Search Results (251)

Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the factors that influence the generation of CRISPR/Cas9-generated repair edits, the overall profiles, and outcome prediction(s), as well as the analytical tools that have been developed to date. Finally, how this technology has been used towards a functional HIV-1 cure is discussed. Full article

Background: Messenger RNA (mRNA) vaccines have emerged as a versatile platform beyond SARS-CoV-2, with expanding applications in infectious diseases and oncology. However, comprehensive evidence synthesis of non-SARS-CoV-2 mRNA vaccines remains limited. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261323500). MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, and WHO ICTRP were systematically searched for studies published between 1 January 2000 and 28 February 2026. Eligible studies included phase I–III clinical trials and in vivo preclinical studies evaluating non-SARS-CoV-2 mRNA vaccines. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2, ROBINS-I, and SYRCLE tools. Findings were synthesized narratively because of substantial heterogeneity. Results: A total of 40 studies met the eligibility criteria and were included in the review, comprising 20 clinical studies and 20 preclinical studies. Advanced clinical programs targeted influenza and respiratory syncytial virus (RSV), with phase III trials displaying seroconversion rates above 70% with good safety profiles. Preliminary phase I studies for HIV, cytomegalovirus, rabies, and personalized cancer mRNA vaccines showed promising humoral and cellular immune responses. Preclinical studies showed strong antibody and T-cell responses against malaria, tuberculosis, Group B Streptococcus, and Zika virus. Most adverse events were mild to moderate, while serious vaccine-related adverse events were uncommon. Conclusions: Non-SARS-CoV-2 mRNA vaccines demonstrate substantial translational potential across infectious disease and oncology applications. Although the vaccine candidates have demonstrated promising immunogenicity and safety, most are in the early stages of development. This highlights the need for large trials, long-term safety follow-up and better global representation. Full article

Human papillomavirus (HPV) infection is a major driver of anogenital disease and virus-related carcinogenesis. Although most infections resolve spontaneously, persistent infection with high-risk genotypes may progress to high-grade squamous intraepithelial lesions (HSILs) and cancer, particularly in the setting of impaired immune surveillance. Unlike previous HPV-related reviews focused primarily on cervical disease, vaccination, or isolated immunosuppressed populations, this narrative review comparatively examines the clinical expression, colposcopic findings, screening strategies, and therapeutic implications of HPV-related disease across the immunological spectrum. This narrative review provides an integrative synthesis of HPV-related disease in the female lower genital tract across the immunological spectrum. A structured, non-systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted using terms related to “human papillomavirus”, “HPV”, “cervical intraepithelial neoplasia”, “colposcopy”, “immunosuppression”, “HIV”, and “vaccination”. Immunosuppressed populations, including individuals living with HIV, transplant recipients, and patients receiving immunosuppressive therapy, exhibit higher rates of persistent infection, multifocal disease, recurrence, and progression to HSIL and invasive malignancy. These patients also present greater diagnostic complexity, broader anatomical involvement, and reduced response to conventional treatment. Rather than representing a uniform condition, HPV-related disease reflects a biologically dynamic spectrum shaped by host immune competence. This review highlights the distinct clinical, colposcopic, and therapeutic challenges observed in immunosuppressed populations and reinforces the need for individualized, risk-adapted strategies integrating contemporary advances in screening, vaccination, and HPV-related disease management. Full article

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction is increasingly recognized as a key contributor to a broad spectrum of human diseases beyond classical cystic fibrosis (CF). CFTR is a cAMP-regulated chloride and bicarbonate ion channel expressed in both epithelial and non-epithelial tissues, where it regulates ion homeostasis, mucosal hydration, and cellular signaling. Both inherited CFTR mutations and acquired dysfunction resulting from environmental or inflammatory factors can disrupt these physiological processes and drive disease progression. Current evidence linking CFTR dysregulation to respiratory diseases, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), asthma, and HIV-associated airway disease, as well as cardiovascular, renal, neurological diseases, and cancer, is comprehensively discussed. Mechanistically, impaired CFTR function promotes oxidative stress, chronic inflammation, epithelial barrier dysfunction, altered mucociliary clearance, and dysregulation of signaling pathways, including NF-κB, TGF-β, PI3K/Akt, MAPK, and Wnt/β-catenin. In the context of HIV infection and cigarette smoke exposure, CFTR suppression is mediated in part by TGF-β signaling and miRNA-dependent mechanisms, resulting in compromised airway defense and increased susceptibility to pulmonary complications. Recent studies further demonstrate that CFTR dysregulation alters the expression of genes involved in fibrosis, inflammation, angiogenesis, and epithelial–mesenchymal transition (EMT). Notably, CFTR may act as either a tumor suppressor or a context-dependent oncogene, depending on tissue type and signaling milieu, highlighting its complex role in cancer biology. Advances in CFTR-targeted therapies, including potentiators, correctors, gene therapy, and combination approaches, have markedly improved outcomes in CF and may offer therapeutic potential for diseases associated with acquired CFTR dysfunction. We summarize the systemic consequences of CFTR dysregulation and the need for further mechanistic and translational research to clarify its role across diverse human diseases. Full article

