Search Results (7,942)

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

Background: Pneumocystis jirovecii pneumonia (PJP) increasingly affects non-HIV immunocompromised patients; however, the spectrum of computed tomography (CT) findings in this population remains poorly defined. Objectives: To describe and compare chest CT findings of PJP in patients with and without HIV infection and to evaluate the impact of respiratory coinfections on imaging patterns. Methods: This retrospective single-centre cohort study included 72 adult patients with confirmed PJP diagnosed between 2011 and 2024, 27 HIV-positive and 45 non-HIV immunocompromised patients. Chest radiography was available in 71 patients and chest CT in 62. Imaging studies were independently reviewed for predefined patterns, including ground-glass opacities, alveolo-interstitial pattern, mosaic attenuation, crazy paving, pulmonary cysts, consolidation, and pleural effusion. CT findings were compared between HIV-positive and non-HIV patients, and a subgroup analysis was performed in non-HIV patients according to the underlying type of immunosuppression. Respiratory coinfections were recorded and classified based on microbiological results. Results: Chest radiography was normal in 32.4% of patients. An interstitial pattern tended to be more frequent in HIV-positive patients, whereas consolidations were more commonly observed in non-HIV patients (p = 0.051). On CT, ground-glass opacities were the predominant finding in both groups. HIV-positive patients more frequently demostrated an alveolo-interstitial pattern, mosaic attenuation, and pulmonary cysts, while consolidations and pleural effusions were more common in non-HIV patients, particularly among solid organ transplant recipients. Respiratory coinfections were identified in 63.9% of patients; however, no statistically significant differences in CT patterns were observed between patients with and without coinfections. Conclusions: PJP demonstrates different CT presentations according to immune status. HIV-positive patients more frequently demonstrated alveolo-interstitial patterns, mosaic attenuation, and pulmonary cysts, whereas consolidations were more commonly observed in non-HIV immunocompromised patients. Respiratory coinfections do not appear to significantly influence CT patterns. Full article

Introduction: Drug resistance testing may improve the management of people living with HIV (PLWH) in several scenarios in low- and middle-income countries (LMICs). To guide assay development, the WHO published a target product profile (TPP) outlining two priority use cases (scenarios) for genotypic resistance testing: (1) PLWH with confirmed virological failure (VF) on an integrase strand transfer inhibitor (INSTI)-based regimen, such as tenofovir (TFV) disoproxil fumarate, lamivudine (3TC), and dolutegravir (DTG) and (2) heavily treated PLWH, including infants and young children, with confirmed VF after receiving multiple regimens including a boosted protease inhibitor (PI). An additional potential scenario includes PLWH testing positive for HIV-1 while on pre-exposure prophylaxis (PrEP). Methods: To identify drug-resistance mutations (DRMs) most likely to influence clinical management of PLWH in each WHO TPP scenarios and to inform development of assays that detect individual DRMs and the interpretation of sequence-based assays, we reviewed prevalence and in vitro susceptibility data on HIV-1 DRMs in the Stanford HIV Drug Resistance Database associated with the nucleoside RT inhibitor (NRTI), nonnucleoside RT inhibitor (NNRTI), PI, and INSTI classes and the capsid inhibitor lenacapavir. Results: In the first scenario, the most informative NRTI DRMs were K65R and M184V/I; and the most informative INSTI DRMs were G118R, N155H, Q148H/K/R, and R263K. In the second scenario, a broader spectrum of DRMs is likely to be clinically relevant, including additional NRTI DRMs, the PI DRMs associated with reduced susceptibility to darunavir, and the NNRTI DRMs associated with reduced susceptibility to etravirine and doravirine. In PLWH testing positive for HIV-1 despite PrEP, the most informative NRTI and INSTI DRMs overlap with those in the first scenario, together with the capsid DRMs reported in persons experiencing VF while receiving lenacapavir. Conclusions: As global ART programs increasingly rely on INSTI-based regimens, and as the number of heavily treated individuals and difficult-to-treat pediatric cases grows, many LMICs have begun introducing HIV drug resistance testing for patient management. Although sequence-based assays provide the most comprehensive information for managing individual PLWH, assays that detect individual DRMs are also likely to be highly useful in the three WHO TPP scenarios. Full article

