Expanding the use of a common medicine to prevent dangerous HIV-TB inflammatory reaction

What it is

The PredART trial showed that prednisone, a common and inexpensive steroid drug used to treat Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS), can also be used to prevent it. In patients with both TB and HIV who start HIV therapy, a four-week course of prednisone has been shown to reduce the chance of developing this complication by about 30%.

Why it matters

For people living with HIV and tuberculosis, starting antiretroviral therapy (ART) can trigger TB-IRIS, a serious inflammatory reaction caused by the recovering immune system response to the tuberculosis infection. This can rapidly worsen a patient’s condition after initial improvement, sometimes leading to hospitalisation or even death. This not only creates major health risks but can also disrupt confidence in HIV treatment. Before the PredART trial, there was no evidence-based way to prevent TB-IRIS.

The story

The journey to this breakthrough began in Khayelitsha, a community on the outskirts of Cape Town, South Africa, with very high rates of TB and HIV infections. With funding from the EDCTP and the South African Department of Science and Technology, a team at the University of Cape Town launched the PredART trial (SP.2011.41304.074) at an integrated HIV-TB clinic. [1]

The study involved 240 participants with advanced HIV who were already receiving TB treatment. Half the participants received a tapering dose of prednisone, while the other half received a placebo.

The results showed that the preventive use of prednisone at the start of antiretroviral therapy (ART) reduced the incidence of TB-IRIS from 47% to 30%. [2] Because prednisone is already off-patent and manufactured globally, this discovery provided an immediate, low-cost solution that could be implemented in resource-limited settings without waiting for the development of new, expensive pharmaceuticals.

In a 2022 sub-study, researchers evaluated the health-related quality of life across physical, psychological and social domains in the PredART trial participants. [3] The analysis confirmed the usefulness of prednisone and showed that it improved the physical health and symptoms.

Today, the findings from the PredART trial have been included in international guidelines such as the South African National Standard Treatment Guidelines [4], the Western Cape Consolidated Guidelines for HIV Treatment [5], the Southern African HIV Clinicians Society guidance [6], and US [7] and European HIV/TB guidance [8], providing a clearer path to recovery for thousands of patients across the continent.

Hear the project explained by its Principal Investigator, Dr Graeme Meintjes, who was awarded the 2013 EDCTP Outstanding African Scientist Prize and the 2020 EDCTP Scientific Leadership Prize, as he shares the story behind the trial.