Immune Reconstitution Inflammatory Syndrome Research Articles

Suspected Case of Histoplasmosis-Related Immune Reconstitution Inflammatory Syndrome Manifesting as Unilateral Pleural Effusion

Background: Histoplasmosis is a prevalent endemic mycosis that frequently causes opportunistic infections among individuals living with HIV (human immunodeficiency virus), and acquired immunodeficiency syndrome (AIDS). The initiation of antiretroviral therapy (ART) can result in a rare histoplasma-associated immune reconstitution inflammatory syndrome (IRIS) that may be difficult to distinguish between active progressive disease and inflammatory reaction to the medication. Case report: A 35-year-old male with newly diagnosed HIV and cervical biopsy-confirmed histoplasmosis was admitted from the emergency department with disseminated histoplasmosis for HIV antiretroviral treatment and antifungal treatment. Discharged after a 2-week inpatient treatment the patient returned 1 week later with a large left pleural effusion. Two liters of serosanguinous fluid were removed and all fluid cultures and cytology were negative. An extensive work-up remained negative, and given the timeline of presentation in relation to the initiation of ART, it was felt that this isolated left-sided pleural effusion was a manifestation of IRIS. Eventually, corticosteroids were given for IRIS and the patient improved and was discharged on long-term treatment. Conclusions: Immunocompromised subjects are at serious risk for a virulent, aggressive, rapidly advancing histoplasma infection and should be counselled accordingly. Any clinical signs or symptoms of organ system deterioration or compromise should be reported to the provider and a workup for histoplasmosis considered. In patients treated with antiretrovirals, IRIS is particularly confounding since it is difficult to differentiate from active disease. Using corticosteroids in already immunocompromised patients with an established fungal infection requires caution. Compliance with treatment is one of the most important components of care, especially considering the months of protocol.

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient

BackgroundHepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.Case presentationThe 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.ConclusionEnhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Predictors of Fatal Outcome in Newly Diagnosed Tuberculosis/HIV Co-Infection with Chronic Alcoholism (Clinical Case)

Our own case of tuberculosis/HIV co-infection’s diagnosis in chronic alcoholism and analysis of the fatal outcome predictors are presented. The patient abused alcohol for a long time in the presented case, he was hospitalised with acute psychosis in a psychoneurological dispensary, where pulmonary tuberculosis and HIV infection were diagnosed for the first time during additional examination. The patient was admitted to the department in serious condition after prolonged alcohol intoxication. The patient’s condition stabilized after detoxification therapy. Antimycobacterial therapy according to the scheme of an individual treatment regimen, antiretroviral therapy, treatment of hepatitis B and C, detoxification therapy, prophylaxis with Biseptol and Fluconazole and symptomatic therapy were prescribed. After 20 days immune reconstitution inflammatory syndrome developed. It was manifested with meningitis and cryptococci were detected in the cerebrospinal fluid 17 days later. Prescribed treatment of cryptococcal meningoencephalitis with fluconazole in high doses intravenously had a significant positive effect, which made it possible to reduce the dose of the drug to the maintenance level. The treatment was not stopped, but sterility of the liquor was not achieved. After 98 days the patient entered a coma and after 113 days he died from the progression of multiple organ failure and cryptococcal meningitis. It should be noted that the patient was diagnosed with tuberculosis with multiple drug resistance for the first time, the treatment of which had positive dynamics, despite the progression of multiple organ failure and the presence of cryptococcal meningoencephalitis. Therefore, although tuberculosis was not the direct cause of the patient’s death, the disease itself deepened the severity of the general condition. Considering the presented clinical case, it was established that predictors of the fatal outcome of newly diagnosed tuberculosis/HIV co-infection in chronic alcoholism are: antisocial lifestyle; concomitant diseases (tuberculosis, chronic viral hepatitis B and C); cryptococcal meningoencephalitis; fever, altered mental status, cryptococci in the cerebrospinal fluid; the number of CD4+ lymphocytes is less than 200/μL; lack of early screening for CrAg; early initiation of antiretroviral therapy before the diagnosis of cryptococcal meningoencephalitis, which provokes immune reconstitution inflammatory syndrome, against the background of which cryptococcal infection progresses; monotherapy of cryptococcal meningoencephalitis with Fluconazole. Knowledge and practice gaps among medical practitioners contribute to the high fatality rate of cryptococcal meningoencephalitis in tuberculosis/HIV co-infection in chronic alcoholism.

