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11 pages, 579 KiB  
Article
Prevalence of Sexually Transmitted Infections Among Cisgender Women Coming to a Walk-In Center
by Gaia Catalano, Tommaso Clemente, Sara Diotallevi, Riccardo Lolatto, Benedetta Trentacapilli, Martina Ranzenigo, Elena Bruzzesi, Paola Cinque, Antonella Castagna and Silvia Nozza
Viruses 2025, 17(4), 498; https://doi.org/10.3390/v17040498 (registering DOI) - 29 Mar 2025
Abstract
The general female population is not considered a high-risk group for screening for sexually transmitted infections (STIs). This retrospective study describes the prevalence of Human Immunodeficiency Virus (HIV), Treponema pallidum (T. pallidum), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae ( [...] Read more.
The general female population is not considered a high-risk group for screening for sexually transmitted infections (STIs). This retrospective study describes the prevalence of Human Immunodeficiency Virus (HIV), Treponema pallidum (T. pallidum), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae), Trichomonas vaginalis (T. vaginalis), Mycoplasma spp., Ureaplasma spp., genital Herpes simplex virus (HSV), Monkeypox (mpox), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infections in asymptomatic and symptomatic cisgender women attending our walk-in STI clinic for the first time. Furthermore, it analyzes the number of individuals who returned for follow-up and were diagnosed with new STIs. Over 20 months, 189 women with a median age of 28.4 years were screened [129 (68.3%) asymptomatic and 60 (31.8%) symptomatic]. In order of prevalence, the most common STIs were: Ureaplasma spp. infections (50.3%), C. trachomatis (10.6%), N. gonorrhoeae (5.8%), Mycoplasma hominis infections (5.8%), T. pallidum (2.65%), HSV2 infections (2.65%), and mpox (0.53%). No diagnosis of HIV, trichomoniasis, HBV, or HCV was registered. After the initial evaluation, 128 (67.7%) women returned for follow-up, but only 43 (22.8%) repeated screening; among them, 11 (25.6%) were diagnosed with new STIs. Given the high prevalence of STIs in cisgender women, awareness measures to improve screening and prevention strategies in this neglected population are required. Full article
30 pages, 930 KiB  
Review
The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice
by Manlio Tolomeo, Francesco Tolomeo and Antonio Cascio
Int. J. Mol. Sci. 2025, 26(7), 3184; https://doi.org/10.3390/ijms26073184 (registering DOI) - 29 Mar 2025
Abstract
Antiretroviral therapy (ART) has significantly improved the prognosis of human immunodeficiency virus type 1 (HIV-1) infection. Although ART can suppress plasma viremia below detectable levels, it cannot eradicate the HIV-1 DNA (provirus) integrated into the host cell genome. This integration often results in [...] Read more.
Antiretroviral therapy (ART) has significantly improved the prognosis of human immunodeficiency virus type 1 (HIV-1) infection. Although ART can suppress plasma viremia below detectable levels, it cannot eradicate the HIV-1 DNA (provirus) integrated into the host cell genome. This integration often results in unrepaired DNA damage due to the HIV-1-induced inhibition of DNA repair pathways. Furthermore, HIV-1 infection causes telomere attrition in host chromosomes, a critical factor contributing to CD4+ T cell senescence and apoptosis. HIV-1 proteins can induce DNA damage, block DNA replication, and activate DNA damage responses across various organs. In this review, we explore multiple aspects of the intricate interactions between HIV-1 and the host genome involved in CD4+ T cell depletion, inflammaging, the clonal expansion of infected cells in long-term-treated patients, and viral latency. We discuss the molecular mechanisms of DNA damage that contribute to comorbidities in HIV-1-infected individuals and highlight emerging therapeutic strategies targeting the integrated HIV-1 provirus. Full article
(This article belongs to the Special Issue Molecular Insights into Zoonotic Diseases)
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25 pages, 1993 KiB  
Systematic Review
Telemedicine Adoption and Prospects in Sub-Sahara Africa: A Systematic Review with a Focus on South Africa, Kenya, and Nigeria
by Abayomi O. Agbeyangi and Jose M. Lukose
Healthcare 2025, 13(7), 762; https://doi.org/10.3390/healthcare13070762 (registering DOI) - 29 Mar 2025
Viewed by 147
Abstract
Background/Objectives: Telemedicine has emerged as a transformative solution to healthcare access challenges in Sub-Saharan Africa, where many populations remain underserved. This systematic review focuses on the adoption, implementation, and technological prospects of telemedicine in South Africa, Kenya, and Nigeria, three countries leading the [...] Read more.