Background: Concomitant HIV/HBV infection results in worse health outcomes, with HBV reactivations being observed in immunocompromised individuals. However, data on HBV infection in people with advanced HIV disease (AHD) remains sparse in Botswana. We aimed to determine the prevalence and molecular characteristics of HBV in people living with HIV (PLHIV) with CD4+ T-cell counts ≤100 cells/µL in Botswana. Methods: Plasma samples (n = 1097) of PLHIV with CD4+ T-cell count ≤100 cells/uL collected between 2014 and 2016 were screened for hepatitis B surface antigen (HBsAg) and HBV core antibodies (anti-HBc). A 415bp region of the HBV surface gene was amplified and sequenced using Sanger sequencing. Genotypic and mutational analysis was performed using Geno2pheno. Adjusted prevalence ratios (aPRs) were estimated from a modified Poisson regression model to explore factors associated with HBV infection. p-values < 0.05 indicated statistical significance. Results: The median age was 37 years (IQR: 32–43), and 565/1097 (51.5%) were male. HBsAg prevalence was 10.6% (95%CI: 8.8–12.5%) and anti-HBc prevalence was 50.0% (95%CI:46.9–52.9%). Factors associated with HBV infection were male sex [aPR: 1.6 (p < 0.01)] and those that were ART-experienced [aPR: 1.43 (p = 0.04). Eighteen samples were successfully genotyped. The prevalence of genotype A was (12/18, 66.7%) and D (6/18, 33.3%). Sixty-three mutations were identified as associated with drug resistance and immune and diagnostic escape. Highly prevalent immune escape mutations in the surface region were S207N (12/63, 19%) and A194V (9/63, 14.3%). V163I (12/63, 19%) and M129L (12/63, 19%) were highly prevalent in the reverse transcriptase region. Two classical lamivudine-associated drug resistance mutations were observed, each occurring in one participant (L180M and V173L). Conclusions: The prevalence of HBV in people with AHD is high, highlighting the importance of HBV screening and HIV/HBV co-management in this population. Full article

This perspective outlines the ongoing necessity for an HIV vaccine and immune-based prevention strategies in an era of availability of multiple behavioral and pharmacological HIV prevention interventions, including safe and highly effective pre-exposure prophylaxis (PrEP). We describe the approach of the National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS (DAIDS), based on key scientific progress, critical steps, and persistent challenges in achieving broad and durable immune protection against HIV. We highlight DAIDS coordinated infrastructure, clinical trial networks, and partnerships that enable iterative development and de-risk innovation for these interventions. Finally, we consider implications for trial design and priorities for advancing scalable HIV immune-based prevention. Full article

