Latent TB in 12 Weekly Doses: CDC Widens 3HP to Children, People With HIV and Self-Dosing

Treating latent tuberculosis infection (LTBI) — infection that hasn't become active disease — is key to controlling and eliminating TB in the United States. In 2011, CDC recommended a short regimen called 3HP: isoniazid and rifapentine once a week for 12 weeks, taken under directly observed therapy (DOT), with limits for children under 12 and people with HIV. After a 2017 review of the evidence, CDC updated those recommendations.

The evidence

A CDC Work Group reviewed studies published from January 2006 to June 2017. From 292 citations, 19 articles covering 15 studies met the criteria. The meta-analysis found that 3HP is as safe and effective as other recommended LTBI regimens and is completed far more often. Key trials showed:

In July 2017, CDC consulted nine outside experts, who reported higher acceptance and completion with 3HP, health departments already using it in children as young as 2, and that requiring DOT held its use back. In December 2017, the Advisory Council for the Elimination of Tuberculosis (ACET) and the public weighed in; ACET recommended allowing parent-given SAT for children.

The recommendations

CDC continues to recommend 3HP for adults, and now also recommends it:

1. for people with LTBI aged 2–17
2. for people with LTBI and HIV, including AIDS, who take antiretroviral drugs with acceptable interactions with rifapentine
3. by DOT or SAT for anyone 2 or older

Providers should choose DOT or SAT based on local practice, the patient's preferences and circumstances, and their risk of severe TB — some experts still prefer DOT for children 2–5, who are at higher risk. Treating LTBI alongside HIV medicines should be guided by clinicians experienced in both.

Side effects and monitoring

• About 4% of patients get flu-like or other whole-body reactions — fever, headache, dizziness, nausea, muscle and bone pain, rash, itching, red eyes — typically after the first 3–4 doses, about 4 hours after taking them. Patients should stop while the cause is found; symptoms usually clear within 24 hours.
• About 5% stop treatment because of side effects.
• Low blood pressure and fainting are rare — about 2 per 1,000 treated. Low white cell counts and raised liver enzymes are uncommon.
• Some patients need liver and blood tests before starting.
• Rifapentine speeds the breakdown of many drugs, so patients on medicines such as methadone or warfarin need monitoring. It can make hormonal birth control less effective — women should add or switch to a barrier method and tell their provider if they plan to become or become pregnant.
• People on SAT should log their doses, and everyone on 3HP should be checked monthly, in person or by phone.

Serious side effects leading to hospitalization or death should be reported to the health department; drug problems can also go to FDA's MedWatch (1-800-FDA-1088). More research is needed on 3HP in children under 2, SAT in people under 18, and use during pregnancy. More: CDC's LTBI resources.

Sources

Based on Andrey S. Borisov, Sapna Bamrah Morris, Gibril J. Njie and colleagues, "Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection," MMWR, volume 67, Centers for Disease Control and Prevention; a work of the United States government in the public domain.