Real-World Data Confirms TB Preventive Treatment Saves Lives in People With HIV

Tuberculosis preventive treatment (TPT) has long been shown in clinical trials to reduce tuberculosis (TB) incidence and mortality among people with HIV, but its effectiveness had not been evaluated in real-world programs since antiretroviral therapy (ART) was expanded to all people with HIV regardless of CD4 cell count. A new study led by the CDC's Division of Global HIV and Tuberculosis and Emory University's Rollins School of Public Health set out to close that gap by evaluating outcomes across six countries with high TB and HIV burdens: Haiti, Kenya, Nigeria, Uganda, Ukraine, and Zimbabwe. The findings were published in The Lancet HIV.

Researchers used electronic health record data from 235,424 people with HIV initiating ART, applying a target trial emulation approach to compare outcomes between those who started TPT within an eight-week window and those who did not. The pooled hazard ratio for TB was 0.39, meaning TPT was associated with a 61% reduction in TB incidence, with minimal variation across countries. The pooled hazard ratio for mortality was 0.55, reflecting a 45% reduction in all-cause death, though this effect varied more substantially by country.

Why the Real-World Data Matters

"What is powerful about these findings is that they come from routine HIV programs, not from a controlled clinical trial," said Anand Date, chief of the CDC's Global TB Branch. "This is program data showing what happens when countries deliver TB preventive treatment at scale."

TB remains the leading cause of infectious disease death worldwide, with more than 10.7 million people sick with TB and 1.2 million deaths in 2024. Among people with HIV specifically, TB is responsible for roughly a quarter of all AIDS deaths and was the leading cause of death in this population in 2024, despite being both preventable and curable. Implementation of TB preventive treatment in program settings was slow until the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) made a major commitment in 2018; since then, more than 13 million people living with HIV worldwide have received the treatment, most commonly a six-month course of isoniazid.

Timing Matters

The study found that TPT worked best when initiated early in HIV care, ideally within the first two weeks, though it remained effective when started within eight weeks of entering care. Researchers noted this reinforces the importance of integrating TB prevention into the earliest stages of HIV treatment, rather than treating it as a secondary consideration.

A Vulnerable Moment for Global TB and HIV Programs

The findings arrive amid significant disruption to global TB and HIV prevention infrastructure, including freezes on U.S. foreign aid, the dissolution of USAID, and interruptions to PEPFAR funding. Reduced funding for TB programs has been projected to result in more than half a million additional TB deaths and increased catastrophic financial costs for affected families.

"Taken together, the findings support the critical role of tuberculosis preventive treatment in HIV care programs," said Sarita Shah, M.D., M.P.H., professor of epidemiology and global health at Rollins. "This is important in the current context of reduced funding for global health programs to ensure that gains made in HIV care over the last two decades are sustained."

TB Risk Extends Beyond Global Programs

The CDC also noted that TB remains a domestic concern, occurring in all 50 U.S. states. An estimated 13 million Americans are living with latent TB infection, representing a reservoir of potential future active TB cases. TB preventive treatment, when taken correctly, can halt progression from latent infection to active disease, and newer U.S. treatment regimens have shortened the required course to as little as one to three months, including for people with HIV.