Background/Objectives: Telemedicine has emerged as a transformative solution to healthcare access challenges in Sub-Saharan Africa, where many populations remain underserved. This systematic review focuses on the adoption, implementation, and technological prospects of telemedicine in South Africa, Kenya, and Nigeria, three countries leading the region in healthcare innovations. Methods: A systematic search of PubMed, Scopus, and Web of Science, guided by PRISMA protocols, identified 567 studies published between 2014 and 2024, of which 53 met the inclusion criteria with a focus on telemedicine adoption, implementation, and technological prospects in the selected countries. A structured critical appraisal was used to assess potential biases in the included studies’ design, selection criteria, and reporting, while findings were thematically analysed to provide actionable and comparative insights. Results: The findings reveal that South Africa has the highest adoption rate, focusing on specialist teleconsultations, chronic disease management, and mental health services. Kenya demonstrates strong mHealth integration and advanced mobile applications, particularly in maternal health, HIV care, and sexual and reproductive health. While facing infrastructural and regulatory constraints, Nigeria is advancing innovations for remote diagnosis and teleconsultation. Conclusions: By synthesising evidence from peer-reviewed literature, the review identifies adoption trends, enabling factors, and opportunities for scaling telemedicine in these contexts. Despite these advancements, challenges persist, including regulatory gaps, digital literacy limitations, and infrastructure constraints. Addressing these barriers requires targeted investments in broadband expansion, policy harmonisation, and healthcare workforce training to optimise telemedicine’s impact and ensure its sustainability as a healthcare delivery model in Sub-Saharan Africa. Full article
(This article belongs to the Section TeleHealth and Digital Healthcare)
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4 pages, 284 KiB  
Editorial
Doxycycline Post-Exposure Prophylaxis for Sexually Transmitted Infections: One Shot for How Many Infections?
by Alessandra Latini
Venereology 2025, 4(2), 4; https://doi.org/10.3390/venereology4020004 (registering DOI) - 28 Mar 2025
Viewed by 39
Abstract
Over the past decade, the landscape of sexually transmitted infections (STIs) has evolved considerably. Epidemiological data indicate a steady increase in bacterial STIs [1], such as chlamydia, gonorrhea, and syphilis, across various populations worldwide.  [...] Full article
15 pages, 1425 KiB  
Review
Exploring a Rare Association: Systematic Review of Hypercalcemia in Nontuberculous Mycobacterial Infections
by Ramon Cohen, Viviana Ostrovsky, Lior Zornitzki, Daniel Elbirt and Taiba Zornitzki
Microorganisms 2025, 13(4), 773; https://doi.org/10.3390/microorganisms13040773 - 28 Mar 2025
Viewed by 131
Abstract
Hypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illustrative case of Mycobacterium simiae. A meticulous [...] Read more.
Hypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illustrative case of Mycobacterium simiae. A meticulous literature search identified 24 cases relevant to this phenomenon (11 HIV-positive and 13 non-HIV), which were included in the analysis. Key clinical and laboratory findings reveal significant contrasts between HIV-positive and non-HIV patients. In the HIV-positive cohort, hypercalcemia is commonly developed after the initiation of highly active antiretroviral therapy (HAART) or treatment for NTM infections despite severe underlying immunosuppression. Conversely, in the non-HIV group, a spectrum of immunosuppressive conditions, including chronic renal failure and prolonged use of immunosuppressive drugs, was implicated in the pathogenesis of NTM infections with hypercalcemia. Two distinct mechanistic pathways likely underlie this association. In HIV-positive patients, immune restoration following HAART appears to drive granuloma formation and excessive 1,25-dihydroxyvitamin D production. In non-HIV individuals, prolonged immune suppression may facilitate macrophage activation associated with NTM infections, thereby contributing to hypercalcemia. Treatment strategies varied and included bisphosphonates, corticosteroids, and hemodialysis. Notably, bisphosphonates emerged as a safe and effective option in most cases. Antibiotic therapy was deemed unnecessary when hypercalcemia was the sole symptom of NTM infection. This review underscores the importance of recognizing hypercalcemia as a potential complication of NTM infections and tailoring management strategies to the patient’s underlying immunological status. Full article
(This article belongs to the Section Medical Microbiology)
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14 pages, 2089 KiB  
Article
Subtype AD Recombinant HIV-1 Transmitted/Founder Viruses Are Less Sensitive to Type I Interferons than Subtype D
by Denis Omara, Fortunate Natwijuka, Anne Kapaata, Frank Kato, Laban Kato, Christian Ndekezi, Angella Nakyanzi, Mercy L. Ayebale, Ling Yue, Eric Hunter, Obondo J. Sande, Christina Ochsenbauer, Pontiano Kaleebu and Sheila N. Balinda
Viruses 2025, 17(4), 486; https://doi.org/10.3390/v17040486 - 28 Mar 2025
Viewed by 166
Abstract
Initial interactions between HIV-1 and the immune system at mucosal exposure sites play a critical role in determining whether the virus is eliminated or progresses to establish systemic infection. The virus that successfully crosses the mucosal barrier to establish infection in the new [...] Read more.
Initial interactions between HIV-1 and the immune system at mucosal exposure sites play a critical role in determining whether the virus is eliminated or progresses to establish systemic infection. The virus that successfully crosses the mucosal barrier to establish infection in the new host is referred to as the transmitted/founder (TF) virus. Following mucosal HIV-1 transmission, type 1 interferons (IFN-I) are rapidly induced at sites of initial virus replication. The resistance of TF variants to these antiviral effects of the IFN-I has been studied among HIV-1 subtypes B and C. However, their role in restricting HIV-1 replication among subtypes D and AD recombinant remains unexplored. This study assessed the sensitivity of HIV-1 subtype D and AD recombinant TF viruses to IFN-I by infecting peripheral blood mononuclear cells in vitro with infectious molecular clones of these viruses. Cells were exposed to varying concentrations of interferon-α and interferon-β, and viral replicative capacity was measured using HIV-1 p24 antigen ELISA from culture supernatants. Sensitivity to IFN-I was quantified based on viral replication levels. The results showed that interferon-α was more effective in inhibiting viral replication than interferon-β, regardless of the varying amounts of IFN-I used. However, recombinant AD viruses were found to be more resistant to the antiviral effects of IFN-I compared to subtype D viruses. These findings highlight the differential sensitivity of HIV-1 subtypes AD recombinant and D TF viruses to IFN-I and underscore the potential of IFN-I as a therapeutic strategy to target TF viruses and reduce HIV-1 transmission, particularly in populations where subtype D is prevalent. Full article
(This article belongs to the Special Issue Innate Immunity to Virus Infection 2nd Edition)
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14 pages, 2290 KiB  
Article
Incidence of Confirmed Influenza and Pneumococcal Infections and Vaccine Uptake Among Virologically Suppressed People Living with HIV
by Edith Wolder Ejlersen, Josefine Amalie Loft, Marco Gelpi, Safura-Luise Heidari, Omid Rezahosseini, Johan Runge Poulsen, Dina Leth Møller, Zitta Barrella Harboe, Thomas Benfield, Susanne Dam Nielsen and Andreas Dehlbæk Knudsen
Vaccines 2025, 13(4), 358; https://doi.org/10.3390/vaccines13040358 - 27 Mar 2025
Viewed by 105
Abstract
Background/Objectives: Influenza and Streptococcus pneumoniae infections are common vaccine-preventable diseases to which people living with HIV (PLWH) may be more susceptible. This study aims to investigate the incidence of confirmed influenza and pneumococcal infections, and to determine the incidence rate (IR) and factors [...] Read more.