Molecular Diagnostics of Cryptococcus spp. and Immunomics of Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome.

Cryptococcal infection poses a significant global public health challenge, particularly in regions near the equator. In this review, we offer a succinct exploration of the Cryptococcus spp. genome and various molecular typing methods to assess the burden and genetic diversity of cryptococcal pathogens in the environment and clinical isolates. We delve into a detailed discussion on the molecular pathogenesis and diagnosis of immune reconstitution inflammatory syndrome (IRIS) associated with cryptococcosis, with a specific emphasis on cryptococcal meningitis IRIS (CM-IRIS). Our examination includes the recent literature on CM-IRIS, covering host cellulomics, proteomics, transcriptomics, and genomics.

Immune reconstitution is the trigger of herpes zoster with lymphopenia and high neutrophil-to-lymphocyte ratio in a retrospective cohort study.

Herpes zoster (HZ) rarely results in subsequent death, but predictive biomarkers for mortality necessitate further elucidation. To investigate immune dynamics prior to an HZ event, risk factors for HZ onset and immune status at initial HZ. This retrospective study extracted from patient records the absolute neutrophil and lymphocyte counts (ANC and ALC, respectively) at the initial HZ date of appearance and up to 30 days before HZ. A follow-up survey was completed within 180 days of onset of illness. Patients with HZ showed a higher neutrophil-to-lymphocyte ratio (NLR) and lower ALC than patients in the control group at the initial date and had a poorer prognosis. In the pre-onset examination, the maximum and minimum ALC values were significantly lower in patients with HZ than in the control group, and the maximum ALC value in patients with HZ was lower than the minimum value in the control group. The lowest ALC was observed 7 days before the onset of HZ. An NLR of 4.53 or more and an ALC of 0.64 × 109 cells L-1 or less were predictive markers of HZ development within 30 days. Patients who died after HZ had a lower minimum ALC than those who survived longer. HZ develops in a state of immune reconstitution in patients with immunocompromised conditions, as part of 'unmasking' the immune reconstitution inflammatory syndrome. Lymphopenia prior to HZ onset is one of the most crucial factors in its pathogenesis and vital prognosis. Limitations of the study were small population size, varying age distribution, retrospective nature, and potential overestimation of pre-onset data.

An Uncommon Cause of Elevated Liver Transaminases: Immune Reconstitution Inflammatory Syndrome from Unmasking of Occult Mycobacterium Avium Complex Infection in an HIV Infected Patient

Abnormal liver chemistry from the development of immune reconstitution inflammatory syndrome (IRIS) may reflect an unmasking of subclinical disease. We present the case of a 37-year-old female with a mixed pattern of liver injury from disseminated mycobacterium avium complex infection after starting antiretroviral therapy (ART). Presenting symptoms were fever, confusion, dysphagia, and abdominal discomfort for one week. Exam revealed a fever of 103.2°F, hypotension, encephalopathy, and abdominal tenderness. Lab work was significant for acute normocytic anemia, leukopenia, absolute CD4 count 28 cells/cmm, HIV viral load 276 viral copies/ml (vc/ml), ALT 267 U/L, AST 484 U/L, alkaline phosphatase 342 U/L, and normal total bilirubin. Imaging revealed hepatomegaly with steatosis and mesenteric and retroperitoneal lymphadenopathy. Percutaneous liver biopsy demonstrated noncaseating granulomas with AFB-positive organisms, with AFB blood cultures growing Mycobacterium avium complex (MAC), consistent with disseminated MAC infection. Clinicians must have a high index of suspicion for IRIS when determining the etiology of elevated liver transaminases in patients with HIV.

