Search Results (2,079)

Background: Human polyomavirus JC (JCV) causes progressive multifocal leukoencephalopathy (PML), a deadly brain demyelinating illness stemming from oligodendrocyte lytic infection in immunocompromised patients, especially those with untreated HIV infection. Methods: We conducted a case series report on patients with HIV/AIDS who presented progressive multifocal leukoencephalopathy and were hospitalized at the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi, northeastern Romania, to emphasize the comorbidities of HIV/AIDS cases. Hospital medical data from 10 January 2025 to 30 September 2025 served as the basis for this investigation. Results: We examined three cases that presented neurological symptoms (ataxia, aphasia, language comprehension, and expression disorders). The cases were evaluated imagistically via nuclear magnetic resonance, and we conducted a polymerase chain reaction test on the spinal fluid to confirm the presence of JCV. It was necessary to take a multidisciplinary approach with a neurologist or pneumologist. All cases were evaluated immunologically, revealing low Ly T CD4 levels and increased HIV viremia levels. Progressive multifocal leukoencephalopathy is an AIDS-defining disease, manifesting in immunocompromised patients, including late presenter cases, and patients who are non-adherent to their antiretroviral treatment. Therefore, it is important to test every patient who has mild to severe neurological symptoms for HIV. Furthermore, some cases require a multidisciplinary approach to ensure a better quality of life. Conclusions: Treating a patient with HIV requires a multidisciplinary strategy that includes a neurology specialist and access to antiretroviral treatment. To boost ART uptake, we must identify and remove barriers that impact patients and the healthcare system. Full article

We present the single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMC) from individuals during acute HIV-1 infection caused by viral strains circulating in Russia and the Former Soviet Union (FSU) countries. Using 10x Genomics single-cell RNA sequencing (scRNA-seq) on the Illumina NextSeq 550 platform, we have analyzed scRNA-seq data from three treatment-naive patients (viral load > 1 × 10⁶ copies/mL, estimated infection duration ≤ 4 weeks) and three healthy donors. Data integration (Seurat, Harmony), automated cell-type annotation (CellTypist), and GeneOntology (GO) enrichment analysis for highly expressed and low-expressed genes revealed a profound reorganization of transcriptional programs across key immune populations, including memory CD4⁺ and CD8⁺ T cells, non-classical monocytes and natural killer cells (NK-cells). We observed signatures of hyperactivation of pro-inflammatory pathways (NF-kB, TNF, and type I/II interferon signaling), upregulation of genes associated with cellular migration (CXCR4, CCR7) and metabolic adaptation (oxidative phosphorylation components), alongside a mixed pro- and anti-apoptotic expression profile. Notably, our data pointed to a pronounced dysregulation of the TGF-β and mTOR signaling cascades, disrupted intercellular communication networks—particularly between cytotoxic cells and their regulators—altered expression of genes implicated in disease progression (OLR1, SERPINB2, COPS9) and viral persistence control (NEAT1, NAF1). This work provides an initial single-cell transcriptional atlas characterizing early immune responses to HIV-1 sub-subtypes A6 and CRF63_02A6, the predominant drivers of the HIV epidemic across the FSU region. Full article

Background/Objectives: The study primarily examined whether an IoT-based medication assistance system enhances ART adherence relative to standard care, and secondarily evaluated device feasibility and error patterns over time. Methods: This prospective study was conducted between June 2022 and October 2023 at a tertiary hospital in South Korea. Adults (≥19 years) living with HIV and prescribed ART were included; those with comorbid hepatitis B or C were excluded. People living with HIV who agreed to use the IoT-based InPHRPILL system (Sofnet Inc., Seoul, Republic of Korea) were assigned to the intervention group, whereas those who declined were assigned to the control group. Viral suppression, CD4⁺ cell counts, and adherence rates were measured. Additional analyses evaluated 12-month longitudinal adherence using pill-count data in both groups, and device-measured adherence and device-associated error rates in the intervention group. Results: Thirty-five participants (12 in the intervention group and 23 in the control group) were included. The intervention group demonstrated marginally shorter durations since HIV diagnosis and ART initiation at study enrollment, as well as slightly higher baseline HIV-RNA levels; however, these differences did not reach statistical significance. The median pill-counting and IoT device adherence rates were 100% and 87.4%, respectively (median deviation error rate = 4.4%). Poisson regression revealed significantly reduced error rates over time (β = −0.06493, p < 0.01), suggesting improved device use proficiency. Conclusions: IoT-based medication assistance systems may provide objective, real-time monitoring of ART adherence and facilitate identification of discrepancies between clinical evaluations and actual adherence patterns. Larger studies targeting individuals with suboptimal adherence are warranted to determine whether such systems can enhance adherence outcomes. Full article

The development of next-generation HIV-1 therapeutics, including ultralong-acting antivirals, novel mechanistic classes, and curative immunotherapies, promises to overcome the limitations of lifelong, daily antiretroviral therapy (ART). However, the real-world efficacy of these treatments depends on the complex epidemiological landscapes in which they are used. In South America, HIV-1 epidemics intersect hyperendemic arboviruses, including dengue, Zika, chikungunya, and yellow fever, and regionally isolated pathogens, such as mammarenaviruses. These co-infections cause profound episodic immune activation and organ dysfunction that alter drug pharmacokinetics, disrupting healthcare access and adherence. These factors can compromise ART efficacy, promote resistance, and influence latent reservoir dynamics. This review synthesizes clinical and translational evidence of this intersection. We evaluate how emergent agents, such as capsid inhibitors (lenacapavir), long-acting injectables (cabotegravir/rilpivirine), maturation inhibitors (GSK3640254), and broadly neutralizing antibodies (bNAbs), perform in the context of co-endemic viral challenges. Specifically, we argue that therapeutic development must become “co-infection-aware” to progress toward a cure and achieve durable HIV-1 control. We provide a translational roadmap that explicitly incorporates co-infection endpoints into clinical trials, develops preclinical models that better reflect real-world viral exposures, and prioritizes implementation strategies that remain effective in the case of recurrent outbreaks. Integrating regional viral ecology into HIV-1 therapeutic research is therefore a necessary step toward developing interventions that are durable and effective on a global scale. Full article

Hemostasis and thrombosis reflect a delicate balance, regulated by the interplay between procoagulant and anticoagulant mechanisms. Hemophilia is traditionally viewed as a bleeding disorder, but emerging evidence highlights the paradoxical risks of thrombosis in hemophilia patients. We explore the landscape of hemophilia management, emphasizing challenges of balancing hemostasis in the context of aging, novel non-factor replacement therapies (NRTs), and comorbidity-driven thrombotic complications. Therapeutic approaches, including innovative NRTs, such as emicizumab, or rebalancing agents (e.g., concizumab, marstacimab, fitusiran), offer promising advancements in bleeding prophylaxis but may increase thrombotic risks. Conversely, novel anticoagulants, such as FXI inhibitors, offer potential thrombosis protection with minimal bleeding risk. Our review examines the impact of aging-related comorbidities, including cardiovascular disease, atrial fibrillation, HIV-associated complications, and acute coronary syndromes, on thrombotic risk in hemophilia patients. Evidence-based strategies for balancing hemostasis and thrombosis are outlined alongside experimental models, thrombin generation assays, and advancements in rebalancing coagulation through natural anticoagulant modulation. FXI inhibition emerges as a paradigm shift in thrombosis management, offering reduced bleeding risks while preserving vascular health. Finally, this review highlights the need for global laboratory assays to personalize treatments, emphasizing strategies to optimize safety and efficacy, particularly as hemophilia patients live longer with complex comorbidity profiles. Full article

Tuberculosis (TB) rarely occurs in isolation; most people with TB experience multiple coexisting conditions, including HIV, diabetes, undernutrition, depression, and substance use disorders, which worsen disease severity and compromise treatment outcomes. Although the World Health Organization has issued disease-specific guidance for managing key comorbidities, TB care remains largely siloed and poorly equipped to address the growing burden of multimorbidity, particularly in African health systems. In this perspective article, we propose a phased framework for multimorbidity-centered TB care. The first phase emphasizes systematic screening for common comorbidities and establishment of basic referral pathways. The second phase focuses on strengthening coordination between TB programs and existing health and social services, including task sharing and longitudinal follow-up. The third phase advances toward fully integrated, co-located, multidisciplinary models of care that embed TB services within broader multimorbidity platforms. Together, this framework offers a pragmatic roadmap for TB programs to deliver more person-centered, equitable, and efficient care, strengthen primary care systems, and accelerate progress toward ending TB as a public health threat in Africa. Full article

The use of antiretroviral therapy (ART) as the only effective way to control human immunodeficiency virus (HIV) infection results in HIV drug resistance. Next-generation sequencing (NGS) has become a common method for identifying drug-resistant variants and reducing analysis costs. The aim of this study was to develop an NGS-based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using NGS. HIV-1 drug resistance analysis was conducted using the Stanford University HIVdb database. CXCR4 cell tropism was predicted using an empirical rule classifier. A protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. High levels of resistance were observed to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced patients and to NNRTIs in treatment-naïve patients. Low levels of resistance were observed to protease and integrase strand transfer inhibitors (INSTIs). CXCR4 cell tropism was extremely rare. NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS-based protocols allows for performing ART efficiency and tropism monitoring at scale. Full article

Human immunodeficiency virus (HIV) infection remains a major global health burden. Untreated HIV infection leads to CD4⁺ T-cell depletion and severe immune dysfunction, resulting in opportunistic infections, neoplastic changes, and death. Highly active antiretroviral therapy (HAART) is currently the standard treatment for HIV infection, but it cannot eliminate latent reservoirs. Post-translational modifications (PTMs) regulate protein trafficking, function, and degradation, and their in-depth investigation plays a crucial role in identifying novel biomarkers and therapeutic targets. PTMs exert a central regulatory role in HIV infection by both enhancing host restriction factors and contributing to latent infection. This dual role offers novel insights into potential therapeutic targets for activating latent viruses to make them visible to the immune system. This review highlights numerous PTMs associated with HIV infection, including acetylation, phosphorylation, palmitoylation, etc., and assesses their potential for curing HIV infection. Full article

HIV neuroinvasion results in neuronal dysregulation and compromised neurocognition. Neuroplasticity measures, such as HIV cognitive rehabilitation, have shown potential for partially reversing cognitive deficits after HIV invasion. Previous functional NIRS (fNIRS) studies have demonstrated that customized attention brain training (ABT) has the potential to alter brain activity in adolescent HIV. Nonetheless, the effects of ABT on brain functional connectivity in adolescent HIV remain unclear. This study investigated behavioral and functional connectivity changes in adolescent HIV amongst participants (n = 26) receiving 12 weeks of ABT compared to treatment-as-usual (TAU) controls. Twenty-six adolescents living with HIV were recruited and randomly assigned to either the ABT group (n = 13) or the TAU group (n = 13). Participants completed NEPSY-II and fNIRS measures before and after the training. Functional connectivity (FC) measures were evaluated using seed-based correlation analysis, located in the central executive network (CEN) and across the hemispheres. No significant behavioral differences were noted on the NEPSY-II and BRIEF scores; however, functional connectivity measures indicated that the ABT group exhibited significantly increased FCs in the left hemisphere (p < 0.05) following brain training. Additionally, thresholding analysis indicated that the dorsolateral prefrontal cortex may serve as a potential marker for brain training in adolescent neuro-HIV. Full article

