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Síndrome da Imunodeficiência Adquirida , Leucoencefalopatia Multifocal Progressiva , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Masculino , Síndrome da Imunodeficiência Adquirida/complicações , Hospedeiro Imunocomprometido , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Vírus JC/isolamento & purificação , Adulto , Infecções Oportunistas Relacionadas com a AIDS/diagnósticoRESUMO
Human retro-viral disease and the myriad opportunistic infections associated with it continue to pose a diagnostic challenge to clinicians. Disseminated Kaposi sarcoma (KS) and KS-associated immune reconstitution inflammatory syndrome (IRIS) are entities that can be associated with adverse clinical outcomes unless recognized early by the treating physician. We present the case of a 36-year-old homosexual HIV-positive male who presented with unusual symptoms of KS and KS IRIS with lower gastrointestinal bleeding and respiratory distress devoid of any cutaneous manifestations.
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Background: The advent of anti-tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα. Methods: This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure. Results: Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery). Conclusions: TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy.
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Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.
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Antituberculosos , Interações Medicamentosas , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Tuberculose , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Tuberculose/tratamento farmacológico , Tuberculose/complicações , Antituberculosos/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Resultado do TratamentoRESUMO
BK virus (BKV) encephalitis is a rare complication after hematopoietic stem cell transplantation (HSCT). A 43-year-old woman with recurrent follicular lymphoma after autologous HSCT received allogeneic bone marrow transplantation from a human leukocyte antigen-matched related donor. Neutrophil engraftment was achieved on post-transplant day 13. Memory loss and noncooperative attitude toward the medical staff were observed on day 16, and her mental status worsened progressively. Magnetic resonance imaging (MRI) showed nonspecific findings on day 19; however, cerebrospinal fluid (CSF) analysis including real-time polymerase chain reaction on day 20 revealed elevated levels of BKV 4.67 × 104 copy/mL. BKV encephalitis was diagnosed based on CSF findings, intravenous administration of immunoglobulin and cidofovir was started, and the immunosuppressive agent dose was reduced. Diffusion-weighted MRI on day 28 showed signal abnormalities in the bilateral periventricular white matter. Although the follow-up CSF analysis on day 35 was negative for BKV, her mental status and MRI findings did not improve, and she died on day 55 because of respiratory failure. This case emphasizes the importance of considering BKV encephalitis as a differential diagnosis of post-transplant encephalitis, considering the central nervous system-associated immune reconstitution inflammatory syndrome in patients with worsening central nervous system findings after eradication of BKV in the CSF.
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Opportunistic infections have significantly decreased in individuals living with human immunodeficiency virus and receiving antiretroviral therapy. However, in approximately 10%-25% of patients, severe skin reactions during immune reconstruction are constantly increasing. This may manifest as either an exacerbation of a chronic disease or the development of a new disorder, referred to as immune reconstitution inflammatory syndrome. This review focuses on the current knowledge regarding the dermatological symptoms of immune reconstitution inflammatory syndrome observed in recent years. These symptoms encompass various pathogens, neoplasms, and certain autoimmune diseases. In addition to the most common skin reactions, attention is directed towards conditions not previously described in any review, such as psoriasis.
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Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Humanos , Síndrome Inflamatória da Reconstituição Imune/imunologia , Síndrome Inflamatória da Reconstituição Imune/etiologia , Infecções por HIV/imunologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Psoríase/imunologia , Psoríase/complicações , Dermatopatias/imunologia , Dermatopatias/etiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêuticoRESUMO
After initiating combined antiretroviral therapy (cART), individuals with human immunodeficiency virus (HIV) may develop Hodgkin/non-Hodgkin lymphoma due to immune reconstitution inflammatory syndrome (IRIS). This retrospective cohort study evaluated the incidence, clinical features and prognosis of IRIS-associated lymphomas in Brazilian patients. Incidence in 2000-2019 was 9.8% (27/276 patients with HIV and lymphoma; viral load drop >1 log). Time between HIV diagnosis and cART initiation was <1 year in 70.3% of cases. Time between cART initiation and lymphoma diagnosis was <3 months in 11 cases and 3-6 months in 16 cases. Overall and progression-free survival rates were similar between cases of non-IRIS-associated lymphoma and IRIS-associated lymphoma.
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PURPOSE: To describe an unusual case of Whipple's disease (WD) complicated by uveitis, and subsequent paradoxical worsening after effective antibiotic treatment targeting Tropheryma whipplei (TW). METHODS: Case report. RESULTS: A 53-year-old male presented with bilateral knee arthritis, weight loss, chronic low-grade fever, and cognitive disorders. He was under treatment with tumor necrosis factor α inhibitors (TNFi) for seronegative spondyloarthritis. Given this unusual clinical presentation, further investigations were performed and revealed blood, saliva, stool, synovial fluid and cerebrospinal fluid positivity for TW, confirming the diagnosis of systemic WD. Ophthalmologic examination revealed bilateral posterior uveitis and an aqueous humor sample confirmed the presence of intraocular TW. TNFi were stopped, and the patient was subsequently treated with adequate antibiotics (ceftriaxone, followed by doxycycline and hydroxychloroquine), and subconjunctival corticosteroid injections. After a transient improvement of the ocular symptoms, he presented a recurrence of posterior segment inflammation, leading to repeated PCR testing for TW which were negative. Therefore, paradoxical worsening of the inflammation in the context of immune recovery uveitis (IRU) was thought to be the culprit. The patient was treated with systemic corticosteroid therapy, allowing for rapid improvement of the ocular findings. CONCLUSIONS: This case underlines the possibility of IRU complicating WD. Ophthalmologists, rheumatologists, and internists should be aware of this rare complication, particularly in the context of previous immunosuppressive therapy.
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PURPOSE OF REVIEW: This review highlights the difficulties in diagnosing and treating persons with a prior history of cryptococcal meningitis who improve but suffer from a recurrence of symptoms. This scenario is well known to those who frequently care for patients with cryptococcal meningitis but is not well understood. We highlight major gaps in knowledge. RECENT FINDINGS: We recently summarized our experience with 28 persons with paradoxical immune reconstitution inflammatory syndrome (IRIS) and 81 persons with microbiological relapse. CD4 count and cerebrospinal fluid white blood cell count were higher in IRIS than relapse but neither was reliable enough to routinely differentiate these conditions. Second-episode cryptococcal meningitis remains a difficult clinical scenario as cryptococcal antigen, while excellent for initial diagnosis has no value in differentiating relapse of infection from other causes of recurrent symptoms. Updated research definitions are proposed and rapid, accurate diagnostic tests are urgently needed.
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Criptococose , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Meningite Criptocócica , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/microbiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Criptococose/complicações , Criptococose/diagnóstico , Contagem de Linfócito CD4 , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/etiologia , RecidivaRESUMO
Se presenta el caso clínico de persona viviendo con VIH, con mala adherencia a tratamiento, sin vacunación previa para mpox, que evolucionó con un cuadro clínico probable de síndrome de reconstitución inmune posterior a reinicio de TAR, debido a la progresión de las lesiones cutáneas. Recibió tratamiento con tecovirimat por siete días, con evolución clínica favorable. Corresponde al primer caso reportado que recibió terapia con tecovirimat en Chile.
We report a clinical case of a person living with HIV with poor adherence to treatment, no previous mpox vaccination, who had a probable mpox syndrome immune reconstitution after restarting ART, due to worsening of skin lesions. He received treatment with tecovirimat for 7 days, clinically improved and was discharged in good condition. We reported this first clinical case that received tecovirimat in Chile.
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Humanos , Masculino , Adulto , Infecções por HIV/complicações , Mpox/complicações , Mpox/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/etiologia , Antivirais/uso terapêutico , Ftalimidas/uso terapêutico , Benzamidas/uso terapêuticoRESUMO
Paradoxical tuberculosis reaction is defined as the aggravation of lesions present at diagnosis or the development of new lesions under anti-tuberculosis treatment, after exclusion of other alternate causes. It affects 5 to 30% of tuberculosis patients, with a variable prevalence depending on the site of infection and the clinical background. The diagnosis of paradoxical reaction is one of elimination, and requires having ruled out therapeutic failure, notably linked to poor compliance and/or to the presence of mycobacterial antibiotic resistance. The severity of paradoxical tuberculosis reaction lies in its neurological impairment. Despite its clinical importance, the mechanisms involved remain poorly understood and its management is not consensual. Corticosteroids are the cornerstone in the medical management. The role of anti-TNF agents, currently proposed in cases of corticodependence or corticoresistance, remains to be properly defined.
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Antituberculosos , Tuberculose , Humanos , Antituberculosos/uso terapêutico , Antituberculosos/efeitos adversos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/complicaçõesRESUMO
A 72-year-old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1-hypointense area. Multiple T2/FLAIR-hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high-dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR-hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+ /CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti-viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD-1 and PD-L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD-1/PD-L1 immune-checkpoint regulation.
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Leucoencefalopatia Multifocal Progressiva , Linfoma , Idoso , Feminino , Humanos , Antígeno B7-H1 , Linfócitos T CD8-Positivos/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Prognóstico , Receptor de Morte Celular Programada 1RESUMO
We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.
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Agranulocitose , Aspergilose , Pneumopatias , Linfo-Histiocitose Hemofagocítica , Pneumotórax , Sepse , Humanos , Feminino , Aspergillus flavus , Dipirona , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Hemorragia , Necrose , Linfo-Histiocitose Hemofagocítica/microbiologiaRESUMO
Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is a condition that affects immunosuppressed individuals recruited to antiretroviral therapy. In a recent publication, Kawano and colleagues used a mouse model to demonstrate that pulmonary dysfunction, one of the fatal complications of C-IRIS, is caused by T cell-driven neurodegeneration in a vital medullary nucleus of the brain responsible for respiratory control.
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Infecções Oportunistas Relacionadas com a AIDS , Infecções por HIV , Meningite Criptocócica , Animais , Camundongos , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Meningite Criptocócica/complicações , Meningite Criptocócica/tratamento farmacológico , Antifúngicos/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , MesencéfaloRESUMO
BACKGROUND: Diabetes that develops in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) is usually type 2 diabetes mellitus (T2DM); however, autoimmune diabetes, such as type 1 diabetes mellitus (T1DM) can also develop in this population. After treatment with ART, patients might experience clinical deterioration following an increase in the CD4 cell count, which is termed immune reconstitution inflammatory syndrome (IRIS). Here, we describe an HIV-infected patient on ART who developed T1DMat due to IRIS, highlighting the clinical complexity in diagnosis and treatment. CASE PRESENTATION: A 36-year-old man infected with HIV had a nadir CD4 cell count of 15.53/µL before medication, which increased to 429.09/µL after 9 months of regular ART. The fasting serum glucose at 9 months was between 96 mg/dL and 117 mg/dL. After 11 months of ART, the patient was admitted to hospital for diabetic ketoacidosis (DKA) and Graves' disease (GD). Noninsulin antidiabetics (NIADs) were prescribed following the resolution of DKA. However, poor glycemic control was noted despite well-titrated NIADs. Further investigation demonstrated poor pancreatic beta cell function and elevated anti-glutamic acid decarboxylase (anti-GAD) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) titers. According to the results, he was diagnosed with T1DM and received multiple daily injections(MDI) of insulin. The regimen of MDI was insulin degludec as basal insulin and insulin aspart as prandial insulin. After MDI therapy, his glycemic control was improved. CONCLUSION: In this case, T1DM was ascribed to IRIS. Although this phenomenon has been demonstrated in previous case reports, further study is necessary to realize the mechanism of this association. Therefore, we emphasize that when HIV-infected patients on ART experience an unstable blood glucose level and abnormal thyroid function, physicians should consider T1DM and GD associated with ART-induced IRIS to reduce the subsequent complications and more serious endocrine dysfunction.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Masculino , Humanos , Adulto , HIV , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome Inflamatória da Reconstituição Imune/etiologia , Hipoglicemiantes , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
Chronic disseminated candidiasis (CDC) is a severe form of disseminated fungal infection that commonly affects the liver, spleen, and kidneys. In rare cases, CDC can be further complicated by an excessive immune response known as immune reconstitution inflammatory syndrome (IRIS). This syndrome occurs during the phase of immune recovery and is characterized by a systemic inflammatory response and excessive release of cytokines. We present a case of a two-year-old female with a medical history of acute lymphocytic leukemia on chemotherapy. She was admitted with high fever refractory to conservative management that included broad-spectrum antimicrobials. Additionally, multiple skin lesions and a left-sided limp were noted. Whole-body imaging revealed multiple abscesses in the spleen, kidneys, scalp, and left lower limb. The culture of an aspirate material from skin lesions grew Candida tropicalis. Despite receiving appropriate antifungals, the patient showed no signs of improvement, leading to the diagnosis of CDC-induced IRIS. The patient was started on systemic corticosteroids, which resulted in rapid improvement in the patient's clinical status, resolution of fever, and significant reduction in inflammatory markers.
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BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PMAH) combined with infection by an opportunistic pathogen is complicated. Clinical evidence on managing PMAH patients with infections by opportunistic pathogens is insufficient. CASE PRESENTATION: A 66-year-old male was admitted with bilateral adrenal masses and was diagnosed with PMAH. Fever and disturbance of consciousness appeared after laparoscopic left adrenalectomy. Cryptococcal meningitis was confirmed by cerebrospinal fluid (CSF) culture. The exacerbation of his medical condition was suspected to result from immune reconstitution inflammatory syndrome (IRIS), and he had been treated with antifungal therapy and glucocorticoid replacement, but he responded poorly and eventually died of multiorgan failure. We summarized the clinical observations of 12 Cushing's syndrome (CS) patients infected by Cryptococcus. Seven out of nine patients who were treated for cryptococcus infection before receiving CS survived, while three patients treated for cryptococcus infection after CS treatment developed signs of IRIS and eventually died. CONCLUSION: Cushing's syndrome, complicated with cryptococcal infection, has a high mortality rate, mainly when IRIS emerges. Carefully identifying the presence of the suspected infection, and controlling cryptococcal infection before removing the culprit adrenals could be the rational choice.
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Criptococose , Síndrome de Cushing , Meningite Criptocócica , Masculino , Humanos , Idoso , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/etiologia , Adrenalectomia/efeitos adversos , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Glândulas SuprarrenaisRESUMO
Transplant physicians should be aware of the immune deviation-related clinical conditions as allogeneic hematopoietic stem cell transplantation is widely used for the treatment of patients with malignant and non-malignant disorders. Neurological manifestations and graft-versus-host disease (GVHD) may commonly develop in transplant recipients. However, overlapping clinical immunological conditions may lead to diagnostic challenges. Herein, we discussed the differential diagnosis of a patient with immune reconstitution inflammatory syndrome (IRIS) developing on the basis of chronic GVHD.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco , Doença Enxerto-Hospedeiro/terapia , Transplante HomólogoRESUMO
Chylothorax is a rare cause of pleural effusion and occurs due to leakage of chyle into the pleural space. In most cases, it results from trauma, with malignancy accounting for most of the non-traumatic causes. Chylothorax resulting from immune reconstitution inflammatory syndrome (IRIS), during treatment of Mycobacterium avium complex (MAC) infection, is an extremely infrequent cause of chylothorax, with only a handful of cases reported in the literature.
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BACKGROUND: Actinomycosis is an unusual chronic bacterial infection, even rarer in people living with HIV. It is not considered an AIDS-defining disease. However, the role in co-presentation or overlap with other opportunistic conditions of advanced HIV is unknown. CASE PRESENTATION: A 49-year-old Peruvian male presented with a 4-month history of dysphagia, odynophagia, hyporexia and wasting. He underwent an upper digestive endoscopy, in which ulcers with a necrotic center were observed, therefore, the initial diagnostic assumption was esophageal cancer. Subsequent pathology report excluded neoplasms and confirmed the diagnosis of actinomycosis. Serology for human immunodeficiency virus was requested, yielding a positive result. Antimicrobial treatment with amoxicillin and antiretroviral therapy were indicated, with slow clinical improvement. After 4 months, epigastric discomfort presented, for which a new upper digestive endoscopy was performed, revealing a deep gastric ulcer, which was compatible with diffuse large B-cell non-Hodgkin lymphoma. CONCLUSION: Esophageal actinomycosis in people living with HIV is very rare. We suggest HIV-associated immunosuppression is not enough to allow for actinomycosis to develop, and masked underlying entities should be sought. The existence of such entities in people living with HIV should raise awareness of the possibility of unmasked immune reconstitution inflammatory syndrome once treatment has started.