Background/Objectives: Influenza and Streptococcus pneumoniae infections are common vaccine-preventable diseases to which people living with HIV (PLWH) may be more susceptible. This study aims to investigate the incidence of confirmed influenza and pneumococcal infections, and to determine the incidence rate (IR) and factors associated with vaccine uptake in a population of virologically suppressed PLWH. Methods: We included 1031 virologically suppressed PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Data on infections and vaccinations between 2015 and 2020 were collected from nationwide registries. Incidence rates with 95% confidence intervals (CIs) of confirmed influenza and pneumococcal infections and vaccine uptake were calculated, and predictors of vaccine uptake were explored using logistic regression. Results: The IR of influenza showed variation from year to year and ranged between 0 (95% CI: 0.0, 7.6) and 18.0 (95% CI: 8.2, 34.1) per 1000 person-years at risk with an overall IR of 8.4 per 1000 person-years at risk (95% CI: 5.4, 12.3). The overall IR of pneumococcal infections was 5.5 per 1000 person-years at risk (95% CI: 3.9, 7.5). Among PLWH, 53.2% were influenza-vaccinated at least once, 72.3% and 22.6% of PLWH were vaccinated at least twice and in all six seasons, respectively, while 31% had at least one pneumococcal vaccine. Previous pneumonia or bronchitis, higher body mass index, use of drugs to treat heart conditions, and longer time with HIV were independently associated with vaccine uptake. Conclusions: We found high incidences of confirmed influenza and pneumococcal infections in virologically suppressed PLWH, but vaccine uptake was below recommendations, highlighting the need for improved vaccination counseling. Full article
(This article belongs to the Section Epidemiology)
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19 pages, 2336 KiB  
Review
Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers?
by Kaci Craft, Athina Amanor, Ian Barnett, Clarke Donaldson, Ignacio Anegon, Srinivas Madduri, Qiyi Tang and Moses T. Bility
Int. J. Mol. Sci. 2025, 26(7), 3082; https://doi.org/10.3390/ijms26073082 - 27 Mar 2025
Viewed by 286
Abstract
Over the past three decades, immunodeficient mouse models carrying human immune cells, with or without human lymphoid tissues, termed humanized immune system (HIS) rodent models, have been developed to recapitulate the human immune system and associated immune responses. HIS mouse models have successfully [...] Read more.
Over the past three decades, immunodeficient mouse models carrying human immune cells, with or without human lymphoid tissues, termed humanized immune system (HIS) rodent models, have been developed to recapitulate the human immune system and associated immune responses. HIS mouse models have successfully modeled many human-restricted viral infections, including those caused by human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV). HIS mouse models have also been used to model human cancer immunobiology, which exhibits differences from murine cancers in traditional mouse models. Variants of HIS mouse models that carry human liver cells, lung tissue, skin tissue, or human patient-derived tumor xenografts and human hematopoietic stem cells-derived-human immune cells with or without lymphoid tissue xenografts have been developed to probe human immune responses to infections and human tumors. HCMV-based vaccines are human-restricted, which poses limitations for mechanistic and efficacy studies using traditional animal models. The HCMV-based vaccine approach is a promising vaccine strategy as it induces robust effector memory T cell responses that may be critical in preventing and rapidly controlling persistent viral infections and cancers. Here, we review novel HIS mouse models with robust human immune cell development and primary and secondary lymphoid tissues that could address many of the limitations of HIS mice in their use as animal models for HCMV-based vaccine research. We also reviewed novel HIS rat models, which could allow long-term (greater than one year) vaccinology studies and better recapitulate human pathophysiology. Translating laboratory research findings to clinical application is a significant bottleneck in vaccine development; HIS rodents and related variants that more accurately model human immunology and diseases could increase the translatability of research findings. Full article
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19 pages, 1201 KiB  
Article
Temporal Trends in HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in Istanbul, Türkiye (2021–2024): A Next-Generation Sequencing Study
by Murat Yaman, Begüm Saran Gülcen, Kübra Özgüler, Muammer Osman Köksal, Serap Demir Tekol and Arzu İlki
Viruses 2025, 17(4), 478; https://doi.org/10.3390/v17040478 - 27 Mar 2025
Viewed by 208
Abstract
HIV-1 genotyping and drug resistance tests are routinely performed in virology laboratories in some countries, aiding clinical management. In Istanbul, between January 2021 and March 2024, plasma samples from 1029 HIV-1-infected patients were analyzed using the NGS method, and mutation and drug resistance [...] Read more.
