Kaposi's sarcoma revealing an immune restoration syndrome

Introduction: Highly active antiretroviral therapy (HAART) leads to reconstitution of immune responses in HIV-infected patients. This immune reconstitution may reveal an immune reconstitution syndrome (IRS). While tuberculosis is the most common manifestation of IRS in southern countries, other more serious conditions such as Kaposi's disease may reveal it. Observation: We report a case of Kaposi's disease revealing an immune restoration syndrome with the aim of contributing to a better management. The patient was 38 years old and HIV1 positive, severely immunocompromised with a TCD4 lymphocyte count of 138 cells/mm3. He was admitted to the YO University Hospital for fever associated with a progressive deterioration of the general condition. On admission, he showed signs of anemic cardiomyopathy (functional systolic murmur + edema of the lower limbs + severe anemia at 4.7g/dl) and signs of functional renal failure (creatinine=182 micromol/l). Under treatment, the evolution was favorable and he was discharged from the hospital on antiretroviral treatment (ARV). Three months after the start of ARV treatment, the follow-up assessment noted an increase in TCD4 lymphocytes to 300 cells/mm3 and the skin examination revealed Kaposi's lesions on the thigh. With specific treatment, the evolution was favorable. Conclusion: Early detection and management of HIV infection can prevent some serious manifestations of immune restoration syndrome, such as Kaposi's disease.

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage human immunodeficiency virus (HIV) infection who have commenced antiretroviral treatments (ART). Virtually any opportunistic pathogen can provoke this type of immune restoration disorder. In this review, we focus on recent developments in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the prediction and diagnosis of cryptococcal meningitis IRIS (CM-IRIS). We assess current therapeutic regimens and novel treatment approaches to combat CM-IRIS. We discuss the utility of biomarkers for clinical monitoring and adjusting treatment modalities in acquired immunodeficiency syndrome (AIDS) patients co-infected with Cryptococcus who have initiated ART.

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage HIV infection who commenced antiretroviral treatments. Virtually, any opportunistic pathogen can provoke this type of immune restoration disorders. In this review, we focus on recent development in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the diagnosis of cryptococcal meningitis IRIS. We assess the utility of these biomarkers to identify putative host-based targets, which may justify a clinical need for improvement in monitoring a patient’s laboratory results and adjusting treatment modalities in AIDS patients co-infected with Cryptococcus.

Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.

Descriptive account of 18 adults with known HIV infection hospitalised with SARS-CoV-2 infection

ObjectiveTo report on the clinical characteristics and outcome of 18 people living with HIV (PLWH) hospitalised with SARS-CoV-2 infection in a London teaching hospital.MethodsThe hospital notes of 18 PLWH hospitalised with SARS-CoV-2 infection were retrospectively reviewed alongside data concerning their HIV demographics from an established HIV Database.ResultsThe majority (16/18) had positive PCR swabs for SARS-CoV-2, and two had negative swabs but typical COVID-19 imaging and history. Most were male (14/18, 78%), median age 63 years (range 47–77 years). Two-thirds were migrants, nine (50%) of Black, Asian and minority ethnicity (BAME). All were diagnosed with HIV for many years (range 8–31 years), and all had an undetectable HIV viral load (<40 copies/mL). The median CD4 prior to admission was 439 (IQR 239–651), and 10/16 (63%) had a CD4 nadir below 200 cells/mm3. Almost all (17/18) had been diagnosed with at least one comorbidity associated with SARS-CoV-2 prior to admission. 3/18 patients died. None received mechanical ventilation. Hospital stay and clinical course did not appear prolonged (median 9 days).ConclusionsOur data suggest that PLWH may not necessarily have prolonged or complex admissions to hospital when compared with the general hospital and national population admitted with COVID-19. Many had low nadir CD4 counts and potentially impaired functional immune restoration. The PLWH group was younger than generally reported for COVID-19, and the majority were male with multiple complex comorbidities. These patients had frequent contact with hospital settings increasing potential for nosocomial acquisition and increased risk of severe COVID-19.