Reactivations, paradoxical reactions, and immune reconstitution in human immunodeficiency virus-associated leprosy: A scoping review of global case patterns, immunopathogenesis, and therapeutic gaps

Abstract

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/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.

Introduction

Leprosy (Hansen’s disease), caused by Mycobacterium leprae, remains a significant global health challenge, with around 200,000 new cases reported annually–primarily in South Asia, Latin America, and sub-Saharan Africa. Despite the effectiveness of multidrug therapy (MDT), late diagnosis and insufficient treatment often lead to irreversible nerve damage and disability. Meanwhile, the parallel burden of human immunodeficiency virus (HIV), which affects over 38 million people worldwide, further complicates disease management in many of these same regions.[1,2,3]

A notable complication in HIV care is immune reconstitution inflammatory syndrome (IRIS), where antiretroviral therapy (ART)-induced immune recovery paradoxically worsens or unmasks underlying infections. While IRIS is well-studied in tuberculosis, leprosy-associated IRIS (L-IRIS) has received less attention. Since its first description in 2003, most documented L-IRIS cases present as borderline clinical forms with type 1 reactions (T1R), typically 2–6 months after ART initiation. Delayed diagnosis is common, particularly in Brazil, India, and French Guiana, due to atypical presentations and overlap with other opportunistic infections. Histologically, L-IRIS is marked by granulomatous infiltration and increased pro-inflammatory markers, but there is a lack of studies utilizing diagnostic biomarkers to guide management.[4,5]

Current treatment for L-IRIS combines standard MDT with systemic corticosteroids. While outcomes are generally favorable, consensus is lacking on the optimal use of corticosteroids, and rifampicin-ART drug interactions can complicate therapy. Alternatives like thalidomide are rarely used. Major knowledge gaps persist, including the absence of standardized definitions or severity criteria for L-IRIS, and few prospective studies on long-term outcomes like relapse, nerve damage, and quality of life. Stigma, psychosocial issues, and fragmented health systems also remain inadequately addressed.[6,7]

This scoping review seeks to map the global evidence on L-IRIS by analyzing epidemiological patterns, clinical and histopathological features, immunological mechanisms, treatment strategies, and health system challenges. By highlighting key findings and existing gaps, the review aims to inform future research priorities and policy development for improved care.

Methods

This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) guidelines to ensure methodological rigor and transparency. Prior to starting, a protocol detailing objectives, inclusion/exclusion criteria, search strategy, and data extraction methods was developed and prospectively registered to reduce bias.

Eligible studies included original case reports, case series, cohort studies, cross-sectional studies, and systematic reviews with original data, published in English, Spanish, Portuguese, or French from January 2003 to June 2025. Included studies documented adults (≥18 years) with HIV and leprosy coinfection and clear evidence of immune reconstitution phenomena (e.g., paradoxical reactions, reactivation, or L-IRIS). Studies focused solely on pediatric populations, animals, in vitro research, reviews without new data, conference abstracts without full text, and publications outside specified languages or timeframes were excluded.

A comprehensive search was conducted across PubMed/MEDLINE, Embase, Web of Science, LILACS, and Cochrane Library, along with Google Scholar, World Health Organization (WHO) Global Health Observatory, and manual reference checks of included studies and reviews. Search terms combined MeSH headings and keywords for HIV/AIDS, leprosy, immune reconstitution, and reactional states, using Boolean operators to maximize article retrieval. All citations were imported into reference management software; duplicates were removed. Two independent reviewers screened titles and abstracts; full texts were assessed independently, with disagreements resolved by consensus or, if needed, a third reviewer. The selection process was mapped using a PRISMA-ScR flow diagram [Figure 1].

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review flow diagram provides a transparent overview of the identification, screening, eligibility assessment, and inclusion phases, in line with (PRISMA-ScR) 2020 recommendations

A standardized data extraction form was used to chart study characteristics and findings, capturing bibliographic information, participant demographics, leprosy and immunological classifications, therapy details, and outcomes. Extraction was performed by two reviewers with discrepancies resolved through discussion. Data were synthesized descriptively and thematically to highlight the frequency and nature of reactional states, immunological patterns, management approaches, and outcomes. In line with scoping review methodology, no meta-analysis was conducted; instead, thematic mapping identified key clinical trends, evidence gaps, and implications for practice and research.

