Search Results (4,147)

Background/Objectives: Hepatitis B remains a major public health concern in the Democratic Republic of the Congo (DRC). This study investigated HBV seroprevalence in Kinshasa and evaluated the diagnostic performance of rapid diagnostic tests (RDTs) compared with dried blood spot (DBS)–based immunoassays. Methods: DBS samples collected between 2016 and 2022 were transported to Spain for HBsAg and HBc-Ab testing using two chemiluminescence platforms (ECLIA-COBAS (Roche) and ELFA-miniVIDAS (bioMerieux)). A subset of participants also underwent on-site HBsAg screening using Determine™ (Abbott) RDTs. Results: Overall, active HBV infection was detected in 4.3% of participants and resolved infection in 14.3%, with no significant differences by age, sex, cohort, or HIV/HCV status. The RDT showed poor sensitivity (60% (95% CI: 26–88)) but high specificity (100% (95% CI: 98–100)), resulting in a 40% misdiagnosis rate. In contrast, DBS-based HBsAg immunoassays demonstrated excellent diagnostic accuracy, with both platforms achieving 100% sensitivity (ECLIA-COBAS 100%, 95% CI: 66–100; ELFA-miniVIDAS 100%, 95% CI: 99–100) and specificity (ECLIA-COBAS 100%, 95% CI: 98–100; ELFA-miniVIDAS 100%, 95% CI: 99–100). HBc-Ab detection showed platform-dependent variability, with lower sensitivity on ELFA-miniVIDAS (66% (95% CI: 46–82)) compared with ECLIA-COBAS (100% (95% CI: 96–100)). Predictive values were high across all assays, and inter-method agreement for HBsAg between RDT and chemiluminescence was good (Cohen’s kappa 0.71, p < 0.001). Conclusions: These findings indicate moderate HBV transmission in Kinshasa and highlight the limited reliability of RDT-based screening. DBS proved to be a practical, robust, and scalable sampling method with outstanding diagnostic performance, making it well-suited for HBV testing in low-resource settings. 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

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

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

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

Viral comorbidities elicit complex host responses by activating redox-sensitive signaling pathways, prominently those regulated by NADPH oxidase (Nox) enzymes. Nox are critical components of host defense, generating reactive oxygen species (ROS) that modulate key cellular signaling cascades. Under normal physiological conditions, Nox activity is tightly controlled; however, viral infections frequently disrupt this regulation, leading to aberrant upregulation of specific Nox isoforms. Elevated expression of individual Nox enzymes has been observed in infections such as influenza A and hepatitis C virus, while simultaneous activation of multiple Nox isoforms occurs in HIV and SARS-CoV infections. Similar patterns of dual or multi-isoform Nox activation are also reported in complex disease states, including diabetes, thrombosis, and fibrosis. MicroRNAs play a crucial role in this process by selectively regulating Nox isoform expression during viral infection, thereby remodeling the host redox environment. Nox-derived ROS influence multiple downstream signaling pathways, including SMAD, MAPK, CXCR-mediated signaling, and the JNK/ERK axis, promoting inflammation and fibrosis that worsen viral disease outcomes. Additionally, several FDA-approved drugs, investigational agents, and microRNA-based therapeutics show promise in modulating Nox activity. Therefore, this article substantiates how viral infections reprogram host transcriptomic and redox signaling networks, contributing to viral pathogenesis and offering potential therapeutic intervention strategies. Full article

HIV-associated neurocognitive disorders (HAND) arise from HIV infection of the central nervous system, resulting in chronic neuroinflammation and progressive neuronal damage that impair cognitive, motor, and behavioral functions. Clinically, HAND encompasses a spectrum of neurological impairments ranging from asymptomatic neurocognitive impairment to severe HIV-associated dementia. Despite the widespread use of combination antiretroviral therapy (cART) and significant improvements in the life expectancy of people living with HIV, HAND remains prevalent and continues to pose a major clinical challenge. One of the primary limitations of cART is the limited penetration of many antiretroviral drugs across the blood–brain barrier (BBB), thereby allowing the persistence of viral reservoirs within the CNS and contributing to sustained neuroinflammation and neuronal damage. To address these challenges, novel nanotherapeutic strategies have been developed to enhance the delivery of antiretroviral agents to the brain. These approaches include targeted delivery systems and the co-delivery of therapeutics across the BBB through mechanisms such as receptor-mediated transcytosis and other transport pathways. In this review, we discuss the pathophysiological challenges associated with HAND and recent advances in nanotherapeutic approaches designed to improve treatment efficacy. We also discuss the current state of the art in vitro and in vivo models used to test the efficacy of these advanced therapeutics. Finally, we outline the remaining challenges and future prospects for the development of nanotherapeutics to improve the treatment of HAND. Full article

A within-host HIV dynamics model incorporating latent reservoirs, distributed time delays, and a B-cell-mediated humoral immune response is developed and analyzed mathematically. The model includes five compartments: uninfected CD4⁺ T cells, latently infected cells, actively infected cells, free virions, and B cells. Four distinct distributed delays are introduced to account for the periods between viral entry and the emergence of latently or actively infected cells, reactivation of latently infected cells, and intracellular virion production. For the non-delayed system, the basic reproduction number ${\mathcal{R}}_0$ is derived using the next-generation matrix method. Using Lyapunov functions and LaSalle’s Invariance Principle, a sharp threshold dynamic is proven: the infection-free equilibrium is globally asymptotically stable (GAS) when ${\mathcal{R}}_0\le 1$, whereas a unique endemic equilibrium is GAS when ${\mathcal{R}}_0>1$. For the full distributed-delay system, a delay-dependent reproduction number ${\mathcal{R}}_0^d$ is defined. The global asymptotic stability of the infection-free equilibrium is established for ${\mathcal{R}}_0^d\le 1$, and the global asymptotic stability of the endemic equilibrium is established for ${\mathcal{R}}_0^d>1$, using suitably constructed Lyapunov functionals that account for the delay history. Numerical simulations validate the analytical threshold behavior. A sensitivity analysis of ${\mathcal{R}}_0^d$ identifies the most influential parameters for potential intervention. A treatment-dependent reproduction number is derived, and the critical drug efficacy required for viral eradication is determined. The intracellular production delay is shown to act as a critical threshold for infection clearance. Full article

Women living with HIV face an increased burden of spontaneous preterm birth (sPTB); however, the underlying immunological mechanisms of sPTB and its association with HIV infection are poorly understood. Although the limited earlier literature implicates sphingosine-1-phosphate (S1P), a lysosphingolipid signaling molecule, in reproductive biology, the association of S1P signaling with HIV and sPTB has not been investigated. We examined whether two S1P signaling components, S1P receptors and sphingosine kinases, are expressed in the female reproductive tract and whether levels are associated with HIV status or spontaneous preterm birth. We quantified the mRNA expression of sphingosine-1-phosphate receptors 1 and 3 (S1PR1/S1PR3) and sphingosine kinases 1 and 2 (SPHK1/SPHK2) in 167 banked vaginal swab specimens collected between 14 and 26 weeks of gestation in a longitudinal pregnancy cohort in Lusaka, Zambia. We evaluated the expression of S1PR1, S1PR3, SPHK1, and SPHK2 by real-time quantitative reverse transcription PCR (RT-qPCR) in four groups (n = 41–42 each): women without HIV (WWoH) with term birth (≥37 weeks of gestation; TB), WWoH with spontaneous preterm birth (<37 weeks of gestation, sPTB), women with HIV (WWH) with TB, and WWH with sPTB. We found that S1P receptors and sphingosine kinases are expressed in the female reproductive tract. SPHK1 and SPHK2 mRNA expression were generally comparable among women independent of HIV status or birth outcome, though SPHK2 trended toward higher expression in women with HIV and women with sPTB. In contrast, S1PR1 mRNA trended toward higher expression in WWH vs. WWoH overall, as well as in WWH vs. WWoH among women with sPTB. Similarly, S1PR3 mRNA expression was greater in women with HIV than in women without HIV, and WWH, both with TB and sPTB, had higher S1PR3 mRNA expression than WWoH with TB. Perturbations in S1PR1 and S1PR3 mRNA expression may be associated with inflammation related to HIV infection and spontaneous preterm birth, suggesting that further studies of S1P signaling in pregnancy, especially among women with HIV, are warranted. Full article

