Search Results (1,976)

Background: Acute rheumatic fever (ARF) is a clinical syndrome triggered by group A streptococcal (GAS) infections and characterized by fever, carditis, and arthritis as its main manifestations. Diagnosis relies on the revised Jones criteria. We report a rare case of ARF diagnosed in Switzerland. Case Presentation: An 18-year-old woman presented to the emergency department five days after returning from a one-week stay in Egypt with intermittent fever and a transient sore throat, followed by migratory joint pain. Laboratory testing revealed leukocytosis, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Chest X-ray, urine analysis, and (travel-associated) pathogen-testing (Epstein–Barr virus, Cytomegalovirus, human immunodeficiency virus, Malaria, Dengue, Zika, Chikungunya) were unremarkable. Blood cultures remained negative. Initially, a viral respiratory infection was suspected and symptomatic treatment established. Days later the patient was re-evaluated due to persistent symptoms. Leukocyte count (Lc) and CRP further increased and subcutaneous nodules appeared. The antistreptolysin-O (ASO)-titer was elevated more than three times higher than the normal upper limit and proofed serological evidence of a preceding streptococcal infection (GAS throat culture had not been performed). ARF was diagnosed according to the Jones criteria. Treatment with amoxicillin and a high dose of acetylsalicylic acid (ASA) led to a rapid clinical improvement. Secondary prophylaxis with depot penicillin (benzathine penicillin G; 1.2 million units; once monthly) was initiated to prevent rheumatic heart disease. Conclusions: This case highlights a rare occurrence of ARF following travel to Egypt, with probable acquisition of group A streptococcal infection during the trip. It emphasizes consideration of ARF even in Western countries with low ARF-prevalence if clinical history is suggestive. Early recognition and initiation of antimicrobial and anti-inflammatory therapy is crucial to prevent cardiac involvement. To the best of our knowledge, this represents one of the first cases diagnosed in Switzerland in the past 20 years. Full article

Background: Tauopathies are neurodegenerative disorders characterized by the abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau, leading to disrupted neuronal connectivity and progressive brain dysfunction. Despite their clinical relevance, most in vitro models have focused primarily on molecular and cellular aspects, with limited emphasis on alterations in network dynamics and functional connectivity. Methods: We developed an in vitro tauopathy model based on mouse primary neuronal cultures, enabling the investigation of network-level alterations under controlled conditions. We compared three experimental groups: untreated control cultures, cultures exposed to extracellular wild-type tau, and cultures treated with pathological tau (pTau) isolated from the sarkosyl-insoluble fraction of P301S (+/−) transgenic mice. To increase susceptibility to tau-induced pathology, all conditions were additionally transduced with adeno-associated viral vectors encoding human P301L tau. To quantify for damage, spontaneous neuronal activity was monitored throughout network maturation—from day in vitro (DIV) 7 to 16—using fluorescence calcium imaging, and multiple metrics describing network dynamics and functional organization were compared at DIV 12. Results: We observed that exposure to pTau did not induce overt cytotoxicity or major disruptions in global network dynamics, although a mild increase in network bursting activity was observed. Longitudinal analysis of network maturation further revealed largely similar developmental trajectories across experimental groups, with only subtle and persistent differences in bursting-related activity in pTau-treated cultures. Conclusions: We propose that the early developmental stage of the cultures, together with the intrinsic bursting and ongoing synaptic plasticity of primary neuronal networks, masks subtle pathological effects. This may limit the sensitivity of two-dimensional in vitro systems to detect network-level dysfunction, suggesting that more mature or structurally complex models, such as brain organoids, may be required to reveal robust functional deficits. Full article

