Discuss with your doctor
CDC guidance favors short rifamycin-based regimens.
20 Options for Latent TB
Standard Drug-Susceptible LTBI
1. 3HP — Isoniazid + Rifapentine
Once weekly
3 months
One of the CDC-preferred regimens.
2. 4R — Rifampin
Daily
4 months
Particularly useful when isoniazid cannot be used.
3. 3HR — Isoniazid + Rifampin
Daily
3 months
CDC-preferred short-course option.
4. 6H — Isoniazid
Daily
6 months
Alternative regimen.
5. 9H — Isoniazid
Daily
9 months
Alternative regimen when shorter regimens are unsuitable.
6. Twice-Weekly 6H
Isoniazid twice weekly for 6 months
Generally requires directly observed therapy when using this schedule.
7. Twice-Weekly 9H
Isoniazid twice weekly for 9 months
Also an alternative administration schedule requiring appropriate DOT.
WHO Additional Option
8. 1HP — Isoniazid + Rifapentine
Daily
1 month
WHO recognizes this as a TB-preventive-treatment option and it is used in multiple countries.
Resistance-Specific Approaches
9. 4R for Isoniazid-Resistant, Rifampin-Susceptible Exposure
Four months rifampin
Appropriate in selected contacts when the source organism is known to be INH-resistant but rifampin-susceptible.
10. 6H/9H for Selected Isoniazid-Susceptible Exposure
Particularly relevant when rifamycin interactions make rifampin/rifapentine problematic.
11. 6Lfx — Levofloxacin for MDR/RR-TB Exposure
Daily levofloxacin
6 months
WHO now recommends this as TPT for appropriate contacts of MDR/RR-TB.
12. 6Lfx in Children Exposed to MDR/RR-TB
Pediatric levofloxacin formulation/dosing
Six months
Requires evaluation of the source case’s resistance pattern.
Patient-Specific Regimen Selection
13. Choose 4R When INH Is Poorly Tolerated
CDC specifically lists 4R for people unable to tolerate isoniazid.
14. Choose a Non-Rifamycin Regimen When Major Rifamycin Drug Interactions Exist
Rifampin/rifapentine alter metabolism of numerous medications.
This can make 6H or 9H preferable in selected patients.
15. Select Regimen According to HIV/ART Interactions
3HP, 3HR, 4R and other regimens have different compatibility with antiretroviral therapy.
The ART regimen must be checked before selecting the TPT regimen.
16. Pregnancy-Specific Regimen Selection
Regimen selection changes during pregnancy.
CDC specifically does not recommend 3HP for women who are pregnant or expecting pregnancy during the 3-month course.
17. Pediatric Regimen Selection
Children can receive several of the same preventive regimens, but age restrictions and formulations matter.
For example, CDC does not recommend 3HP under age 2.
18. Baseline Hepatic-Risk Assessment Before Choosing INH
Liver disease, alcohol use, pregnancy/postpartum status and other factors can influence selection and monitoring.
This can favor a shorter rifamycin regimen in appropriate patients.
19. Rifamycin Interaction Assessment
Review all medications before 3HP, 3HR or 4R.
This includes anticoagulants, anticonvulsants, some antiretrovirals, hormonal contraceptives and numerous other drugs.
20. Defer LTBI Therapy Until Active TB Is Excluded
This is critical rather than simply another regimen.
Symptoms, chest imaging and microbiologic evaluation should be used when indicated.
Do not treat presumed LTBI alone if active TB has not been excluded.
Master Table
| # | Approach | Duration | Main Setting |
|---|---|---|---|
| 1 | 3HP | 3 mo | Standard |
| 2 | 4R | 4 mo | Standard |
| 3 | 3HR | 3 mo | Standard |
| 4 | 6H | 6 mo | Alternative |
| 5 | 9H | 9 mo | Alternative |
| 6 | Twice-weekly 6H | 6 mo | Alternative administration |
| 7 | Twice-weekly 9H | 9 mo | Alternative administration |
| 8 | 1HP | 1 mo | WHO option |
| 9 | 4R after INH-resistant exposure | 4 mo | Resistance-specific |
| 10 | 6H/9H after appropriate susceptible exposure | 6–9 mo | When rifamycins unsuitable |
| 11 | 6Lfx | 6 mo | MDR/RR exposure |
| 12 | Pediatric 6Lfx | 6 mo | Child MDR/RR contacts |
| 13 | 4R for INH intolerance | 4 mo | INH intolerance |
| 14 | Non-rifamycin regimen | 6–9 mo | Major interactions |
| 15 | HIV/ART-adjusted regimen | Variable | HIV |
| 16 | Pregnancy-adjusted regimen | Variable | Pregnancy |
| 17 | Pediatric-adjusted regimen | Variable | Children |
| 18 | Hepatic-risk-based selection | Variable | Liver-risk patients |
| 19 | Drug-interaction-based selection | Variable | Polypharmacy |
| 20 | Exclude active TB first | — | Required before TPT |
The Key Point
There are not 20 independently validated antimicrobial regimens for ordinary LTBI. The core U.S. regimens are 3HP, 4R, 3HR, 6H and 9H; WHO additionally recognizes 1HP, and 6 months of levofloxacin (6Lfx) is now an important option for appropriate MDR/RR-TB contacts.
References
Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020;69(1):1–11.
CDC. Treatment for Latent Tuberculosis Infection. Updated April 17, 2025.
CDC. Clinical Overview of Latent Tuberculosis Infection. Updated April 17, 2025.
WHO. WHO consolidated guidelines on tuberculosis: Module 1—prevention: tuberculosis preventive treatment. 2nd ed. Geneva: World Health Organization; 2024.
WHO. Options for TB preventive treatment regimens: drug-resistant TB. WHO TB Knowledge Sharing.