High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection

Abstract

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings.

Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation.

Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment.

Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Figure 1. Profile of Persons with Latent TB Infection Who Took 3HP

^aTreatment reason per local policy are dichotomous factors: therefore, n does not equal 3288 ^bRecent contact of person with contagious TB ^cPerson with baseline tuberculin skin test who has ≥10mm increase in induration, or positive IGRA with a documented negative TB test, within a 2-year period Abbreviations: 3HP, a 3-month regimen of isoniazid and rifapentine; HAART, highly active antiretroviral treatment; HIV, human immunodeficiency virus; IGRA, interferon-gamma release assay; LTBI, latent tuberculosis infection; TB, tuberculosis.

Figure 2. Number and Percentage of Patients with Medication Reactions After any 3HP dose, n=1174^a

^a Patients could report ≥1 reaction, after ≥1 dose ^b Other symptoms reported by ≥1 patient includes dermatological-related symptoms, gastro-intestinal symptoms, cough, mental health symptoms, weight loss, blurred vision, flu-like symptoms, breathing issues, back pain, gynecologic symptoms, chest discomfort, diaphoresis, angioedema, bleeding, palpitations, easy bruising, swelling, neurologic symptoms, hypotension/near syncope and syncope, flushing, red eyes, upper respiratory infection, genitourinary symptoms, other eye symptoms, black stool, pain, pneumonia, and sepsis.