The considerable HIV-1 genetic diversity has several implications for viral adaptive and evolutionary capabilities. Its genetic diversity is due to its high mutational rates derived from the error-prone viral reverse transcriptase activity, which generates highly heterogeneous viral populations. Moreover, genetic diversity can also increase due to intra- or intersubtype viral genomic recombination following multiple infections. This study examines HIV-1 intersubtype recombinant viruses and their increased genomic diversity over a 12-month period in five individuals from São Paulo state, Brazil. We collected peripheral blood mononuclear cells once every three months from selected participants at five distinct visits. Molecular clones of 1.15 Kbp fragments of the Pol polyprotein, spanning the protease and a portion of the reverse transcriptase (RT) genes, were generated by bulk PCR. Pol sequences were used for evolutionary analysis, including phylogenetics (using TnT), genetic diversity (using Highlighter), and hypermutation frequency (using Hypermut). Recombination detection experiments were conducted with a jumping profile-hidden Markov model (jpHMM), SimPlot++, and RDP5. We observed great genetic diversity and frequent recombination events in all patients. Furthermore, most of the patients presented hypermutations. These findings highlight the dynamic nature of HIV-1 genetic diversity, driven by frequent recombination and hypermutation, which can accelerate viral adaptation and diversification, underscoring the challenges for treatment, prevention, and disease control. Full article

Pediatric tuberculosis (TB) remains a critically underrecognized contributor to global childhood morbidity and mortality, with the highest burden concentrated in low-resource settings. Although children comprise a minority of overall TB cases, mortality is disproportionately high, particularly among those under five years of age, driven largely by delayed diagnosis, inadequate linkage to care, and limited access to effective treatment. The continued rise of pediatric multidrug-resistant TB (MDR-TB), especially in regions with low sociodemographic development, further highlights persistent gaps in current control strategies. This review synthesizes key aspects of pediatric TB pathogenesis and host immune responses that predispose young children to rapid disease progression and severe outcomes, including immune immaturity and paucibacillary infection. We summarize pulmonary and extrapulmonary disease manifestations and identify populations at heightened risk, including children with HIV, malnutrition, type 1 diabetes mellitus, and congenital or treatment-related immunosuppression. Ongoing challenges in diagnosis and treatment are discussed, including limitations of existing microbiologic and immunologic tests, specimen collection constraints, regimen toxicity, and barriers to adherence. Prevention remains central to reducing pediatric TB mortality. We highlight the sustained importance of bacille Calmette–Guérin (BCG) vaccination in preventing severe disease and death, the context-dependent variability in vaccine effectiveness, and the structural and socioeconomic determinants of vaccine coverage. We conclude that integrating equitable vaccine delivery, scalable preventive therapy, and child-adapted diagnostic strategies is essential to meaningfully reduce the global pediatric TB burden. Full article

In Spain, Leishmania infantum causes both cutaneous (CL) and visceral leishmaniasis (VL). This study aimed to analyse trends in the clinical presentation, diagnosis, management, and epidemiology of leishmaniasis at Severo Ochoa University Hospital in Leganés, an endemic area in Southern Madrid affected by Europe’s largest outbreak (2009–2015). A retrospective study was conducted, including all confirmed cases from January 1992 to December 2024, using clinical records. Cases were stratified into pre-outbreak, outbreak, and post-outbreak periods. A total of 151 cases were identified, including 129 VL, 21 CL, and 1 simultaneous VL/CL. VL predominated among adults during the HIV epidemic, later shifting to elderly and non-HIV immunosuppressed patients, while paediatric cases remained stable. Diagnostic methods evolved from bone marrow microscopy, culture, and IFAT to molecular and chemiluminescence assays. VL treatment also evolved, with amphotericin B gradually replacing meglumine antimoniate as first-line VL treatment. Most patients required hospitalisation, with 8.5% mortality, mainly among immunocompromised or elderly individuals. A persistent concentration of cases near recently urbanised areas adjacent to the parks of Polvoranca and Bosquesur was observed. Despite advances in diagnosis and therapy, endemic transmission and underreporting continue, highlighting the need for ongoing surveillance and preventive measures. Hospital record review proved useful for monitoring compliance with mandatory VL notification, though its applicability to cutaneous cases remains limited. Full article