Residual inflammation remains a hallmark of treated HIV infection despite durable viral suppression. Whether previous SARS-CoV-2 infection is associated with residual inflammation in people living with HIV (PLWH) remains incompletely understood. This study evaluated the association between previous COVID-19 and persistent inflammation in virally suppressed PLWH. In this retrospective observational single-center study, 286 adults receiving antiretroviral therapy between January 2023 and December 2025 were included. Patients were stratified according to documented SARS-CoV-2 infection history. A secondary analysis included 231 individuals with sustained viral suppression (HIV-RNA < 50 copies/mL). Inflammatory biomarkers, immune recovery parameters, metabolic characteristics, and independent predictors of elevated inflammatory biomarker levels were evaluated. Previous SARS-CoV-2 infection was associated with significantly higher concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-α, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (all p < 0.01). Among virally suppressed patients, elevated inflammatory biomarker levels were associated with lower CD4+ T-cell counts, lower CD4/CD8 ratios, obesity, metabolic syndrome, dyslipidemia, and hepatic steatosis. Previous SARS-CoV-2 infection, obesity, metabolic syndrome, and CD4+ T-cell counts < 500 cells/mm³ were independently associated with elevated inflammatory biomarker levels. Previous SARS-CoV-2 infection was independently associated with an unfavorable inflammatory profile in virally suppressed people living with HIV. Given the retrospective observational design, these findings should be interpreted as associations rather than evidence of causality. These findings suggest that long-term host-related and metabolic factors may contribute to residual inflammation beyond viral control and highlight the need for prospective studies investigating strategies to reduce residual immune activation in treated HIV infection. Full article

Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the blood–brain barrier (BBB) are central mechanisms for acute and chronic ischemic and hemorrhagic cerebral events. Understanding these mechanisms is vital to reducing their impact on population health, whether through treatment or prevention of adverse outcomes. The objective of this study is to perform a review of the scientific literature on the post-infection effects of SARS-CoV-2 affecting the cerebral endothelium and the BBB, correlating them with potential clinical outcomes. Material and Methods: Analysis of studies extracted from the PubMed database using the following terms: Long-COVID “AND” SARS-CoV-2 “AND” blood–brain barrier. Inclusion criteria: keywords, publications related to the topic, and primary studies published after peer review. Exclusion criteria: preprint studies, publication outside of the timeframe 2020–2025, study design not compatible with this research, and full text not available. Results: An initial 121 studies were identified, of which 105 were excluded due to not meeting all inclusion criteria and 6 studies were inaccessible due to not being in the English language and full-text access limitations. Fifteen articles were included in the analysis, for topics as expression of viral receptors in the endothelium, markers of their activation, cerebral microvascular injury and coagulopathies. To clarify the pathogenic cascade, the evidence was stratified by biological model where in vitro evidence demonstrates that the Spike protein induces direct endothelial toxicity and platelet aggregation, establishing the primary molecular insult. Animal models confirm the translation of this insult into structural degradation of the BBB and pericyte loss. Clinically, infection-phase findings, characterized by multifocal microthrombosis and permeability spikes, act as the determining event that predisposes to the persistent neuroinflammatory environment. Biomarkers of BBB disruption and neuronal damage were consistently reported, with persistence of BBB dysfunction modifying risk stratification and rehabilitation efforts. Reported cases of Long-COVID demonstrated normalization of BBB markers without correlation with long-term symptoms, suggesting that other mechanisms are involved in Long-COVID. Conclusion: Cerebral endotheliopathies and BBB dysfunction in patients with COVID-19 continue to impact the health of the population. The scientific literature indicates that SARS-CoV-2 induces cerebral endothelial injury, BBB disruption, and an increased risk of vascular events related to endotheliopathy, inflammation, and hypercoagulability. Understanding the impact of COVID-19 pathology on the population and developing prospective studies is essential to quantify the prevalence and mechanisms of brain injury. The identification of molecular targets and infection pathways are promising toward defining both preventive and therapeutic strategies to improve outcomes in the Long-COVID population. Full article

Compelling research has consistently demonstrated a strong relationship between immunometabolism and infectious disease, including the ways in which viral infections alter the metabolic state of immune cells to promote survival. Human immunodeficiency virus (HIV) has been particularly noted for its ability to reprogram the metabolism of cells that contribute to viral persistence. The purpose of this review is to summarize current knowledge of the metabolic state of CD4 T cells and myeloid cells (monocytes/macrophages), two of the primary cell types targeted by HIV. The studies discussed reveal distinct metabolic profiles in both cell types during initial infection, active replication, and latency. In addition, we examine how these metabolic alterations may contribute to the increased frequency and severity of comorbidities observed in people with HIV (PWH). Understanding the impact of HIV infection and latency on immunometabolism may provide deeper insight into long-term viral persistence and support the identification of novel therapeutic targets to reduce chronic inflammation and inform future cure strategies for PWH. Full article