Severe BCG immune reconstitution inflammatory syndrome lymphadenitis successfully managed with pre-antiretroviral counseling and a non-surgical approach: a case report

BackgroundBacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate antiretroviral therapy (ART). There is limited evidence regarding the incidence of BCG-IRIS; however, reports from outpatient cohorts have estimated that 6–9% of infants who initiated ART developed some form of BCG-IRIS within the first 6 months. Various treatment approaches for infants with BCG-IRIS have been reported, but there is currently no widely accepted standard-of-care.Case PresentationA 5-month-old male HIV-exposed infant BCG vaccinated at birth was admitted for refractory oral candidiasis, moderate anemia, and moderate acute malnutrition. He had a HIV DNA-PCR collected at one month of age, but the family never received the results. He was diagnosed with HIV during hospitalization with a point-of-care nucleic acid test and had severe immune suppression with a CD4 of 955 cells/µL (15%) with clinical stage III disease. During pre-ART counseling, the mother was educated on the signs and symptoms of BCG-IRIS and the importance of seeking follow-up care and remaining adherent to ART if symptoms arose. Three weeks after ART initiation, he was readmitted with intermittent subjective fevers, right axillary lymphadenopathy, and an ulcerated papule over the right deltoid region. He was subsequently discharged home with a diagnosis of local BCG-IRIS lymphadenitis. At six weeks post-ART initiation, he returned with suppurative lymphadenitis of the right axillary region that had completely eviscerated through the skin without signs of disseminated BCG disease. He was then started on an outpatient regimen of topical isoniazid, silver nitrate, and oral prednisolone. Throughout this time, the mother maintained good ART adherence despite this complication. After 2.5 months of ART and one month of specific treatment for the lymphadenitis, he had marked mass reduction, improved adenopathy, increased CD4 count, correction of anemia, and resolution of his acute malnutrition. He completely recovered and was symptom free two months after initial treatment without surgical intervention.ConclusionsThis case details the successful management of severe suppurative BCG-IRIS with a non-surgical approach and underlines the importance of pre-ART counseling on BCG-IRIS for caregivers, particularly for infants who initiate ART with advanced HIV.

150 From pancytopenia to hyperleukocytosis, an unexpected presentation of immune reconstitution inflammatory syndrome in an infant with methylmalonic acidemia

150 From pancytopenia to hyperleukocytosis, an unexpected presentation of immune reconstitution inflammatory syndrome in an infant with methylmalonic acidemia

Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.

People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts; however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4+ and CD8+ T cells, nadir CD4+ count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197 PWH with median age of 42 years, using a 56-gene panel. Seventy-nine percent had a CD4+ nadir below 200 cells/μL, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8+ T cells and nadir CD4+ counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of patients 35 years of age and older. Inflammatory biomarkers were higher in CH carriers compared with noncarriers, supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4+ and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.

Spinal cord involvement in progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging.

The Unusual Adverse Effects of Antituberculosis Therapy in Kidney Patients.

Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.

Immune reconstitution inflammatory syndrome (IRI S) in reproductive health

Immune reconstitution inflammatory syndrome (IRI S) in reproductive health

Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.

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.

Steroid-Induced Progressive Multifocal Leukoencephalopathy (PML) in HIV Patient: A Paradoxical Effect

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system predominantly found in patients with acquired human immunodeficiency syndrome (AIDS). Case Presentation: This report details a case involving a male HIV-positive patient with PML who discontinued his highly active antiretroviral therapy (HAART) treatment 10 days after being diagnosed with HIV. The patient had no history of neurological symptoms either before or after his HIV diagnosis until he was administered corticosteroids. Notably, he began experiencing ataxia shortly after starting dexamethasone. Progressive multifocal leukoencephalopathy was diagnosed through polymerase chain reaction (PCR) testing for the John Cunningham virus (JCV) in the cerebrospinal fluid (CSF). The PML lesions were confined to the cerebellum. Conclusions: The occurrence of neurological symptoms (activation of JCV) after administering corticosteroids to a patient with HIV-who had not received any antiretroviral treatment for 4 years-raises a critical question: Is the use of corticosteroids, which are a primary treatment for immune reconstitution inflammatory syndrome (IRIS), a double-edged sword in CNS-IRIS?

Mycobacterial spindle cell pseudotumor of the spinal cord: Case report and literature review

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.

Skin and mucosal manifestations of immune reconstitution inflammatory syndrome in people living with HIV: a review.

