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

Recommended Treatment for Latent Tuberculosis Infection

The recommended first-line treatment for latent tuberculosis infection (LTBI) is a 9-month course of daily isoniazid, which provides more than 90% protection when completed adequately. 1

Treatment Regimens for LTBI

Several evidence-based regimens are available for treating LTBI, with varying durations and efficacy:

Preferred Regimens:

1. 9-month isoniazid (9H)

   • Dosing: Daily self-administered therapy or twice-weekly directly observed therapy (DOT)
   • Efficacy: >90% protection when completed adequately 1
   • Population: Recommended for all age groups, including pregnant women

2. 4-month rifampin (4R)

   • Advantages: Higher completion rates and less hepatotoxicity than isoniazid 1, 2
   • Efficacy: Non-inferior to 9-month isoniazid for prevention of active TB 2
   • Particularly useful for: Patients who cannot tolerate isoniazid or when isoniazid resistance is suspected

3. 3-month once-weekly isoniazid plus rifapentine (3HP)

   • Administration: Once weekly for 12 weeks as directly observed therapy 1, 3
   • Population: Approved for patients ≥2 years of age 1, 3
   • Dosing: Weight-based (see table below) 3

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

Alternative Regimens:

• 6-month isoniazid (6H): Provides substantial protection but less than the 9-month regimen 1
• 3-4 month isoniazid plus rifampin (3-4HR): Comparable efficacy to 9H, with better completion rates in children 1

Special Populations

Children

• Children under 5 years have a higher risk of progression to active TB if untreated 1
• Children generally tolerate isoniazid better than adults, with minimal risk of hepatotoxicity 1
• For children 2-11 years receiving 3HP regimen: rifapentine (weight-based) plus isoniazid 25 mg/kg (900 mg maximum) 3
• For children ≥12 years receiving 3HP regimen: rifapentine (weight-based) plus isoniazid 15 mg/kg (900 mg maximum) 3

HIV-infected Persons

• HIV-infected persons with positive TST (≥5 mm) should receive treatment for LTBI 1
• 3HP or 3HR regimens have shown similar tuberculosis rates to 6H in HIV-infected persons in high TB incidence settings 4

Pregnant Women

• 9-month isoniazid is recommended for pregnant women with LTBI 1

Monitoring and Adverse Effects

Monitoring

• Monthly clinical evaluations to assess adherence and adverse effects 1
• Baseline liver function tests only for patients with risk factors (HIV infection, liver disorders, etc.) 1

Common Adverse Effects

• Isoniazid: Hepatotoxicity (less common in children), peripheral neuropathy
• Rifampin: Drug interactions with medications metabolized by CYP450 3
• Rifapentine + Isoniazid: Hypersensitivity reactions (most common adverse effect) 3, 5, flu-like reactions (more frequent than with isoniazid alone), but hepatotoxicity occurs less frequently 5

Pyridoxine (Vitamin B6) Supplementation

• Recommended for breastfeeding infants, children with diets likely deficient in pyridoxine, and children experiencing paresthesias 1

Common Pitfalls to Avoid

1. Failing to rule out active TB before starting LTBI treatment

   • Can lead to drug resistance and treatment failure 1
   • Adding a single drug to a failing regimen promotes further resistance

2. Inadequate monitoring for hepatotoxicity

   • Particularly important with isoniazid regimens 1

3. Overlooking drug interactions with rifampin-containing regimens

   • Rifamycins interact with drugs metabolized by CYP450 3

4. Confusing LTBI with active TB

   • LTBI is not infectious and requires no isolation 1

5. Poor adherence to lengthy regimens

   • Shorter regimens like 4R and 3HP have better completion rates 2, 5