Search Results (664)

HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited dose-dependent virucidal activity against multiple enveloped viruses, including herpes simplex virus type 1 and 2 (HSV-1, HSV-2), human immunodeficiency virus type 1 (HIV-1), and Zika virus (ZIKV), with IC₅₀ values ranging from 14.7 to 56.1 µg/mL. No activity was observed against the non-enveloped human rhinovirus 14 (HRV14), suggesting strict dependence on a viral lipid envelope. Consistent with a membrane-targeting mechanism, HP1090 induced rapid and concentration-dependent permeabilization of virus-like liposomes. HP1090 also displayed antibacterial activity against selected clinically relevant pathogens in agar-based growth inhibition assays. However, antibacterial effects required substantially higher concentrations (>125 µg/mL) and varied between bacterial species, with some strains showing little or no susceptibility. Membrane permeabilization assays in Listeria monocytogenes demonstrated disruption of bacterial membrane integrity as a contributing mechanism. No cytotoxicity was observed on mammalian cell lines at effective antiviral concentrations. Together, these findings establish HP1090 as a membrane-active venom peptide and, by linking envelope-dependent viral inactivation with bacterial membrane permeabilization, support a shared biophysical mode of action relevant to the development of membrane-targeting anti-infectives. Full article

Background/Objectives: Rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection remain major contributors to morbidity and mortality, particularly in high-burden settings. HIV-related clinical factors, including viral suppression, CD4-defined immune status, HIV drug resistance, virological failure, and ART failure, may influence RR-TB treatment response; however, existing evidence remains fragmented. This systematic review and meta-analysis protocol aims to synthesize evidence on the impact of HIV viral suppression, immune status, and HIV drug resistance/ART resistance status on RR-TB treatment outcomes. Methods: This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Published peer-reviewed studies and relevant grey literature from January 2005 to December 2025 will be searched in PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, ScienceDirect, EBSCOhost, PsycINFO, Google Scholar, and other relevant sources. No language restriction will be applied at the search stage. Where feasible, non-English records will be translated for title/abstract and full-text screening. Two reviewers will independently screen studies, extract data, and assess study quality, with disagreements resolved by a third reviewer. Study-level risk of bias will be assessed using design-appropriate tools, and the certainty of evidence for each outcome will be evaluated using GRADE. Results: Evidence will be synthesized narratively and, where studies are sufficiently homogeneous, quantitatively through meta-analysis. Outcomes of interest will include treatment success, treatment failure, mortality, treatment completion, microbiological cure, and adverse events. Subgroup analyses will be considered by viral suppression status, CD4-defined immune status, HIV drug resistance/ART resistance status, geographic region, and treatment regimen where data permit. Conclusions: This review will provide evidence on how HIV viral suppression, immune status, and HIV drug resistance/ART resistance influence RR-TB treatment outcomes. The findings may inform integrated TB/HIV care, clinical monitoring, and treatment strategies for individuals co-infected with HIV and RR-TB. Full article

Background/Objectives: Obesity is an increasing challenge among people living with HIV (PLWH). This study aimed to assess the prevalence of general and abdominal obesity and its association with lifestyle in adult Romanian PLWH, providing the first national data. Methods: A single-center, cross-sectional study involved 106 adult PLWH. Eating behavior was assessed using the Rapid Eating Assessment for Participants—Short Version (REAP-S) and physical activity with the General Practice Physical Activity Questionnaire (GPPAQ), both standardized and validated. Anthropometric, clinical, and virological data were collected from medical records and direct measurement. Results: Median age was 36 years [IQR 33–42], 83.3% were male, and 73.6% lived in urban areas. Median time since HIV diagnosis was 11 years, and 60.4% had AIDS-defining illness. General obesity (BMI ≥ 30 kg/m²) occurred in 17.9%, overweight in 29.2%, and high-risk abdominal obesity in 22.6%. Physical inactivity was reported by 20.8%. Multivariable analysis showed that being moderately or physically active was the only independent predictor of abdominal obesity (OR 0.19; 95% CI, 0.07–0.51; p = 0.001). Conclusions: In this young Romanian cohort of PLWH, physical activity reduces the risk of abdominal obesity, underscoring the need to integrate such interventions into the standard of care to reduce metabolic risk associated with HIV. Full article

