Alternatives to 3HP Treatment for Latent Tuberculosis Infection
The preferred alternatives to 3HP (3-month isoniazid and rifapentine) for latent tuberculosis infection treatment are 4 months of daily rifampin or 3 months of daily isoniazid plus rifampin, as these regimens offer excellent effectiveness, safety, and high treatment completion rates compared to longer isoniazid monotherapy regimens. 1
Preferred Alternative Regimens
4 Months of Daily Rifampin (4R)
- Strongly recommended for HIV-negative adults and children of all ages 1
- Clinically equivalent effectiveness to 9 months of isoniazid with less toxicity 1
- Noninferior in preventing TB disease compared to 9 months of isoniazid 1
- Lower rate of treatment discontinuation due to adverse effects 1
- Lower hepatotoxicity risk (0.03 odds ratio compared to 6 months of isoniazid) 1
- Higher treatment completion rates than longer isoniazid regimens 1
3 Months of Daily Isoniazid Plus Rifampin (3HR)
- Conditionally recommended for both HIV-negative and HIV-positive individuals 1
- Similar risk for TB disease, hepatotoxicity, and adverse effects requiring discontinuation compared to ≥6 months of isoniazid 1
- Particularly effective in children <15 years, with effectiveness comparable to 6-month or longer courses of isoniazid 1
- In HIV-positive persons, no difference in TB disease incidence compared to ≥6 months of isoniazid 1
- Less frequent hepatotoxicity than longer isoniazid regimens 1
Alternative Regimens (Less Preferred)
6 Months of Daily Isoniazid (6H)
- Alternative regimen with strong recommendation for HIV-negative individuals 1
- Conditional recommendation for HIV-positive individuals 1
- Efficacious but has higher toxicity risk than rifamycin-based regimens 1
- Lower treatment completion rates than shorter regimens 1
9 Months of Daily Isoniazid (9H)
- Alternative regimen with conditional recommendation 1
- Historically considered the standard comparator regimen 1
- Efficacious but has higher toxicity risk and lower completion rates than rifamycin-based regimens 1
- Optimal protection from isoniazid appears to be obtained by 9 months of treatment 1
Important Considerations for Rifamycin-Based Regimens
- Drug interactions are a significant concern with rifamycin-based regimens, including interactions with:
- Warfarin
- Oral contraceptives
- Azole antifungals
- HIV antiretroviral therapy 1
- Rifabutin has fewer drug interactions and may be used when rifampin is contraindicated and isoniazid cannot be used 1
- Careful exclusion of active TB disease is essential before starting any LTBI treatment to prevent development of drug resistance 1
- For HIV-positive patients, drug-drug interactions with antiretroviral therapy should be carefully evaluated 1
Regimens Not Recommended
- Pyrazinamide-containing regimens are not recommended due to high documented toxicity 1
- 2-month regimen of rifampin plus pyrazinamide is not recommended due to risk of severe hepatotoxicity 1
Emerging Regimens Under Investigation
- Daily isoniazid plus rifapentine for 1 month (1HP) is under evaluation as an ultrashort antimicrobial regimen 2
- 6-week rifapentine monotherapy (6wP) is being studied and may provide equal or better efficacy than 1HP and 3HP without the added toxicity of isoniazid 3
Selection Algorithm Based on Patient Factors
For HIV-negative adults and children:
For HIV-positive individuals:
For patients with drug intolerability or significant drug-drug interactions: