Integrated management of cryptococcal and opportunistic infections to improve outcomes in advanced HIV disease.

Background: Cryptococcal meningitis is a brain infection caused by a fungus.

Approximately 250,000 cases occur every year and despite our best current treatments between a quarter and a half of all patients who develop cryptococcal meningitis will die.

Key goals: There is an urgent need to improve our understanding of why patients with cryptococcal meningitis die and to determine whether secondary infections including viral infections, bacterial bloodstream infections, and tuberculosis (TB) contribute to the extremely high mortality. We aim to determine whether early identification and treatment of secondary infections can improve survival.

Study plan: People with HIV and cryptococcal meningitis who agree to take part will be recruited into a hospital-based study in Uganda.

In addition to routine meningitis treatment and care, they will have intensive investigations for secondary infections: bacterial bloodstream infections, herpes viruses and TB using innovative diagnostics. Secondary infections will be treated. We will determine the preferred treatment strategy for latent TB infection.

With the agreement of the families, an autopsy will be performed for patients that die to understand the cause of death.

Information from this study will be used to design an enhanced treatment package for patients with cryptococcal meningitis to try to improve outcomes.