{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:14:15Z","timestamp":1783433655388,"version":"3.54.6"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune reconstitution inflammatory syndrome (IRIS) is a frequent complication of advanced human immunodeficiency syndrome (HIV)\u2013tuberculosis (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\u00a0cells\/mm3) who developed disseminated TB 2\u00a0weeks 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.<\/jats:p>","DOI":"10.1093\/trstmh\/trag040","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:36:25Z","timestamp":1774956985000},"page":"812-817","source":"Crossref","is-referenced-by-count":0,"title":["IRIS, HLH and persistent TB in a patient with HIV"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-5885","authenticated-orcid":false,"given":"Praveen Kumar","family":"Tirlangi","sequence":"first","affiliation":[{"name":"Kasturba Medical College, Manipal Academy of Higher Education Department of Infectious Diseases, , Manipal, Udupi, Karnataka 576104 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4536-7449","authenticated-orcid":false,"given":"Venkata Swathi Kiran","family":"Pothumarthy","sequence":"additional","affiliation":[{"name":"Kasturba Medical College, Manipal Academy of Higher Education Department of Infectious Diseases, , Manipal, Udupi, Karnataka 576104 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8022-1086","authenticated-orcid":false,"given":"Anjely","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Kasturba Medical College, Manipal Academy of Higher Education Department of Infectious Diseases, , Manipal, Udupi, Karnataka 576104 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9687-2836","authenticated-orcid":false,"given":"Nitin","family":"Gupta","sequence":"additional","affiliation":[{"name":"Kasturba Medical College, Manipal Academy of Higher Education Department of Infectious Diseases, , Manipal, Udupi, Karnataka 576104 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"2","key":"2026070709065090900_bib1","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/QAI.0000000000002937","article-title":"Risk of immune reconstitution inflammatory syndrome with integrase inhibitors versus other classes of antiretrovirals: a systematic review and meta-analysis of randomized trials","volume":"90","author":"Zhao","year":"2022","journal-title":"J Acquir Immune Defic Syndr 1999"},{"issue":"9","key":"2026070709065090900_bib2","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1086\/630208","article-title":"Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort","volume":"49","author":"Haddow","year":"2009","journal-title":"Clin Infect Dis"},{"issue":"3","key":"2026070709065090900_bib3","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1086\/499356","article-title":"Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort","volume":"42","author":"Ratnam","year":"2006","journal-title":"Clin Infect Dis"},{"issue":"3","key":"2026070709065090900_bib4","doi-asserted-by":"crossref","first-page":"e561","DOI":"10.1093\/cid\/ciac717","article-title":"Severe mycobacterial immune reconstitution inflammatory syndrome (IRIS) in advanced human immunodeficiency virus (HIV) has features of hemophagocytic lymphohistiocytosis and requires prolonged immune suppression","volume":"76","author":"Rocco","year":"2023","journal-title":"Clin Infect Dis"},{"issue":"2","key":"2026070709065090900_bib5","first-page":"103430","article-title":"Performances of the H-score and the HLH-2004 score in the positive diagnosis of secondary hemophagocytic lymphohistiocytosis","volume":"72","author":"Fatma","year":"2024","journal-title":"Curr Res Transl Med"},{"key":"2026070709065090900_bib6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40164-022-00362-2","article-title":"The role of etoposide in the treatment of adult patients with hemophagocytic lymphohistiocytosis","volume":"12","author":"Zondag","year":"2023","journal-title":"Exp Hematol Oncol"},{"issue":"Suppl","key":"2026070709065090900_bib7","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1016\/j.clml.2017.02.017","article-title":"Diagnostic challenges of hemophagocytic lymphohistiocytosis","volume":"17","author":"Otrock","year":"2017","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"9927","key":"2026070709065090900_bib8","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","article-title":"Adult haemophagocytic syndrome","volume":"383","author":"Ramos-Casals","year":"2014","journal-title":"Lancet"},{"issue":"6","key":"2026070709065090900_bib9","doi-asserted-by":"crossref","first-page":"819","DOI":"10.5588\/ijtld.15.0803","article-title":"Therapeutic drug monitoring in anti-tuberculosis treatment: a systematic review and meta-analysis","volume":"20","author":"Mota","year":"2016","journal-title":"Int J Tuberc Lung Dis"}],"container-title":["Transactions of The Royal Society of Tropical Medicine and Hygiene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/trstmh\/article-pdf\/120\/7\/812\/68147003\/trag040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/trstmh\/article-pdf\/120\/7\/812\/68147003\/trag040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:22:01Z","timestamp":1783430521000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/trstmh\/article\/120\/7\/812\/8661677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":9,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4,24]]},"published-print":{"date-parts":[[2026,7,7]]}},"URL":"https:\/\/doi.org\/10.1093\/trstmh\/trag040","relation":{},"ISSN":["0035-9203","1878-3503"],"issn-type":[{"value":"0035-9203","type":"print"},{"value":"1878-3503","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,4,24]]}}}