03502nas a2200337   4500000000100000008004100001260005500042653002700097653002100124653001400145653001200159653001700171653003100188653003300219653004800252653001500300653002000315653002200335653002200357653001200379100001100391700001800402700001500420700001400435245020300449856026000652300001200912490000700924520220800931022002503139       2025                            d  c12/2025bOvid Technologies (Wolters Kluwer Health)10aAntiretroviral therapy10aClinical outcome10aDiagnosis10aendemic10aEpidemiology10aGranulomatous inflammation10aHuman immunodeficiency virus10aImmune Reconstitution Inflammatory Syndrome10aImmunology10aIntegrated care10aMultidrug therapy10aReversal reaction10aleprosy1 aAnil A1 aVellaisamy SG1 aManickam N1 aGopalan K00aReactivations, paradoxical reactions, and immune reconstitution in human immunodeficiency virus-associated leprosy: A scoping review of global case patterns, immunopathogenesis, and therapeutic gaps  uhttps://www.researchgate.net/publication/398550549_Reactivations_paradoxical_reactions_and_immune_reconstitution_in_human_immunodeficiency_virus-associated_leprosy_A_scoping_review_of_global_case_patterns_immunopathogenesis_and_therapeutic_gaps/fulltext/6  a112-1180 v463 a<p>The intersection of human immunodeficiency virus (HIV) and Mycobacterium leprae infection creates unique diagnostic and therapeutic challenges. The roll-out of antiretroviral therapy (ART) has revealed leprosy-associated immune reconstitution inflammatory syndrome (L-IRIS), marked by paradoxical clinical worsening as immune function recovers. This review explores the clinical profiles, immunological mechanisms, and treatment outcomes of L-IRIS and leprosy reactivation in people living with HIV. Scoping review, preferred reporting items for systematic reviews and meta-analyses extension for Scoping review, systematic search: We searched PubMed, Scopus, Embase, Web of Science, LILACS(Latin America and the Caribbean Literature on Health Sciences), and Cochrane Library for original case reports, case series, and cohort studies documenting HIV-leprosy coinfection and IRIS. Data were extracted across six domains: epidemiology, clinical manifestations, histopathology, immunology, therapy, and evidence gaps. Geographic clustering, immunodeficiency, reversal reactions: Eighteen studies were included, predominantly from Brazil, India, and French Guiana. Borderline tuberculoid (BT) leprosy was the commonest clinical form; type 1 reactions (T1R) were the most frequent immune events, usually 2–6 months after ART initiation. Most patients had advanced immunosuppression (CD4+ &lt;100/μL), with clinical IRIS coinciding with immune recovery. Histopathology revealed granulomatous inflammation and CD68+ macrophage infiltration. Standard treatment included World Health Organization-recommended multidrug therapy (MDT) and corticosteroids, yielding generally favorable outcomes; however, there was a lack of consensus on IRIS management, long-term follow-up, and no validated biomarkers for L-IRIS, which remains under-recognized, with significant diversity in presentation and limited standardized diagnostic criteria. Improvement in care requires biomarker validation, consistent outcome tracking, and the creation of context-adapted management pathways. Expanded integrated surveillance and patient-centered research in endemic areas are essential to reduce the dual disease burden.</p>
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