Background: Immunosuppressed women are at increased risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2–3) after excisional treatment, yet long-term comparative data remain limited. Previous studies are often small and heterogeneous, and they rarely compare outcomes directly with immunocompetent populations. This study evaluated the long-term incidence, timing and associated factors of CIN 2–3 recurrence after large loop excision of the transformation zone (LLETZ), stratified by immune status. Methods: We conducted a retrospective cohort study including 283 women treated with LLETZ for CIN 2–3 between 1996 and 2016 at Bellvitge University Hospital in Barcelona, Spain. Of these, 41 were immunosuppressed and 242 immunocompetent. Clinical, histopathological, virological, and immunological variables were extracted from hospital and pathology registries. Kaplan–Meier estimates and Cox proportional hazards models adjusted for immunosuppression status were used to evaluate time-to-recurrence and factors associated with recurrence. Results: At 36 months post-treatment, the probability of residual/recurrent CIN 2–3 was 44% in immunosuppressed women versus 5% in immunocompetent women (HR = 10.42, 95% CI 4.70–23.08, p < 0.001). Recurrence appeared earlier in immunosuppressed women (median 7 vs. 13 months). Persistent high-risk HPV infection at first follow-up (HR = 23.6, 95% CI 5.44–102, p < 0.001) and positive surgical margins (HR = 3.88, 95% CI 1.45–10.3, p = 0.007) were among the factors most strongly associated with recurrence, and advanced immunodeficiency (CD4+ < 200 cells/mm³ or detectable HIV viral load) was associated with earlier recurrences, though this association was not maintained after accounting for immunosuppression status in Cox models. Conclusions: Immunosuppressed women are at significantly higher and earlier risk of residual/recurrent CIN 2–3 after LLETZ. These findings support a risk-adapted, multidisciplinary follow-up integrating gynecologic, infectious disease, and immunologic care. Tailored surveillance and perioperative HPV vaccination may enhance secondary prevention in this high-risk population. Full article

Inflammatory bowel diseases (IBDs) are diseases of chronic inflammation and intestinal epithelial cell (IEC) death that affect an estimated 7 million people worldwide. Intestinal barrier restoration is the most important determinant of remission in IBD, yet there are very few existing therapies that protect IECs from damage or support epithelial repair. The goal of this study was to develop a model system and tools that can be used to identify therapeutics that promote IEC survival in IBD. We developed a Beclin-1 cleavage reporter (BICR) that detects calpain-mediated Beclin-1 cleavage and the switch from autophagy to programmed cell death. We modified BICR with the HIV Tat peptide (BICR-Tat) and tested it in a model of live bacterial stress using commensal E. coli and IEC. BICR sensitively and specifically detected calpain activity in cell-free assays, and BICR-Tat successfully detected Beclin-1 cleavage and autophagy failure in IEC. Achieving IEC survival in the microbe-challenged IBD gut would be an important advance toward intestinal barrier restoration in this intractable disease. The BICR-Tat reporter coupled with the model of microbial stress developed in this study could enable high-throughput screening approaches to identify therapeutics with the potential to achieve barrier healing and sustained remission in IBD. Full article

Advances in antiretroviral therapy have transformed infection with HIV into a manageable chronic disease, increasing the survival of people living with HIV, who are also undergoing a demographic aging process marked by the emergence of non-communicable chronic diseases. This study aims to map and analyze how the scientific literature addresses the organization and integration of care in the HIV-NCD syndemic, identifying implications for nursing and for health systems. This is a Rapid Scoping Review, using the databases PubMed, Scopus, CINAHL, and LILACS. Data synthesis was conducted using Microsoft Excel. The research was structured using the PCC framework: Population—people living with HIV (≥18 years); Concept—organization and integration of care in the HIV-NCD syndemic, including care models, care coordination, service integration, and the role of nursing; and Context—health services and systems. Twenty-three studies were included, most of which used qualitative methodology, were conducted in sub-Saharan Africa, and had predominantly female samples. This study demonstrated that the organization of care in the HIV-NCD syndemic remains predominantly characterized by fragmented models, which are insufficient to address the complexity of multimorbidity. Integrated care models emerge as a promising strategy; however, their effects remain limited in settings marked by health inequalities. Full article

