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

Treatment for Latent Tuberculosis Infection

The preferred treatment for latent tuberculosis infection (LTBI) is 3 months of once-weekly isoniazid plus rifapentine, as this regimen offers excellent efficacy with shorter duration and higher completion rates than traditional regimens. 1

Recommended Treatment Regimens

The CDC and National Tuberculosis Controllers Association (2020) recommend the following regimens in order of preference:

Preferred Regimens:

1. 3 months of once-weekly isoniazid plus rifapentine (3HP)

   • Strong recommendation with moderate quality evidence
   • Administered as directly observed therapy (DOT)
   • Dosing:
     • Rifapentine: Weight-based dosing up to 900 mg once weekly
     • Isoniazid: 15 mg/kg (maximum 900 mg) once weekly for adults
   • Benefits: High completion rates, shorter duration, excellent efficacy

2. 4 months of daily rifampin (4R)

   • Strong recommendation with moderate quality evidence (HIV-negative)
   • Dosing: Rifampin daily for 4 months
   • Benefits: Shorter than isoniazid regimens, better completion rates, fewer hepatotoxic effects

3. 3 months of daily isoniazid plus rifampin (3HR)

   • Conditional recommendation with very low quality evidence (HIV-negative)
   • Conditional recommendation with low quality evidence (HIV-positive)

Alternative Regimens:

1. 6 months of daily isoniazid (6H)

   • Strong recommendation for HIV-negative, conditional for HIV-positive
   • Moderate quality evidence

2. 9 months of daily isoniazid (9H)

   • Conditional recommendation with moderate quality evidence
   • Historically the standard regimen but limited by poor completion rates

Special Considerations

• HIV-positive patients: When using isoniazid, the 9-month regimen is preferred over 6 months 1

• Pregnant women: Isoniazid (daily or twice weekly) for 9 or 6 months is recommended

  • For high-risk pregnant women (HIV-infected or recently infected), treatment should not be delayed

• Children and adolescents: Isoniazid for 9 months is traditionally recommended 1, but newer evidence supports 3HP for children ≥2 years old 1, 2

• Drug-resistant TB contacts:

  • For isoniazid-resistant, rifampin-susceptible TB contacts: 4 months of rifampin
  • For multidrug-resistant TB contacts: Consider consultation with TB experts

Dosing for 3HP Regimen (Preferred)

Weight range	Rifapentine dose	Number of tablets
10–14 kg	300 mg	2
14.1–25 kg	450 mg	3
25.1–32 kg	600 mg	4
32.1–50 kg	750 mg	5
>50 kg	900 mg	6

• Take with food to increase bioavailability and reduce gastrointestinal upset 2
• Tablets may be crushed and added to semi-solid food if needed

Monitoring During Treatment

• Clinical evaluation should occur:

  • Monthly for isoniazid or rifampin monotherapy
  • At 2,4, and 8 weeks for rifampin/pyrazinamide combination

• Monitor for:

  • Hepatotoxicity: Educate patients about symptoms (nausea, vomiting, abdominal pain, jaundice)
  • Hypersensitivity reactions: More common with rifapentine-containing regimens
  • Drug interactions: Particularly with rifamycins which induce CYP450 enzymes

Treatment Efficacy and Completion Rates

• The 3HP regimen has shown similar efficacy to 9 months of isoniazid with significantly higher completion rates (82.1% vs. 69.0%) 3

• The 4R regimen is non-inferior to 9 months of isoniazid with fewer hepatotoxic events and higher completion rates 4

Common Pitfalls and Caveats

1. Always rule out active TB before starting LTBI treatment through history, physical examination, chest radiography, and when indicated, bacteriologic studies

2. Drug interactions: Rifamycins (rifampin, rifapentine) have significant interactions with many medications including antiretrovirals, oral contraceptives, and warfarin

3. Hepatotoxicity monitoring: Baseline liver function tests are not routinely required for all patients but should be considered for those with risk factors (e.g., liver disease, alcohol use)

4. Flu-like reactions: More common with rifapentine-containing regimens but typically manageable 5

5. Discoloration of body fluids: Rifamycins can permanently stain contact lenses or dentures red-orange 2

By selecting the most appropriate regimen based on patient factors and ensuring proper monitoring, LTBI treatment can effectively prevent progression to active TB disease while minimizing adverse effects.