Pneumocystis jirovecii is an opportunistic fungal pathogen responsible for Pneumocystis pneumonia (PCP), a severe infection that remains a major cause of morbidity and mortality among immunocompromised patients, particularly in non-HIV immunosuppressed populations. Despite its recognized clinical relevance and inclusion in the World Health Organization’s Fungal Priority Pathogens List, important gaps persist in its diagnosis, epidemiology, and therapeutic management. This study provides a comprehensive bibliometric analysis of global scientific production on P. jirovecii using Scopus as the primary data source. Publications were evaluated for temporal trends, document types, authorship patterns, institutional productivity, collaboration networks, funding sources, thematic evolution, and journal distribution, with additional comparison against other major pneumonia-associated pathogens. A total of 27,396 articles published between 1916 and 2025 were identified. Over the last 50 years, scientific output increased from 10,382 publications in 1975–2000 to 16,496 in 2001–2025, representing an overall growth of 58.9%. Early research expansion was strongly shaped by the HIV/AIDS epidemic, whereas the post-2000 period reflected advances in molecular diagnostics, taxonomic clarification, and broader attention to non-HIV immunosuppressed populations. Although the field has become more diversified and clinically integrated, persistent structural inequities and underinvestment continue to limit progress, particularly in low- and middle-income settings. Full article

Digestive candidiasis is a major opportunistic infection among people living with HIV (PLHIV). In Gabon, data on antifungal resistance remain limited. This study aimed to characterise Candida colonisation and antifungal resistance according to anatomical site and species in Libreville. In this cross-sectional study, 108 PLHIV provided paired oral and stool samples. Candida spp. was identified using conventional phenotypic methods. Antifungal susceptibility to azoles and polyenes was assessed by disc diffusion following CLSI guidelines. Resistance burden was classified by drug class and by cumulative number of antifungal agents involved. Digestive colonisation was detected in 97 (89.8%) participants. Oral and intestinal colonisation rates were 78.7% and 66.7%, respectively, with dual-site involvement in 55.6%. Among resistant isolates, Candida albicans accounted for 55.2% (oral) and 48.9% (intestinal), while non-albicans Candida represented 29.8% and 44.4%, respectively. Multidrug resistance was significantly higher in intestinal than oral isolates (36.2% vs. 11.8%; OR = 4.99; 95% CI: 2.04–12.16; p < 0.01). Resistance was predominantly azole-driven, with complex cumulative resistance profiles in intestinal isolates. The intestinal tract showed resistance profiles consistent with a preferential accumulation of MDR Candida populations in PLHIV. Site-specific resistance patterns underscore the importance of targeted sampling and antifungal stewardship strategies in resource-limited settings. Full article

Background/Objectives: Onychomycosis is a fungal nail infection that may present with severe, atypical, or treatment-resistant features in people living with HIV. Despite its clinical importance, evidence regarding its epidemiology, causative agents, and relationship with immune status remains limited. This systematic review aimed to evaluate the association between onychomycosis and HIV, focusing on prevalence, clinical characteristics, etiologic agents, and CD4+ T lymphocyte counts at diagnosis. Methods: A systematic review was conducted following PRISMA guidelines. MEDLINE/PubMed, SciELO, Scopus, and Scilit were searched for studies published between October 2015 and July 2025 in English and Spanish. Eligible studies included case reports, case series, and observational studies involving people with HIV and confirmed onychomycosis. Data extraction was performed independently, and findings were analyzed descriptively. Results: Thirty studies comprising 1296 patients were included; 306 had detailed clinical descriptions. Most cases were reported in the Americas (85.8%) and predominantly involved male patients. CD4+ counts were available in 123 individuals; 52% had <200 cells/µL, including 18 with <50 cells/µL. Trichophyton rubrum was the most frequently identified etiologic agent. Conclusions: Onychomycosis in HIV shows etiologic diversity and commonly affects patients with advanced immunosuppression, though it may also occur with partial immune preservation. Prospective standardized studies are needed. Full article

