UCT-led site contributes to landmark EFFECT trial on HIV-related fungal disease

A major international clinical trial testing a combination antifungal therapy for HIV-related cryptococcal disease has suggested a survival benefit, with an Institute of Infectious Disease and Molecular Medicine (IDM)-led team playing a leading role in the South African arm of the study.

Cryptococcal disease is a life-threatening fungal infection caused by Cryptococcus species. People become infected by inhaling fungal spores commonly found in the environment, but the disease primarily affects people with weakened immune systems, particularly those living with weakened immune systems due to untreated HIV. If left untreated, the infection can spread to the brain, causing cryptococcal meningitis. Cryptococcal meningitis remains one of the world's deadliest HIV-associated opportunistic infections, causing an estimated 110,000 deaths each year and accounting for almost one in five HIV-related deaths worldwide.

The EFFECT (Efficacy of Flucytosine and Fluconazole as Early Cryptococcal Treatment) trial, presented by Dr Kyla Murphy (IDM, University of Cape Town) at the International AIDS Conference 2026 in Rio de Janeiro, enrolled 604 adults living with HIV across 11 sites in South Africa and Tanzania. Participants had early cryptococcal infection, identified through routine blood antigen screening, a state that precedes the development of meningitis symptoms.

Researchers found that participants who received the combination of fluconazole and flucytosine pre-emptive treatment had a 21% lower risk of death after six months compared with those receiving the current standard treatment of fluconazole alone.

The Cape Town trial site was lead by IDM member Prof Graeme Meintjes and Dr Kyla Murphy serving as site co-principal investigators. The trial site was supported by CIDRI-Africa, the IDM and the Neuroscience Institute.

Dr Murphy also served as the lead clinician for the international trial, while Prof Meintjes was the South African National Principal Investigator, overseeing the study across participating South African sites.

Prof Meintjes commented: “This was a complex trial to undertake and its successful completion can be credited to the collaborative effort of investigators spanning the UK, Tanzania and South Africa. The combination of flucytosine with fluconazole showed a trend towards reducing deaths by 21%. The combination was also safe. We will be engaging with bodies that develop clinical guidelines globally in order to have this evidence reviewed towards informing future treatment practices for HIV-related cryptococcal disease.”

The trial was funded by a £5.1m grant from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office , the UK Medical Research Council and Wellcome. This UK funded award was part of the EDCTP2 programme supported by the European Union.

Source: Risk of death 21% lower in people with HIV-related fungal disease given combination drug treatment (City St George's, University of London).