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.

Meningitis and Tuberculosis: A Correlation along with Diagnosis and Management of Tuberculosis Meningitis

Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), is a communicable disease and a leading cause of death globally, especially in developing countries. It exists in active and latent forms, affecting both pulmonary and extrapulmonary sites. The pathophysiology of TB involves interactions with various immune cells, particularly T cells, in defense against the infection. On the other hand, meningitis is the inflammation of the membranes surrounding the brain and spinal cord, and it can be caused by bacteria or viruses. Bacterial meningitis, associated with high mortality and risk of disability. The article highlights the promulgation of TB into the brain and the immune responses within the brain, shedding light on the migration of M. tb into the central nervous system (CNS) and the innate immune responses involving microglia and cytokine secretion. The diagnostic methods for TB meningitis encompass neuroimaging, adenosine deaminase measurement in cerebrospinal fluid (CSF), microscopy, polymerase chain reaction (PCR) techniques, and enzyme-linked immunosorbent assay (ELISA). Moreover, it discusses the treatment of TB meningitis, emphasizing traditional antimicrobial therapies, systemic corticosteroid therapy, adjunctive therapy, fluid management, surgical intervention for hydrocephalus, and considerations for patients co-infected with HIV. The treatment approaches stress the importance of timely and empirical treatment, the use of newer generation fluoroquinolones, systemic corticosteroids as adjunctive therapy, and surgical interventions for hydrocephalus. The article also addresses the potential challenges and considerations for patients co-infected with HIV, such as the risk of immune reconstitution inflammatory syndrome (IRIS), drug interactions, and the efficacy of adjunctive corticosteroids. Overall, the document provides a comprehensive overview of the correlation between TB and meningitis, covering their pathophysiology, diagnostic methods, and treatment approaches. It emphasizes the complexity of managing TB meningitis and the importance of considering various factors, including immune responses, diagnostic accuracy, and tailored treatment strategies, particularly in the context of HIV co-infection.

Fatal form of immune reconstitution inflammatory syndrome (IRIS) developed post pneumonia in a solid organ transplant recipient

BackgroundImmune reconstitution inflammatory syndrome (IRIS) is a complex phenomenon commonly diagnosed with human immunodeficiency virus (HIV). However, rarely, IRIS can develop with other diseases outside of HIV. We are discussing a rare presentation of IRIS following a pseudomonal infection.Case presentationWe present a 79-year-old Hispanic male who completed a course of cefepime for Pseudomonas aeruginosa hospital-acquired pneumonia. The patient had a 21-year history of solid organ transplant and immunosuppressive therapy, and he developed a fatal form of IRIS post-Pseudomonas aeruginosa.ConclusionsIRIS may occur in any immunocompromised patient who develops an insidious onset of unexplained clinical and serological deterioration.

Paradoxical and Unmasking HIV Immune Reconstitution Inflammation Syndrome in Antiretroviral-Naïve Pregnant Women: A Prospective Cohort Study.

Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load. An active records study was conducted between June 2019 and March 2020 among ART-naïvepregnant women attending the antenatal care units (ANCu) at the Kenyatta National and MbagathiHospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital's clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed. From a pool of 532 ART-naïvepregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS. For ART-naïvepregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïvepregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.

The nature and origin of immunosuppressive disorders

This publication reflects modern ideas about the main aspects of etiology, pathogenesis and the latest achievements of clinical practice in the field of the most common primary and secondary immunodeficiency. The features of laboratory diagnostics of congenital immunodeficiency, risk factors and early clinical guidelines that allow the patient to suspect an immunosuppressive state are considered. Special attention is paid to the problem of secondary immunodeficiency, their prevalence and polyetiology. When covering immunopathogenesis, infection caused by the human immunodeficiency virus (HIV), attention is paid to the multimorbidity of clinical manifestations of HIV-associated immunosuppression and concomitant diseases, the importance of timely administration of antiretroviral therapy (ART) and its role in the development of immune reconstitution syndrome (IRS). The criteria for the diagnosis of SVI based on their own experience and the opinion of foreign colleagues, the tactics of patient management are presented in detail.