Results

Geographic and temporal patterns of reported human immunodeficiency virus-leprosy immune reconstitution inflammatory syndrome cases

The distribution of reported HIV-leprosy IRIS cases shows strong geographic clustering, with Brazil, India, and French Guiana accounting for most published cases. This pattern mirrors their high HIV and leprosy burdens, robust disease surveillance, and research capacity. Together, Brazil and India represent over three-quarters of identified cases, with French Guiana contributing significantly despite its small population. Temporally, publication peaks followed major ART rollouts, with increased reporting in the mid-2000s and mid-2010s, reflecting both expanded ART access and heightened clinical awareness of IRIS.[8] These trends–summarized visually in Figure 2–highlight the global need for integrated surveillance, provider education, and targeted research where HIV and leprosy overlap most closely [Figure 2]. Moreover, the long-term outcomes—such as relapse rates, nerve damage, and quality-of-life—have not been adequately evaluated in prospective studies.[9]

Figure 2.

Geographic and temporal patterns of reported human immunodeficiency virus-leprosy immune reconstitution inflammatory syndrome cases

Study characteristics of human immunodeficiency virus-associated leprosy: Key studies overview

A comprehensive understanding of HIV-associated leprosy and related IRIS requires synthesizing data from diverse settings and study designs. Table 1 collates detailed characteristics from seminal studies published between 2003 and 2025, focusing on country or region, study design, sample size, leprosy type (WHO/Ridley-Jopling classification), HIV/ART status, nature of reaction or IRIS, timing relative to ART, and clinical outcomes. This structured summary illustrates the diversity and complexity of real-world presentations and management scenarios in this dual-infection context. Key outcomes: Includes response to MDT, need for corticosteroids or thalidomide, relapse, persistence/complications, and overall clinical status at outcome assessment.

Table 1.

