What is the recommended treatment for latent tuberculosis (TB)?

Treatment for Latent Tuberculosis Infection

The preferred first-line treatment for latent tuberculosis infection is 3 months of once-weekly isoniazid plus rifapentine (3HP), which offers equivalent efficacy to 9 months of isoniazid with significantly higher completion rates and lower hepatotoxicity. 1, 2

Preferred First-Line Regimens (Choose One)

The CDC, American Thoracic Society, and Infectious Diseases Society of America recommend three preferred regimens, listed in order of preference:

1. Three Months of Once-Weekly Isoniazid Plus Rifapentine (3HP)

• This is the top choice for most patients including HIV-negative adults and children ≥2 years old 2
• Equally effective in HIV-positive and HIV-negative persons 2
• Must be given as directly observed therapy (DOT) 3
• Dosing for adults and children ≥12 years: Rifapentine 10-14 kg = 300 mg, 14.1-25 kg = 450 mg, 25.1-32 kg = 600 mg, 32.1-50 kg = 750 mg, >50 kg = 900 mg once weekly; Isoniazid 15 mg/kg (max 900 mg) once weekly 3
• Dosing for children 2-11 years: Same rifapentine dosing; Isoniazid 25 mg/kg (max 900 mg) once weekly 3
• Take with meals to increase bioavailability and reduce GI upset 3

2. Four Months of Daily Rifampin (4R)

• Strongly recommended as preferred alternative for HIV-negative adults and children of all ages 1, 2
• Non-inferior to 9 months of isoniazid with significantly better completion rates and lower toxicity, especially hepatotoxicity 1, 4
• In the landmark NEJM trial of 6,859 adults, 4R had treatment completion rates 15.1 percentage points higher than 9H, with 1.2 percentage points fewer hepatotoxic events 4
• Dose: 600 mg daily for adults 1

3. Three Months of Daily Isoniazid Plus Rifampin (3HR)

• Recommended by CDC with excellent efficacy and higher completion rates than longer regimens 1
• Can be used for all ages 1

Alternative Regimens (When Preferred Regimens Cannot Be Used)

Nine Months of Daily Isoniazid (9H)

• This is the mandatory choice (not optional) for HIV-infected persons when isoniazid monotherapy is selected 1, 2
• 9 months is preferred over 6 months for HIV-infected persons or those with radiographic evidence of prior TB 2
• Has >90% efficacy if completed properly, but poor adherence limits real-world effectiveness 5

Six Months of Daily Isoniazid (6H)

• Strongly recommended for HIV-negative adults and children only 1
• Do NOT use for HIV-infected persons 2

Critical Pre-Treatment Requirements

Active TB disease MUST be ruled out before starting LTBI treatment through: 1, 2

• History and physical examination
• Chest radiography
• Bacteriologic studies when indicated

Special Population Considerations

HIV-Infected Patients

• 3HP regimen is equally effective and can be used 2
• If using isoniazid monotherapy, must use 9 months (not 6 months) 1, 2
• Isoniazid plus antiretroviral therapy decreases TB incidence more than either alone 1
• Consider rifabutin as substitute for rifampin when drug interactions with antiretrovirals occur 1

Pregnant Women

• For women at high risk (HIV-infected or recently infected), treatment should not be delayed based on pregnancy alone, even in first trimester 2

Patients with Liver Disease

• Obtain baseline liver function tests for patients with suspected liver disorders, HIV infection, pregnancy/postpartum period, or chronic conditions increasing liver disease risk 2
• Give PRIFTIN only in cases of necessity under strict medical supervision 3

Monitoring Requirements

All Patients

• Monthly clinical evaluations assessing for hepatitis symptoms 2
• Discontinue treatment if evidence of liver injury occurs 2, 3

High-Risk Patients

• Baseline laboratory testing for those with risk factors for hepatotoxicity 1
• Serum transaminases every 2-4 weeks for patients with abnormal baseline liver tests or liver disease 3

Critical Pitfalls to Avoid

Drug Interactions

• Rifamycins interact with warfarin, oral contraceptives, antifungals, and HIV antiretroviral therapy 1
• Monitor patients on rifamycin-based regimens closely, especially those with abnormal baseline liver tests 1

Contraindicated Regimens

• Never use rifapentine as monotherapy 2
• Never use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults due to unacceptably high hepatotoxicity risk 2, 5
• Do NOT use 3HP or 4R for individuals presumed exposed to rifamycin-resistant or isoniazid-resistant M. tuberculosis 3
• Do NOT use once-weekly rifapentine plus isoniazid in HIV-infected patients with active pulmonary TB due to higher failure/relapse rates 3

Hypersensitivity

• PRIFTIN is contraindicated in patients with history of hypersensitivity to rifamycins 3