Tuberculosis (TB) remains the most common cause of death for people living with HIV worldwide. In resource-limited settings, death within six months of beginning antiretroviral therapy (ART) for advanced HIV disease is common, and often due to the tuberculosis co-infection. TB is difficult to diagnose in patients with advanced HIV disease and may be missed. In an effort to reduce the number of deaths, researchers at the University of North Carolina along with other institutions compared empirical TB treatment with isoniazid preventative therapy. They found that empirical TB therapy did not reduce the number of deaths when compared with isoniazid preventative therapy. These results were published in The Lancet on Thursday, March 17.
“We enrolled patients with extremely advanced disease with a working hypothesis that the empiric TB therapy approach would reduce mortality by directly targeting one of the primary causes of death in this population,” said Mina Hosseinipour, MD, MPH, study co-author, scientific director of UNC-Project Malawi and professor of medicine in the Division of Infectious Diseases at UNC School of Medicine. “First, we were surprised to have such low mortality in this population. Only 5 percent of patients died, which is remarkably low compared to historical estimates. While both regimens were well tolerated, we didn’t see any difference in mortality between the arms. But, unexpectedly, there were actually more new TB cases in the patients receiving empiric TB treatment, which fueled a difference in HIV disease progression for those receiving empiric TB therapy. “
The trial, known as REMEMBER (Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis), enrolled 850 people living with advanced HIV at 18 sites in 10 resource-limited countries in Africa, South America and the Caribbean. Study participants were randomized to receive either empirical TB therapy and ART or isoniazid preventative therapy and ART. After 24 weeks, there was no difference in Mortality between the arms. Paradoxically, participants on the empiric TB arm had more new infections with tuberculosis. The study’s results will improve the clinical care and disease management of people living with HIV.
“We have the current tools required to identify and prevent TB and reduce mortality,” said Hosseinipour. “Implementation of systematic TB screening with currently available TB diagnostics, and isoniazid preventive therapy is enough to reduce mortality. “
Hosseinipour and her team at UNC Project-Malawi collaborated with scientists at the Perelman School of Medicine at the University of Pennsylvania and Johns Hopkins School of Medicine. This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) through the AIDS Clinical Trials Group (ACTG) (UM1 AI068634, UM1 AI068636, and UM1 AI106701).