Detailed characteristics of included studies on HIV-leprosy coinfection

Study ID	First author (year)	Country/region	Study design	Sample size/demographics	Leprosy type[1]	HIV/ART/immunological status[2]	Reaction/IRIS type[3]	timing (relative to ART)[4]	Key outcome[5]
S001	Mouchard (2022)[1]	French Guiana, Global	Retrospective + systematic review	73; Median 37 years, 67% months	56.2% BT, 15.1% BB	Advanced HIV, CD4<200, all on ART	74% reactions (68.5% T1R, some ENL)	Median 2.5 months after ART	100% MDT response, no relapse; ulceration (22%), neuritis
S002	Batista (2015)[2]	Brazil (Amazon)	Comparative Cohort	40 HIV+/107 HIV−; mean 37 years, 67% Months	HIV+: 70% PB, 45% BT	HIV + confirmed, ART (mixed), CD4<200	32.5% T1R (HIV+), 31.8% (HIV−)	≤6 months post-ART	Good MDT response, more neural symptoms in HIV+
S003	Sales (2020)[3]	Brazil	Cross-sectional	12	66.7% BT	All on ART	66.7% T1R	2–6 months post-ART	Good outcomes, reactions resolved, severe reversal, ulceration
S004	Illarramendi (2013)[4]	Brazil	Cross-sectional	Not specified	BT predominant	All on ART	T1R	Not specified	Severe reversal, neuritis, good outcomes
S005	de Andrade (2017)[5]	Brazil	Retrospective cohort	22 HIV+/28 HIV−	BT	All on ART, advanced HIV	T1R	≤6 months post- ART	Good; ulceration, more sensory loss in HIV+
S006	Nery (2021)[6]	India	Case report	1; month, 32 years	LL	CD4 120, on ART	ENL (Type 2)	3 months post-ART	Complete resolution with thalidomide; nodules, fever
S007	Lawn (2003)[7]	UK (Uganda origin)	Case report	1; month, 37 years	BT	CD4 7→112→>700, on ART	T1R (IRIS)	≤2 years post-ART	Hypopigmented macules, nodules, good outcome
S008	Sarno (2008)[8]	Brazil	Longitudinal cohort	59	TT/BT predominant	All on ART	T1R	Not specified	Granuloma formation, good MDT response
S009	Rao (2012)[9]	India	Case report	1	BT	On ART	T1R	18 months post-ART	Reversal reaction, regression, skin lesions, neuritis
S010	Talhari (2007)[10]	Brazil	Case report	1	BL→BT spectrum shift	On ART	T1R	After ART commencement	Spectrum shift, good outcome
S011	Trindade (2005)[11]	Brazil	Retrospective case series	5	BT/BB	All on ART	4/5 T1R after ART	2–4 months post-ART	Erythematous plaques, neuritis, good outcomes
S012	Lu (2007)[12]	USA	Case series	2; months, 37 years	TT/BT	CD4 <50→>100; on ART	T1R (IRIS)	5–24 months post-ART	Macules, nodules, MDT, good outcomes
S013	Machado (2010)[13]	Brazil	Prospective cohort	25	Mixed	All on ART	Upgrading reactions	After ART	Shifting forms, granuloma, good MDT outcomes
S014	Silva (2023)[14]	Global	Scoping review	53 studies (HIV subset)	PB mostly	Mixed	T1R/ENL, high reaction rate	Not specified	Favorable outcomes, high reaction rates
S015	Faye (2017)[15]	Mali	Case reports	2; months, 34 and 38 years	BL/BB	On ART, rising CD4	T1R (IRIS)	4–8 months post-ART	Both cases improved with MDT, steroids
S016	Bachaspatimayum (2018)[16]	India	Case report	1; month, 49 years	MB	Low CD4, on HAART	T1R (IRIS)	3 weeks after HAART	Prompt recovery with MDT, steroids, dry skin, and numbness
S017	Bezerra (2023)[17]	Brazil	Integrative literature review	12 publications	Mixed	Not specified	T1R/ENL, review of IRIS	Not specified	Highlights diagnostic/treatment challenges
S018	Balita-Crisostomo (2019)[18]	Philippines	Case report	1	MB (solitary plaque)	On ART	Atypical IRIS	Shortly after ART	Reversal managed with steroids, good outcome

WHO/Ridley-Jopling classification=Immunological status based on CD4+ T cell count at ART start, viral load (if available), and ART use at leprosy or IRIS diagnosis. Reaction/IRIS type=T1R=type 1 reaction (reversal reaction), ENL=Erythema nodosum leprosum (type 2 reaction); “IRIS” indicates a temporal association with immune recovery after ART. Timing relative to ART=Indicates interval between ART initiation and leprosy/reaction onset; ranges given for studies reporting aggregate data only. Key outcomes=Includes response to MDT, need for corticosteroids or thalidomide, relapse, persistence/complications, and overall clinical status at outcome assessment. PB=Paucibacillary, MB=Multibacillary, BT=Borderline tuberculoid, BB=Borderline-borderline, BL=Borderline lepromatous, LL=Lepromatous leprosy; TT=Tuberculoid, MDT=Multidrug therapy

Clinical presentations in human immunodeficiency virus-associated leprosy: Spectrum, reactions, and key features

Leprosy in people living with HIV is most often identified within 2–6 months after starting ART, coinciding with a period of rapid immune restoration and increased risk for IRIS. Median diagnosis time across major studies is 8–12 weeks post-ART, underscoring the role of restored cell-mediated immunity in unmasking latent M. leprae infections. Frequently, leprosy or related inflammatory reactions emerge as new IRIS events, sometimes with no preceding symptoms, highlighting the need to consider leprosy as a possible IRIS cause when new skin or neurological symptoms develop during early immune recovery. Diagnosis is often delayed due to overlap with other opportunistic infections, evolving histopathological patterns after ART, and a concentration of reports from a few high-burden regions–predominantly Brazil, India, and French Guiana–which reflects both epidemiological burden and differing levels of clinical awareness and reporting infrastructure [Figure 2]. Notably, data on children, pregnant women, and marginalized groups are minimal, leaving important knowledge gaps. Integrating HIV and leprosy services and developing unified care pathways, as summarized in Table 2, are strongly recommended to enable earlier detection, coordinated treatment, and better outcomes for this vulnerable population.[10,11] Figure 3 below summarizes the frequency of these core manifestations across published studies which shows Borderline tuberculoid (BT) is most common, T1R reactions dominate, and granuloma formation is frequent. Ulceration, neuritis, erythematous plaques, and erythema nodosum leprosum (ENL)/systemic symptoms occur less often but are important for clinical recognition

Table 2.

