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

Treatment of Latent Tuberculosis Infection

For most patients with latent TB, the preferred first-line regimen 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 less hepatotoxicity. 1

Preferred First-Line Regimens

3 Months of Isoniazid Plus Rifapentine (3HP)

• This is the strongly recommended preferred regimen for HIV-negative adults and children ≥2 years old 1, 2
• Administered once weekly (900 mg rifapentine + 900 mg isoniazid for adults; weight-based dosing for children) for 12 weeks 2, 3
• Demonstrated non-inferior effectiveness compared to 9 months of isoniazid with treatment completion rates of 82.1% versus 69.0% 3
• Significantly lower hepatotoxicity (0.4%) compared to 9-month isoniazid (2.7%) 3
• Can be given as directly observed therapy (DOT) or self-administered, though completion rates are highest with DOT 1, 2
• Important caveat: Requires taking 10 pills simultaneously once weekly and carries risk of systemic drug reaction/flu-like syndrome (usually mild and self-limited) 1

4 Months of Daily Rifampin (4R)

• Strongly recommended as a preferred alternative regimen for HIV-negative adults and children of all ages 1
• Clinically equivalent effectiveness to 9 months of isoniazid with significantly lower toxicity and better completion rates 1
• Particularly useful for patients who cannot tolerate isoniazid or pyrazinamide 1, 4
• No evidence available for effectiveness in HIV-positive persons 1

Alternative Regimens

9 Months of Daily Isoniazid (9H)

• Historically the standard regimen with >90% efficacy when completed properly 4, 5
• Can be administered daily (self-administered) or twice weekly (requires DOT) 1
• For HIV-infected persons, 9 months is preferred over 6 months 1, 4
• Lower completion rates (69%) and higher hepatotoxicity risk compared to rifamycin-based regimens 3

6 Months of Daily Isoniazid (6H)

• Provides substantial protection but less optimal than 9-month regimen 1
• May be acceptable in certain situations based on cost-effectiveness considerations 1
• Not preferred for HIV-infected persons or those with radiographic evidence of prior TB 1

3 Months of Daily Isoniazid Plus Rifampin (3HR)

• Demonstrated equivalent effectiveness to 6-9 months of isoniazid in multiple trials 1
• May have similar completion rates and toxicity as isoniazid monotherapy despite shorter duration 5

Special Population Considerations

HIV-Infected Patients

• 3HP regimen is equally effective in HIV-positive and HIV-negative persons 1, 3
• If using isoniazid monotherapy, 9 months is recommended rather than 6 months 1, 4
• 4R has no evidence for effectiveness in HIV-positive persons 1

Pregnant Women

• For HIV-negative pregnant women, isoniazid (9 or 6 months) is recommended 1, 4
• For women at high risk (HIV-infected or recently infected), treatment should not be delayed based on pregnancy alone, even in first trimester 1
• For lower-risk women, some experts recommend waiting until after delivery 1

Children and Adolescents

• 3HP is approved for children ≥2 years with weight-based dosing 2
• For children 2-11 years: isoniazid 25 mg/kg (max 900 mg) weekly; for ≥12 years: 15 mg/kg (max 900 mg) weekly 2
• Isoniazid for 9 months (daily or twice weekly) is the traditional recommended regimen 1, 4
• Short-course rifamycin regimens (3-4 months) appear superior to 9-month isoniazid in children 6

Drug-Resistant Exposure

• For contacts of isoniazid-resistant, rifampin-susceptible TB: rifampin plus pyrazinamide for 2 months or rifampin alone for 4 months 1
• For multidrug-resistant (MDR) TB exposure in high-risk patients: pyrazinamide plus ethambutol OR pyrazinamide plus fluoroquinolone for 6-12 months 1
• 3HP is not recommended for rifamycin-resistant or isoniazid-resistant exposure 2

Critical Pre-Treatment Requirements

Active TB disease must be ruled out before initiating LTBI treatment through: 1, 4, 7

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

Monitoring During Treatment

Baseline Assessment

• Obtain baseline liver function tests for patients with: 4, 7
  • Suspected liver disorders
  • HIV infection
  • Pregnancy or immediate postpartum period
  • Chronic conditions increasing liver disease risk

Ongoing Monitoring

• Monthly clinical evaluations for all patients 4
• Assessment for hepatitis symptoms (nausea, vomiting, abdominal pain, jaundice, dark urine) 7
• For patients with abnormal baseline liver tests: obtain serum transaminases every 2-4 weeks 2
• Discontinue treatment if evidence of liver injury occurs 2

Common Pitfalls to Avoid

• Never use rifapentine as monotherapy - must always be combined with isoniazid 2
• Do not use 2-month rifampin-pyrazinamide (2RZ) in HIV-negative adults - unacceptably high hepatotoxicity risk despite good efficacy 5
• Ensure adequate interval between doses for twice-weekly regimens (minimum 72 hours for rifapentine) 2
• Active TB must be excluded before starting LTBI treatment - failure to do so risks acquired drug resistance 1
• Consider drug interactions with rifamycins, particularly with antiretrovirals, anticoagulants, and hormonal contraceptives 1