Background and Objectives: Despite global commitment to the World Health Organization triple elimination initiative, evidence on integrated antenatal service delivery models that simultaneously address human immunodeficiency virus (HIV), syphilis, and hepatitis B virus (HBV) remains fragmented, particularly across diverse health-system contexts. Eliminating vertical transmission of HIV, syphilis, and HBV is a global priority. Pregnant women are disproportionately affected by these infections, and untreated maternal disease leads to significant infant morbidity. Integrating antenatal screening and treatment provides an opportunity to address all three conditions simultaneously. Purpose: This systematic review and meta-analysis aimed to identify and synthesise evidence on integrated antenatal service delivery models addressing HIV, syphilis, and HBV simultaneously within maternal health services. It specifically examined model characteristics, screening uptake, treatment and follow-up outcomes, implementation barriers and facilitators, and evidence on cost-effectiveness. Methods: This systematic review and meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261342186). We searched Scopus, PubMed, Web of Science, and Dimensions for studies published between January 2007 and January 2026. Of 423 records identified, 11 met the inclusion criteria after excluding two studies that did not provide empirical results for an integrated service model addressing all three target infections simultaneously. Data on study characteristics, service delivery, diagnostics, outcomes, and implementation factors were extracted. A random-effects meta-analysis of proportions was conducted using the DerSimonian–Laird estimator with logit transformation. Results: Eleven studies covered Asia, Africa, Europe, and Latin America, mostly in low- and lower-middle-income countries. Integration ranged from rapid test packages in community clinics to comprehensive programmes including STI treatment, malaria testing, and HBV birth-dose vaccination. Pooled triple testing uptake was 97% (95% CI 92 to 100%). Large programmes achieved over 99% coverage and reduced HIV vertical transmission to below 3%. Pilot studies showed feasibility but noted stockouts, data gaps, and weak treatment linkage. Economic analyses supported cost-effectiveness. Conclusions: Integrated antenatal services appear feasible and can achieve high testing uptake, particularly in well-supported programmes. However, evidence remains uneven regarding treatment completion, infant follow-up, HBV prophylaxis, long-term transmission outcomes, and sustainability in resource-constrained settings. Key challenges include supply constraints, workforce limitations, and follow-up gaps. Future research should evaluate the full care cascade, not screening uptake alone. Full article

Background/Objectives: As important post-transcriptional and epigenetic regulators of gene expression, miRNAs play a pivotal role in modulating host–virus interactions. While prior reviews have addressed either direct miRNA–HIV genome interactions or miRNA-mediated immune modulation in isolation, the integrated dual functionality of these molecules has not been systematically characterized. This review aimed to comprehensively explore how miRNAs that target the HIV-1 genome simultaneously modulate key innate and adaptive host immune signaling pathways. The conceptual novelty of this study is determined not by the identification of previously unknown miRNA-target gene pairs, but by the systemic integration of two regulatory levels (direct inhibition of the viral genome and modulation of the host cell immune signaling pathways) within a unified analytical framework. Such an integrated approach reveals a proviral regulatory network that remains non-obvious when each of these levels is examined separately. Methods: A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar (all years through 2025). In Stage 1, publications reporting experimentally confirmed interactions between host miRNAs and the HIV-1 genome were identified, yielding a curated set of 15 miRNAs. In Stage 2, target genes for each miRNA were retrieved from miRTarBase, TarBase (experimentally validated) and TargetScan 8.0 (in silico predicted). In Stage 3, target genes were manually mapped to key immune signaling pathways (TLR, NF-κB, JAK-STAT). In Stage 4, targeted literature searches were performed for each miRNA–target gene pair to identify direct experimental evidence of interaction. All stages were performed by two independent researchers, with discrepancies resolved by a third. Results: Fifteen host miRNAs with experimentally confirmed binding to the HIV-1 genome were identified, targeting viral genes including nef, pol, vpr, gag, env, vif, and the 3′-UTR. Thirteen of these miRNAs were found to regulate components of major immune pathways. miR-92a-3p, miR-29a/b-3p, miR-150-5p, and miR-125b-5p emerged as the most pleiotropic regulators, simultaneously suppressing TLR signaling (TLR3, TLR7, TLR8, MyD88, TRAF3/6, IRAK1/4), NF-κB components (REL, RELA, NFKB1), JAK-STAT effectors (STAT1–3, STAT5A/B, JAK2), and negative regulators of cytokine signaling (SOCS and PIAS family proteins). miR-133b and miR-196b-5p were found to selectively regulate SOCS/PIAS proteins without involvement in other analyzed pathways, suggesting potential for selective therapeutic targeting. Conclusions: The analyzed miRNAs exhibit functional dualism, acting as direct post-transcriptional suppressors of the HIV-1 genome while simultaneously functioning as epigenetic modulators of host immune signaling. These two modes of action are not independent but together form a conceptual framework of a self-reinforcing proviral regulatory network that, based on the synthesis of published evidence, is proposed to promote viral latency and immune evasion. The identified miRNAs represent promising, albeit complex, targets for novel therapeutic strategies aimed at eliminating latent HIV reservoirs. Full article