The HIV-1 genome is initially transcribed as a single primary RNA that undergoes extensive splicing to produce over 40 linear and 15 circular RNA (circRNA) isoforms sharing common sequences. Conventional methods for circRNA detection, such as Northern blotting and hybridization-based assays, are inadequate for distinguishing specific circRNA isoforms when multiple circular and linear species originate from the same transcript. We previously identified 15 HIV-1 circRNAs generated by backsplicing and demonstrated that some enhance viral replication by sequestering cellular miRNAs. PCR-based approaches using divergent primers (RT-qPCR) offer greater specificity for detecting individual circular RNAs under these conditions. Building on this, we have developed a TaqMan qPCR assay capable of specifically detecting 14 HIV circRNA isoforms using backsplicing junction-directed divergent primers coupled to a hydrolysis probe for signal confirmation. Compared with matched SYBR Green assays, the TaqMan platform showed lower background in non-infected controls and reduced variance across donor-derived samples. This method provides a robust platform for selective and qualitative analysis of HIV-1 circRNAs. Full article

Endophytic fungi are promising sources of novel antiviral compounds, and the crude extract from Alternaria alternata PO4PR2 has previously shown anti-HIV-1 activity. This study evaluated its efficacy against integrase strand-transfer inhibitor (INSTI)-resistant HIV-1 and its mechanism of action. Key resistance mutations (Y143H, G118R, N155H, and R263K) were introduced into the HIV-1 pNL4.3 clone via site-directed mutagenesis and confirmed through Sanger sequencing. Viral infectivity was assessed in TZM-bl cells, while cytotoxicity was measured using an MTT assay. Antiviral activity was determined through a luciferase-based assay, and integration inhibition was evaluated using integrase activity assays and Alu-gag nested PCR. The extract demonstrated potent inhibition of resistant mutants, with low IC₅₀ values (0.02971–0.1652 μg/mL), and showed minimal cytotoxicity (CC₅₀ = 300 μg/mL), maintaining over 80% cell viability. It inhibited integrase activity by 67%, specifically targeting the strand-transfer step, and significantly reduced integrated viral DNA. Molecular docking of 14 compounds identified coumarin derivatives as key bioactive metabolites, exhibiting mutation-tolerant binding within the integrase catalytic pocket. Overall, these findings highlight PO4PR2 as a promising source of compounds for developing new therapies targeting drug-resistant HIV-1 integrase. Full article

Background/Objectives: Aim: Dental practice involves continuous exposure to saliva and blood, creating persistent opportunities for cross-infection if contaminated instruments are not processed correctly. This study aimed to evaluate dental students’ knowledge regarding blood-borne infections and infection prevention measures, and to compare knowledge levels according to academic year and sex. Materials and Methods: A structured questionnaire consisting of 21 single-best-answer questions was administered to 93 undergraduate dental students (Years I–VI) from the Faculty of Dental Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, Iași, Romania. The questionnaire evaluated knowledge related to instrument classification, cleaning and disinfection procedures, sterilization parameters, autoclave monitoring tests, and storage conditions. Demographic data were also collected. Statistical analysis was performed using IBM SPSS Statistics version 31, and associations between responses and demographic variables were assessed using chi-square tests. Associations between responses and demographic variables (academic year and sex) were evaluated using chi-square tests (p < 0.05). Results: Most participants correctly identified several key steps in the instrument processing circuit, including the use of high-level disinfectant–detergent solutions (88.2%) and the need for disinfection followed by sterilization (76.3%). However, important knowledge gaps were identified regarding autoclave pre-use checks, correct sterilization temperatures and exposure times, recommended sterile storage periods, and the interpretation of sterilization monitoring tools such as type 5 chemical integrators, Bowie–Dick tests, and Helix tests. Knowledge levels differed significantly according to academic year (p < 0.05). Conclusions: Although overall awareness of instrument processing procedures among dental students was generally satisfactory, several inconsistencies were observed in critical technical aspects of sterilization and monitoring. These findings highlight the need for strengthened infection control education and repeated practical training to reduce the risk of cross-infection in dental practice. Full article