Summary of clinical presentations and reaction types across key studies

Study (year)	Country/region	Leprosy type*	Reaction/IRIS Type	IRIS/reaction timing	Key clinical features
Mouchard et al. (2022)[1]	French Guiana, Global	56% BT, 15% BB	68% T1R, some ENL	Median 2.5 months post-ART	Ulceration (22%), neuritis, erythematous plaques
Batista et al. (2015)[2]	Brazil (Amazon)	70% PB/BT	32% T1R (HIV+)	≤6 months post-ART	More neural symptoms, good MDT response
Sales et al. (2020)[3]	Brazil	67% BT	67% T1R	2–6 months post-ART	Severe reversal, ulceration, and reaction resolution
Illarramendi et al. (2013)[4]	Brazil	BT predominant	T1R	Not specified	Severe reversal, neuritis, good outcomes
de Andrade PJS (2017)[5]	Brazil	BT	T1R	≤6 months post-ART	Ulceration, more sensory loss in HIV+
Nery (2021)[6]	India	LL	ENL (Type 2)	3 months post-ART	Nodules, fever, complete resolution (thalidomide)
Lawn (2003)[7]	UK/Uganda origin	BT	T1R (IRIS)	≤2 years post-ART	Macules, nodules, good outcome
Sarno (2008)[8]	Brazil	TT/BT predominant	T1R	Not specified	Granuloma formation, good MDT response
Rao (2012)[9]	India	BT	T1R	18 months post-ART	Regression, skin lesions, neuritis
Talhari (2007)[10]	Brazil	BL→BT spectrum shift	T1R	After ART start	Spectrum shift, good outcome
Trindade (2005)[11]	Brazil	BT/BB	4/5 T1R after ART	2–4 months post-ART	Erythematous plaques, neuritis
Lu (2007)[12]	USA	TT/BT	T1R (IRIS)	5–24 months post-ART	Macules, nodules, good outcomes

BT=Borderline tuberculoid, BB=Borderline-borderline, LL=Lepromatous, PB=Paucibacillary, T1R=type 1 (reversal) reaction; ENL=Erythema nodosum leprosum, MDT=Multidrug therapy, IRIS=Immune reconstitution inflammatory syndrome, ART=Antiretroviral therapy

Figure 3.

Frequency of key clinical manifestations in human immunodeficiency virus-associated leprosy immune reconstitution inflammatory syndrome

Immunological findings in human immunodeficiency virus-leprosy immune reconstitution inflammatory syndrome

In HIV-leprosy coinfection, the immunological hallmark of IRIS is a sharp increase in CD4+ T-cell counts following ART. Prior to ART, most patients have advanced immunosuppression, typically with CD4+ counts below 100 cells/μL. After ART initiation, CD4+ levels rise rapidly, and IRIS or leprosy reactivation frequently occurs when counts reach 200-250 cells/μL. This sudden restoration of immune capacity enables a robust inflammatory response, unmasking subclinical or latent M. leprae infection and driving leprosy symptoms.[12,13]

During IRIS episodes, immune profiling reveals distinct cellular activation: the percentage of activated CD8+ T cells (CD8+/CD38+) surges–often reaching 77% at the peak of IRIS–then drops to roughly 30% after corticosteroid treatment and symptom resolution. Simultaneously, skin and nerve biopsies show substantial infiltration by CD68+ activated macrophages, reflecting both immune surveillance and effector activity against M. leprae bacilli. Local production of pro-inflammatory cytokines, such as interferon-γ and interleukin-12, further amplifies this inflammatory milieu.

