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Background Mycobacterium genavense is an opportunistic pathogen in HIV patients that is difficult to culture and difficult to manage clinically. Here we describe three cases of HIV patients with Mycobacterium genavense with courses representing the spectrum of M.genavense presentations in the current ART era complicated by differing divergent immune responses. Methods Two patients were in a longitudinal study at NIAID enrolling patients with HIV and suspected IRIS (PANDORA) (NCT02147405) and one was seen at St. James’s hospital in Dublin. Frozen peripheral blood mononuclear cells were collected at the time of presentation and were used for in vitro stimulation with irradiated M. genavenese in cases 1 and 2 to detect production of cytokines by CD4 T cells. Results Pt 1: 27-year old male with M. genavense presenting as diarrhea, abdominal pain, skin nodules, hepatosplenomegaly, and lymphadenopathy (LAN) that persisted on one year of anti-mycobacterial therapy and ART. No CD4 T-cell cytokine response to M. genevense genavense was detected (Fig 1). He received interferon-g and optimization of his antimycobacterial regimen with improvement of symptoms and decreased pathogen burden on repeated biopsies. Pt 2: 55-year old female with M. genavense IRIS manifesting as fevers and abdominal pain that persisted for 10 months on ART (CD4 109 cells/µmL) requiring intermittent corticosteroid use complicated by adrenal insufficiency. She had evidence of CD4 T-cell response to M. genavense in vitro and improved with optimization of her anti-mycobacterial and corticosteroid regimen. Pt 3: 39-year-old male with M. genavense IRIS presenting as fevers, LAN, pleuritic chest pain, and abdominal pain on ART (CD4 19 c/mµL) persisting despite immunologic response to ARV therapy (CD4 recovery to 419 c/mL), appropriate anti-mycobacterial therapy and corticosteroids. He required 4 doses of infliximab (5 mg/kg IV) that facilitated tapering of prednisone. Conclusion The clinical presentation of Mycobacterium genavense in HIV patients in the ARV era range from disseminated disease with poor immune reconstitution to persistent or severe IRIS requiring immune suppression. Effective clinical outcomes relied on appropriate anti-mycobacterial and either immune-boosting or immune-suppressive therapies. Disclosures All authors: No reported disclosures.

1381. M.genavense in the ART Era: From Persistent Disseminated Disease to Severe Disease