Background: Advanced cirrhosis induces profound CD4⁺ T-cell depletion through splenic sequestration and immune dysregulation. Pneumocystis jirovecii pneumonia risk thresholds remain undefined in non-HIV immunocompromised populations, necessitating investigation in cirrhotic patients. Objectives: To investigate the potential association between peripheral CD4⁺ T-cell counts and opportunistic infections (OI)—specifically Pneumocystis jirovecii (PJ)—in hospitalized patients with liver disease, and to characterize clinical outcomes across immunological risk strata. Methods: We retrospectively analyzed 455 adults hospitalized in a single institution with hepatic disorders. CD4⁺ T-cell counts were available in 227/455 patients. Among these, 22 patients met predefined immunological risk criteria (CD4⁺ < 500/µL and/or HIV positivity) and were classified into three immunological risk clusters (IRCs): IRC-A (HIV−, CD4⁺ < 200/µL; n = 9), IRC-B (HIV+, CD4⁺ < 200/µL; n = 7), and IRC-C (HIV−, CD4⁺ 200–499/µL; n = 6). PJ PCR testing was evaluated when available. Results: Among 455 patients, in-hospital mortality was 103/455 (22.6%). Of the 22 immunologically at risk patients, 15/22 had cirrhosis. PJ PCR was performed in 8/22 patients (IRC-A: 2; IRC-B: 4; IRC-C: 2), with 3/8 positive (37.5%): IRC-A (1/2), IRC-B (1/4), IRC-C (1/2). Ct values ranged from 27.0 to 31.7. Two PJ-PCR–positive cirrhotic patients (IRC-A: n = 1; IRC-C: n = 1) survived without specific anti-PJ therapy; one HIV-positive patient (IRC-B) received trimethoprim-sulfamethoxazole and survived. In-hospital mortality was 5/9 (55.6%) in IRC-A, 2/7 (28.6%) in IRC-B, and 3/6 (50.0%) in IRC-C; none of the deaths were attributable to PJ pneumonia. Conclusions: Severe CD4⁺ T-cell depletion (<200/µL) was common among cirrhotic patients and associated with PJ detection (3/8 tested), but not with PJ-related mortality (0/3). Mortality was primarily driven by hepatic decompensation and bacterial infections. CD4⁺ assessment may improve risk stratification in cirrhosis; however, prospective, multicenter studies are warranted to validate these findings and to evaluate CD4-guided strategies for the prevention of opportunistic infections. Full article

Mpox is a rare but potentially serious vaccine-preventable disease. The 2022 United States outbreak disproportionately impacted gay, bisexual, and other men who have sex with men, people living with HIV, and people of transgender experience. Early vaccination efforts revealed substantial racial and geographic inequities, with lower uptake among Black and Hispanic cisgender men, transgender women, and residents of rural areas. To address these challenges, Fairview’s Minnesota Immunization Networking Initiative (MINI), a 20-year-old mobile health collaborative, partnered with state and local public health agencies and community-based organizations to expand mpox vaccine access. With support from governmental outbreak response funding and stockpiled vaccine, mobile clinics were deployed in trusted community settings, including Pride events and recurring community sites. Targeted outreach, education, and coordination with local providers supported stigma reduction and second-dose series completion. Program data were collected from October 2022 through December 2024. MINI hosted 125 community-based mpox vaccination events, administered 2259 doses to individuals from 220 cities across the United States, including 195 cities in the Midwest. Pride events were key entry points for first-dose vaccination, particularly in rural areas; urban non-Pride clinics played a complementary role in facilitating second-dose completion. Program-level vaccination-to-case ratios were highest among populations experiencing disproportionate mpox burden, including Black, Hispanic, and American Indian/Alaska Native male participants, suggesting alignment of preventive resources with community need. MINI’s mobile, partnership-driven approach demonstrates the value of pairing large-scale community events with recurring clinics to address barriers to both vaccine access and series completion. These findings underscore the importance of flexible, community-centered infrastructure in advancing health equity and strengthening outbreak preparedness. Full article

The human virome, comprising eukaryotic viruses, bacteriophages, and viral genetic material, is a dynamic component of the microbiome with growing relevance in infectious diseases. This narrative review is structured to: (i) summarize the general composition of the human virome and methodological challenges, including the fraction of unclassified viral “dark matter”; (ii) describe virome alterations in chronic infections; and (iii) explore site-specific virome dynamics across respiratory, intestinal, and genito-urinary tracts in both chronic and acute infections. In chronic viral infections such as HIV, HBV, HCV, and HPV, a recurrent feature is the expansion of Anelloviridae—particularly torque teno virus—reflecting impaired immune surveillance rather than direct pathogenicity, suggesting their potential as surrogate biomarkers of immune competence. Evidence on virome changes in chronic bacterial and parasitic infections remains limited, highlighting a critical knowledge gap. Acute infections are associated with compartment-specific shifts in eukaryotic viruses and bacteriophage communities, often paralleling changes in bacterial populations and inflammatory responses, with implications for disease severity. Despite advances in metagenomic approaches, a substantial proportion of viral sequences remains unclassified, limiting functional interpretation. Nevertheless, virome profiling provides an ecosystem-level perspective, offering insights beyond single-pathogen detection and supporting emerging applications in diagnostics, immune monitoring, prognosis, and infectious disease surveillance. Full article

