Treatment Regimens

III. Treatment of Latent TB Infection (LTBI)

Last Updated April 2026

Treatment regimens for LTBI are outlined in Table 4. Several different LTBI treatment regimens are recommended by CDC and the National Tuberculosis Coalition of America (NTCA).

These include:

Rifampin⌃
Rifampin for 4 months is a preferred CDC treatment regimen for the treatment of LTBI among persons presumed to be infected with drug-susceptible TB (isoniazid [INH] and rifampin susceptible) and is the regimen of choice for the treatment of LTBI among persons thought to be infected with INH-resistant strains of M. tuberculosis. Rifampin is also preferred by many clinicians and public health clinics because of the shorter duration of therapy compared to INH and because rifampin has less hepatotoxicity compared to INH for the treatment of LTBI. Rifampin for 4 months has been shown to be noninferior to 9 months of INH for the treatment of LTBI in a randomized controlled trial. In addition, rifampin was associated with higher completion rates and fewer adverse effects compared to INH. Rifampin has a large number of drug -drug interactions (as discussed on page 78) including warfarin, oral contraceptives, azole antifungals, and HIV antiretroviral therapy. Other medications that a person with LTBI is taking is an important consideration when determining whether rifampin or other LTBI regimens which include rifampin or other rifamycins can be prescribed. Drug-drug interactions between rifamycins and antiretroviral therapy are regularly updated by the U.S. Department of Health and Human Services (for LTBI regimens and rifampin/rifamycins: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium ); rifampin and antiretroviral drug interactions: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf
INH plus Rifapentine (3HP) ⌃
A short course regimen of weekly INH plus rifapentine for 12 weekly doses is another CDC-preferred regimen for the treatment of LTBI (due to presumed infection with drug-susceptible M. tuberculosis) in adults as well as children > 2 years of age. In 2011, when CDC first recommended 3HP for the treatment of LTBI it indicated it should be delivered by directly observed therapy [DOT]. However, based on further studies and updated data, CDC revised guidelines for the use of 3HP in 2018 expanded the patient populations for which this regimen could be used and included an option for self-administration of the 3HP regimen. CDC recommendations for 3HP in the treatment of LTBI include:
- use of 3HP in adults and persons aged 2–17 years with LTBI;
- use of 3HP in persons who are living with HIV with LTBI including those with AIDS and taking antiretroviral medications with acceptable drug-drug interactions with rifapentine* [updated DHHS guidelines on treatment of HIV among adults and adolescents indicate that rifapentine as part of a 3HP regimen is acceptable to use among persons living with HIV on and ART regimen that includes once daily dolutegravir but not bictegravir]; and
- use of 3HP by directly observed therapy (DOT) or self-administered therapy (SAT) in persons aged ≥ 2 years. Per CDC recommendations, “the health care provider should choose the mode of administration (DOT versus SAT) based on local practice, individual patient attributes and preferences, and other considerations, including risk for progression to severe forms of TB disease” (MMWR 2018; 67:723-72).
The 3HP is regimen is NOT recommended for pregnant women, children < 2 years old, persons living with HIV who are on antiretroviral drugs that have significant drug-drug interactions with rifapentine, or patients infected with suspected INH-resistant, rifampin-resistant, or multidrug resistant (MDR) isolates. Other potential challenges in using the 3HP regimen in addition to the drug-drug interactions due to rifapentine (similar to those seen with other rifamycin drugs such as rifampin) include cost of medications that are greater than most alternatives; the need to take numerous pills simultaneously (10 pills once weekly compared with two or three pills daily for other regimens for most adults); and the association with a systemic drug reaction or influenza-like syndrome that can include syncope and hypotension (although the risk of hospitalization is low, 0.1% in published studies).
Isoniazid (INH) ⌃

In the CDC 2020 LTBI treatment guidelines, 6 or 9 months of daily INH is a recommended alternative regimen for the treatment of LTBI (due to presumed infection with drug susceptible M. tuberculosis) as shown in Table 4. A regimen of 6 months of daily INH is strongly recommended for HIV-negative adults and children of all ages and conditionally recommended for adults living with HIV and children of all ages; INH daily for 9 months is conditionally recommended for adults and children of all ages, both HIV-seronegative and HIV-positive. One practical approach for the use of INH for LTBI is to aim for a 9 month regimen with the goal of completion of at least 6 months. INH can be given daily (e.g., by self-administered therapy) as outlined in Table 5. INH should be used for the treatment of LTBI when there are serious potential drug-drug interactions with rifampin or other rifamycins.
Isoniazid (INH) plus Rifampin ⌃
A regimen of 3 months of daily INH plus daily rifampin is a CDC conditionally recommended regimen for the treatment of LTBI in adults and children of all ages. Because this regimen contains rifampin, clinicians must closely review other medications that a person with LTBI is on to assess whether there are drug-drug interactions that would prohibit the use of this regimen (as discussed above for rifampin).

Table 4. Recommendations for regimens to treat latent tuberculosis infection

Regimes	3 months isoniazid plus rifapentine	4 months rifampin	3 months isoniazid plus rifampin
Frequency	Once weekly	Daily	Daily
Recommendation (Strong or Conditional)	Strong	Strong	Conditional
Evidence (High, Moderate, Low, or Very Low)	Moderate	Moderate (HIV negative) i	Very low (HIV negative) / Low (HIV positive) i

Regimes	6 months isoniazid	6 months isoniazid	9 months isoniazid
Frequency	Daily	Daily	Daily
Recommendation (Strong or Conditional)	Strong i	Conditional	Conditional
Evidence (High, Moderate, Low, or Very Low)	Moderate (HIV negative)	Moderate (if living with HIV)	Moderate

Abbreviation: HIV = human immunodeficiency virus

1. Preferred: excellent tolerability and efficacy, shorter treatment duration, higher completion rates than longer regimens, and therefore higher effectiveness.
2. Alternative: excellent efficacy but concerns regarding longer treatment duration, lower completion rates, and therefore lower effectiveness.

