Background: Tumor necrosis factor (TNF) blockade in the treatment of autoimmune diseases has been linked to reactivation of tuberculosis (TB). Immune reconstitution inflammatory syndrome (IRIS) can complicate anti-retroviral therapy (ART) initiation in HIV patients with mycobacterial disease and can cause significant morbidity and even mortality. Corticosteroid use is the mainstay of therapy. We report the use of infliximab (anti-TNF antibody) in 3 patients with steroid-unresponsive mycobacterial-IRIS.
Methods: Patients were participants of a completed observational study evaluating predictors of IRIS in HIV-infected patients with CD4 count ≤100cells/µL starting ART. CD4 count and HIV-RNA were tested at week (wk) 0, 2, 4, 8, 12, 24, 36 and 48. T cell responses to mycobacterial antigens were assessed on batched cryopreserved samples using flow cytometry, after stimulation with tuberculin-PPD or heat-killed Mycobacterium avium complex (MAC).
Results: Patient (Pt) 1: 31 yo man with culture-positive MAC unmasking IRIS manifesting as cervical lymphadenopathy that failed to resolve despite anti-MAC therapy, drainage and prednisone over 4 months. Lymphadenopathy reduced after infliximab 5mg/kg every 2 wks, 3 doses. Pt 2: 41 yo man with culture positive disseminated TB (pulmonary and knee arthritis) and paradoxical TB-IRIS. He improved after high dose systemic and intra-articular corticosteroids but subsequently developed chylothorax due to obstruction of thoracic duct by enlarged lymph nodes. He improved after a single dose of infliximab 4mg/kg. Pt 3: 42 yo man with culture positive disseminated TB and paradoxical TB-IRIS manifesting as fevers and lymphadenopathy not responding to prednisone or drainage. Lymphadenopathy resolved gradually after infliximab 5mg/Kg every 2 wks, 3 doses. Prednisone was successfully tapered off in all patients after infliximab.
All patients had sterile mycobacterial cultures prior to infliximab and did not experience a clinical relapse. After infliximab administration, CD4 T cell cytokine responses to mycobacterial antigens were preserved (Fig). At week 48, HIV-RNA was <50 copies/mL and CD4 count improved for all patients (Fig).
Conclusions: Infliximab use was associated with clinical improvement in steroid-unresponsive mycobacterial IRIS without obvious adverse impact on immune recovery and virologic control in 3 patients. TNF blockade for severe mycobacterial IRIS merits further assessment in clinical trials.
CD4 T cell IFN-y and TNF responses after stimulation with mycobacterial antigens are preserved post infliximab use.