Plasma anti-CD4 IgG levels are associated with poor immune recovery in people with HIV initiating antiretroviral therapy.

A segment of people with HIV on effective antiretroviral therapy (ART) continue to experience poor immune recovery, leaving them at heightened risk of non-AIDS-defining events (NAEs). The production of anti-CD4 IgG autoreactive antibodies is suggested as one contributing mechanism to these complications. Here, we found that plasma anti-CD4 levels do not discriminate immunological responders from nonresponders nor predict the occurrence of NAEs, suggesting it is unlikely a contributing immunopathological factor associated with these complications.

A Transcriptional Signature of Induced Neurons Differentiates Virologically Suppressed People Living With HIV from People Without HIV.

Neurocognitive impairment is a prevalent and important co-morbidity in virologically suppressed people living with HIV (PLWH), yet the underlying mechanisms remain elusive and treatments lacking. Here, we explored for the first time, use of participant-derived directly induced neurons (iNs) to model neuronal biology and injury in PLWH. iNs retain age- and disease-related features of the donors, providing unique opportunities to reveal novel aspects of neurological disorders.

Alterations in circulating immunoregulatory proteins discriminate poor CD4 T lymphocyte trajectories in people with HIV on suppressive antiretroviral therapy.

Unlabelled: Despite the success in the management of HIV with antiretroviral therapy (ART), people with HIV (PWH) have a heightened state of immune activation and inflammation, and an estimated 10%-40% demonstrate poor CD4 T-cell reconstitution, thereby increasing their mortality and morbidity risk burden. Soluble immunoregulatory proteins that function in lymphocyte activation or inhibition are elevated in PWH and associate with T-cell dysfunction, HIV persistence, and are predictive of comorbid outcomes. Here, we measured a panel of 35 circulating immunoregulatory proteins in 116 PWH with variations in CD4 T-cell counts (poor CD4 trajectory: <200 cells/μl, = 34 or immune competent: CD4 >500 cells/μl, = 82) by Luminex.

Integrated epigenomic exposure signature discovery.

The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis. Here we developed and implemented a machine learning algorithm, the exposure signature discovery algorithm (ESDA), to identify the most important features present in multiple epigenomic and transcriptomic datasets to produce an integrated exposure signature (ES).

Machine learning models based on fluid immunoproteins that predict non-AIDS adverse events in people with HIV.

Despite the success of antiretroviral therapy (ART), individuals with HIV remain at risk for experiencing non-AIDS adverse events (NAEs), including cardiovascular complications and malignancy. Several surrogate immune biomarkers in blood have shown predictive value in predicting NAEs; however, composite panels generated using machine learning may provide a more accurate advancement for monitoring and discriminating NAEs. In a nested case-control study, we aimed to develop machine learning models to discriminate cases (experienced an event) and matched controls using demographic and clinical characteristics alongside 49 plasma immunoproteins measured prior to and post-ART initiation.

Circulating plasma-derived extracellular vesicles expressing bone and kidney markers are associated with neurocognitive impairment in people living with HIV.

Background: Although effective antiretroviral therapy (ART) has improved the life expectancy of people with HIV (PWH), the prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) persist, and it is associated with systemic and neuro-inflammatory processes that could impact other organ systems. However, the complex signaling mechanisms between the bone-kidney systems and the brain in HAND remain unknown. Extracellular vesicles (EVs) play a potential role in inter-organ communication and are involved in regulating cell activity in distant tissues.

Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.

Objective: Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored.

Design: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n  = 15), ART-naive ( n  = 15), and adolescents without HIV (AWOH; n  = 10)] and Myanmar [AWH on ART ( n  = 54) and AWOH ( n  = 22)] were studied.

Multiplex Analysis of Cytokines and Chemokines in Persons Aging With or Without HIV.

People with HIV (PWH) on combination antiretroviral therapy (cART) are living longer lives due to modern cART advances and increased routine medical care. The full landscape of aging with HIV is unclear; given that HIV emerged relatively recently in human history and initially had a high mortality rate, there has not been a substantially aged population to evaluate. In this study, we set out to perform high-throughput plasma analyte profiling by multiplex analysis, focusing on various T helper (Th)-related cytokines, chemokines, and proinflammatory and anti-inflammatory cytokines.

Plasma extracellular vesicles and cell-free mitochondrial DNA are associated with cognitive dysfunction in treated older adults with HIV.

