Sepsis is the world’s leading cause of death in hospitals, which occurs when the body’s response to infection damages tissue and causes organ failure. Africa bears the largest burden of sepsis in the world, with approximately 48 million cases each year leading to approximately 11 million deaths. People living with HIV face the greatest risk of dying from the condition.
A new study has found that tuberculosis, a chronic bacterial lung disease, is a major and neglected cause of fatal sepsis among people living with HIV. A related Phase 3 clinical trial called the ATLAS study found that prompt initiation of tuberculosis (TB) treatment, even before a TB diagnosis is confirmed, could significantly reduce deaths from sepsis among HIV patients.
The ATLAS study and trial were conducted by Tulane University and the University of Virginia in collaboration with Mbarara University in Uganda and the Kibong’oto Infectious Diseases Hospital in Tanzania, among others. The study and clinical trial findings were published in Lancet E-Clinical Medicine and Lancet Infectious Diseaserespectively.
“Our analysis of clinical trial results found that Mtb (the bacterium that causes tuberculosis) is a much more common cause of sepsis than we thought,” said Dr. Eva Otoupalova, assistant professor of Pulmonary and Critical Care at Tulane University School of Medicine, who co-led the study and was also an author on the ATLAS trial. “Normally, anti-TB treatments are reserved for those diagnosed with TB. We found that, in African hospitals where HIV and TB are a common co-infection, patients with sepsis may benefit from being given anti-TB drugs as soon as possible.”
The ATLAS trial found that immediate treatment of patients with HIV-related sepsis with anti-tuberculosis drugs resulted in a 23% reduction in mortality compared with those treated only after TB diagnosis. In other words, early anti-TB treatment saved 1 in 4 patients.
An immediate but higher dose of the same drug was not associated with a reduction in mortality.
In the follow-up study looking at the trial results, Mtb was the most common pathogen, detected in 52% of patients with HIV-related sepsis.
“Previous studies have shown that TB can cause sepsis, but these studies are few and far between, and I don’t think we realized how high the prevalence is,” Otoupalova said. “Our analysis also found that our diagnostic tools are missing a lot of TB sepsis, which has an impact if TB treatment is given only to those diagnosed with the disease.”
It is known that tuberculosis can be difficult to detect in children, the elderly, people with HIV and pulmonary tuberculosis, all cases where the sputum needed for testing is more difficult to obtain. However, the researchers found that combined urine and sputum screening missed 32% of Mtb bloodstream infections.
The findings highlight the need for both early treatment and improved diagnostic tools for TB.
“These studies highlight two things: First, we successfully intervened in the sepsis associated with TB, and second, we used every rapid test available and found that they just don’t detect all Mtb,” Otoupalova said.
Source:
Journal References:
Otoupalova, E., et al. (2026). Etiology of sepsis in adults living with HIV in East Africa: a secondary analysis of an open-label, multicenter, randomized, controlled phase 3 trial. eClinical Medicine. doi: 10.1016/j.eclinm.2025.103719.
Heysell, SK, et al. (2026). Immediate or high-dose antituberculosis therapy for HIV-associated sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomized, controlled, 2 × 2 factorial, superiority trial. Lancet Infectious Diseases. doi: 10.1016/s1473-3099(25)00747-9.
