What is the current recommended treatment for latent Tuberculosis (TB) infection?

Current Treatment for Latent Tuberculosis Infection

The preferred first-line treatment for latent TB infection is 3 months of once-weekly isoniazid plus rifapentine, which offers equivalent efficacy to 9 months of isoniazid with significantly higher completion rates (82% vs 69%) and lower hepatotoxicity (0.4% vs 2.7%). 1, 2

Preferred Regimens (in order of priority)

First Choice: 3-Month Isoniazid-Rifapentine (3HP)

• Dosing: Once-weekly directly observed therapy for 12 weeks 1, 3
  • Adults and children ≥12 years: Weight-based rifapentine (300-900 mg) plus isoniazid 15 mg/kg (max 900 mg) 3
  • Children 2-11 years: Weight-based rifapentine (300-900 mg) plus isoniazid 25 mg/kg (max 900 mg) 3
• Advantages: Highest completion rate (82.1%), lowest hepatotoxicity (0.4%), and proven non-inferiority to 9 months isoniazid 1, 2
• Evidence strength: Strong recommendation with moderate quality evidence 1, 4

Second Choice: 4-Month Daily Rifampin (4R)

• Dosing: 600 mg daily for 4 months, self-administered 1
• Advantages: Non-inferior to 9 months isoniazid with 15% higher completion rate and significantly lower hepatotoxicity (grade 3-5 events: 1.1% lower, hepatotoxic events: 1.2% lower) 1, 5
• Evidence strength: Strong recommendation with moderate quality evidence for HIV-negative individuals 1, 4

Third Choice: 3-Month Daily Isoniazid-Rifampin (3HR)

• Dosing: Daily isoniazid plus rifampin for 3 months 1
• Advantages: Shorter duration with better compliance than 9-month isoniazid monotherapy 1, 6
• Evidence strength: Conditional recommendation with very low quality evidence for HIV-negative, low quality for HIV-positive 1, 4

Alternative Regimens

6-Month Daily Isoniazid (6H)

• Use when: Rifamycins contraindicated due to drug interactions 1, 4
• Evidence: Strong recommendation for HIV-negative adults/children; conditional for HIV-positive 1, 4

9-Month Daily Isoniazid (9H)

• Use when: All rifamycin-based regimens contraindicated 1, 4
• Mandatory for: HIV-positive patients when isoniazid is chosen (9 months preferred over 6 months) 1, 4
• Evidence: Conditional recommendation for all populations 1, 4

Critical Drug Interaction Considerations

Rifamycins have extensive drug interactions that may necessitate alternative regimens: 1, 4

• Major interactions: Warfarin, oral contraceptives, azole antifungals, HIV antiretroviral therapy 1
• When rifampin contraindicated: Consider rifabutin (fewer interactions) or weekly isoniazid-rifapentine (fewer interactions than rifampin) 1, 4
• HIV patients: Check current Department of Health and Human Services guidelines for antiretroviral compatibility 1

Special Population Algorithms

HIV-Positive Patients

• First choice: 3-month isoniazid-rifapentine (if no antiretroviral conflicts) 1, 3
• If rifamycin contraindicated: 9 months isoniazid (not 6 months) 1, 4
• Critical caveat: Do NOT use once-weekly rifapentine-isoniazid for active TB treatment in HIV patients due to higher failure/relapse rates 3
• Additional benefit: Isoniazid plus antiretroviral therapy decreases TB incidence more than either alone 4

Pregnant Women

• HIV-negative, lower risk: May defer until postpartum 1
• HIV-positive or recent infection: Initiate immediately, even in first trimester—9 months isoniazid daily or twice-weekly 1

Children and Adolescents

• Ages 2-11 years: 3-month isoniazid-rifapentine (weight-based dosing) 3
• Ages ≥12 years: Same options as adults 3
• Alternative: 9 months isoniazid daily or twice-weekly 1

Suspected Drug-Resistant Exposure

• Isoniazid-resistant, rifampin-susceptible: 4 months daily rifampin 1
• Rifamycin-resistant or isoniazid-resistant: 3HP and 3HR NOT recommended; consult TB specialist 3

Mandatory Pre-Treatment Requirements

Active TB must be ruled out before initiating LTBI treatment: 1, 4, 3

• Detailed symptom history (cough, fever, night sweats, weight loss) 1, 4
• Physical examination 1, 4
• Chest radiography 1, 4
• Bacteriologic studies when clinically indicated 1, 4

Monitoring and Safety Protocol

Baseline Assessment

• All patients: Symptom review, liver disease history 4
• High-risk patients: Baseline serum transaminases if risk factors for hepatotoxicity present (pre-existing liver disease, alcohol use, concurrent hepatotoxic medications, HIV infection, pregnancy/postpartum) 4, 3

Follow-Up Schedule

• Isoniazid or rifampin monotherapy: Monthly clinical evaluation 4
• Rifampin plus pyrazinamide: Weeks 2,4, and 8 4
• Abnormal baseline liver tests: Serum transaminases every 2-4 weeks 3
• All patients: Monitor for symptoms of liver injury (nausea, vomiting, abdominal pain, jaundice, dark urine) 4, 3

Discontinuation Criteria

• Stop immediately if: Evidence of liver injury develops 3
• Higher hepatotoxicity risk: Rifampin plus pyrazinamide together (avoid this combination in non-HIV adults) 4

Administration Details

• Take with meals: Increases bioavailability and reduces GI upset 3
• Cannot swallow tablets: Crush and mix with semi-solid food, consume immediately 3
• Directly observed therapy: Required for all once-weekly regimens; recommended for twice-weekly isoniazid 1, 3

Common Pitfalls to Avoid

• Do not use rifapentine-isoniazid once weekly for active TB continuation phase in HIV patients (higher failure rates) 3
• Do not use 2-month rifampin-pyrazinamide in non-HIV adults (unacceptably high hepatotoxicity) 1
• Do not use rifamycin-based regimens without checking drug interactions (particularly antiretrovirals, warfarin, contraceptives) 1, 4
• Do not assume 6 months isoniazid is adequate for HIV-positive patients (9 months required) 1, 4