Background: Sexually transmitted infections (STIs) remain a major public health concern among adolescent girls and young women (AGYW) in sub-Saharan Africa (SSA). Although routine STI screening is essential for early diagnosis and prevention, uptake among AGYW is often suboptimal and influenced by multiple individual and contextual factors. This study assessed factors associated with STI screening uptake among AGYW enrolled in HIV prevention programs in Namibia. Methods: A secondary analysis of anonymized programmatic data was conducted among AGYW aged 15–24 years who received services through the DREAMS project and REACH PHN activity between 2018 and 2024. Descriptive statistics, Chi-square tests, and multivariable logistic regression analyses were performed to identify factors associated with STI screening uptake. Results: A total of 26,689 AGYW were included in the analysis, of whom 97.2% were screened for STIs. STI screening uptake was significantly associated with district of residence, year of enrolment, inconsistent or no condom use, perceived risk of HIV infection, use of family planning, and having had sex under the influence of alcohol or drugs. AGYW who perceived themselves to be at risk of HIV and those using family planning methods had higher odds of STI screening, while those who reported sex under the influence of alcohol or drugs were less likely to be screened. Significant geographic disparities in screening uptake were also observed across districts. Conclusions: STI screening uptake among AGYW enrolled in HIV prevention programs in Namibia was high. While this may reflect the effectiveness of integrated, community-based service delivery models, the results should be interpreted with caution, as they are based on a convenience sample. However, behavioural and geographic disparities persist. Strengthening integrated sexual and reproductive health services, addressing substance-related barriers, and implementing targeted district-level interventions may further improve equitable access to STI screening among AGYW. Full article

The first six contributions considered in this Editorial provide a coherent view of the modern laboratory as an integrated system of safety governance, digital education, measurement confidence, diagnostic implementation, and clinical quality assurance. The papers considered here address occupational hygiene and health monitoring in university laboratories, the predictive modeling of chemical exposure risks among cleaning staff, the design of an immersive virtual reality laboratory for multidisciplinary student experiences, the evolving concept of measurement uncertainty in accredited laboratories, the field implementation of a near point-of-care HIV drug-resistance assay in Kenya, and the optimization of embryo culture conditions in IVF laboratories. Although these studies span different fields, they converge on a common message: laboratory excellence depends not only on instruments and protocols but also on human factors, training, exposure control, usability, uncertainty management, and translation into real-world decisions. This Editorial synthesizes these contributions and identifies future priorities for Laboratories as a forum for interdisciplinary laboratory science and practice. Full article