Table 5. Dosages for Recommended LTBI Treatment Regimens

Duration	3 months
Dosage And Age Group	Adults and children aged ≥ 12 yrs Isoniazid i: 15 mg/kg rounded up to the nearest 50 or 100 mg; 900 mg maximum Rifapentine i: 10 - 14.0 kg, 300 mg 14.1 - 25.0 kg, 450 mg 25. 1 - 32.0 kg, 600 mg 32.1 - 49.9 kg, 750 mg > 50.0 kg, 900 mg maximum Children aged 2 - 11 yrs Isoniazid i: 25 mg/kg; 900 mg maximum Rifapentine i: see above
Frequency	Once weekly
Total doses	12

Duration	4 months
Dosage And Age Group	Adults 10 mg/kg Children 15 - 20 mg/kg i Maximum dose 600 mg
Frequency	Daily
Total doses	120

Duration	3 months
Dosage And Age Group	Adults Isoniazid i: 5 mg/kg; 300 mg maximum Rifampin i: 10 mg/kg; 600 mg maximum Children: Isoniazid i: 10 - 20 mg/kg i ; 300 mg maximum Rifampin i: 15 - 20 mg/kg; 600 mg maximum
Frequency	Daily
Total doses	90

Duration	9 months	6 months
Dosage And Age Group	Adults 5 mg/kg Children 10 - 20 mg/kg i Maximum dose 300 mg	Adults 5 mg/kg Children 10 - 20 mg/kg i Maximum dose 300 mg
Frequency	Daily	Daily
Total doses	270	180

1. Isoniazid is formulated as 100-mg and 300-mg tablets.
2. Rifapentine is formulated as 150-mg tablets in blister packs that should be kept sealed until use. Rifapentine should not be used for children <2 years of age due to lack of pharmacokinetic data.
3. Rifampin (rifampicin) is formulated as 150-mg and 300-mg capsules.

Table 6. LTBI Treatment Drug Adverse Reactions

Adverse Reactions	Gastrointestinal (GI) upset, hepatic enzyme elevations, hepatitis, peripheral neuropathy, mild effects on central nervous system (CNS), drug interactions
Monitoring	Order baseline hepatic chemistry blood tests (at least AST or ALT) for patients with specific conditions: Living with HIV, liver disorders, postpartum period (<3 months after delivery), regular alcohol use, injection drug use, or use of medications with known possible interactions. [Some clinicians prefer to obtain baseline tests on all adults]. Repeat measurements if: baseline results are abnormal client is at high-risk for adverse reactions client has symptoms of adverse reactions
Comments	Hepatitis risk increases with age and alcohol consumption. Pyridoxine can prevent isoniazid-induced peripheral neuropathy.

Adverse Reactions	Orange discoloration of body fluids (secretions, tears, urine) , GI upset, drug interactions, hepatitis, thrombocytopenia, rash, fever, influenza-like symptoms, hypersensitivity reaction i Many drug-drug interactions
Monitoring	Complete blood count (CBC), platelets and liver function tests. Repeat measurements if: baseline results are abnormal client has symptoms of adverse reactions Prior to starting RIF or RPT: need to carefully review all medications being taken by the patient with LTBI and ensure there is no contraindication to the use of that medication and RIF, RBT or RPT.
Comments	Hepatitis risk increases with age and alcohol consumption. Rifampin monotherapy is associated with lower risk of hepatotoxicity compared to INH monotherapy for patients being treated for LTBI. Need to carefully review for possible drug-drug interactions prior to starting RIF, RBT or RPT and ensure there are no contraindications to these agents prior to using them for the treatment of LTBI.

Adverse Reactions	See adverse effects associated with isoniazid alone and a rifamycin alone (see above)
Monitoring	Complete blood count (CBC), platelets and liver function tests. Repeat measurements if: baseline results are abnormal client has symptoms of adverse reactions Prior to starting RIF or RPT: need to carefully review all medications being taken by the patient with LTBI and ensure there is no contraindication to the use of that medication and RIF or RPT.
Comments	Approximately 4% of all patients using 3HP experience flu-like or other systemic drug reactions, with fever, headache, dizziness, nausea, muscle and bone pain, rash, itching, red eyes, or other symptoms. Approximately 5% of persons discontinue 3HP because of adverse events, including systemic drug reactions; these reactions typically occur after the first 3–4 doses, and begin approximately 4 hours after ingestion of medication.

Additional Notes:

Hypersensitivity reaction to rifamycins (rifampin, rifabutin, or rifapentine): reactions may include a flu-like syndrome (e.g. fever, chills, headaches, dizziness, musculoskeletal pain), thrombocytopenia, shortness of breath or other signs and symptoms including wheezing, acute bronchospasm, urticaria, petechiae, purpura, pruritus, conjunctivitis, angioedema, hypotension or shock.
If moderate to severe reaction (e.g. thrombocytopenia, hypotension), hospitalization or life-threatening event: Discontinue treatment.
If mild reaction (e.g. rash, dizziness, fever): Continue to monitor patient closely with a low threshold for discontinuing treatment.
A flu-like syndrome appears to be the most common side effect profile leading to discontinuation of the 3HP regimen.
Rifabutin can rarely cause uveitis.