Syphilitic panuveitis is a severe and diagnostically highly challenging manifestation of ocular syphilis. Its predominant posterior-segment involvement and its tendency to mimic noninfectious or viral uveitis may delay etiologic recognition and increase the risk of permanent vision loss. Rhegmatogenous retinal detachment (RRD) is a rare but vision-threatening complication that likely reflects advanced, inflammation-induced disruption of the vitreoretinal interface. A narrative literature review was conducted using the PubMed, Scopus, and Web of Science databases (January 2000 to 10 September 2025). Studies addressing the clinical presentation, imaging findings, pathophysiology, and management of syphilitic panuveitis and associated rhegmatogenous retinal detachment were analyzed. Infectious mimickers were also presented, with particular emphasis on West Nile virus (WNV). Evidence was synthesized qualitatively. Posterior uveitis and panuveitis are one of the most common ocular manifestations of syphilis. Posterior segment involvement in ocular syphilis is frequently bilateral, typically presenting with dense vitritis, retinal vasculitis, and optic neuropathy. RRD is a rare presenting complication, most often developing in areas of prior inflammatory retinitis and arising due to retinal necrosis, persistent vitreoretinal traction, and early proliferative vitreoretinopathy, which increases surgical complexity and may limit functional recovery. HIV coinfection often modifies disease severity. In relevant endemic or seasonal settings, WNV-associated ocular inflammation represents an important diagnostic pitfall. Syphilitic panuveitis should be considered early in patients presenting with unexplained posterior uveitis or panuveitis. Routine testing for syphilis and HIV in the uveitic laboratory palette, together with targeted evaluation for infectious mimickers, is essential to reduce diagnostic delay and avoid inappropriate immunosuppression. RRD should be recognized as a marker of advanced, inflammation-induced vitreoretinal interface damage requiring timely antimicrobial therapy and early involvement of vitreoretinal surgery. Full article

Cryptococcal meningitis occurs in 62% of persons with HIV-associated meningitis, making Cryptococcus an important cause of meningitis among adults with advanced HIV disease in regions with elevated prevalence of HIV. Despite efforts to advance treatment, the in-hospital death rate of 19% remains unprecedentedly high. Aggregate published clinical trial data evaluating cryptococcosis treatment with survival as the primary endpoint show a significant reduction in the proportion of survivors from diagnosis to 88.5% at 2 weeks of treatment and further to 74% survival at 10 weeks of follow-up (p = 0.001). Disease complications concomitant with unveiling symptoms and reoccurrence of fungal infections, deferment in treatment, and high prevalence of other comorbidities increase the risk of individuals succumbing to cryptococcal meningitis. Among clinical trials of cryptococcal meningitis, the World Health Organization-recommended standard of care was used to randomize participants to the control trial arm. The proportion of participants surviving in the trial was not statistically different between trial randomization arms. In summary, high in-hospital death rates and continued participants’ deterioration post-hospital discharge are challenges for evidence-based new therapies seeking to improve outcomes. Full article

Field-effect transistor (FET) biosensors using graphene have become one of the most promising biosensing platforms for the early diagnosis of diseases with features such as high sensitivity, label-free detection and application compatibility with point-of-care systems. Herein, we critically discuss recent advances in graphene FET (GFET) biosensor development toward clinically relevant biomarkers associated with representative diseases including cancer, neurodegenerative disease, infectious disease, and inflammatory conditions. Recent progress was reviewed to evaluate GFET architectures, surface functionalization methods, and detection quality. The biomarkers explored were clusterin in Alzheimer’s disease, thrombin in coagulopathy, estrogen receptor α (ER-α) in breast cancer, Carcinoembryonic antigen in lung cancer, microRNAs for malignant tumors, exosomes derived from HepG2 for the hepatocellular carcinoma (HCC) cell line, interleukin-6 (IL-6) for chronic obstructive pulmonary disease (COPD), Polyclonal antibodies and antigens (P24) for HIV and prostate-specific antigen for prostate cancer. The developed devices demonstrate ultralow detection limits at femtomolar to attomolar concentrations with the aid of designed antibodies, aptamers and nanomaterials. Herein, this review presents the sensing mechanisms and biomedical application of various GFET platforms, focusing on their emerging potential as next-generation platforms for rapid, non-invasive and point-of-care diagnostics. Full article