Implementing the 4R and 9H regimens for TB preventive treatment in Indonesia

Area of Science:

• Public Health
• Infectious Disease Epidemiology
• Clinical Trial Research

Background:

• Tuberculosis preventive treatment (TPT) implementation faces challenges, particularly in resource-limited settings.
• A Phase 3 trial evaluated the efficacy and safety of a 4-month rifampicin (4R) regimen versus a 9-month isoniazid (9H) regimen in Indonesia.
• Understanding TPT effectiveness is crucial for global tuberculosis control efforts.

Purpose of the Study:

• To compare treatment completion rates between 4R and 9H regimens for latent tuberculosis infection.
• To assess the incidence of Grade 3-5 adverse events (AEs) and active tuberculosis occurrence.
• To evaluate the health costs associated with each TPT regimen.

Main Methods:

• A randomized controlled trial involving 157 children and 860 adults with latent TB infection.
• Participants were randomized to receive either 4R or 9H.
• Follow-up extended to 16 months for children and 28 months for adults, monitoring primary and secondary outcomes.

Main Results:

• The 4R regimen demonstrated a significantly higher treatment completion rate (78.7%) compared to 9H (65.5%).
• Fewer Grade 3-5 adverse events were observed in adults on 4R (0.4%) versus 9H (2.8%), with no such events in children.
• Active TB incidence was lower with 4R (0.09/100 person-years) than 9H (0.36/100 person-years), and 4R was more cost-effective.

Conclusions:

• The 4-month rifampicin regimen is superior to the 9-month isoniazid regimen in terms of completion rates and efficacy.
• The 4R regimen offers improved safety in adults and comparable safety in children, alongside lower costs.
• These findings suggest the 4R regimen could significantly benefit the Indonesian tuberculosis control program.