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

Treatment for Latent Tuberculosis Infection

Preferred First-Line Regimen

The preferred treatment for latent TB is 3 months of once-weekly isoniazid plus rifapentine (3HP) for HIV-negative adults and children ≥2 years old, offering equivalent efficacy to 9 months of isoniazid with superior completion rates and lower hepatotoxicity. 1

• This regimen is equally effective in both HIV-positive and HIV-negative persons 1
• The 3HP regimen must be given as directly observed therapy (DOT) 2
• Dosing is weight-based: rifapentine ranges from 300 mg (10-14 kg) to 900 mg (>50 kg) once weekly, combined with isoniazid 15 mg/kg (adults/children ≥12 years) or 25 mg/kg (children 2-11 years), up to maximum 900 mg weekly 2

Alternative Preferred Regimen

Four months of daily rifampin (4R) is strongly recommended as an alternative preferred regimen for HIV-negative adults and children of all ages. 1

• This regimen demonstrates clinically equivalent effectiveness to 9 months of isoniazid with significantly lower toxicity 1, 3
• Treatment completion rates are 15.1 percentage points higher than 9-month isoniazid 3
• Hepatotoxicity rates are 1.2 percentage points lower than with isoniazid 3
• The 4R regimen showed rate differences of less than 0.01 cases per 100 person-years compared to 9-month isoniazid, meeting noninferiority criteria 3

Regimens for HIV-Infected Persons

For HIV-infected individuals, 9 months of daily isoniazid (9H) is preferred over 6 months. 1, 4

• The 3HP regimen (isoniazid plus rifapentine for 3 months) is equally effective in HIV-positive persons and represents an excellent alternative 1
• Six months of isoniazid should not be used in HIV-infected persons or those with radiographic evidence of prior TB 1
• Isoniazid plus antiretroviral therapy decreases TB incidence more than either intervention alone in high TB incidence areas 5

Additional Alternative Regimens

Six Months of Daily Isoniazid (6H)

• Strongly recommended for HIV-negative adults and children, conditionally recommended for HIV-positive persons 5
• Provides substantial protection but less optimal than 9-month regimen 4
• Should be avoided in HIV-infected persons and those with fibrotic lesions 1

Three to Four Months of Isoniazid Plus Rifampin

• Can be administered for 3-4 months as an alternative 6
• Shows superior radiographic outcomes compared to 9-month isoniazid monotherapy (11-14% vs 24% new findings) 6
• Compliance is better than with isoniazid monotherapy 6

Critical Pre-Treatment Requirements

Active TB disease must be ruled out before initiating LTBI treatment through history, physical examination, chest radiography, and bacteriologic studies when indicated. 1, 4

• Rifapentine must never be used as monotherapy 1
• Do not use these regimens if exposure to rifamycin-resistant or isoniazid-resistant M. tuberculosis is suspected 2

Monitoring During Treatment

Obtain baseline liver function tests for patients with suspected liver disorders, HIV infection, pregnancy or immediate postpartum period, or chronic conditions increasing liver disease risk. 1, 4

• Perform monthly clinical evaluations for all patients 1, 4
• Assess for hepatitis symptoms at each visit 1
• Discontinue treatment immediately if evidence of liver injury occurs 1
• For patients on rifampin alone, clinical evaluations should occur at least monthly 4

Special Population Considerations

Pregnancy

• For women at high risk (HIV-infected or recently infected), treatment should not be delayed based on pregnancy alone, even in the first trimester 1
• Isoniazid for 9 or 6 months is recommended for pregnant, HIV-negative women 4

Children

• The 3HP regimen is approved for children ≥2 years old 1, 2
• Four months of rifampin is preferred for children of all ages 1
• Isoniazid for 9 months is recommended for children and adolescents 4

Administration Details

Take rifapentine-containing regimens with meals to increase bioavailability and reduce gastrointestinal side effects. 2

• For patients unable to swallow tablets, crush and mix with semi-solid food, consuming immediately 2
• When using 3HP, maintain an interval of at least 3 consecutive days (72 hours) between doses if used for active TB 2

Critical Pitfalls to Avoid

Never use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults due to unacceptably high hepatotoxicity risk. 1

• Do not use rifapentine once weekly in the continuation phase for active TB in HIV-infected patients due to higher failure rates and rifampin-resistant organisms 2
• Avoid 6-month isoniazid in HIV-infected persons when 9-month regimens or shorter rifamycin-based regimens are available 1
• Never initiate LTBI treatment without first excluding active TB disease 1, 2