Background/Objectives: Girls living with HIV (GLHIV) or vulnerable to HIV have a higher risk of HPV infection and cervical cancer as they age. We determined acceptability and vaccination uptake after integrating HPV vaccination into HIV prevention and treatment services for girls in Mozambique and Zimbabwe. Methods: Pre-integration and integration HPV vaccination information were abstracted from routine records of girls aged 9–14 years offered HPV vaccine through HIV services in 54 health facilities (HFs) and surrounding communities between February and December 2025. Caregivers participated in quantitative surveys about vaccine perceptions and integration model experiences in a subset of 16 HFs. Results: In total, 6377 records of girls (median age: 11 years) were abstracted. Among the vaccine recipients, 63 (3.0%) girls received vaccine pre-integration and 2019 (97.0%) post-integration in Mozambique and 743 (17.3%) pre-integration and 3541 (82.7%) post-integration in Zimbabwe. Among GLHIV, 95.8% and 69.6% received a first HPV vaccine in Zimbabwe and Mozambique, respectively. Full vaccination with two doses occurred in 49.1% of eligible girls in Mozambique and 73.9% in Zimbabwe. Overall, 461 (67.8%) caregivers had heard of the HPV vaccine and 85.9% of cervical cancer, 99.6% were satisfied with vaccination in integration settings, and 78.6% preferred facility-based vaccination models. Conclusions: We demonstrated that HPV/HIV service integration was an effective strategy to increase HPV vaccine uptake among young girls at increased risk of HPV and cervical cancer. We found high vaccine and model acceptability and awareness of cervical cancer among caregivers. Optimization of this approach requires better integrated tools and model adaptations to fit the needs of girls and health systems. Full article

Combined antiretroviral therapy (cART) has transformed HIV into a manageable chronic disease. However, people living with HIV (PLWH) experience a 16-year reduction in comorbidity-free life expectancy compared to HIV-negative individuals, driven by persistent chronic immune activation despite virological suppression. Serious non-AIDS events (SNAEs)—including cardiovascular disease, metabolic disorders, and malignancies—now represent the predominant cause of morbidity. This narrative review provides a clinician-oriented synthesis of immunopathophysiological mechanisms driving chronic inflammation in treated HIV infection, focusing on the gut–immune axis, restriction factors, trained immunity, biomarker-guided risk stratification, and therapeutic strategies. We searched PubMed/MEDLINE, Embase, and Web of Science through April 2026 using terms related to HIV chronic immune activation, gut-associated lymphoid tissue, microbial translocation, inflammaging, restriction factors, trained immunity, and biomarkers. This review followed the SANRA checklist. Irreversible destruction of gut-associated lymphoid tissue (GALT), intestinal barrier dysfunction, microbial translocation, maladaptive trained immunity, persistent myeloid activation with NLRP3 inflammasome signaling and cellular senescence, and viral reservoir persistence collectively perpetuate systemic inflammation. Biomarkers, including sCD14, IL-6, and suPAR, independently predict mortality but are not pathogen-specific. The REPRIEVE trial demonstrated a 36% reduction in cardiovascular risk with pitavastatin (HR 0.64, 95% CI 0.48–0.84), validating inflammation as a therapeutic target. Integration of early cART, statin therapy, optimal antiretroviral selection, and emerging strategies—including GLP-1 receptor agonists and gut-directed therapies—offers a practical framework for reducing inflammation-associated comorbidities in virologically suppressed PLWH. Full article

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20–30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional “second hits”, including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53–86% of heritable PAH and 14–35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH. Full article

Objectives: Membrane-enveloped virus-like particles (VLPs) constitute a versatile vaccine platform allowing for the display of heterologous viral surface antigens. The density of displayed antigens is paramount for the efficient elicitation of a strong cellular and humoral immune response. SARS-CoV-2 spike protein variants with engineered cytoplasmic tails (CTs) were generated to enhance decoration efficiency on the surface of VLPs formed by the HIV core protein Gag. These HIV (SARS-CoV-2) chimeric particles serve as a vaccine component prototype. Methods: Spike variants were first analyzed for cellular and surface expression as well as incorporation into extracellular vesicles (EVs) and VLPs using flow cytometric analysis and Western blot analysis. Receptor binding, fusogenicity, i.e., mediating the fusion of spike-positive with receptor-containing membranes, and the proteins’ potential to mediate lentiviral vector gene transduction into susceptible target cells was examined by employing syncytia-formation assays and vector titration experiments. The display of a neutralization-sensitive epitope was examined utilizing immuno-precipitation using a neutralizing antibody. Results: All four variants were shown to be cell-surface expressed, to recruit the cognate receptor, to mediate membrane fusion and cell entry of lentiviral pseudotype vector particles and to decorate VLPs and EVs. However, the spike variant encompassing a truncated CT derived from the gibbon ape leukemia virus (GaLV) transmembrane (TM) envelope protein was most efficiently incorporated into HIV Gag-formed VLPs. All variants exposed a neutralization-sensitive epitope in the receptor binding domain. Conclusions: Engineering of the CTs of viral surface antigens can enhance VLP decoration, while required functionality of the ecto-domain such as receptor recognition, fusogenicity and neutralization-sensitive epitope presentation are not abrogated. This indicates the preservation of the structural integrity of the antigen required to elicit a neutralizing humoral immunity upon vaccination. The identified truncated CT of GaLV TM may be of utility to improve the incorporation of other viral surface antigens into a variety of membrane-enveloped VLPs derived from a range of different parental viruses. Full article

