Incidence and pattern of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients on anti-retroviral therapy: An observational study.

BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome is an atypical, immoderate immune response mounted by the refurbishing immune system against the mycobacterium tuberculosis, commonly seen in HIV-infected individuals. ART significantly enhances one's immunity. However, this enhancement in immunity also sets off a number of inflammatory processes termed as Immune Reconstitution Inflammatory Syndrome (IRIS). METHODS: This observational study was conducted with the aim of assessing the incidence and pattern of TB-IRIS in people living with HIV/AIDS on ART registered at the ART Centre of S.C.B. Medical College and Hospital, Cuttack. They were evaluated for their plasma viral load and CD4 count at baseline. Thereafter, the plasma viral load was assessed every week and the CD4 count was assessed fortnightly. Each study participant was followed-up for a period of three months to look for any onset of TB-IRIS. RESULTS: A total of 286 patients were included the study. The overall incidence of TB-IRIS was 7.7%. The occurrence of paradoxical TB-IRIS was nearly double than ART-associated TB-IRIS. There was a significant rise in the CD4 cell count in the patients of both paradoxical (p = 0.001) and ART-associated (p = 0.017) TB-IRIS. The plasma viral load at baseline also showed significant differences from the levels documented at the appearance of the TB-IRIS both in both the types i.e. paradoxical (p = 0.001) and ART-associated (p = 0.012) TB-IRIS. CONCLUSION: People with HIV/TB coinfection experience high morbidity and death from all kinds of TB-IRIS, necessitating specific attention. As HIV-positive cases and implementation of ART continue to rise, it's vital to quickly rule out TB coinfection.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Stroke, HIV and the Immune Reconstitution Inflammatory Syndrome in the absence of opportunistic infections.

INTRODUCTION: Stroke in people living with HIV (PLWH) has been described to occur soon after the initiation of antiretroviral therapy (ART) possibly related to the Immune Reconstitution Inflammatory Syndrome (IRIS). We sought to investigate whether there was a temporal association between stroke and recent ART initiation in the absence of opportunistic infections (OIs), and to identify risk factors for this. METHODS: This cross-sectional study recruited PLWH with new-onset stroke at a hospital in Johannesburg, South Africa, from 2014 to 2017, excluding all patients with OIs. Patients were assessed for ART duration, CD4 count, HIV viral load, inflammatory markers and cardiovascular risk factors. RESULTS: 77 PLWH were recruited, of which 35 were on ART at the time of stroke. Of the patients with confirmed ART duration (n = 28), 9 (32.1%) had a stroke within the first 6 months of starting ART (crude incidence rate of 0.73 cases per patient year). In the period beyond 6 months, 19 strokes occurred (crude incidence rate of 0.21 cases per patient year), translating to a 3.5 times greater risk in the first 6 months (p = 0.0002). There were no clearly identified risk factors when comparing those who had strokes in the first 6 months to those after 6 months and ART-naïve patients. CONCLUSION: Almost a third of strokes in PLWH may be related to IRIS, with a crude incidence rate 3.5 times higher in the first 6 months following ART-initiation compared to beyond 6 months. This appears to be independent of OIs. Risk factors are unclear.

Síndrome inflamatorio multisistémico en niños asociado a COVID-19 / Multisystem inflammatory syndrome related to COVID-19 in children

Las manifestaciones clínicas de la infección por SARS-CoV-2 son menos frecuentes y graves en niños que en adultos; sin embargo, recientes publicaciones sugieren la posibilidad de un cuadro clínico severo secundario a la infección por este coronavirus en pacientes pediátricos, denominado síndrome inflamatorio multisistémico. El objetivo de este trabajo es examinar los aspectos relacionados con la epidemiologia, patogenia, presentación clínica, diagnóstico y tratamiento del síndrome inflamatorio multisistémico en niños. Este síndrome tiene un carácter posinfeccioso y su fisiopatología probablemente resulte de una activación anormalmente organizada del sistema inmune, en un contexto genético de predisposición y activada por la peculiar biología del SARS-CoV-2. Las características clínicas de los pacientes afectados incluyen fiebre mantenida, con afectación de múltiples órganos y sistemas y resultados positivos de marcadores inflamatorios, además de cumplir con los criterios de infección reciente o concurrente por SARS-CoV-2. Para el tratamiento, además de las medidas de apoyo vital y el uso de antibióticos en la etapa inicial, se recomienda el empleo de terapias específicas inmunomoduladoras, como la inmunoglobulina intravenosa y los esteroides, así como el ácido acetilsalicílico. El correcto abordaje de esta entidad requiere mantener un alto nivel de alerta, con una definición clara de los casos sospechosos, la participación multidisciplinaria y la implementación de una estrategia terapéutica inmediata(AU)

The clinical manifestations of the infection by SARS-CoV-2 are less frequent and severe in children than in adults; however, recent publications suggest the possibility of a severe clinical picture called multisystem inflammatory syndrome which is caused by the infection with coronavirus in pediatric patients. The objective of this work is to examine the aspects related to the epidemiology, pathogenesis, clinical presentation, diagnosis and treatment of the multisystem inflammatory syndrome in children. This syndrome has a post-infection nature and its physiopathology is probably the result of an abnormally organized activation of the immune system, in a genetic context of predisposition and activated by the peculiar biology of the SARs-CoV-2.The clinical characteristic of the affected patients include constant fever, affectation of multiple organs and systems, and positive results of inflammatory markers, and in addition meeting the criteria of recent or concurrent infection by SARS-CoV-2. For the treatment, apart from the measures of vital support and the use of antibiotics in the initial stage, it is recommended the use of specific immunomudolatory therapies, as intravenous immunoglobulin and steroids; as well as acetylsalicylic acid. The right approach to this entity requires maintaining a high level of alerts, with a clear definition of the suspected cases, the multidisciplinary participation and the implementation of an immediate therapeutic strategy(AU)

