STARSHydrocortisone and Enhanced Antimicrobial Regimen for HIV-Related Sepsis in Sub-Saharan Africa

Sepsis is a serious condition where the body's response to an infection can cause organ dysfunction, leading to high mortality rates worldwide. This is particularly prevalent in sub-Saharan Africa, with an estimated 17 million cases and 3.5 million deaths each year. Many of these patients also have HIV. The leading cause of sepsis in this region is tuberculosis (TB), which is responsible for a significant number of bloodstream infections in septic patients. This study aims to improve treatment for sepsis in HIV-positive patients in Africa, focusing on addressing the high mortality rates associated with TB sepsis and the resistance of causative pathogens to standard antimicrobial treatments. The study also addresses the issue of low circulating drug concentrations in septic patients and the high burden of corticosteroid insufficiency observed in critically ill patients at the study sites in Uganda and Tanzania. The study will test two hypotheses: first, that administering hydrocortisone for 7 days followed by a 7-day taper will improve 28-day mortality rates compared to the standard of care without hydrocortisone; and second, that an enhanced antimicrobial regimen for 14 days targeting TB and other drug-resistant bacteria (rifampin, isoniazid, levofloxacin, and linezolid) will improve 28-day mortality rates compared to the standard care of ceftriaxone alone. Participants hospitalized with HIV and sepsis will be randomly assigned to one of four groups: 1) hydrocortisone or standard care without hydrocortisone, and 2) the enhanced antimicrobial regimen plus ceftriaxone or standard care with ceftriaxone alone. This randomized clinical trial is endorsed by stakeholders in Tanzania and Uganda, and if successful, the treatment could be scaled up for adults with sepsis in HIV-endemic regions of sub-Saharan Africa.