IRIS, HLH and persistent TB in a patient with HIV

Immune reconstitution inflammatory syndrome (IRIS) is a frequent complication of advanced human immunodeficiency syndrome (HIV)-tuberculosis (TB) coinfection and, in severe cases, may overlap with secondary haemophagocytic lymphohistiocytosis (HLH), creating significant diagnostic and therapeutic uncertainty. We report a 34-year-old man with newly diagnosed HIV infection (CD4 count 54 cells/mm3) who developed disseminated TB 2 weeks after initiation of antiretroviral therapy, consistent with unmasking TB-associated IRIS. Despite appropriate antitubercular therapy (ATT) and corticosteroids, he developed persistent fever, progressive cytopenias, hyperferritinaemia and bone marrow haemophagocytosis, fulfilling criteria for secondary HLH, with transient clinical improvement following etoposide therapy. During corticosteroid tapering, recurrent fever occurred with persistent splenic lesions despite radiologic resolution of pulmonary disease. Splenectomy demonstrated necrotizing granulomatous inflammation with a heavy acid-fast bacillary load, confirming a microbiologically active splenic sanctuary focus. Subsequent therapeutic drug monitoring revealed markedly subtherapeutic rifampicin and ethambutol concentrations, prompting dose escalation and optimization of ATT. Following antimicrobial optimization and gradual withdrawal of immunosuppression, the patient achieved sustained clinical recovery, virologic suppression and immune reconstitution. This case illustrates a sequential continuum linking TB-IRIS, secondary HLH and infection-sustained inflammation driven by inadequate antimicrobial exposure, emphasizing the importance of reassessing persistent inflammation in HIV-TB for occult infection and pharmacokinetic failure before escalation of immunosuppressive therapy.