Profiling serum immunodominance following SARS-CoV-2 primary and breakthrough infection reveals distinct variant-specific epitope usage and immune imprinting.

Over the course of the COVID-19 pandemic, variants have emerged with increased mutations and immune evasive capabilities. This has led to breakthrough infections (BTI) in vaccinated individuals, with a large proportion of the neutralizing antibody response targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike glycoprotein. Immune imprinting, where prior exposure of the immune system to an antigen can influence the response to subsequent exposures, and its role in a population with heterogenous exposure histories has important implications in future vaccine design.

Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications.

Objective: Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose.

Methods: We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021.

Cerebral function parameters in people with HIV switching integrase inhibitors: a randomized controlled trial.

Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH). PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt neuropsychiatric symptoms were randomly allocated on a 1:2 basis to remain on raltegravir or switch to dolutegravir 50 mg once daily for 120 days.

Dolutegravir-based Antiretroviral Therapy for Patients Coinfected With Tuberculosis and Human Immunodeficiency Virus: A Multicenter, Noncomparative, Open-label, Randomized Trial.

Background: The concurrent treatment of tuberculosis and human immunodeficiency virus (HIV) is challenging, owing to drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir (DTG) were assessed in adults with HIV and drug-susceptible tuberculosis.

Methods: International Study of Patients with HIV on Rifampicin ING is a noncomparative, active-control, randomized, open-label study in HIV-1-infected antiretroviral therapy-naive adults (CD4+ ≥50 cells/mm3).

Tryptophan metabolism and its relationship with central nervous system toxicity in people living with HIV switching from efavirenz to dolutegravir.

The mechanisms underlying central nervous system (CNS) toxicities in antiretroviral-treated persons living with HIV (PLWH) remain elusive. We investigated the associations between markers of tryptophan metabolism and measurements of CNS toxicity in PLWH. In a prospective study, virologically suppressed PLWH receiving efavirenz-containing antiretroviral regimens with ongoing CNS toxicity were switched to dolutegravir-containing regimens and followed up for 12 weeks.

Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection.

The human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques.

Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals.

Objective: Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals.

A case of idiopathic colonic varices.

Colonic varices, usually detected by means of colonoscopy, are extremely rare and typically indicative of portal hypertension or chronic hepatopathology. Even more rare are those cases with no underlying disease, or idiopathic colonic varices. The authors report a case of these unexplained varices found during colonoscopy of a 30-year-old man with a 10-year history of diarrhea and occasional bloody stool.