Histopathological analysis underscores these changes: before ART, tissue samples from immunosuppressed individuals typically exhibit poorly formed or absent granulomas with scant macrophage presence. Once ART is started and IRIS develops, there is a marked shift toward pronounced granulomatous inflammation, with numerous epithelioid macrophages and multinucleated giant cells. This transition coincides with expression of immune activation markers, consistent with a Th1-skewed tissue response, and signals the immune system’s renewed ability to mount an effective defense.[14]

Together, these findings confirm that IRIS in HIV-leprosy is not just a function of CD4+ count restoration, but involves complex, coordinated cellular immunity, especially the interplay between activated cytotoxic T-cells and macrophages, culminating in dramatic inflammatory responses [Figure 4].

Figure 4.

Immunological findings in human immunodeficiency virus-leprosy immune reconstitution inflammatory syndrome. (a) CD4+ T cell recovery at immune reconstitution inflammatory syndrome onset; (b) CD8+ T cell activation during and after immune reconstitution inflammatory syndrome; (c) Histopathological shift to granulomatous inflammation postantiretroviral therapy

Therapeutic approaches in human immunodeficiency virus-associated leprosy

MDT–using rifampicin, dapsone, and clofazimine–remains the universal standard of care for leprosy in people living with HIV, with nearly all reported cases also receiving ART in accordance with HIV management guidelines. Nonetheless, clinicians face notable therapeutic challenges arising from drug–drug interactions: rifampicin, a key MDT component, can decrease the efficacy of many ART agents, particularly protease inhibitors and certain integrase inhibitors, necessitating careful regimen selection, ongoing monitoring, or medication adjustments for optimal virologic and mycobacterial control.

For managing immune reactions–especially type 1 (reversal) reactions and IRIS–corticosteroids constitute first-line therapy, providing effective reduction of inflammation and prevention of nerve damage when initiated early. Thalidomide is used selectively in severe or steroid-refractory cases of ENL, though its application is limited by concerns over severe adverse effects and teratogenicity.[14]

Clinical outcomes are generally favorable, with most patients achieving resolution of acute inflammatory episodes and successful completion of MDT. However, key complications still occur: ulceration is reported in up to 22% of cases, particularly during intense reversal reactions; persistent neuritis can lead to lasting motor or sensory deficits; and granuloma formation is frequently observed in post-ART tissue biopsies, occasionally correlating with more severe clinical manifestations [Table 3].

Table 3.

Summary of treatments and outcomes across key studies

Study ID	Study name (first author, year)	MDT use	ART use	Reaction management	Thalidomide use	Key outcomes and complications
S001	Couppié P, 2022[1]	Yes	All	Steroids for T1R/IRIS	Rare	100% MDT response; ulceration (22%), neuritis
S002	Batista MD, 2015[2]	Yes	All	Prednisone	No	Good MDT response; more neural symptoms in HIV+
S003	Sales AM, 2020[3]	Yes	All	Steroids	No	Good; reactions resolved, severe reversal, ulceration
S004	Illarramendi X, 2013[4]	Yes	All	Steroids for T1R	No	Good; severe reversal, neuritis
S005	de Andrade PJS, 2017[5]	Yes	All	Steroids for T1R	No	Good; ulceration, more sensory loss in HIV+
S006	Nery JA, 2021[6]	Yes	Yes	Thalidomide for ENL	Yes	Complete resolution; nodules, fever
S007	Lawn SD, 2003[7]	Yes	Yes	Steroids	No	Good; macules, nodules
S008	Sarno EN, 2008[8]	Yes	All	Steroids for T1R	No	Good; granuloma formation
S009	Rao GR, 2012[9]	Yes	Yes	Steroids for T1R	No	Regression; skin lesions, neuritis

MDT=Multidrug therapy, IRIS=Immune reconstitution inflammatory syndrome, ART=Antiretroviral therapy

Additional insights in human immunodeficiency virus-associated leprosy: Diagnosis, manifestation, and care integration