The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4⁺ T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome–HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions—including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics—and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication. 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

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KS-associated immune reconstitution inflammatory syndrome (IRIS-KS). Quantifying HHV-8 DNA in whole blood is clinically relevant, yet laboratory practices remain heterogeneous. Here, we developed and validated an in-house quantitative PCR (qPCR) assay targeting ORF26, optimized for whole blood. Assay calibration used plasmid, BCBL-1 cell–derived, and commercial HHV-8 DNA standards. Analytical validation was performed following the Clinical and Laboratory Standards Institute (CLSI) guidelines and the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines and showed a 95% limit of detection of 65.7 copies/reaction, efficiencies of 90–101% (R² > 0.99), and intra/inter-assay coefficients of variation < 6.5%. Strong correlations were observed among the three calibrators (R² > 0.97).Clinical validation against a composite reference yielded 100% sensitivity, specificity, PPV, and NPV. Viral loads (log₁₀ copies/mL) varied by clinical condition: classic KS and transplant-associated KS showed the lowest medians (2.30–2.23), MCD HIV− and PEL intermediate values (2.83–3.72), and epidemic KS, MCD HIV+, and IRIS-KS the highest (4.12, 4.86, and 5.03, respectively). Viremia > 5 log₁₀ copies/mL was associated with uncontrolled E-KS, MCD HIV+, and IRIS-KS. Longitudinal follow-up revealed viral load decline paralleled clinical improvement. This validated assay provides a robust, affordable tool for HHV-8 quantification in whole blood and supports its integration into diagnostic workflows and patient monitoring. Full article

Background: Oropharyngeal cancer (OPC) incidence has been increasing among males in the United States, reflecting a complex interplay among social, behavioral, and biological determinants of health. This study aimed to quantify cumulative risk profiles and their relationship with the burden of comorbid conditions in men with OPC using the All of Us Research Program cohort. Methods: We developed a cumulative risk index from nine biological, clinical, and social variables for males with OPC in the United States. Comorbidity burden was measured by the number of unique comorbid diagnoses per patient, excluding HIV/AIDS and primary OPC to reduce circularity. Poisson regression was performed to estimate incidence rate ratios (IRR) for comorbidity by risk group/count. Results: Under strict criteria requiring data for each risk factor, mean comorbidity was 1.90 in the low-risk and 2.29 in the moderate-risk groups; in an inclusive, ‘liberal’ analysis, most cases (74%) were moderate risk with much lower mean comorbidities (mean = 0.050–0.205), with only 5% having any comorbidity recorded. Each additional risk factor was associated with an 81% increase in unique comorbidities (IRR = 1.81, 95% CI: 1.16–2.91; p = 0.01). The high-risk group had substantially higher comorbidity but comprised only two individuals. The most common comorbid diagnoses were essential hypertension and hyperlipidemia, and the most frequent risk factor co-occurrence was having a family history of head and neck cancer and having no insurance. Conclusions: Our analysis demonstrated male OPC patients to have multiple risk factors, but comorbidity burden was concentrated in a small minority, supporting the need for risk stratification and integrated, multidomain prevention and care strategies. Full article