Treatment of Latent Tuberculosis Infection
The preferred first-line treatment for latent TB infection is 3 months of once-weekly isoniazid plus rifapentine (3HP), which has equivalent efficacy to 9 months of isoniazid but with significantly higher completion rates and lower hepatotoxicity. 1, 2
Preferred First-Line Regimens
3 months of once-weekly isoniazid plus rifapentine (3HP) is the CDC's preferred regimen for HIV-negative adults and children ≥2 years old, demonstrating equivalent efficacy to 9 months of isoniazid with treatment completion rates of 82.1% versus 69.0% for isoniazid alone 1, 3
4 months of daily rifampin (4R) is strongly recommended as a preferred alternative for HIV-negative adults and children of all ages, with clinically equivalent effectiveness to 9 months of isoniazid but significantly lower toxicity (hepatotoxicity 0.4% vs 2.7%) 1, 2, 4
3 months of daily isoniazid plus rifampin is also recommended as a preferred regimen with excellent efficacy and higher completion rates than longer regimens 2
Dosing Specifications for 3HP Regimen
For adults and children ≥12 years:
- Rifapentine: weight-based dosing up to 900 mg maximum once weekly 5
- Isoniazid: 15 mg/kg (rounded to nearest 50-100 mg) up to 900 mg maximum once weekly 5
For children 2-11 years:
- Rifapentine: weight-based dosing up to 900 mg maximum once weekly 5
- Isoniazid: 25 mg/kg (rounded to nearest 50-100 mg) up to 900 mg maximum once weekly 5
Weight-based rifapentine dosing:
- 10-14 kg: 300 mg (2 tablets)
- 14.1-25 kg: 450 mg (3 tablets)
- 25.1-32 kg: 600 mg (4 tablets)
- 32.1-50 kg: 750 mg (5 tablets)
50 kg: 900 mg (6 tablets) 5
Alternative Regimens When Rifamycins Are Contraindicated
9 months of daily isoniazid (9H) is conditionally recommended when rifamycin-based regimens cannot be used, with 60-90% protective efficacy if completed 1
6 months of daily isoniazid (6H) is strongly recommended for HIV-negative adults and children but should NOT be used for HIV-infected persons or those with radiographic evidence of prior TB, where 9 months is mandatory 1, 2
Special Population Considerations
HIV-infected patients:
- The 3HP regimen is equally effective in HIV-positive and HIV-negative persons and is preferred 1, 2
- If isoniazid monotherapy is chosen, use 9 months rather than 6 months 1, 2
- Isoniazid plus antiretroviral therapy decreases TB incidence more than either alone 2
- Rifabutin may substitute for rifampin when drug interactions with antiretrovirals preclude rifampin use 2
Pregnant women:
- For HIV-negative women, isoniazid (9 or 6 months) is recommended 1
- 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
- Rifampin is not recommended during pregnancy 1
Children and adolescents:
- Short-course rifampin-based regimens (3-4 months) appear superior to 9 months of isoniazid in children, with better completion rates and fewer radiographic findings suggestive of disease progression 1, 6
Drug-Resistant Exposure Management
Isoniazid-resistant, rifampin-susceptible TB contacts:
- Treat with rifampin plus pyrazinamide for 2 months, OR
- Rifampin alone for 4 months if pyrazinamide is not tolerated 1
Multidrug-resistant TB contacts:
- Treat with 6-12 months of a later-generation fluoroquinolone alone or with a second drug based on source-case susceptibility 7
- Pyrazinamide should NOT be routinely used as the second drug due to increased toxicity 7
- Treatment is suggested over observation alone for MDR-TB contacts 7
Critical Pre-Treatment Requirements
Active TB disease MUST be ruled out before initiating LTBI treatment through: 1, 2, 5
- History and physical examination focusing on TB symptoms (cough, fever, night sweats, weight loss)
- Chest radiography
- Bacteriologic studies when clinically indicated
Monitoring During Treatment
Baseline assessment:
- 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
- Baseline laboratory testing is recommended for patients with risk factors for hepatotoxicity 2
Ongoing monitoring:
- Monthly clinical evaluations for all patients on isoniazid or rifampin monotherapy, assessing for hepatitis symptoms 1
- Evaluations at 2,4, and 8 weeks for patients on rifampin plus pyrazinamide regimens 1
- Discontinue treatment immediately if evidence of liver injury occurs 1
- For patients with abnormal baseline liver tests or liver disease, obtain serum transaminases every 2-4 weeks while on therapy 5
Administration Guidelines
- Administer rifapentine with meals to increase oral bioavailability and reduce gastrointestinal upset 5
- For patients unable to swallow tablets, crush tablets and add to semi-solid food, consuming immediately 5
- The 3HP regimen must be administered as directly observed therapy (DOT) 5
Critical Pitfalls to Avoid
Never use rifapentine as monotherapy for LTBI treatment—it must always be combined with isoniazid 1, 5
Never use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults due to unacceptably high hepatotoxicity risk, though it may be acceptable in HIV-infected persons and children 1, 8
Never add a single drug to a failing regimen—always add at least 2 drugs to which the organism is susceptible to prevent resistance 1
Do not use 3HP in individuals presumed exposed to rifamycin-resistant or isoniazid-resistant M. tuberculosis 5
Watch for drug interactions with rifamycins, particularly with warfarin, oral contraceptives, antifungals, and HIV antiretroviral therapy 2
Warn patients that rifamycins may permanently stain contact lenses or dentures red-orange due to discoloration of body fluids 5
Avoid rifamycins in patients with porphyria 5