Tuberculosis remains one of the leading infectious causes of morbidity and mortality worldwide, disproportionately affecting women of reproductive age, particularly in low- and middle-income countries. Tuberculosis during pregnancy represents a major clinical challenge, as physiological and immunological changes associated with pregnancy may obscure symptoms, delay diagnosis, and contribute to adverse maternal and perinatal outcomes. This narrative review provides an updated and clinically oriented overview of tuberculosis during pregnancy, with particular emphasis on diagnostic challenges, imaging strategies, microbiological testing, maternal–fetal complications, and therapeutic management. Key topics include symptom-based screening, tuberculin skin test and interferon gamma release assays, as well as molecular diagnostic methods such as GeneXpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) and Xpert MTB/RIF Ultra, chest radiography, computed tomography, and emerging biomarkers. We also discuss the impact of tuberculosis on pregnancy outcomes, including prematurity, low birth weight, maternal morbidity, and neonatal complications, as well as the particular challenges posed by human immunodeficiency virus HIV coinfection and multidrug-resistant tuberculosis. Current treatment strategies, preventive approaches, postpartum care, neonatal management, and Bacille Calmette–Guérin vaccination are reviewed in light of contemporary evidence and international recommendations. Finally, we highlight practical diagnostic algorithms, current evidence gaps, and priorities for future research aimed at improving maternal and neonatal outcomes in both high- and low-resource settings. 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

Angola is one of the countries with the highest HIV-1 genetic diversity, yet the implications of this diversity for antiretroviral therapy remain insufficiently characterised. Following the introduction of dolutegravir (DTG) in Angola in 2021, evaluating transmitted drug resistance prior to its widespread implementation is essential to inform treatment strategies and establish a baseline for future surveillance. In this study, 243 blood samples were collected from treatment-naïve people living with HIV attending the General Hospital of Benguela, Angola. The integrase coding region of proviral DNA was amplified and sequenced using the Sanger method. Phylogenetic relationships were inferred using a maximum likelihood approach, recombinant forms were characterised by bootscanning analysis, and resistance-associated mutations to integrase strand transfer inhibitors were identified using Stanford HIVdb, ANRS-MIE, and IAS-USA algorithms. A total of 92 integrase sequences were successfully obtained, revealing 16 distinct genetic forms, with unique recombinant forms accounting for 50.0%, followed by subtype C (10.9%) and sub-subtype F1 (8.7%). Five accessory mutations (L74I, L74M, Q95K, T97A, and E157Q) and one major mutation (E92G) were detected, corresponding to an overall prevalence of 28.8% (23/80). These findings highlight the extensive HIV-1 genetic complexity in Angola and support the continued use of DTG-based regimens, while underscoring the importance of sustained surveillance of integrase inhibitor resistance. Full article

The high case fatality rate, cross-species transmission, and ongoing evolution of H5 avian influenza viruses pose an imminent threat of an influenza pandemic, particularly with the currently predominant clade 2.3.4.4b lineage. Existing seasonal influenza vaccines and licensed H5 vaccines provide limited cross-protection against H5 viruses, underscoring an urgent need for the development of broadly protective H5 vaccines. In this study, we analyzed all human-infected H5 hemagglutinin (HA) sequences using bioinformatics approaches and subsequently designed a novel H5 influenza vaccine through algorithm optimization. The predicted structure of this vaccine closely resembles that of the wild-type H5 HA trimer. In animal studies, the algorithm-optimized H5 mRNA vaccine not only induced high levels of neutralizing antibodies against multiple clade 2.3.4.4b H5 viruses but also elicited cross-neutralizing antibodies against clade 2.3.4.4 and clade 2.2.1 H5 viruses, as well as robust cellular immune responses. These findings highlight the potential of algorithm-based approaches in developing broadly protective vaccines against pandemic viruses and suggest that this vaccine candidate could serve as a strategic stockpile for preventing H5 influenza pandemics. 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

