Latent TB Infection Treatment FAQs for Clinicians

People who are infected with TB bacteria (Mycobacterium tuberculosis) but are not sick have a condition called latent TB infection. A person with latent TB infection does not have symptoms, does not feel sick, and cannot spread TB bacteria to others. Many people who have latent TB infection never develop TB disease. Some people develop TB disease soon after becoming infected (within weeks) before their immune system can fight the TB bacteria. Other people may get sick with TB disease when their immune system becomes weak for another reason. Latent TB infection can be treated to prevent the development of TB disease.

Treatment of latent TB infection is essential to controlling TB in the United States because it substantially reduces the risk that latent TB infection will progress to TB disease. In the United States, up to 13 million people may have latent TB infection, according to estimates from the U.S. Centers for Disease Control and Prevention (CDC). Without treatment, people with latent TB infection can develop TB disease in the future. The risk is higher for people with HIV, diabetes, or other conditions that affect the immune system, as well as for people from countries where TB is common. For more information about persons who are at high risk for getting sick with TB disease see Who should be given high priority for latent TB infection treatment?

More than 80% of people who get sick with TB disease in the United States each year get sick from longstanding, untreated latent TB infection. Eliminating TB disease in the United States requires expanding testing and treatment of latent TB infection.

In 2020, CDC and the National Tuberculosis Controllers Association (NTCA) published new guidelines for the treatment of latent TB infection. CDC and NTCA preferentially recommend short-course, rifamycin-based, 3- or 4-month latent TB infection treatment regimens over 6- or 9-month isoniazid monotherapy. Short-course latent TB infection treatment regimens are effective, safe, and have higher completion rates than longer 6 to 9 months of isoniazid monotherapy.

In 2018, CDC updated the recommendations for use of a short-course regimen of once-weekly isoniazid-rifapentine for 12 weeks (3HP) for treatment of latent TB infection.

The last comprehensive update to latent TB infection guidelines was published in the United States in 2000. Since then, several new treatment regimens have been evaluated in clinical trials. CDC and NTCA convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of latent TB infection among people in the United States. Results from the systematic review supported new guidelines for latent TB infection treatment. The new guidelines were published in the Morbidity and Mortality Weekly Report: Recommendations and Reports on February 14, 2020.

A diagnosis of latent TB infection is made if a person has a positive tuberculin skin test (TST) or TB blood test (interferon-gamma release assays, or IGRA) result and a medical evaluation does not indicate TB disease. TB blood tests are the preferred TB test for persons born outside the United States, many of whom have received the bacille Calmette-Guerin (BCG) vaccine.

There are several treatment regimens recommended in the United States for latent TB infection. The medications used to treat latent TB infection include the following on their own or in combination, as shown in the table below:

• Isoniazid (INH)
• Rifapentine (RPT)
• Rifampin (RIF)

In 2020, CDC and the National Tuberculosis Controllers Association (NTCA) published new guidelines for the treatment of latent TB infection. CDC and NTCA preferentially recommend short-course, rifamycin-based, 3- or 4-month latent TB infection treatment regimens over 6- or 9-month isoniazid monotherapy. Short-course latent TB infection treatment regimens are effective, safe, and have higher completion rates than longer 6 to 9 months of isoniazid monotherapy. Short-course, rifamycin-based, 3- or 4-month latent TB infection treatment  regimens include:

• Three months of once-weekly isoniazid plus rifapentine (3HP)
• Four months of daily rifampin (4R)
• Three months of daily isoniazid plus rifampin (3HR)

Shorter, rifamycin-based treatment regimens generally have a lower risk of hepatotoxicity than longer 6 to 9 months of isoniazid monotherapy (6H/9H, respectively).

If short-course treatment regimens are not a feasible or available option, 6H and 9H are alternative, effective latent TB infection treatment regimens. Although effective, 6H and 9H have higher toxicity risk and lower treatment completion rates than most short-term treatment regimens. All treatment must be modified if the patient is a contact of an individual with drug-resistant TB disease. Clinicians should choose the appropriate treatment regimen based on drug susceptibility results of the presumed source case (if known), coexisting medical conditions (e.g., HIV), and potential for drug-drug interactions. Consultation with a TB expert is advised if the known source of TB infection has drug-resistant TB.

Read Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020 to learn more about treatment regimens for latent TB infection. Read Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection for more information about the 3HP treatment regimen.

Short-course, rifamycin-based treatment regimens are recommended for people diagnosed with latent TB infection to prevent development of TB disease. Short course regimens are preferred for reasons of convenience and higher rates of treatment completion.

