The Use of Adjunctive Interferon-γ Therapy for Complex Mycobacterial Disease in Patients with Advanced HIV: A Case Series.

Management of mycobacterial opportunistic infection remains challenging in patients living with HIV, particularly when infection persists despite antiretroviral therapy (ART) and optimised antimycobacterial therapy (AMT). Interferon-γ is a key mediator of macrophage activation and intracellular pathogen killing, providing a rationale for its use as adjunctive host-directed therapy in selected patients. We describe three patients with advanced HIV and complex mycobacterial disease treated with adjunctive interferon-γ. One patient had disseminated tuberculosis with recurrent psoas abscesses after completion of AMT, while two had disseminated macrolide-resistant Mycobacterium avium complex (MAC) infection with persistent disease despite optimised therapy. Interferon-γ initiation was followed by improvement in all three cases, including radiological resolution of a recurrent psoas abscess and culture sterilisation in the two patients with disseminated MAC. Treatment was well tolerated, with only mild influenza-like symptoms. Concurrent ART-mediated immune reconstitution and AMT optimisation limit causal inference, but the temporal association between interferon-γ initiation and improvement supports further evaluation of interferon-γ as adjunctive therapy in refractory mycobacterial disease in patients with advanced HIV.