Background and Clinical Significance: Foreign body aspiration is an important cause of morbidity and mortality in children younger than three years of age. Although laryngeal foreign bodies are uncommon, they may be life-threatening and are frequently misdiagnosed because of their variable clinical presentation. Eggshell aspiration is exceptionally rare, with only a few cases reported in the literature. We report a case of delayed diagnosis of a glottic eggshell foreign body in a toddler presenting with persistent upper airway symptoms. Case Presentation: A 16-month-old previously healthy girl was referred to our hospital for evaluation of persistent hoarseness and barking cough following a witnessed choking episode while eating boiled egg. The choking episode had occurred 15 days before presentation during an episode of viral upper respiratory tract infection. Initial symptoms were attributed to laryngitis and persisted despite medical treatment. Flexible laryngoscopy revealed a foreign body impacted at the glottic level, while neck radiography demonstrated a radiopaque calcified lesion corresponding to the foreign body. Microlaryngoscopy under deep sedation was performed, and an approximately 10-mm eggshell fragment was successfully removed. A small amount of granulation tissue was observed at the posterior commissure, corresponding to the site of foreign body impaction. The postoperative course was uneventful, and repeat endoscopic examination on postoperative day three demonstrated satisfactory laryngeal healing with regression of the granulation tissue. Conclusions: This case highlights the importance of considering a retained laryngeal foreign body in young children with persistent hoarseness or barking cough following a choking episode, even in the presence of concomitant respiratory infection. Early endoscopic evaluation is essential to avoid diagnostic delay and facilitate prompt treatment. In addition, this report emphasizes the importance of food choking prevention and caregiver education in children younger than three years of age. Full article

HIV-associated neurocognitive disorders (HAND) persist despite effective antiretroviral therapy, indicating that chronic neuroimmune dysfunction extends beyond active viral replication. Among HIV-1-derived factors, the viral proteins Tat and gp120 are contributors to sustained brain inflammation. Nevertheless, their comparative impact in genetically vulnerable neural environments remains unclear. Here, we performed a secondary transcriptomic analysis of publicly available RNA-seq data derived from the striatal tissue of hSNCA^A53T Gba1^+/L444P mice, a model combining α-synuclein overexpression with Gba1-associated lysosomal impairment, following unilateral intrastriatal injection of Tat or gp120. Both proteins induced robust transcriptional remodelling selectively in the injected striatum. Tat primarily elicited a broad inflammatory amplification programme encompassing innate immune sensing, chemokine recruitment, adaptive immune engagement, and loss of homeostatic support. gp120 preferentially activated antigen presentation, complement, oxidative stress, and lysosomal–phagocytic effector pathways consistent with immune-mediated synaptic stress. Despite these distinct profiles, Tat and gp120 converged on a shared microglia-centred effector core. Contralateral striatal tissue was analyzed as distal non-injected tissue to explore the spatial distribution of transcriptional responses and minimal and protein-specific effects were reported. These findings provide a mechanistic framework for HAND heterogeneity and suggest that HIV protein-driven neuroimmune transcriptional programmes may create a molecular environment compatible with increased neurodegenerative vulnerability in lysosome-compromised, α-synuclein-sensitized brains. Full article