In 2020, CDC and the National Tuberculosis Controllers Association (NTCA) published new guidelines for the treatment of latent TB infection. CDC and NTCA preferentially recommend short-course, rifamycin-based, 3- or 4-month latent TB infection treatment regimens over 6- or 9-month isoniazid monotherapy. Short-course latent TB infection treatment regimens are effective, safe, and have higher completion rates than longer 6 to 9 months of isoniazid monotherapy. Short-course, rifamycin-based, 3- or 4-month latent TB infection treatment  regimens include:

• Three months of once-weekly isoniazid plus rifapentine (3HP)
• Four months of daily rifampin (4R)
• Three months of daily isoniazid plus rifampin (3HR)

If short-course treatment is not a feasible or available option (for example, due to drug interactions with rifamycins), CDC and NTCA recommend six or nine months of daily isoniazid (6H/9H, respectively) as alternative, effective latent TB infection treatment regimens.

Clinicians should choose the appropriate treatment regimen based on the following:

• drug susceptibility results of the presumed source case, if known
• coexisting medical conditions
• potential for drug–drug interactions

For persons with HIV/AIDS, see the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIVexternal icon.

Treating latent TB infection is especially important for people with a higher risk of developing TB disease once infected, including children under age five and people with medical conditions, like HIV, diabetes, or other conditions that weaken the immune system.

Read Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020 to learn more about treatment regimens for latent TB infection. Read Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection for more information about the 3HP treatment regimen.

Latent TB Infection Treatment Regimens

*Isoniazid (INH) is formulated as 100 mg and 300 mg tablets.
^†Rifapentine (RPT) is formulated as 150 mg tablets in blister packs that should be kept sealed until use.
^‡Intermittent regimens must be provided via directly observed therapy (DOT), that is, a health care worker observes the ingestion of medication.
^§Rifampin (rifampicin; RIF) is formulated as 150 mg and 300 mg capsules.
^‖The American Academy of Pediatrics acknowledges that some experts use RIF at 20–30 mg/kg for the daily regimen when prescribing for infants and toddlers (American Academy of Pediatrics. Tuberculosis. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31^st ed. Itasca, IL: American Academy of Pediatrics; 2018:829–853).
^¶The American Academy of Pediatrics recommends an INH dosage of 10–15 mg/kg for the daily regimen and 20–30 mg/kg for the twice weekly regimen.

The decision about treatment for latent TB infection should be based on a person’s chances of developing TB disease by considering their risk factors.

Persons who are at high risk for progression to TB disease once infected should be given high priority for latent TB infection treatment.  Groups who should be given high priority for latent TB infection treatment include:

• People with a positive TB blood test (interferon-gamma release assays, or IGRA) result
• People with a tuberculin skin test (TST) reaction of five or more millimeters and who are
  • HIV-infected persons
  • Recent contacts to a patient with active TB disease
  • Persons with fibrotic changes on chest radiograph consistent with old TB
  • Organ transplant recipients
  • Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-α antagonists)

• People with a TST reaction of 10 or more millimeters and who are
• • Persons from countries where TB is common, including Mexico, the Philippines, Vietnam, India, China, Haiti, and Guatemala, or other countries with high rates of TB. (Of note, people born in Canada, Australia, New Zealand, or Western and Northern European countries are not considered at high risk for TB infection, unless they spent time in a country with a high rate of TB.)
  • Injection drug users
  • Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities)
  • Mycobacteriology laboratory personnel
  • Children under four years of age, or children and adolescents exposed to adults in high-risk categories

Persons with no known risk factors for TB may be considered for treatment of latent TB infection if they have either a positive TB blood test (interferon-gamma release assays, or IGRA) result or if their reaction to the TST is 15 mm or larger. All testing activities should be accompanied by a plan for follow-up care for persons with latent TB infection or TB disease. Treatment of latent TB infection should be initiated after the possibility of TB disease has been excluded.

Clinicians should choose the appropriate treatment regimen based on the following:

• drug susceptibility results of the presumed source case, if known
• coexisting medical conditions
• potential for drug–drug interactions

When choosing a treatment regimen for patients with HIV/AIDS, see the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIVexternal icon.

Clinicians should contact state and local TB control offices for additional information on diagnosing and treating latent TB infection.

Clinicians should evaluate all patients for signs and symptoms of active TB disease before treatment of latent TB infection. See clinical guidelines for more information: Diagnosis of Tuberculosis in Children and Adultsexternal icon.