HIV-1 genotyping and drug resistance tests are routinely performed in virology laboratories in some countries, aiding clinical management. In Istanbul, between January 2021 and March 2024, plasma samples from 1029 HIV-1-infected patients were analyzed using the NGS method, and mutation and drug resistance results were retrospectively evaluated alongside demographic data. Subtype B (54.4%) was most frequent in Turkish patients, while Subtype A1 (43.5%) was predominant among foreign nationals. The most common CRFs were CRF02_AG (3.8%) and CRF56_cpx (1.6%). According to the change in detection rates during the study period, Subtype B decreased, and Subtype A increased. The most frequent mutations detected were A62V (38.7%) and M184V (22.4%) for NRTIs; E138A (55.5%) and E138G (11.5%) for NNRTIs; M46I (33.3%) and M46L (25%) for PIs; and E92Q and G for INIs (total rate: 35.2%). Darunavir/ritonavir had the highest sensitivity rate, while resistance rates for NNRTIs and INIs increased over time. We anticipate that this study, in which we evaluate the routine use of an FDA-approved NGS kit alongside integrated bioinformatics data analysis and automated reporting software for the first time in Türkiye, will contribute to both national and international molecular epidemiological data and public health strategies by providing reliable results that align with international standarts. Full article
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18 pages, 243 KiB  
Article
Sextagram: Evaluating an Italian Instagram-Based Health Campaign Against AIDS
by Pina Lalli and Claudia Capelli
Societies 2025, 15(4), 79; https://doi.org/10.3390/soc15040079 - 26 Mar 2025
Viewed by 76
Abstract
The use of social media for disseminating health information to adolescents and young adults has garnered significant ttention, showing promising results. Younger audiences increasingly prefer social media and mobile aggregators for their informative needs, considering these platforms reliable sources, particularly for sexual health [...] Read more.
The use of social media for disseminating health information to adolescents and young adults has garnered significant ttention, showing promising results. Younger audiences increasingly prefer social media and mobile aggregators for their informative needs, considering these platforms reliable sources, particularly for sexual health and general health topics. This paper discusses the findings of a two-year project conducted in Italy—in collaboration with a group of non-profit organizations—funded by The Ministry of Health, intending to explore social media-based health communication strategies aimed at prevention for individuals aged 18 to 25. The objective was to leverage Instagram to engage young people, enhancing awareness about the risks of STIs and HIV/AIDS and promoting preventive behaviors. By analyzing two contrasting perspectives on health communication methods and the results in terms of engagement metrics and user feedback in the chosen profile, the study provides insights into social approaches for health communication and social representations of sexuality in the digital age, demonstrating risks and advantages of the use of platforms to influence health knowledge among young audiences. Full article
21 pages, 2590 KiB  
Article
A Data-Driven Intelligent Methodology for Developing Explainable Diagnostic Model for Febrile Diseases
by Constance Amannah, Kingsley Friday Attai and Faith-Michael Uzoka
Algorithms 2025, 18(4), 190; https://doi.org/10.3390/a18040190 - 26 Mar 2025
Viewed by 71
Abstract
Febrile diseases such as malaria, typhoid fever, tuberculosis, and HIV/AIDS pose significant diagnostic challenges in Low- and Middle-Income Countries (LMICs). Misdiagnosis leads to delayed treatment, increased healthcare costs, and higher mortality rates. This study presents a prototype diagnostic framework integrating machine learning (ML) [...] Read more.
