Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With HIV.

Due to the increased burden of non-AIDS-related comorbidities in people living with HIV (PLHIV), identifying biomarkers and mechanisms underlying premature aging and the risk of developing age-related comorbidities is a priority. Evidence suggests that the plasma proteome is an accurate source for measuring biological age and predicting age-related clinical outcomes. To investigate whether PLHIV on antiretroviral therapy (ART) exhibit a premature aging phenotype, we profiled the plasma proteome of two independent cohorts of virally suppressed PLHIV (200HIV and 2000HIV) and one cohort of people without HIV (200FG) using O-link technology.

Innate Immune Cell Functions Contribute to Spontaneous HIV Control.

Purpose Of Review: To review the role of innate immune cells in shaping the viral reservoir and maintenance of long-term viral control of spontaneous Elite and Viremic HIV controllers.

Recent Findings: HIV controllers exhibit a smaller and transcriptionally suppressed viral reservoir. Different studies report that early responses from innate cells play a pivotal role in this reservoir configuration.

Mental health and its consequences in people living with HIV: A network approach.

Objectives: Psychiatric symptoms occur frequently in people living with human immunodeficiency virus (PLWH), which may affect quality of life, sexual risk behavior, and adherence to antiretroviral therapy (ART). Data from large cohorts are limited, and symptoms are often analyzed in isolation. Therefore, we applied a network analysis to assess the interrelatedness of mental health indicators in a large cohort of PLWH.

Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study.

Background: Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.

Methods: We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort.

Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study.

Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics.

Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands.

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens.

Identification of drug candidates targeting monocyte reprogramming in people living with HIV.

Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers.

Methods: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study.

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV.

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease.

Evaluation and optimization of the syndromic management of female genital tract infections in Nairobi, Kenya.

Background: Genital tract infections pose a public health concern. In many low-middle-income countries, symptom-based algorithms guide treatment decisions. Advantages notwithstanding, this strategy has important limitations.

Longitudinal proteomic profiling of the inflammatory response in dengue patients.

Background: The immunopathogenesis of dengue virus (DENV) infection remains incompletely understood. To increase our understanding of inflammatory response in non-severe dengue, we assessed longitudinal changes in the inflammatory proteome in patients with an acute DENV infection.

Methods: Using a multiplex proximity extension assay (PEA), we measured relative levels of 368 inflammatory markers in plasma samples from hospitalized patients with non-severe DENV infection in the acute (n = 43) and convalescence (n = 35) phase of the infection and samples of healthy controls (n = 10).

Targeted proteomics identifies circulating biomarkers associated with active COVID-19 and post-COVID-19.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the highly infectious Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is an urgent need for biomarkers that will help in better stratification of patients and contribute to personalized treatments. We performed targeted proteomics using the Olink platform and systematically investigated protein concentrations in 350 hospitalized COVID-19 patients, 186 post-COVID-19 individuals, and 61 healthy individuals from 3 independent cohorts.

Hyperresponsive Platelets and a Reduced Platelet Granule Release Capacity Are Associated with Severity and Mortality in COVID-19 Patients.

Background:  Coronavirus disease 2019 (COVID-19) is often associated with mild thrombocytopenia and increased platelet reactivity.

Objective:  The aim of the current study was to investigate the adenosine triphosphate (ATP) release kinetics of platelets in hospitalized SARS-CoV-2-infected patients.

Methods:  We studied time-dependent platelet activation in whole blood by monitoring the ATP release kinetics upon stimulation with a PAR1 receptor agonist in 41 hospitalized critically ill COVID-19 patients, 47 hospitalized noncritically ill COVID-19 patients, and 30 healthy controls.

Targeted plasma proteomics reveals upregulation of distinct inflammatory pathways in people living with HIV.

Despite antiretroviral therapy (ART), people living with HIV (PLHIV) display persistent inflammation leading to non-AIDS-related co-morbidities. To better understand underlying mechanisms, we compared targeted plasma inflammatory protein concentration (n = 92) between a cohort of 192 virally suppressed PLHIV, who were followed-up for five years, and 416 healthy controls (HC). Findings were validated in an independent cohort of 649 virally suppressed PLHIV and 98 HC.

Non-AIDS Events in Individuals With Spontaneous Control of HIV-1: A Systematic Review.

Background: Despite antiretroviral therapy (ART), people living with HIV (PLHIV) are at increased risk for non-AIDS-defining events (nADEs), including cardiovascular events, non-AIDS malignances, hepatic disease, and bacterial pneumonia.

Setting: This systematic review seeks to answer the question: are PLHIV who spontaneously control HIV-1 subject to an increased risk of various nADEs relative to noncontrolling PLHIV on ART and people without HIV?

Methods: Databases were searched on June 9, 2021 with a search syntax focused on the elements "HIV," "spontaneous control," and "clinical outcomes": Embase.com (includes Embase and Medline), Medline Ovid (includes PubMed), Cochrane library, Web of Science, and Google Scholar.

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells.

CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess determinants of CCR5 expression. This cross-sectional study included 209 PLHIV and 323 controls.

Comprehensive phenotyping of circulating immune cell subsets in people living with HIV.

Systemic chronic inflammation and immune dysfunction are recognized as drivers of the development of non-AIDS related comorbidities (NARCs) in people living with HIV (PLHIV). In order to lower the risk of NARCs, it is critical to elucidate what is the contribution of alterations in the composition and function of circulating immune cells to NARCs-related pathogenesis. Findings from previous immunophenotyping studies in PLHIV are highly heterogeneous and it is not fully understood to what extent phenotypic changes on immune cells play a role in the dysregulated inflammatory response observed.

Effectiveness of a group intervention to reduce sexual transmission risk behavior among MSM living with HIV: a non-randomized controlled pilot study.

With an annual incidence of about 1.5 million new infections, HIV is an ongoing public health concern. Sexual transmission risk behavior (STRB) is a main driver of the HIV epidemic in most Western countries, particularly among specific populations such as men who have sex with men (MSM).

Gut microbiome-mediated metabolism effects on immunity in rural and urban African populations.

The human gut microbiota is increasingly recognized as an important factor in modulating innate and adaptive immunity through release of ligands and metabolites that translocate into circulation. Urbanizing African populations harbor large intestinal diversity due to a range of lifestyles, providing the necessary variation to gauge immunomodulatory factors. Here, we uncover a gradient of intestinal microbial compositions from rural through urban Tanzanian, towards European samples, manifested both in relative abundance and genomic variation observed in stool metagenomics.