patients had a positive IGRA test, and 5% of patients had a positive TST. Of the 225 patients who received LTBI treatment, 71% completed treatment. Notably, 39% of patients receiving LTBI treatment were new immigrants and accounted for a lower completion rate of 58%. Of patients who did not verifiably complete treatment, 22% had treatment discontinued due to adverse effects, and the remaining 78% were lost to follow-up. Ultimately, patients on the 1HP regimen completed treatment 64% of the time vs 72% of patients on other regimens (P = .460). Many patients missed their follow-up appointments, so patients on 1HP were adherent 82% of the time at last contact vs 78% for other regimens. Those on 1HP had adverse events 41% of the time vs 25% for other regimens (P = .107); however, only 1 patient in the 1HP group discontinued therapy due to adverse events.

Overall, the authors concluded that a novel 1-month regimen of daily isoniazid plus rifapentine was well tolerated and had completion rates similar to those of standard LTBI regimens. There were several limitations in this study, including the lack of DOT. The study cited a lack of staffing support to monitor DOT and thus relied on patients’ self-reported adherence. The ability to perform DOT would likely have improved follow-up rates and possibly the primary outcome of verified completion of LTBI therapy, given that fewer patients discontinued therapy due to adverse events. The study also only encompassed 3 centers governed by 1 countywide department of health, which may not be generalizable to all populations or locations. However, given the high percentage of new immigrants included, other studies could show similar or even improved rates of adherence and follow-up. In addition, the number of patients in the novel 1HP group was quite low compared with the other regimens, limiting the ability to draw more concrete conclusions.

The retrospective and shared decision-making designs, with a lack of prospective randomization, limit the possibility of patient-matched groups. However, the overall uptake of LTBI treatment was similar to other reports. Nursing follow-up and subsequent patient response were strongly associated with completion, underscoring the importance of carefully monitoring these patients. This study utilized medication delivery and provided coverage for patients who were uninsured, which was advantageous for those with social determinants of health. This is the first known study assessing the implementation of 1HP as a treatment for LTBI, which, with further convincing evidence, could be a viable alternative to other regimens. Rifapentine has fewer drug interactions than rifampin, so its combination with isoniazid and its shorter duration could be advantageous for future patients.

References

1.Shea KM, Kammerer JS, Winston CA, Navin TR, Horsburgh CR Jr. Estimated rate of reactivation of latent tuberculosis infection in the United States, overall and by population subgroup. Am J Epidemiol. 2014;179(2):216-225. doi:10.1093/aje/kwt246

2.Alsdurf H, Hill PC, Matteelli A, Getahun H, Menzies D. The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis. Lancet Infect Dis. 2016;16(11):1269-1278. doi:10.1016/S1473-3099(16)30216-X

3.Holzman SB, Perry A, Saleeb P, et al. Evaluation of the latent tuberculosis care cascade among public health clinics in the United States. Clin Infect Dis. 2022;75(10):1792-1799. doi:10.1093/cid/ciac248

4.Rustage K, Lobe J, Hayward SE, et al. Initiation and completion of treatment for latent tuberculosis infection in migrants globally: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21(12):1701-1712. doi:10.1016/S1473-3099(21)00052-9

5.Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent tuberculosis infection: recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020;69(1):1-11. doi:10.15585/mmwr.rr6901a1

6.Swindells S, Ramchandani R, Gupta A, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380(11):1001-1011. doi:10.1056/NEJMoa1806808

7.Huang HL, Lee MR, Lee CH, et al. One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV population: a randomized controlled trial. Clin Microbiol Infect. 2024;30(11):1410-1417. doi:10.1016/j.cmi.2024.06.024

8.Starke S, Thomas K, Jasuja S, Lubelchek R. Short-course tuberculosis preventative therapy in a high migration setting: early experience with 1HP in Cook County, Illinois. Clin Infect Dis.Published online January 21,2026. doi:10.1093/cid/ciaf723