3HP FAQs for Providers

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 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 years later 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, on average 1 in 10 people with latent TB infection will get sick with 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.

Using shorter treatment regimens can help patients to complete treatment.  CDC has 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 3HP regimen has practical advantages such as a shorter timeframe compared with other regimens.

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 who have received the TB vaccine bacilli Calmette-Guerin (BCG) age 5 years and older, and persons who have a difficult time returning for a second appointment to look for a reaction to the TST.

The decision about treatment for latent TB infection should be based on a person’s chances of developing TB disease by considering his/her 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 5 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 4 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.

The four treatment regimens recommended in the U.S. for latent TB infection (LTBI) use isoniazid (INH), rifapentine (RPT), or rifampin (RIF), shown in the table below. 3HP is one of the four recommended regimens.  Short course regimens, like 3HP are preferred for reasons of convenience and higher rates of treatment completion. 3HP is as effective as the isoniazid nine-month daily regimen for treating latent TB infection.

All treatment must be modified if the patient is a contact of an individual with drug-resistant TB disease. Consultation with a TB expert is advised if the known source of TB infection has drug-resistant TB.

Read the latest recommendations for the use of 3HP. For more information about all of the latent TB infection treatment regimens visit: Treatment Regimens for Latent TB Infection (LTBI).

 

Latent TB Infection Treatment Regimens

Latent TB Infection Treatment Regimens 
Drugs Duration Interval Comments
Isoniazid and Rifapentine 3 months Once weekly* Not recommended for persons who are:
  • Less than 2 years old,
  • Living with HIV/AIDS and taking antiretroviral medications with clinically significant or unknown drug interactions with rifapentine,
  • Presumed infected with INH- or RIF-resistant M. tuberculosis, and
  • Women who are pregnant or expect to become pregnant within the 12 week regimen.
Rifampin 4 months Daily Not recommended for persons who are:
  • Living with HIV/AIDS and taking antiretroviral medications with clinically significant or unknown drug interactions with rifampin (rifabutin may be used as a substitute),
  • Presumed infected with RIF-resistant M. tuberculosis, and
  • Women who are pregnant or expect to become pregnant within the 4 month regimen.
Isoniazid 6 months Daily Not recommended for persons who are presumed infected with INH-resistant M. tuberculosis.
Twice weekly** Not recommended for persons who are presumed infected with INH-resistant M. tuberculosis.
Isoniazid 9 months Daily Not recommended for persons who are presumed infected with INH-resistant M. tuberculosis.

Preferred treatment for:

  • Persons living with HIV AIDS and taking antiretroviral medications with clinically significant or unknown drug interactions with once-weekly rifapentine or daily rifampin,
  • Pregnant women (with pyridoxine/vitamin B6 supplements)
Twice weekly** Not recommended for persons who are presumed infected with INH-resistant M. tuberculosis.

Preferred treatment for pregnant women (with pyridoxine/vitamin B6 supplements)

*Use Directly Observed Therapy (DOT) or Self-Administered Therapy (parentally-administered SAT to children)

**Use Directly Observed Therapy (DOT)

Note: Due to the reports of severe liver injury and deaths, CDC recommends that the combination of rifampin (RIF) and pyrazinamide (PZA) should not be offered for the treatment of latent TB infection.

3HP is one of four regimens recommended by CDC for treatment of latent tuberculosis 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 appear in an article in the Morbidity and Mortality Weekly Report (MMWR) published June 28, 2018.

CDC’s previous recommendations from 2011 limited the use of 3HP.  At that time, not enough data were available to recommend 3HP for children under 12 years old, persons living with HIV/AIDS and taking antiretroviral therapy, or as a self-administered therapy.  Based on newly available data, CDC identified use of 3HP in those populations, as well as self-administration of the 3HP regimen, as areas to address in updated recommendations.  Results from a systematic review of published literature and meta-analyses of the 3HP regimen and treatment outcomes conducted by CDC, and input received from subject matter experts and the Advisory Council for the Elimination of Tuberculosis (ACET), supported new recommendations. The updated recommendations appear in an article in the Morbidity and Mortality Weekly Report (MMWR) published June 28, 2018.

3HP is recommended for people diagnosed with latent TB infection to prevent development of TB disease.  Short course regimens, like 3HP are preferred for reasons of convenience and higher rates of treatment completion. Treating latent TB infection is especially important for people with a higher risk of developing TB disease once infected, including children under age 5 and people with medical conditions, like HIV, diabetes, or other conditions that weaken the immune system.

For more information about groups who should be given high priority for latent TB infection treatment please see the response to the question Who should be given high priority for latent TB infection treatment?

  • Persons less than 2 years old
  • Persons who are living with HIV/AIDS and taking antiretroviral medications with clinically significant drug interactions with once-weekly rifapentine
  • Pregnant women or women expecting to become pregnant during treatment
  • Persons infected with tuberculosis bacteria presumed to be INH or RIF resistant

The CDC now recommends use of the 3HP regimen as self-administered therapy (SAT) in persons 2 years old and older in the United States. This recommendation updates the 2011 recommended use of the 3HP regimen by directly observed therapy (DOT).

Providers should make joint decisions about SAT with each individual patient (or parent/legal guardian), considering program resources and the patient’s age, medical history, social circumstances, and risk factors for progression to severe TB disease.  See below information about parentally administered SAT in persons 2-18 years old.

The updated SAT recommendation is based on evidence from recent studies of treatment completion and the safety of 3HP SAT, as well as recommendations from TB experts and the Advisory Council for the Elimination of Tuberculosis (ACET).  The updated recommendations appear in an article in the Morbidity and Mortality Weekly Report (MMWR) published June 28, 2018

The 3HP self-administered therapy (SAT) regimen has not been studied in persons <18 years old. However, based on expert opinion, the recommendations include the option of parentally-administered SAT to children.  Providers should work with parents/legal guardians to determine the best treatment plan.   Some providers may prefer directly observed therapy for treating latent TB infection in young children aged 2-5 years, because the risk of TB progression and of severe disease is higher than in older children and adults.

  • Providers should evaluate all patients for signs and symptoms of active TB disease before treatment of latent TB infection. See clinical guidelines for more information: Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection; Diagnosis of Tuberculosis in Children and AdultsExternal
  • Providers 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
  • Providers should educate patients about possible adverse effects and instruct them to seek medical attention when signs and symptoms of adverse events first appear.
  • Providers should encourage patients to use a symptom checklistCdc-pdf for timely recognition and reporting of adverse events to the provider. Providers should remind patients about possible adverse events and side effects of medication at each clinical visit.
  • Providers should encourage patients on self-administered therapy to record weekly medication intakeCdc-pdf and report any deviations from the prescribed regimen to the provider.
  • Providers should repeat pertinent educational messages about adherence to the prescribed treatment at each clinical visit.
  • Providers 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.
  • Persons on 3HP regimens should be evaluated monthly to assess adherence and treatment-associated adverse events (e.g., symptoms suggestive of systemic drug reactions, loss of appetite, vomiting, yellow eyes, tenderness of liver, easy bruising, rash).
  • Providers should perform a clinical assessment upon the first symptom of a possible adverse effect.
  • Providers should advise patients to stop 3HP in the case of a possible severe adverse reaction (e.g., hypotension, angioedema, or severe thrombocytopenia) and provide medical care.
  • In case of mild to moderate adverse reaction (e.g., dizziness), use conservative management (e.g., treat dizziness with rest, oral fluids), conduct clinical and laboratory monitoring, and consider continuing 3HP treatment under observation.
Page last reviewed: June 26, 2018