Extracellular vesicles (EVs) are nanoparticles with a role in intercellular communication. Cell-free mitochondrial DNA (cf-mtDNA) has been associated with cognitive dysfunction in people with HIV (PWH). We conducted a nested case-control study to test the hypothesis that plasma EVs are associated with cf-mtDNA and cognitive dysfunction in older PWH.

Multiplex analysis of cytokines and chemokines in persons aging with or without HIV.

People with HIV (PWH) on combined antiretroviral therapy (cART) are living longer lives due to modern cART advances and increased routine medical care. The full landscape of aging with HIV is unclear; given that HIV emerged relatively recently in human history and initially had a high mortality rate, there has not been a substantially aged population to evaluate. In the present study, we set out to perform high throughput plasma analyte profiling by multiplex analysis, focusing on various T helper (Th)-related cytokines, chemokines, and pro- and anti-inflammatory cytokines.

Circulating brain-derived extracellular vesicles expressing neuroinflammatory markers are associated with HIV-related neurocognitive impairment.

Background: Neurocognitive impairment remains prevalent in people with HIV (PWH) despite long term virological suppression by antiretroviral therapy (ART) regimens. Systemic and neuro-inflammatory processes are suggested to contribute to the complex pathology leading to cognitive impairment in this population, yet the underlying mechanisms remain unresolved. Extracellular vesicles (EVs) play a central role in intracellular communication and have emerged as key modulators of immunological and inflammatory responses.

A machine learning approach utilizing DNA methylation as an accurate classifier of COVID-19 disease severity.

Since the onset of the COVID-19 pandemic, increasing cases with variable outcomes continue globally because of variants and despite vaccines and therapies. There is a need to identify at-risk individuals early that would benefit from timely medical interventions. DNA methylation provides an opportunity to identify an epigenetic signature of individuals at increased risk.

Mucosal-homing natural killer cells are associated with aging in persons living with HIV.

Natural killer (NK) cells are critical modulators of HIV transmission and disease. Recent evidence suggests a loss of NK cell cytotoxicity during aging, yet analysis of NK cell biology and aging in people with HIV (PWH) is lacking. Herein, we perform comprehensive analyses of people aging with and without HIV to determine age-related NK phenotypic changes.

Plasma CD16 Extracellular Vesicles Associate with Carotid Artery Intima-Media Thickness in HIV Adults on Combination Antiretroviral Therapy.

HIV-infected individuals have increased risk for cardiovascular disease (CVD) despite suppressive antiretroviral therapy (ART). This is likely a result of persistent immune activation and systemic inflammation. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and may drive inflammation contributing to CVD.

Emerging Insights on Caspases in COVID-19 Pathogenesis, Sequelae, and Directed Therapies.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a significant global health emergency with new variants in some cases evading current therapies and approved vaccines. COVID-19 presents with a broad spectrum of acute and long-term manifestations. Severe COVID-19 is characterized by dysregulated cytokine release profile, dysfunctional immune responses, and hypercoagulation with a high risk of progression to multi-organ failure and death.

Correction: Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation.

[This corrects the article DOI: 10.1371/journal.pone.

Plasma anti-CD4 IgG is associated with brain abnormalities in people with HIV on antiretroviral therapy.

Anti-CD4 IgG autoantibodies have been implicated in CD4 T cell reconstitution failure, leaving people with HIV (PWH) at heightened risk of HIV-associated comorbidities, such as neurocognitive impairment. Seventeen PWH on stable anti-retroviral therapy (ART) and 10 HIV seronegative controls had plasma anti-CD4 IgG antibodies measured by enzyme-linked immunosorbent assay. Neuropsychological (NP) tests assessed cognitive performance, and brain volumes were measured by structural magnetic resonance imaging.

Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer.

Liver cancer presents divergent clinical behaviors. There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis, especially since tRNA-derived small RNAs (tsRNA) have rarely been studied. In this study, a random forests (RF) diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation (IV).

Short Communication: Carotid Artery Plaque Burden in HIV Is Associated with Soluble Mediators and Monocytes.

Maximum carotid plaque thickness (MCPT) measures the largest plaque thickness in the carotid artery and reflects atherosclerosis plaque burden. MCPT may be a better predictor of cardiovascular disease than carotid artery intima-media thickness (cIMT) because it identifies potential unstable arterial atherosclerosis plaques. We assessed the relationships of monocyte and T cell populations and plasma soluble mediators with MCPT measures.

Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation.

Background: Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated with HIV immune dysregulation.

Methods: PLWH ≥40 years old and on stable ART ≥3 months were enrolled (N = 149).