Summary

2020 NTCA/CDC update to the 2000 ATS/CDC latent TB infection (LTBI) treatment guidelines, based on GRADE systematic review and network meta-analysis. Short-course (3–4 month) rifamycin-based regimens are now preferred over 6–9 months of isoniazid monotherapy because of equivalent efficacy, lower hepatotoxicity, and higher completion rates. Applies only to LTBI presumed susceptible to isoniazid or rifampin (not MDR-TB contacts).

Key Recommendations

Use a short-course rifamycin-based regimen (3HP, 4R, or 3HR) as preferred therapy for LTBI over isoniazid monotherapy.
3 months of once-weekly isoniazid plus rifapentine (3HP) is strongly recommended for adults and children ≥2 years, including HIV-positive persons when antiretroviral drug interactions allow.
4 months of daily rifampin (4R) is strongly recommended for HIV-negative adults and children of all ages; no efficacy evidence in HIV-positive persons.
3 months of daily isoniazid plus rifampin (3HR) is conditionally recommended for adults and children of all ages, including HIV-positive persons as drug interactions allow.
6 months of daily isoniazid is an alternative regimen — strongly recommended in HIV-negative and conditionally in HIV-positive persons unable to take a preferred regimen.
9 months of daily isoniazid is a conditionally recommended alternative for adults and children regardless of HIV status.
Do not use 2 months of rifampin plus pyrazinamide because of unacceptable hepatotoxicity risk.
Rifampin and rifapentine are not interchangeable — verify the prescribed drug matches the intended regimen.
Substitute rifabutin for rifampin when rifampin is contraindicated by drug-drug interactions and isoniazid cannot be used; weekly rifapentine has fewer interactions than rifampin or rifabutin.
3HP may be given by directly observed therapy or self-administered therapy in the United States; DOT yields highest completion.
Do not use shorter rifamycin-based regimens in patients with contraindications to rifamycins or significant drug-drug interactions.
These regimens do not apply to contacts of MDR-TB (isoniazid- and rifampin-resistant strains) — refer to the 2019 ATS/CDC/ERS/IDSA drug-resistant TB guideline.

Thresholds & Doses

3HP (isoniazid + rifapentine, once weekly × 3 months, 12 doses): isoniazid 15 mg/kg rounded up to nearest 50/100 mg, max 900 mg (adults and children ≥12 yr); children 2–11 yr isoniazid 25 mg/kg max 900 mg.
Rifapentine weight-based dosing: 10–14 kg = 300 mg; 14.1–25 kg = 450 mg; 25.1–32 kg = 600 mg; 32.1–49.9 kg = 750 mg; ≥50 kg = 900 mg max.
4R (rifampin daily × 4 months, 120 doses): adults 10 mg/kg, children 15–20 mg/kg, max 600 mg.
3HR (isoniazid + rifampin daily × 3 months, 90 doses): adults isoniazid 5 mg/kg (max 300 mg) + rifampin 10 mg/kg (max 600 mg); children isoniazid 10–20 mg/kg (max 300 mg) + rifampin 15–20 mg/kg (max 600 mg).
6H (isoniazid daily × 6 months, 180 doses): adults 5 mg/kg, children 10–20 mg/kg, max 300 mg; twice-weekly (DOT only) 15 mg/kg adults / 20–40 mg/kg children, max 900 mg, 52 doses.
9H (isoniazid daily × 9 months, 270 doses): adults 5 mg/kg, children 10–20 mg/kg, max 300 mg; twice-weekly DOT 76 doses, max 900 mg.
3HP minimum age cutoff: ≥2 years.
Untreated LTBI lifetime progression risk to active TB: ~5–10%.
Severe systemic drug reaction requiring hospitalization with 3HP: ~0.1%.

Citations

Table 3 (Recommendations for regimens) — strength of recommendation and quality of evidence for 3HP, 4R, 3HR, 6H, 9H.
Table 4 (Dosages) — drug-, weight-, and age-specific dosing and total doses for each recommended regimen.
Table 2 (Network meta-analysis) — odds ratios for TB prevention and hepatotoxicity vs no treatment across regimens.
Results: Preferred Regimens — rationale for 3HP, 4R, and 3HR as preferred rifamycin-based regimens.
Results: Alternative Regimens — 6 and 9 months daily isoniazid recommendations and HIV-specific considerations.
Discussion — recommendation against 2 months rifampin + pyrazinamide due to hepatotoxicity; warning on rifampin/rifapentine confusion.
Other Considerations — exclusion of MDR-TB contacts and reference to 2019 ATS/CDC/ERS/IDSA drug-resistant TB guideline.
Introduction — epidemiology (5–10% lifetime progression; ~80% of US TB cases from reactivation).