Treatment of Latent Tuberculosis Infection
The preferred first-line regimen for latent TB is 3 months of once-weekly isoniazid plus rifapentine (3HP), which offers equivalent efficacy to 9 months of isoniazid with superior completion rates and lower hepatotoxicity. 1, 2
Preferred First-Line Regimens
3 Months of Once-Weekly Isoniazid Plus Rifapentine (3HP)
- This is the preferred regimen for HIV-negative adults and children ≥2 years old, demonstrating equivalent efficacy to 9 months of isoniazid but with significantly higher completion rates (82% vs 69%) and dramatically lower hepatotoxicity (0.4% vs 2.4%). 1, 2, 3
- This regimen is equally effective in HIV-positive persons, making it an excellent choice across populations. 1, 2
- Must be administered as directly observed therapy (DOT) once weekly for 12 weeks. 4
- Dosing for adults and children ≥12 years: Weight-based from 300 mg (10-14 kg) up to maximum 900 mg (>50 kg), combined with isoniazid 15 mg/kg up to 900 mg weekly. 4
- Dosing for children 2-11 years: Same weight-based rifapentine dosing, but isoniazid dose is 25 mg/kg up to 900 mg weekly. 4
4 Months of Daily Rifampin (4R)
- This is the alternative preferred regimen for HIV-negative adults and children of all ages, demonstrating clinically equivalent effectiveness to 9 months of isoniazid with significantly lower toxicity and higher completion rates. 1, 2, 5
- A landmark 2018 trial of 6,859 patients showed rifampin was non-inferior to isoniazid for preventing active TB, with 15.1% higher treatment completion and 1.2% fewer hepatotoxic events. 5
- This regimen is particularly useful when DOT is not feasible since it can be self-administered daily. 5
- Dose is 600 mg daily for 4 months in adults. 6
Alternative Regimens
9 Months of Daily Isoniazid (9H)
- For HIV-infected persons, 9 months is strongly preferred over 6 months when rifamycin-based regimens cannot be used. 1, 2, 7
- Efficacy exceeds 90% when completed properly, but completion rates are poor (around 69% in trials, often <50% in real-world practice). 7, 8, 3
- Can be administered daily self-administered or twice-weekly as DOT. 6, 7
- For children and adolescents, 9 months of isoniazid is the traditional regimen, though short-course rifamycin-based regimens appear superior. 6, 2, 9
6 Months of Daily Isoniazid (6H)
- Provides substantial protection but is inferior to 9-month regimens. 6, 2
- Should NOT be used in HIV-infected persons or those with radiographic evidence of prior TB—always use 9 months for these populations. 6, 1, 2
- May be considered for HIV-negative adults and children when preferred regimens cannot be used. 1
Critical Pre-Treatment Requirements
Active TB disease must be ruled out before initiating any LTBI treatment through:
- History and physical examination focusing on TB symptoms (cough, fever, night sweats, weight loss). 1, 2, 7
- Chest radiography to exclude pulmonary TB. 6, 1, 2
- Bacteriologic studies (sputum cultures) when clinically indicated. 6, 2
Never initiate LTBI treatment without excluding active disease—this is the most critical pitfall to avoid. 1, 2
Monitoring During Treatment
Baseline Testing
- Obtain baseline liver function tests (AST/ALT, bilirubin) for:
- Baseline testing is NOT routinely indicated for all patients or based solely on age. 6
Follow-Up Monitoring
- Monthly clinical evaluations for patients on isoniazid or rifampin monotherapy, assessing for hepatitis symptoms and signs. 6, 2, 7
- Evaluations at 2,4, and 8 weeks for patients on rifampin plus pyrazinamide regimens. 6, 2
- Educate patients to stop treatment immediately and seek medical evaluation if symptoms of hepatitis develop (nausea, vomiting, abdominal pain, jaundice, dark urine). 6
- Discontinue treatment immediately if evidence of liver injury occurs. 1, 2
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, 2
- For pregnant, HIV-negative women, isoniazid for 9 or 6 months is recommended. 6, 1, 2
- Rifampin is not recommended during pregnancy. 2
- For lower-risk women, some experts recommend waiting until after delivery. 6
HIV-Infected Persons
- The 3HP regimen is equally effective and represents an excellent choice. 1, 2
- If isoniazid is chosen, always use 9 months rather than 6 months. 6, 1, 2, 7
- Isoniazid plus antiretroviral therapy decreases TB incidence more than either intervention alone in high TB incidence areas. 1
- Drug interactions are critical: Rifapentine must never be used with certain antiretrovirals; rifabutin may require dose adjustment. 6
Children
- 3HP is approved for children ≥2 years old with appropriate weight-based dosing. 1, 4
- 4 months of rifampin is preferred for children of all ages. 1
- A 2007 pediatric trial showed 3-4 months of isoniazid plus rifampin was superior to 9 months of isoniazid, with better compliance and fewer radiographic changes suggesting possible disease (11-14% vs 24%). 9
- Traditional 9-month isoniazid regimen remains an option but appears inferior to short-course rifamycin regimens. 2, 9
Drug-Resistant Exposure
- For contacts of isoniazid-resistant, rifampin-susceptible TB: Rifampin plus pyrazinamide for 2 months, or rifampin alone for 4 months if pyrazinamide not tolerated. 6, 2
- For contacts of multidrug-resistant TB: Pyrazinamide plus ethambutol OR pyrazinamide plus a fluoroquinolone (levofloxacin or ofloxacin) for 6-12 months. 6, 2
- Immunocompetent contacts may be observed or treated for 6 months; immunocompromised contacts should be treated for 12 months. 6
Critical Pitfalls to Avoid
Never Use These Regimens
- NEVER use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults—this regimen causes unacceptably high hepatotoxicity (4.59 times higher than isoniazid). 1, 2, 8, 3
- While 2RZ appears acceptable in HIV-infected persons and children, the high toxicity risk in HIV-negative adults makes it contraindicated. 6, 8
- Never use rifapentine as monotherapy—it must always be combined with isoniazid. 1, 2, 4
Administration Errors
- All twice-weekly regimens must be administered as DOT—never allow self-administration of intermittent dosing. 6, 2
- Take rifapentine with meals to increase bioavailability and reduce gastrointestinal upset. 4
- For patients unable to swallow tablets, crush and mix with semi-solid food for immediate consumption. 4