Background: People living with HIV (PLWH) are increasingly reaching older ages due to the success of antiretroviral therapy. However, aging with HIV is associated with increased risk of multimorbidity, neurocognitive impairment, frailty, psychosocial stress, and functional decline. Multidomain geriatric screening framed within an Age-Friendly 4Ms Framework (Mentation, Medication, Mobility, What Matters Most) and consideration of multi-complexity may help identify aging-related vulnerabilities and guide multidisciplinary care with greater impact on patient outcomes. However, real-world implementation of such programs within HIV clinical settings remains limited. Methods: We conducted a retrospective analysis of adults aged ≥50 years enrolled in a multidisciplinary Healthy Aging Program within a large, integrated HIV care system. Multidomain screening assessments included cognitive evaluation (Montreal Cognitive Assessment), mental health screening (PHQ-2, GAD-2), functional assessment (Katz ADL, Lawton IADL), frailty screening (Edmonton Frail Scale), and intrinsic capacity domains using the WHO Integrated Care for Older People (ICOPE) framework. Screening results, referrals, clinical interventions, and cardiometabolic risk management measures were extracted from clinical program databases and electronic medical records. Results: A total of 317 adults aged ≥50 years completed multidomain screening. Participants had well-controlled HIV infection, with viral suppression in 96.2% and a median CD4 count of 660 cells/mm³. Despite this, aging-related vulnerabilities were common. Overall, 78.4% of participants had at least one abnormal screening domain. Cognitive impairment was identified in nearly half of individuals screened, including mild impairment in 39.8% and moderate impairment in 8.7%. Functional limitations were identified in 10.1% of participants, while anxiety symptoms were present in 9.5%. Sensory impairments were common, including vision impairment in 36.5% of participants. Polypharmacy was prevalent, with 33.2% of participants prescribed five or more chronic medications. Screening frequently generated multidisciplinary referrals, including behavioral health services (42.3%), social work support (42.9%), and pharmacist-led cardiometabolic risk review (56.8%). Age-stratified analyses demonstrated similar prevalence of screening abnormalities across age groups, including individuals aged 50–59 years. Modest improvements in cardiometabolic preventive care were observed during follow-up. Statin utilization increased from 65.6% at baseline to 70.0% at 12 months, and LDL cholesterol declined modestly during the observation period. Conclusions: Multidomain screening integrated into routine HIV care identified a high prevalence of aging-related vulnerabilities among PLWH aged ≥50 years despite excellent virologic control. These findings suggest that aging-related risk in HIV is not adequately captured by chronological age alone and support early, universal implementation of multidomain screening within HIV care models. Full article

Protein–protein interactions (PPIs) are fundamental to viral replication, regulating processes such as assembly, genome packaging, and virion maturation. Despite their biological importance, these interactions remain challenging to study and are relatively underexploited as therapeutic targets. Split reporter systems, based on protein-fragment complementation, provide quantitative platforms to measure PPIs by reconstituting reporter activity when interacting protein partners are brought into proximity. These systems can be applied in vitro and in live cells which enables detection of dynamic and multimeric interactions in physiologically relevant contexts. Major classes of split reporter systems include β-lactamase, alkaline phosphatase, luciferase-based platforms, green fluorescent protein, and horseradish peroxidase. Assay performance depends on factors such as fusion protein stability, expression levels, and reporter kinetics, which influence sensitivity, dynamic range, and reliability. These approaches have been applied to study viral protein interactions across diverse systems, including HIV-1 matrix and nucleocapsid proteins, flaviviral capsid proteins, hepatitis B virus core protein, and chikungunya virus capsid. Split reporter assays also enable high-throughput screening for small-molecule inhibitors that disrupt viral PPIs and multimerization. This provides a functional readout linked to viral replication. Despite the challenges that exist in assay optimization and protein stability, the sensitivity and versatility of these systems provide a framework to interrogate viral protein interactions and support the development of antiviral therapeutics.: Full article

Background: The development of an efficacious preventive human immunodeficiency virus (HIV) vaccine remains a central goal of global HIV elimination efforts, yet biological performance alone will not determine a future vaccine’s public health impact. Method: This review draws on behavioral science, communication research, vaccine implementation, and HIV prevention literature to identify cognitive, social, and structural challenges that are likely to shape public acceptance and uptake of a future HIV vaccine, as well as to outline evidence-based opportunities for addressing them. Results: Based on the available literature, mental models of both HIV and vaccination will be a critical determinant of how communities consider a future vaccine, particularly given that emerging mRNA and adjuvanted platforms may generate side effects that could be easily misinterpreted and that highly effective long-acting pre-exposure prophylaxis (PrEP) options already exist and will shape how individuals evaluate a vaccine’s relative value. HIV-related stigma further complicates this landscape by making vaccination a socially interpreted behavior, unlike some other vaccination efforts. Together, these factors suggest that hesitancy and misalignment between public understanding and scientific evidence are predictable and should be anticipated rather than addressed reactively. At the same time, decades of HIV prevention implementation research have established an evidence base for vaccine communication, and existing community engagement infrastructure offers a foundation upon which future rollout efforts can build. We highlight three evidence-based strategies as particularly promising levers for encouraging acceptance and adoption. Conclusions: We conclude with recommendations for HIV vaccine researchers and healthcare professionals to invest in formative research, build community partnerships in advance of vaccine availability, and pilot integrated delivery models within existing HIV prevention services. Full article