Prior to beginning treatment with three months of once-weekly isoniazid plus rifapentine (3HP), clinicians should consider liver function and other baseline blood tests for certain patients:

• Consider a baseline hepatic chemistry blood test for older patients on an individual basis, especially for those taking medications for chronic medical conditions.
• Order baseline hepatic chemistry blood tests (at least aspartate aminotransferase (AST)) for patients with specific conditions:
  • human immunodeficiency virus infection,
  • liver disorders, including viral hepatitis,
  • postpartum period (≤3 months after delivery),
  • regular alcohol usage,
  • intravenous (IV) drug usage

• Clinicians should evaluate all patients for signs and symptoms of active TB disease both before and during treatment of latent TB infection.
• Clinicians should inform the patient (parents/legal guardians of pediatric patient) about possible adverse effects and instruct them to seek medical attention when symptoms of possible adverse effects first appear.
• Clinicians should perform a clinical assessment upon the first sign or symptom of a possible adverse effect.
• Clinicians should conduct monthly evaluations for the findings of treatment-associated adverse events (e.g., symptoms suggestive of systemic drug reactions, loss of appetite, vomiting, yellow eyes, tenderness of the liver, easy bruising, rash).

Clinicians who are treating patients for latent TB infection with three months of once-weekly isoniazid plus rifapentine (3HP) should:

• Conduct blood tests at subsequent clinical encounters for patients whose baseline testing is abnormal and for others at risk for liver disease. Discontinue 3HP if a serum aspartate aminotransferase (AST) concentration is ≥5 times the upper limit of normal in the absence of symptoms or ≥3 times the upper limit of normal in the presence of symptoms.
• Be vigilant for drug hypersensitivity reactions, particularly hypotension or thrombocytopenia.
• Inform patients that rifampin and rifapentine may cause urine or other bodily fluids to turn a reddish-orange color. This side effect is usually not harmful.
• Encourage patients to use a symptom checklist, like the 3HP symptom checklistpdf icon, for timely recognition and reporting of adverse events to the provider. Clinicians should remind patients about possible adverse events and side effects of medication at each clinical visit.
• Encourage patients on self-administered therapy to record medication intake using tools like the 3HP medication trackerpdf icon and report any deviations from the prescribed regimen to the provider.

• Most people can take their TB medicines without any problems. Clinicians should let patients know this, however, . they should also educate patients about possible adverse effects and instruct them to stop taking their medicine and to seek medical attention when signs and symptoms of adverse events first appear.
• Rifampin and rifapentine may cause urine or other bodily fluids to turn a reddish-orange color. This side effect is usually not harmful.
• Clinicians should encourage patients to use a symptom checklist, like the 3HP symptom checklistpdf icon, for timely recognition and reporting of adverse events to the provider. Clinicians should remind patients about possible adverse events and side effects of medication at each clinical visit.
• Clinicians should encourage patients on self-administered therapy to record medication intake using tools like the 3HP medication trackerpdf icon and report any deviations from the prescribed regimen to the provider.

• Clinicians should encourage patients on self-administered therapy to record medication intake using tools like the 3HP medication trackerpdf icon and to report to them any deviations from the prescribed regimen.
• Clinicians should repeat pertinent educational messages about adherence to the prescribed treatment at each clinical visit.
• Clinicians should talk to patients about ways they can remember to take their medication. Examples of these include:
  • Encouraging patients to take medicine at the same date and time each week.
  • Using a medication tracker or calendar to track doses.
  • Setting an alarm on their phone for the date and time to take medicines.
  • Keeping medicines in one place where it will not be forgotten.
  • Writing a reminder note and putting it in a prominent place (like the refrigerator or a bathroom mirror).
  • Asking family members or friends for reminders.

Clinicians may choose to administer latent TB infection treatment through directly observed therapy (DOT) or self-administered therapy (SAT) based on local practice, individual patient attributes and preferences, and other considerations including risk of progression to severe forms of TB disease. For guidance related to the three months of once-weekly isoniazid plus rifapentine (3HP) treatment regimen, see the response to the question Who is recommended for self-administered therapy (SAT) with 3HP?

Yes, rifamycin and rifapentine are different medications. It is important for clinicians and pharmacists to know the difference between rifampin and rifapentine. Rifampin and rifapentine are not interchangeable, and clinicians and pharmacists should ensure that patients receive the correct medication for the prescribed treatment regimen.

Clinicians should contact state and local TB control offices for additional information on diagnosing and treating latent TB infection. In addition, clinicians can contact:

• CDC by email at cdcinfo@cdc.gov or by calling 800-CDC-INFO (800-232-4636).
• TB Centers of Excellence for Training, Education, and Medical Consultation

3HP is one of several regimens recommended by CDC for treatment of latent TB infection.  The term 3HP comes from the regimen duration (once weekly doses for 3 months) and the abbreviations of each of the two drugs (INH and RPT), in the regimen.  Some people refer to 3HP as the “12-dose regimen.” This regimen has been recommended in the United States for treating latent TB infection since 2011.

Updated recommendations for the use of 3HP appeared in an article in the Morbidity and Mortality Weekly Report (MMWR) published June 28, 2018.