Tuberculosis-immune reconstitution inflammatory syndrome

Abstract Tuberculosis-immune reconstitution inflammatory syndrome is an excessive immune response against Mycobacterium tuberculosis that may occur in either HIV-infected or uninfected patients, during or after completion of anti-TB therapy. In HIV-infected patients it occurs after initiation of antiretroviral therapy independently from an effective suppression of HIV viremia. There are two forms of IRIS: paradoxical or unmasking. Paradoxical IRIS is characterized by recurrent, new, or worsening symptoms of a treated case. Unmasking IRIS is an antiretroviral-associated inflammatory manifestation of a subclinical infection with a hastened presentation. The pathogenesis is incompletely understood and the epidemiology partially described. No specific tests can establish or rule out the diagnosis. Treatment is based on the use of anti-tuberculosis drugs sometime with adjunctive corticosteroids. Mortality is generally low

Low plasmatic concentration of intensified antiretroviral therapy in a pregnant woman: a case report

Identifying the most appropriate antiretroviral regimen for pregnant women with Human Immunodeficiency Virus (HIV-1) infection can be challenging, mainly due to pregnancy-related physiological alterations which can significantly reduce maternal drug plasma concentration. We would like to report our experience as it consists of an unusual case of low plasmatic concentration of antiretroviral drugs despite regimen intensification in a HIV-positive pregnant woman. It also underlines the need for accurate monitoring and treatment adjustment in pregnant women with Human Immunodeficiency Virus (HIV)

Performance of alere determine HIV-1/2 Ag/Ab combo rapid test for acute HIV infection: A case report | Performance del test rapido Alere Determine HIV-1/2 Ag/Ab Combo nell?infezione acuta da HIV: Un caso clinic

We describe a case of symptomatic acute HIV infection in a young man where a fourth-generation rapid screening test combining HIV-specific antibody and p24 antigen was negative. In highly suspicious cases of acute HIV infection, plasma HIV RNA assays together with conventional, non-rapid screening tests should be used

Relationship between vertebral fractures, bone mineral density, and osteometabolic profile in HIV and Hepatitis B and C-infected patients treated with ART

Objective: The purpose of our study was to evaluate the alterations of bone metabolism and the prevalence of vertebral fractures in the population with HIV and hepatitis B and C seropositivity in treatment with antiretroviral drugs (HAART). Methods: We selected 83 patients with diagnosis of HIV, HBV, HCV infection. In all these patients biochemical examinations of phospho-calcium metabolism and a densitometry of lumbar spine were performed. We also evaluated lateral spine X-rays in order to analyze the presence of vertebral deformities and to define their severity. As a control group we analyzed the prevalence of vertebral fractures in a group of 40 non-infectious patients. Results: We selected 82 seropositive patients, 46 males and 37 females, with a median age of 55 \ub1 10 years. Out of these patients, 55 were infected by HIV, 12 were infected by HBV, 11 presented HIV and HCV co-infection and 4 were HCV+. The prevalence of hypovitaminosis D in the studied population was 53%, while the prevalence of osteoporosis and osteopenia was 14 and 48%, respectively. The average T-score in the fractured population was -1.9 SD. The viral load and the CD4+ cell count were respectively, directly, and inversely correlated with the number and severity of vertebral fractures. Antiretroviral therapy regimen containing TDF and PI was a significant determinant of the presence of vertebral deformities. The use of these drugs was also associated with lower levels of vitamin D and higher bone turnover levels compared to other antiretroviral drugs. Conclusions: HIV patients suffer from bone fragility, particularly at spine, independently by the level of bone mineral density. In this population, the T-score threshold for the risk of fracture is higher than that usually used in general population. For this reason, it would be indicated to perform an X-ray of the spine in order to detect vertebral deformities even in patients with a normal or slighlty reduced bone mineral density

HIV-1-Associated Neurocognitive Disorders: Is HLA-C Binding Stability to β2-Microglobulin a Missing Piece of the Pathogenetic Puzzle?

AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND) are complications of HIV-1 infection. Viral infections are risk factors for the development of neurodegenerative disorders. Aging is associated with low-grade inflammation in the brain, i.e., the inflammaging. The molecular mechanisms linking immunosenescence, inflammaging and the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease, are largely unknown. ADC and HAND share some pathological features with AD and may offer some hints on the relationship between viral infections, neuroinflammation, and neurodegeneration. β2-microglobulin (β2m) is an important pro-aging factor that interferes with neurogenesis and worsens cognitive functions. Several studies published in the 80–90s reported high levels of β2m in the cerebrospinal fluid of patients with ADC. High levels of β2m have also been detected in AD. Inflammatory diseases in elderly people are associated with polymorphisms of the MHC-I locus encoding HLA molecules that, by associating with β2m, contribute to cellular immunity. We recently reported that HLA-C, no longer associated with β2m, is incorporated into HIV-1 virions, determining an increase in viral infectivity. We also documented the presence of HLA-C variants more or less stably linked to β2m. These observations led us to hypothesize that some variants of HLA-C, in the presence of viral infections, could determine a greater release and accumulation of β2m, which in turn, may be involved in triggering and/or sustaining neuroinflammation. ADC is the most severe form of HAND. To explore the role of HLA-C in ADC pathogenesis, we analyzed the frequency of HLA-C variants with unstable binding to β2m in a group of patients with ADC. We found a higher frequency of unstable HLA-C alleles in ADC patients, and none of them was harboring stable HLA-C alleles in homozygosis. Our data suggest that the role of HLA-C variants in ADC/HAND pathogenesis deserves further studies. If confirmed in a larger number of samples, this finding may have practical implication for a personalized medicine approach and for developing new therapies to prevent HAND. The exploration of HLA-C variants as risk factors for AD and other neurodegenerative disorders may be a promising field of study

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants

Tuberculosis-immune reconstitution inflammatory syndrome

AbstractTuberculosis-immune reconstitution inflammatory syndrome is an excessive immune response against Mycobacterium tuberculosis that may occur in either HIV-infected or uninfected patients, during or after completion of anti-TB therapy. In HIV-infected patients it occurs after initiation of antiretroviral therapy independently from an effective suppression of HIV viremia. There are two forms of IRIS: paradoxical or unmasking. Paradoxical IRIS is characterized by recurrent, new, or worsening symptoms of a treated case. Unmasking IRIS is an antiretroviral-associated inflammatory manifestation of a subclinical infection with a hastened presentation. The pathogenesis is incompletely understood and the epidemiology partially described. No specific tests can establish or rule out the diagnosis. Treatment is based on the use of anti-tuberculosis drugs sometime with adjunctive corticosteroids. Mortality is generally low

Antiretroviral therapy-associated diseases are common in the long-term

No abstract available

A 58-year-old man with B-cell chronic lymphocytic leukemia and multiple strokes

A 58-year-old male with B-cell chronic lymphocytic leukemia presented with fever, chest pain, and acute-onset neurological deficits suggestive of multiple strokes (A). Brain autopsy revealed softening areas in the brain parenchyma (B, C) corresponding to extensive necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F) necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F)

A reduced dose of darunavir/ritonavir is effective in PI-experienced HIV-infected patients

Darunavir (DRV) is an HIV-1 protease inhibitor that is used together with a low boosting dose of ritonavir as part of an antiretroviral therapy (ART) regimen in treatment-experienced and naïve HIVpositive patients. In naïve and experienced patients with no DRV-mutations, DRV is licensed at the dose of 800 mg plus 100 mg of ritonavir once daily. We report our results in seven ART-experienced HIV-infected patients, in whom a reduced dose of darunavir/ritonavir (600/100 mg once daily) successfully controlled viral replicatio