Febrile diseases such as malaria, typhoid fever, tuberculosis, and HIV/AIDS pose significant diagnostic challenges in Low- and Middle-Income Countries (LMICs). Misdiagnosis leads to delayed treatment, increased healthcare costs, and higher mortality rates. This study presents a prototype diagnostic framework integrating machine learning (ML) and explainable artificial intelligence (XAI) to enhance diagnostic performance, interpretability, and usability in resource-constrained settings. A dataset of 3914 patient records from secondary and tertiary healthcare facilities was used to train and validate predictive models, employing Random Forest, Extreme Gradient Boost, and Multi-Layer Perceptron with optimized hyperparameters. To ensure transparency, XAI techniques such as Local Interpretable Model-Agnostic Explanations (LIME) and Large Language Models (LLMs) were integrated, enabling clinicians to understand model predictions. A prototype mobile-based diagnostic system was developed to explore its feasibility for real-time decision-making. The system features an intuitive interface, patient record management, and AI-driven diagnostic insights with visual and textual explanations. While usability testing with simulated case studies demonstrated its potential, real-world deployment and large-scale clinical validation are yet to be conducted. The system is designed with scalability in mind, allowing for future adaptation to different LMIC settings. However, limitations such as dataset imbalance and exclusion of pediatric data remain. Future research will focus on refining the model, expanding the dataset, and conducting extensive clinical validation before real-world implementation. This study serves as a foundational step toward AI-driven diagnostic tools in resource-limited healthcare environments. Full article
(This article belongs to the Special Issue Algorithms for Computer Aided Diagnosis: 2nd Edition)
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13 pages, 528 KiB  
Article
Implications of Cognitive Impairment on Antihypertensive Medication Use in HIV
by Azin Tavasoli, Bin Tang, Mohammadsobhan S. Andalibi, Donald R. Franklin, Scott L. Letendre, Robert K. Heaton and Ronald J. Ellis
Viruses 2025, 17(4), 470; https://doi.org/10.3390/v17040470 - 26 Mar 2025
Viewed by 149
Abstract
Background: Aging-related comorbidities such as cardiovascular disease and neurocognitive impairment are more common among people with HIV (PWH). Hypertension (HTN) has been implicated in cognitive decline, and antihypertensives with anticholinergic properties may exacerbate this decline. Our research probed the relationship between neurocognitive performance [...] Read more.
Background: Aging-related comorbidities such as cardiovascular disease and neurocognitive impairment are more common among people with HIV (PWH). Hypertension (HTN) has been implicated in cognitive decline, and antihypertensives with anticholinergic properties may exacerbate this decline. Our research probed the relationship between neurocognitive performance and antihypertensives in hypertensive PWH and in those without HIV (PWoH), examining whether increased antihypertensives followed the worsening in neurocognitive performance. Methods: This longitudinal analysis encompassed seven visits over five years, enrolled between 1999 and 2022. Participants were included if they reported HTN or used antihypertensives. All participants underwent comprehensive cognitive assessments, and their global cognitive performance was evaluated using summary, demographically corrected T-scores. The association between the global T-score and the number of antihypertensives was evaluated using generalized linear mixed-effects models. Summary regression-based change score (sRCS) was analyzed as an indicator of global performance over time. Results: Among 1158 hypertensive PWH (79.9% were on ART), worsening cognitive performance was associated with an increased number of antihypertensives (p = 0.012) but not in PWoH (p = 0.58). PWH had lower mean arterial pressure (MAP) than PWoH after adjusting for demographics (β = −5.05, p = 2.3 × 10−11). In PWH, an association between mean arterial pressure (MAP) and sRCS suggested that those with cognitive improvement had lower MAP (p = 0.027). PWH taking more anticholinergics were more likely to have worse cognitive performance over time (p < 0.001). Conclusions: PWH with declining neurocognitive performance over time used increasing numbers of antihypertensives, suggesting that their providers prescribed more antihypertensives because of either treatment refractory HTN or poor adherence. Prescribers should avoid using antihypertensives with anticholinergic properties when possible. Full article
(This article belongs to the Special Issue Neurocognitive Dynamics and Biomarkers in HIV)
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22 pages, 4454 KiB  
Article
Analysis of Factors That Regulate HIV-1 Fusion in Reverse
by Ayna Alfadhli, Robin Lid Barklis, Fikadu G. Tafesse and Eric Barklis
Viruses 2025, 17(4), 472; https://doi.org/10.3390/v17040472 - 26 Mar 2025
Viewed by 139
Abstract
Based on observations that HIV-1 envelope (Env) proteins on the surfaces of cells have the capacity to fuse with neighboring cells or enveloped viruses that express CD4 receptors and CXCR4 co-receptors, we tested factors that affect the capacities of lentiviral vectors pseudotyped with [...] Read more.
