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+ <100/mu L), 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.