{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:55:42Z","timestamp":1784908542881,"version":"3.55.0"},"reference-count":15,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J STD AIDS"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:p>Paradoxical reactions, including immune reconstitution inflammatory syndrome (IRIS), are common in patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Paradoxical reactions may confer substantial morbidity and mortality, especially in cases of central nervous system (CNS) TB, or through protracted usage of corticosteroids. No high-quality evidence is available to guide management in this scenario. Interleukin-1-mediated inflammation has been implicated in the pathophysiology of TB\u2013IRIS. We describe two cases where anakinra (human recombinant interleukin-1 receptor antagonist) was used as steroid-sparing therapy for life-threatening protracted paradoxical inflammation in HIV-associated TB. In the first case of disseminated TB with lymphadenitis, protracted TB\u2013IRIS led to amyloid A amyloidosis and nephrotic syndrome. In the second case of disseminated TB with cerebral tuberculomata, paradoxical inflammation caused unstable tuberculomata leading to profound neuro-disability. In both cases, paradoxical inflammation persisted for over a year. Protracted high-dose corticosteroid use led to adverse events yet failed to control inflammatory pathology. In both patients, anakinra successfully controlled paradoxical inflammation and facilitated withdrawal of corticosteroid therapy. Following anakinra therapy, nephrotic syndrome and neuro-disability resolved, respectively. Anakinra therapy for protracted paradoxical inflammation in HIV-associated TB may be a viable therapeutic option and warrants further research.<\/jats:p>","DOI":"10.1177\/0956462420915394","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T14:26:26Z","timestamp":1594045586000},"page":"808-812","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Anakinra in the treatment of protracted paradoxical inflammatory reactions in HIV-associated tuberculosis in the United Kingdom: a report of two cases"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-1157","authenticated-orcid":false,"given":"Alexander J","family":"Keeley","sequence":"first","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease and Florey Institute, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivak","family":"Parkash","sequence":"additional","affiliation":[{"name":"Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Tunbridge","sequence":"additional","affiliation":[{"name":"Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Greig","sequence":"additional","affiliation":[{"name":"Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6696-6826","authenticated-orcid":false,"given":"Paul","family":"Collini","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease and Florey Institute, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"McKane","sequence":"additional","affiliation":[{"name":"Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel S","family":"Tattersall","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sheffield Teaching Hospitals NHS Foundation Trust and Sheffield Children\u2019s Hospital NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"bibr1-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2014.12.030"},{"key":"bibr2-0956462420915394","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.9"},{"key":"bibr3-0956462420915394","first-page":"1","author":"Prasad K","year":"2016","journal-title":"Cochrane Database of Syst Rev"},{"key":"bibr4-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800762"},{"key":"bibr5-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-018-0490-9"},{"key":"bibr6-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1038\/nri2691"},{"key":"bibr7-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9451"},{"key":"bibr8-0956462420915394","first-page":"677","volume":"215","author":"Marais S","year":"2017","journal-title":"J Infect Dis"},{"key":"bibr9-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00094-8"},{"key":"bibr10-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0930-5"},{"key":"bibr11-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001402"},{"key":"bibr12-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1002\/art.41103"},{"key":"bibr13-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.02.002"},{"key":"bibr14-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040573"},{"key":"bibr15-0956462420915394","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1816-4"}],"container-title":["International Journal of STD &amp; 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