Based on observations that HIV-1 envelope (Env) proteins on the surfaces of cells have the capacity to fuse with neighboring cells or enveloped viruses that express CD4 receptors and CXCR4 co-receptors, we tested factors that affect the capacities of lentiviral vectors pseudotyped with CD4 and CXCR4 variants to infect Env-expressing cells. The process, which we refer to as fusion in reverse, involves the binding and activation of cellular Env proteins to fuse membranes with lentiviruses carrying CD4 and CXCR4 proteins. We have found that infection via fusion in reverse depends on cell surface Env levels, is inhibitable by an HIV-1-specific fusion inhibitor, and preferentially requires lentiviral pseudotyping with a glycosylphosphatidylinositol (GPI)-anchored CD4 variant and a cytoplasmic tail-truncated CXCR4 protein. We have demonstrated that latently HIV-1-infected cells can be specifically infected using this mechanism, and that activation of latently infected cells increases infection efficiency. The fusion in reverse approach allowed us to characterize how alteration of CD4 plus CXCR4 lipid membranes affected Env protein activities. In particular, we found that perturbation of membrane cholesterol levels did not affect Env activity. In contrast, viruses assembled in cells deficient for long-chain sphingolipids showed increased infectivities, while viruses that incorporated a lipid scramblase were non-infectious. Our results yield new insights into factors that influence envelope protein functions. Full article
(This article belongs to the Section Animal Viruses)
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11 pages, 560 KiB  
Article
Anti-HIV Activity of Tigliane Derivatives from Euphorbia nicaeensis Roots
by Gordana Krstić, Milka Jadranin, Dominique Schols, Sandra Claes, Vele Tešević, Boris Mandić, Slobodan Milosavljević and Karlo Wittine
Molecules 2025, 30(7), 1452; https://doi.org/10.3390/molecules30071452 - 25 Mar 2025
Viewed by 110
Abstract
Five previously undescribed tigliane diterpenes (14 and 7), along with three known tiglianes (5, 6, and 8) were isolated from the root extract of Euphorbia nicaeensis using chromatographic techniques. The structures of the isolated compounds were [...] Read more.
Five previously undescribed tigliane diterpenes (14 and 7), along with three known tiglianes (5, 6, and 8) were isolated from the root extract of Euphorbia nicaeensis using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques. The isolated compounds were tested for anti-HIV activity against HIV-1 NL4.3 and HIV-2 ROD strains. Two derivatives (2 and 8) exhibited significant anti-HIV activity, with IC50 values ranging from 1.10 to 7.47 µM. This study highlights the potential of E. nicaeensis root as a source of novel bioactive tigliane derivatives, warranting further investigation for possible use in HIV treatment. Full article
(This article belongs to the Special Issue Bioactivity of Natural Compounds: From Plants to Humans)
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17 pages, 1553 KiB  
Article
Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue
by Marieke M. Nühn, Stephanie B. H. Gumbs, Pauline J. Schipper, Irene Drosou, Lavina Gharu, Ninée V. E. J. Buchholtz, Gijsje J. L. J. Snijders, Frederieke A. J. Gigase, Annemarie M. J. Wensing, Jori Symons, Lot D. de Witte and Monique Nijhuis
Viruses 2025, 17(4), 467; https://doi.org/10.3390/v17040467 - 25 Mar 2025
Viewed by 187
Abstract
A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the [...] Read more.
A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b+) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4+ T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4+ T cells, while the remaining viruses replicated only in CD4+ T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies. Full article
(This article belongs to the Special Issue HIV Neurological Disorders: 2nd Edition)
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