Background/Objectives: Patients with diabetes face increased risks during viral respiratory infections. While chronic glycemic control (HbA1c) is a known risk factor, it may fail to capture acute metabolic failure. This study aimed to evaluate the stress hyperglycemia ratio (SHR) at two time points (admission and 72 h) as a prognostic marker. Methods: We conducted a longitudinal analysis of 430 patients (211 with diabetes and 219 without diabetes) hospitalized with viral respiratory infections. The SHR was calculated at admission (SHR_z1) and at 72 h (SHR_z3). The primary outcome was severe clinical deterioration (defined as oxygen requirement >2–HFNO/OTI or mortality). Multivariate logistic regression and ROC curve analysis were used to determine independent predictors and clinical cut-off points. Results: In the global multivariable model (N = 430), continuous SHR_z3 emerged as an independent predictor of severe outcome (OR = 1.86, 95% CI 1.09–3.20, p = 0.0240) alongside chronic glycemic control (HbA1c: OR = 1.41, p < 0.0001) and age (OR = 1.05, p = 0.0001). After stratification, the independent SHR_z3 effect attenuated below statistical significance in both the non-diabetic (p = 0.6168) and diabetic (p = 0.1954) sub-cohorts, while HbA1c (p = 0.0404) and age (p = 0.0036) remained independent predictors within the diabetic subgroup. An exploratory longitudinal phenotype model classifying patients into Stable Normal, Resolvers, Persistent, and Late Spikers showed the highest in-sample discrimination of all models tested (AUC = 0.797, 95% CI 0.756–0.834). Within this model, the Persistent phenotype (SHR ≥ 1.1 sustained at admission and at 72 h) showed a non-significant trend toward higher adjusted odds of severe outcome compared with Stable Normal patients (OR = 1.81, 95% CI 0.91–3.60, p = 0.088) and was associated with a significantly longer hospital stay (Kruskal–Wallis p = 0.004 across phenotypes). Conclusions: Persistent stress hyperglycemia at 72 h is an independent predictor of severe outcome in the unstratified cohort after adjustment for chronic glycemic control, age, and other covariates. Within metabolic strata, the SHR_z3 signal attenuates, and long-standing suboptimal glycemic control (HbA1c) and age dominate, particularly among diabetic patients. Longitudinal SHR trajectories may therefore provide complementary, hypothesis-generating prognostic information when combined with chronic baseline markers, although these findings require external validation in independent cohorts before clinical use. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an idiopathic, multisystem disorder marked by debilitating fatigue, post-exertional malaise, cognitive dysfunction and neuroinflammation. Its etiology remains unclear, yet emerging evidence implicates a complex interplay between immune dysregulation, metabolic impairment, mitochondrial bioenergetics, and environmental stressors such as viral infection or low-dose ionizing radiation (LDIR). To develop treatments for ME/CFS, it is essential to identify suitable targets for therapy. In this narrative review, we discuss recent findings on the overlap of ME/CFS with LDIR effects and examine potential mechanistic links that may arise from LDIR-induced bystander effects (RIBEs). We highlight potential candidate biomarkers that bridge these domains: mitochondrial respiratory dysfunction, altered ornithine transport via SLC25A15 (ORNT1), possible roles of CD38 in the context of immunity and NAD+ depletion, cyclin D1–dependent metabolic reprogramming and modulation of gene expression, and α-synuclein as a potential neuroinflammatory damage-associated molecular pattern (DAMP). While the involvement of these biomarkers in ME/CFS is yet to be confirmed experimentally, evidence from in vitro studies of irradiated cells, exosome profiling, and patient samples suggests that RIBEs can, in theory, produce prominent cellular ME/CFS phenotypes through associated mechanisms, including those exhibiting oxidative stress, impaired ATP production, and immune modulation. We propose a hypothetical, exploratory model wherein LDIR initiates or contributes to adaptive metabolic shifts (including CD38 upregulation and cyclin D1 stabilization) that, coupled with persistent bystander signaling, could potentially culminate in chronic fatigue and neurocognitive symptoms in some reported ME/CFS cases. Finally, we outline a research agenda encompassing the establishment of standardized diagnostic criteria, multi-omics profiling of patient cohorts, exosome analysis, functional mitochondrial assays, and targeted therapeutic trials focusing on possible anti-CD38 antibodies and NAD+ precursor therapy. By integrating recent findings in low-dose radiation biology with ME/CFS pathophysiology, this review aims to promote interdisciplinary investigations that may uncover mechanistic insights and novel biomarkers for diagnosis and treatment of ME/CFS. We further review steps in a proposed model taking us from low-dose radiation exposure to a number of possible targets. Full article

Chronic chikungunya arthritis is a debilitating post-viral inflammatory arthritis with no established evidence-based therapy. Regulatory T cell (Treg) dysfunction may contribute to persistent inflammation, and low-dose interleukin-2 (IL-2) may restore immune regulation. We evaluated the immunomodulatory effects of low-dose IL-2 using peripheral blood mononuclear cells from adults with laboratory-confirmed chronic chikungunya arthritis in Atlántico, Colombia. Cells were treated ex vivo with recombinant IL-2 or an IL-2/anti-IL-2 monoclonal antibody complex in the presence of CD2/CD3/CD28 stimulation beads, followed by flow cytometric assessment of effector T cells and Tregs. Low-dose IL-2 treatments ex vivo did not increase total Treg frequency but selectively increased activated suppressor Tregs while decreasing activated T effector cells, enhancing Treg CTLA-4 and HLA-DR expression, and reducing Ki67 expression in effector T cells. IL-2 complex treatment decreased cytokine-secreting Tregs, and IL-10 and TGF-β were not associated with IL-2 treatment status or with Teff/Treg balance, suggesting limited utility as pharmacodynamic biomarkers of low-dose IL-2 treatments. These findings support the use of activated suppressor Tregs, Treg CTLA-4, and HLA-DR expression as candidate biologic endpoints for evaluation in future trials of low-dose IL-2 in chikungunya arthritis. Full article