Epstein–Barr virus (EBV) is a key oncogenic pathogen implicated in the development of lymphomas, particularly among HIV-positive and immunocompromised individuals. While the association between EBV and lymphoma is well established, the mechanisms underlying progression from infection to malignancy—especially in the head and neck region—remain incompletely understood. This review offers a comprehensive analysis of the pathophysiological pathways by which EBV and HIV contribute to lymphomagenesis, with an emphasis on latency patterns, immune evasion, and epigenetic “hit and run” oncogenesis. Notably, it integrates novel findings on the diagnostic implications of EBV latency proteins, explores HIV-mediated B-cell dysregulation, and evaluates the emerging landscape of targeted therapies, including monoclonal antibodies and lytic cycle inducers. By focusing specifically on head and neck lymphomas, this review underscores a clinically underrepresented domain and offers insights that may guide future diagnostics, surveillance, and treatment strategies in vulnerable patient populations. This review also highlights the pressing need for improved animal models and continued research into EBV-specific therapeutic targets. Full article

The SCANVIR^® project is a regional initiative aimed at accelerating the elimination of hepatitis C virus (HCV) by reaching high-risk populations outside traditional healthcare settings. Launched in 2017 in Limoges and later expanded to Poitiers and Bordeaux, the project organized dedicated screening and treatment days in 43 facilities taking care of intravenous drug users, migrants, and prisoners in Nouvelle-Aquitaine. These events involved multidisciplinary teams and advanced diagnostic tools, including rapid tests for HCV, HBV, and HIV; FibroScan^® for liver assessment; and GeneXpert^® for on-site HCV RNA detection. Patients also received counseling on risk prevention, addiction, psychosocial support, and treatment when needed. Between 2017 and 2024, SCANVIR^® screened 1664 patients, with 98.9% accepting FibroScan^®. Anti-HCV antibodies were detected in 23.4% of participants, among whom 41.5% (N = 162) had a replicative profile. Of these, 83% initiated treatment and 80% were cured or were still undergoing therapy. FibroScan^® assessments showed advanced fibrosis in 17% of patients, severe fibrosis in 7.2%, and severe steatosis in 18%. By promoting a “Test, Treat, Prevent” strategy, SCANVIR^® proved cost-effective in diagnosing and treating individuals distant from care structures, highlighting the value of integrating education and prevention into liver disease screening. SCANVIR^® is an officially registered European trademark. Full article

Background: Pre-exposure prophylaxis (PrEP) offers over 99% protection against HIV when used consistently, but stigma continues to undermine persistence in care. While much research has described the external manifestations of PrEP-related stigma, less is known about how individuals cope with these stigmas and how such coping processes influence persistence. Guided by Social Cognitive Theory, this study examined the psychosocial strategies men who have sex with men (MSM) in Tanzania use to cope with PrEP-related stigma and sustain persistence in care. Methods: Thirty-two in-depth interviews were conducted with purposefully selected MSM aged 18–38 years at Ngamiani Health Centre in Tanga region. The sampling included both persistent and non-persistent PrEP users with variation in age and sexual position preferences. Participants were sampled for variation in persistence status (persistent and non-persistent), age, and sexual position preference to capture heterogeneity in stigma experiences and coping processes. Interviews were conducted in Kiswahili, audio-recorded, transcribed, translated, and analyzed using reflexive thematic analysis. Results: Participants described PrEP-related stigma as socially constructed through narratives that equated PrEP with HIV treatment, labeled it a “gay pill,” associated it with promiscuity, or linked it to bodily harm or increased HIV risk. These stigmas impact persistence in care through discouraging clinic visits and daily pill taking. However, some participants remained persistent in care despite stigma by using protective mental strategies such as personal agency, mental time travel, and affirmation from supportive social connections, which buffered emotional impacts and sustained persistence. Conclusions: Persistence in PrEP care is shaped not only by stigma in the social environment but also by how individuals interpret and respond to it. Interventions should therefore combine structural stigma-reduction efforts with mental health-informed strategies that strengthen agency and supportive social relationships to sustain PrEP engagement among MSM. Full article