Perforación intestinal por citomegalovirus durante un Síndrome de Reconstitución Inmune / Intestinal Perforation for Cytomegalovirus in Immune Reconstitution Syndrome

RESUMEN El síndrome de reconstitución inmune se produce debido a un aumento de la inmunocompetencia en pacientes previamente inmunocomprometidos. La situación es frecuente tras iniciar un tratamiento antirretroviral de alta eficacia, en pacientes con infección por el virus de inmunodeficiencia humana. En determinados casos, puede conllevar un empeoramiento paradójico de una infección previa. El citomegalovirus, es un germen oportunista que, en el seno de un síndrome de reconstitución inmune, puede dar lugar a perforación intestinal multifocal y peritonitis secundaria de difícil tratamiento. Es más frecuente en pacientes con recuento de linfocitos cooperadores inferior a 50 células/mm3 al iniciar el tratamiento antirretroviral. El objetivo es comunicar dicha situación a través, de un caso clínico para facilitar su sospecha lo más pronto posible, y realizar un tratamiento adecuado. Presentamos el caso de un paciente con virus de inmunideficiencia humana de reciente diagnóstico, en tratamiento con terapia antirretroviral de alta eficacia, que acude a urgencias con abdomen agudo secundario a perforación por citomegalovirus. La infección conlleva importante morbimortalidad, siendo imprescindible un diagnóstico temprano e iniciar precozmente el tratamiento antiviral intravenoso, asociado generalmente a tratamiento quirúrgico(AU)

ABSTRACT Immune reconstitution syndrome occurs due to increased immunocompetence in previously immunocompetent patients. The condition is frequent in patients with human immunodeficiency virus infection who have started a highly active antiretroviral therapy. In certain cases, the syndrome can lead to a paradoxical worsening of a previous infection. Cytomegalovirus is an opportunistic germ that, during an immune reconstitution syndrome, can lead to multifocal intestinal perforation and secondary peritonitis, in cases that are difficult to treat. The syndrome is more frequent in patients with CD4 lymphocyte count below 50/mm3 at the time of starting antiretroviral treatment. The objective is to communicate this situation through a clinical case presentation in order to facilitate suspicion as soon as possible, and to carry out appropriate treatment. We present the case of a patient with a recently diagnosed human immunodeficiency virus, under treatment with highly active antiretroviral therapy, who attended the emergency department with an acute abdomen secondary to perforation due to cytomegalovirus. Infection carries significant morbidity and mortality, and early diagnosis is essential and intravenous antiviral treatment should be started early, generally associated with surgical treatment(AU)

Síndrome de reconstitución inmune / Immune reconstitution syndrome

ResumenEl síndrome inflamatorio de reconstitución inmune se presenta en pacientes con infección por VIH o infección avanzada por el virus, días, semanas o meses después del inicio de la terapia antirretroviral. Se caracteriza por una restauración gradual de la inmunidad patógeno-específica donde el sistema inmune es capaz de reconocer atógenos presentes pero clínicamente ocultos. Característicamente se presenta después de iniciar la TARV cuando el sistema inmunitario comienza a recuperarse. Puede ser leve o potencialmente mortal.

AbstractThe immune reconstitution inflammatory syndrome occurs in patients with advanced HIV infection or HIV infection, days, weeks or months after initiation of antiretroviral therapy. It is characterized by a gradual restoration of pathogen specific immunity where the immune system is able to recognize pathogens presents but clinically occult.Characteristically it occurs after starting antiretroviral therapy when the immune system starts to recover. It can be mild or life threatening.

Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients

Tuberculosis is one of the leading causes of development of Immune reconstitution inflammatory syndrome (IRIS) in HIV patients receiving antiretroviral therapy (ART). OBJECTIVE: To determine the incidence of IRIS in HIV-TB coinfected patients, and to find out the possible risk factors associated with IRIS. MATERIALS AND METHODS: Study commenced with 96 patients adhered to standard antitubercular therapy (ATT) and ART without defaultering, and followed up for six months. RESULT: The mean (± SD) CD4 count and CD4 percentage at baseline was 59.16 (± 24.63) per mm³ and 4.59 percent (± 1.73) respectively. Only 18.75 percent developed IRIS after 57.05 (± 14.12) days of initiation of ART. Extrapulmonary tuberculosis was the most significant factor associated with IRIS (83.33 percent) than those without IRIS (44.87 percent) (p = 0.0032). Specifically, tubercular lymphadenitis (38.88 percent, p = 0.0364) and disseminated tuberculosis (33.33 percent, p = 0.0217) were significantly associated with IRIS. The other risk factors associated with appearance of IRIS were higher CD4 count (p = 0.0212) at three months after initiation of ART and increment of CD4 count (p = 0.0063) and CD4 percentage (p = 0.0016) during this period. The major manifestations of IRIS were fever (40 percent), followed by lymphadenitis (38 percent). The mortality rate in IRIS was not higher than those without IRIS. CONCLUSION: Patients with extrapulmonary tuberculosis, especially tubercular lymphadenitis, were more likely to develop IRIS and fever was associated in most of them. Higher increment of CD4 count may indicate development of IRIS in presence of new or worsening tuberculosis lesion.