From the Guidelines
Latent tuberculosis infection should be treated with a 3-month course of once-weekly isoniazid plus rifapentine (3HP) as the preferred treatment regimen. This recommendation is based on the strongest and most recent evidence from the National Tuberculosis Controllers Association and CDC guidelines published in 2020 1. The 3HP regimen has been shown to have excellent tolerability and efficacy, with higher completion rates compared to longer treatment regimens.
Key Considerations for Treatment
- The treatment regimen should be chosen based on the individual patient's characteristics, such as HIV status and ability to tolerate certain medications.
- Patients should be monitored for medication side effects, particularly hepatotoxicity with isoniazid, and baseline liver function tests are recommended before starting therapy.
- Pyridoxine (vitamin B6, 25-50 mg daily) should be given with isoniazid to prevent peripheral neuropathy, especially in patients with diabetes, kidney disease, malnutrition, or alcohol use disorder.
- Alternative regimens include 4 months of daily rifampin, 3 months of daily isoniazid plus rifampin, or 6-9 months of daily isoniazid, but these regimens have lower completion rates and higher toxicity risks compared to the 3HP regimen.
Rationale for Recommendation
The recommendation for the 3HP regimen is based on the GRADE criteria, which assess the quality of evidence and the balance of desirable and undesirable consequences of a treatment regimen. The 3HP regimen has been shown to have moderate-quality evidence for its effectiveness and a favorable balance of desirable and undesirable consequences, making it a strong recommendation for the treatment of latent tuberculosis infection 1.
Important Considerations for Clinical Practice
- Treatment should be initiated after excluding active TB disease through symptom screening, chest radiography, and sometimes sputum testing.
- Patients should be educated on the importance of completing the full treatment regimen to ensure effective prevention of progression to active TB disease.
- Clinicians should be aware of the potential for drug-drug interactions and take necessary precautions to ensure safe and effective treatment.
From the FDA Drug Label
PRIFTIN is indicated for the treatment of latent tuberculosis infection (LTBI) caused by M. tuberculosis in combination with isoniazid in patients 2 years of age and older at high risk of progression to TB disease. PRIFTIN should be administered in combination with isoniazid once weekly for 12 weeks as directly observed therapy.
Latent Tuberculosis Treatment: The recommended treatment for latent tuberculosis infection is a combination of rifapentine and isoniazid, administered once weekly for 12 weeks as directly observed therapy 2.
- The dose of rifapentine is based on weight, with a maximum recommended dose of 900 mg once weekly for 12 weeks.
- Key Considerations:
- Patients should be at high risk of progression to TB disease.
- Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection.
- Rifapentine should not be used in combination with isoniazid for individuals presumed to be exposed to rifamycin-resistant or isoniazid-resistant M. tuberculosis 2.
From the Research
Latent Tuberculosis Treatment Regimens
- The currently recommended preferred regimen is 9 months daily self-administered isoniazid (INH), which has an efficacy of more than 90% if completed properly 3.
- However, INH is associated with serious adverse events, including hepatotoxicity, which can be fatal in some cases 3.
- Alternative regimens, such as 2 months of rifampin and pyrazinamide, 3-4 months of INH and rifampin, and 4 months of rifampin, have been studied as potential replacements for the 9-month INH regimen 3.
- A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection found that the INH/RPT-3 regimen had a generally favorable adverse event profile, with lower frequencies of hepatotoxicity compared to standard treatment 4.
Efficacy and Safety of Different Regimens
- The 12-dose regimen of once-weekly isoniazid and rifapentine has been shown to be noninferior to 9 months of daily isoniazid in a large and well-conducted clinical trial 5.
- Rifampicin monotherapy or rifamycin-combination therapy has been compared to INH monotherapy for preventing active TB in HIV-negative people at risk of developing active TB, with results suggesting that rifampicin may have a higher completion rate and lower hepatotoxicity compared to INH 6.
- A weekly, directly-observed rifapentine plus INH regimen has been found to have higher treatment completion rates and less hepatotoxicity compared to daily, self-administered INH, although treatment-limiting adverse events were more frequent 6.
Treatment Completion and Adherence
- Treatment completion rates are a significant challenge in latent tuberculosis treatment, with many patients failing to complete the full 9-month course of INH 3.
- Alternative regimens, such as the 12-dose regimen of once-weekly isoniazid and rifapentine, may have higher treatment completion rates due to their shorter duration and lower toxicity 5.
- Directly observed therapy, such as the weekly, directly-observed rifapentine plus INH regimen, may also improve treatment completion rates and adherence 6.