Mechanisms for the maintenance of chronic viruses are poorly understood, particularly for archaeal viruses. Here, we identify the product of Sulfolobus spindle-shaped virus 1 (SSV1) ORF a291 as a putative virally encoded toxin required for growth inhibition but dispensable for viral replication and virion production. Viruses lacking ORF a291 replicated their genomes and formed morphologically normal spindle-shaped particles, yet failed to inhibit the growth of uninfected Saccharolobus solfataricus. Substitution of residues at a predicted N-terminal signal peptide cleavage site abolished growth suppression without affecting replication, suggesting that secretion is essential for toxin function. Despite primary sequence divergence among fusellovirus toxin candidates, analysis of protein structure predictions revealed a conserved hydrolase-like fold across SSV1, SSV9 and SSV10 toxins. These findings demonstrate functional separation of viral replication and host growth suppression and support a model in which chronic archaeal viruses modulate host competition through antagonistic factors. This work expands the known diversity of putative viral toxins and suggests that fuselloviruses employ conserved strategies to promote persistence in extreme environments. Full article

Cryo-electron tomography (Cryo-ET) has emerged as a transformative tool for visualizing viral components within their native cellular environment, enabling structural interrogation of viral life cycle events at nanometer resolution without chemical fixation or heavy metal staining. However, a persistent challenge in applying Cryo-ET to virus research is the unambiguous identification of specific viral components within densely crowded tomographic volumes. Electron density encodes mass and shape but not molecular identity, and as the cellular environment grows more complex, the assumption that a given density has no plausible alternative assignment becomes increasingly difficult to defend. This review surveys labeling and localization strategies for in situ Cryo-ET of viral components, encompassing label-free exploitation of native electron density, Cryo-immunogold labeling, genetically encoded and synthetic molecular tags, and correlative Cryo-light/electron microscopy (Cryo-CLEM) combined with Cryo-focused ion beam (Cryo-FIB) milling. We first summarize the landmark structural discoveries that in situ Cryo-ET has delivered across virus families, and then evaluate each labeling strategy against the structural and functional constraints that viral proteins impose, providing a practical framework for matching a labeling approach to a specific viral component and life-cycle stage. Full article

Patients with multiple myeloma (MM) exhibit profound immune dysregulation, predisposing them to severe outcomes following SARS-CoV-2 infection. Current evidence highlights shared immunopathological mechanisms linking MM and COVID-19, with particular emphasis on the interleukin-6 (IL-6) axis as a shared amplifier of inflammation rather than the sole driver of disease. MM is characterized by a baseline pro-inflammatory milieu, in part mediated by IL-6, which is further amplified during SARS-CoV-2 infection, resulting in cytokine escalation, complement activation, coagulopathy, and multi-organ injury. This amplification operates within a broader, redundant network that also includes T-cell exhaustion, NK-cell dysfunction, checkpoint signaling, complement and endothelial injury, and treatment-induced immune defects. This overlap provides a mechanistic basis for the disproportionately high morbidity and mortality observed in this population. Even with advancements in vaccination, antiviral therapy, and clinical practice, patients with MM who exhibit impaired vaccine responses, active disease, or treatment-related immune dysfunction continue to experience considerable vulnerability to COVID-19. In addition, MM patients demonstrate suboptimal vaccine-induced immune responses, contributing to persistent vulnerability to severe and breakthrough infections. Modern MM therapies, including anti-CD38 antibodies, BCMA-directed agents, and bispecific T-cell redirecting antibodies, further reshape antiviral immunity by reducing NK cells, inducing plasma cell aplasia, causing hypogammaglobulinemia, and impairing T-cell function. Emerging treatment approaches targeting this shared pathway have been explored, with a focus on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). EVs exhibit multimodal properties, including suppression of pro-inflammatory cytokines, restoration of immune homeostasis, inhibition of viral entry, and promotion of tissue repair and regeneration. Early clinical experience in severe COVID-19 populations suggests a favorable short-term safety profile; reported efficacy, however, derives from small, largely uncontrolled or early-phase studies, and the single randomized trial reporting a mortality benefit did so only in an exploratory post hoc subgroup, with its pre-specified primary endpoint not met. Overall, EVs constitute a biologically plausible but as yet unproven adjunctive strategy that warrants further investigation. Critically, no MM patient has ever been enrolled in an EV trial; current rationale for EV use in MM is therefore extrapolated entirely from non-MM populations, and no MM-specific data exist. Difficulties such as EV heterogeneity, manufacturing variability, uncertain pharmacokinetics, limited targeting efficiency, and potential prothrombotic effects must be resolved before their application in MM-specific clinical settings. Full article