The gut microbiota produces molecules that trigger responses at the local and distant levels. It affects the brain through several metabolic products, including serotonin (5-HT). Tryptophan hydroxylase type 1 (Tph1) is the rate-limiting enzyme during 5-HT biosynthesis in the gut. Efavirenz (EFV), an antiretroviral agent against HIV, is associated with depression disorders and Tryptophan hydroxylase type 2 (Tph2) deregulation in mice. The possible association between the depressive effects of EFV secondary to dysbiosis and the expression of Tph1 in the intestine is yet to be studied. Therefore, we aimed to elucidate the role of the gut microbiota in depression mechanisms. We reviewed the gut microbiota, their metabolites (short-chain fatty acids [SCFA]), Tph1 expression in the gut, and systemic 5-HT and tryptophan levels in CD1 mice after 36 days of oral EFV (10 mg/kg) treatment. The proportions of Bacteroidota and Bacillota_A_368345 decreased and increased, respectively, following EFV treatment. Additionally, the abundance of Lactobacillus spp. and Faecalbaculum decreased, whereas that of Dubosiella spp., Blautia_A_141780, and Anaerostipes increased. These bacteria contribute to SCFA production and may have counteracted the lack of protective effects provided by Lactobacillus. Tph1 expression was dysregulated in the gut, whereas serum 5-HT levels decreased following EFV treatment. Lactobacillus species promote 5-HT production in the gut, and the deregulation of Tph1 affects 5-HT synthesis. This disruption in the gut–brain axis decreased peripheral 5-HT levels. This affects the serotonergic system in the brain, which could contribute to depression. 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

Background/Objectives: This study aimed to estimate self-reported prevalence of HIV and gonorrhea among primary healthcare attendees in Riyadh and to identify key demographic, behavioral, and clinical predictors, acknowledging that diagnoses were based on participant self-report rather than laboratory confirmation. Methods: A cross-sectional survey was conducted between March and July 2023 across 48 primary healthcare centers in Riyadh. A total of 14,239 adult participants (aged ≥18 years) completed an electronically administered questionnaire that included self-reported prior diagnoses of HIV and gonorrhea. Multivariable logistic regression models were used to identify independent predictors of self-reported HIV and gonorrhea. Results: The self-reported prevalence of HIV was 2.6% (95% CI: 2.35–2.87%), and gonorrhea was 3.1% (95% CI: 2.83–3.40%). Several factors were independently associated with higher odds of self-reported infection. Younger age (<50 years) increased risk (HIV: AOR = 2.19; gonorrhea: AOR = 1.57), as did female sex (HIV: AOR = 1.67; gonorrhea: AOR = 1.59), higher education (HIV: AOR = 1.29; gonorrhea: AOR = 1.23), married status (HIV: AOR = 1.76; gonorrhea: AOR = 1.49), and insurance coverage (HIV: AOR = 2.01; gonorrhea: AOR = 1.88). Behavioral and clinical factors included smoking (HIV: AOR = 4.79; gonorrhea: AOR = 2.41), hypertension (HIV: AOR = 2.58; gonorrhea: AOR = 1.49), obesity (HIV: AOR = 11.55; gonorrhea: AOR = 9.02), hypercholesterolemia (HIV: AOR = 2.24; gonorrhea: AOR = 2.53), and heart disease (HIV: AOR = 11.31; gonorrhea: AOR = 8.77). The notably high associations for obesity and heart disease should be interpreted with caution, as they may be influenced by detection bias or residual confounding within the healthcare-seeking sample. Conclusions: This study provides key insights into the self-reported burden and predictors of HIV and gonorrhea in Saudi Arabia. While identifying significant demographic and metabolic risk profiles, the high magnitude of certain clinical associations must be interpreted with caution due to potential detection bias and residual confounding. Given the reliance on self-reported data, these findings should be viewed as an epidemiological baseline rather than absolute prevalence. Prioritizing clinical context over statistical values and strengthening integrated, laboratory-based surveillance within primary care will be essential for improving early detection and evidence-based prevention strategies in the region. Full article