Timing of diagnosis

Leprosy is most frequently diagnosed within 2–6 months after the initiation of ART in people living with HIV, a period marked by rapid immune restoration and a heightened risk for IRIS. Several comprehensive studies report a median diagnosis window of 8–12 weeks post-ART, suggesting that restored cell-mediated immunity can unmask latent M. leprae infection. While some isolated cases show delayed presentations, the majority cluster within this early phase, underscoring the need for heightened clinical vigilance. In a significant proportion of patients, the first signs of leprosy–or its inflammatory reactions–emerge only after ART begins, an “unmasking IRIS” phenomenon that requires clinicians to consider leprosy as a possible etiology in any new dermatoneurological symptom during early immune recovery. Diagnostic delays remain common due to overlaps with other opportunistic infections, evolving histopathological findings before and after ART, and a concentration of reported cases in a handful of regions, which may reflect reporting disparities as much as epidemiology. Notably, there is a marked lack of data on children, pregnant women, and marginalized groups, revealing an important evidence gap. Numerous studies call for integrated care pathways between HIV and leprosy services to promote timely diagnosis, comprehensive management, and improved patient outcomes.[15]

Discussion

This scoping review synthesizes evidence from 18 studies across 11 countries, focusing on nearly 100 cases of HIV-leprosy coinfection, with particular attention to L-IRIS following ART. Findings underscore that while HIV and leprosy were once thought to interact minimally, ART has revealed L-IRIS as a clinically significant, distinct entity. Reported cases are heavily concentrated in Brazil, India, and French Guiana–regions of overlapping endemicity and robust surveillance. This clustering may reflect both actual disease patterns and disparities in reporting, raising concerns about underdiagnosis in other high-burden regions.[16,17]

Clinically, BT leprosy dominates at L-IRIS presentation, even in patients with advanced immunosuppression. More disseminated forms, such as BL and LL, are unusually infrequent. This persistence of localized, granulomatous disease suggests that effective tissue-level immune responses endure despite low CD4+ counts, enabling rapid inflammation upon immune recovery. Immune-driven events arise mostly within 2–6 months of ART initiation–”unmasking” or “paradoxical” reactions that define L-IRIS. Type 1 reversal reactions are the most common immunological complication, leading to acute skin lesions and potentially disabling neuritis.[18,19] Histopathology demonstrates a dramatic evolution: from poorly formed or absent granulomas pre-ART to robust infiltrates post-ART, reflecting immunological reconstitution not just of CD4+ T cells, but also the activation of CD8+ lymphocytes and tissue macrophages, and upregulation of pro-inflammatory cytokines.[20,21]

Management generally aligned with single-disease standards, with both MDT for leprosy and ART universally applied, and corticosteroids serving as the mainstay for IRIS and inflammatory reactions.[15] Most patients experienced favorable outcomes, but challenges remain, including drug–drug interactions between rifampicin and ART agents, lack of consensus on corticosteroid regimens, and complications such as ulceration, neuritis, and granuloma formation when diagnosis or intervention is delayed. Diagnostic ambiguity is a recurring barrier, particularly when leprosy presents solely as IRIS, is confused with other opportunistic infections, or is documented primarily in high-surveillance regions. Critically, data on children, pregnant women, and marginalized groups remain scarce.[18,22,23]

In summary, L-IRIS is a clinically important but under-recognized complication of HIV therapy, with practical and policy implications. Improved outcomes will depend on early suspicion, rapid dermatological and neurological assessment, integration of MDT and ART, and management of drug interactions. Health systems must prioritize integrated, multidisciplinary care and broaden research and surveillance efforts to address persistent gaps, especially for underrepresented populations.

Conclusion

Leprosy-associated IRIS is an emerging challenge in HIV care, most frequently presenting as BT leprosy with type 1 reactions during early immune recovery on ART in endemic settings. While most patients respond well to standard therapy, delays in diagnosis and fragmented care contribute to significant morbidity. Moving forward, standardized diagnostic criteria, ongoing outcome tracking, biomarker research, and integrated clinical pathways are essential. Broadening focus to include vulnerable and neglected populations–and investing in unified care between HIV and leprosy programs–will be key to reducing the persistent dual burden of these diseases.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.