Despite significant biomedical advances in the prevention of mother-to-child transmission (MTCT) of HIV, residual transmission and suboptimal maternal outcomes persist across Europe. The challenge is no longer primarily virological but structural: aggregated ART coverage indicators mask important discontinuities across the perinatal care pathway. This scoping review maps evidence on clinical and psychosocial dimensions of the perinatal HIV pathway among adult women living with HIV (WLHIV) in Europe, and identifies key gaps in their integration across the continuum of care. Following PRISMA-ScR guidelines, five databases were searched for studies published between 2010 and 2026. Of 1881 records identified, 109 met inclusion criteria. Findings were synthesized thematically using an inductively developed framework spanning preconception through long-term postpartum outcomes. MTCT rates declined from approximately 1–1.2% in the mid-2000s to below 0.5% in recent data, and vaginal delivery rates increased markedly with sustained viral suppression. However, persistent inequalities remain among younger women, migrants, and those with histories of injecting drug use. Stigma, migration-related vulnerability, mental health difficulties, constrained disclosure, and socioeconomic insecurity shape engagement with care, influencing treatment continuity, retention, and virological outcomes, particularly during the postpartum period. Equitable perinatal HIV outcomes require integrated care models that combine clinical HIV and obstetric services with mental health support, social needs screening, and migration-sensitive services to address the structural conditions shaping care trajectories. A substantial proportion of WLHIV in Europe originate from high-prevalence regions, making perinatal HIV in this context a direct interface between global infectious disease burden and migration health. Addressing care in European settings therefore contributes to broader global health equity goals in HIV elimination. The protocol was pre-registered on Open Science Framework with registration number: 10.17605/OSF.IO/9BZGY. Full article

Hepatitis B virus (HBV) infection remains a major driver of liver-related morbidity and mortality among people living with HIV (PLWH), yet vaccine-induced protection is frequently suboptimal. HIV-associated immune dysfunction, including CD4⁺ T-cell depletion, altered antigen presentation, impaired T follicular helper cell support, and B-cell dysregulation, reduces seroprotection after standard recombinant HBV vaccines and may limit durability of antibody responses. Vaccine response is further influenced by HIV viral suppression, age, comorbidities, prior vaccine history, and baseline HBV serologic status, including isolated hepatitis B core antibody (anti-HBc) and occult HBV infection (OBI) considerations. Although antiretroviral therapy (ART) improves vaccine responsiveness, many PLWH fail to achieve protective hepatitis B surface antibody (anti-HBs) titers (≥10 mIU/mL) after conventional schedules, or experience antibody waning over time. Current guidelines recommend HBV vaccination for all susceptible PLWH with post-vaccination serologic testing and revaccination for nonresponders. Persistent implementation barriers, including incomplete series, vaccine hesitancy, stigma, and logistical constraints, continue to limit real-world impact. Emerging clinical trial data support CpG-adjuvanted HBV vaccines (HepB-CpG/Heplisav-B) and intensified dosing and schedules (double-dose or four-dose regimens) to improve seroprotection and generate higher peak anti-HBs titers, which may enhance durability. This review synthesizes guideline recommendations, immunologic mechanisms of hyporesponsiveness, predictors of vaccine response, and practical strategies to optimize HBV vaccination in PLWH. Full article