Search Results (1,748)

Background: Drug–drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women’s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein–protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies. Full article

Background: HIV-associated neurocognitive disorders (HANDs) continue to be a significant concern, despite the advancements in prognosis achieved through Combination Antiretroviral Therapy (cART). Neuropsychological assessment, recommended by international guidelines for HANDs diagnosis, can be resource-intensive. Brief screening tools, like the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA), are crucial in facilitating initial evaluations. This study aims to assess the Italian IHDS (IHDS-IT) and evaluate its sensitivity and specificity in detecting cognitive impairment in HIV patients. Methods: This cross-sectional study involved 294 patients aged ≥30 years, evaluated at the Immunology Unit of the University of Cagliari. Cognitive function was assessed using the MoCA and IHDS. Laboratory parameters, such as CD4 nadir, current CD4 count, and HIV-RNA levels, were also collected. Statistical analyses included Spearman’s correlation, Receiver Operating Characteristic analysis, and the Youden J statistic to identify the optimal IHDS-IT cut-off for cognitive impairment detection. Results: The IHDS and MoCA scores showed a moderate positive correlation (Spearman’s rho = 0.411, p < 0.0001). ROC analysis identified an IHDS-IT cut-off of ≤9, yielding an Area Under the Curve (AUC) of 0.76, sensitivity of 71.7%, and specificity of 67.2%. At this threshold, 73.1% of patients with MoCA scores below 23 also presented abnormal IHDS scores, highlighting the complementary utility of both cognitive assessment instruments. Conclusions: The IHDS-IT exhibited fair diagnostic accuracy for intercepting cognitive impairment, with a lower optimal cut-off than previously reported. The observed differences may reflect this study cohort’s demographic and clinical characteristics, including advanced age and long-lasting HIV infection. Further, longitudinal studies are necessary to validate these findings and to confirm the proposed IHDS cut-off over extended periods. Full article

Mpox has become a significant health concern since the global outbreak that began in 2022. The aim of this study is to present the epidemiological situation of Mpox in Romania during 2022–2023 and to describe a severe case of Mpox in a patient who survived despite multiple co-pathologies. Forty-seven confirmed cases were reported at the national level, all in men, in 2022. The median age was 33 years. Twenty-six cases involved men who have sex with men (MSM), and twenty-three tested positive for HIV. We also describe a severe case involving a 34-year-old bisexual male with newly diagnosed AIDS who developed severe Mpox with persistent necrotic skin lesions, respiratory involvement, and multiple opportunistic infections: tuberculosis, pneumocystis pneumonia, syphilis, and oral candidiasis. The patient presented with fever, night sweats, weight loss, and dyspnea, with a single ulcerative facial lesion that later disseminated. Mpox infection was confirmed through PCR from skin lesion, serum, saliva, urine, rectal, nasal, and pharyngeal swab samples, with high viral loads persisting despite prolonged Tecovirimat therapy. The patient developed immune reconstitution inflammatory syndrome following the initiation of antiretroviral therapy. This case emphasizes the challenges of treating Mpox in immunocompromised patients. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Human Immunodeficiency Virus (HIV) infection remains a major global health issue, with effective antiretroviral therapy (ART) extending life expectancy but also increasing age-related issues like osteopenia and osteoporosis. This cross-sectional study examines bone mineral density (BMD) and related risk factors in Romanian HIV-positive patients, emphasizing regional and therapy influences. The patients varying in HIV infection duration underwent DXA scanning to measure BMD in the lumbar spine, femoral neck, and total femur. A high prevalence of low BMD, especially in the lumbar spine, was identified along with significant associations between reduced BMD and factors such as smoking, alcohol use, vitamin D deficiency and serum phosphorus levels. ART like Protease Inhibitors and Nucleoside Reverse Transcriptase Inhibitors were linked to increased bone loss, emphasizing the multifactorial nature of osteoporosis in HIV-infected individuals and underscore the importance of regular BMD assessments, lifestyle adjustments, and careful management of antiretroviral therapy to minimize fracture risk and enhance overall health and quality of life. Full article

Background/Objectives: The consumption of opioids is a public health problem that significantly affects quality of life. In Spain, 7585 people are enrolled in the Methadone Maintenance Programme (MMP), which is an effective intervention with a low adherence rate. In this study, factors associated with the quality of life of MMP users, especially perceived social support and treatment adherence, were analysed. We hypothesised that low levels of adherence and social support would be associated with poorer quality of life. Methods: This was a cross-sectional observational study with an analytical approach. Quality of life (WHOQoL-BREF), perceived social support (DUKE-UNC-11), and treatment adherence (MMAS-8) among MMP users were studied, and data on sociodemographic and clinical characteristics were collected through ad hoc questionnaires and a review of electronic medical records. Linear and logistic regression models were used. Results: A total of 70 individuals were included in this study. The mean age was 56.9 years, and 83% of the participants were male. The perceived quality of life was low in the four domains evaluated (range of 47.4–48.2). A total of 38.57% of the participants had low perceived social support. Treatment adherence was low or moderate in 77.1% of the participants. Greater perceived social support was associated with better quality of life in all domains (p < 0.05). Quality of social life was negatively associated with the use of nonbenzodiazepine neuroleptics and HIV status. Treatment adherence was lower in insulin therapy users. Conclusions: Social support is a key determinant of the quality of life of MMP users. Health policies should promote social support networks as a strategy to improve the well-being of this population. Full article

Background and Objectives: Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) offers an alternative to daily oral antiretroviral therapy (ART) for people living with HIV (PLWH). Although LA-CAB/RPV has been approved in Turkey, the country remains in the pre-rollout period, and national data on patient perspectives are lacking. This is the first nationwide study from Turkey, a setting of increasing HIV incidence, assessing PLWH perspectives on switching to LA-CAB/RPV and the influence of motivational factors on treatment preferences. Materials and Methods: A prospective, multicenter, cross-sectional study was conducted across 11 HIV treatment centers representing all regions of Turkey. Virologically suppressed PLWH meeting current eligibility criteria for LA-CAB/RPV were included. Treatment preferences (switch to LA-CAB/RPV or remain on oral ART) and five anticipated motivational domains, namely perceived efficacy, safety, convenience, privacy, and cost, were systematically assessed through structured, face-to-face interviews. Results: Among 200 eligible participants, 86% (n = 172) preferred switching to LA-CAB/RPV. In all subgroups, LA-CAB/RPV was preferred over oral ART, except for those with no formal literacy. Prior awareness of LA-CAB/RPV was significantly associated with the switching preference (p < 0.001), with healthcare providers being the most common source of information, at 45.5% (n = 172) (p < 0.001). Residential proximity to the healthcare center (p = 0.018) and all motivational factors significantly influenced the preference (p < 0.05). Notably, when participants who initially chose to remain on oral ART were asked whether they would reconsider switching if injections were administered every six months, overall preference for long-acting therapy increased from 86% to 98%. Conclusions: High clinical eligibility and strong acceptability for LA-CAB/RPV were observed among Turkish PLWH. Our findings demonstrate that structured motivational factors significantly influence the treatment preference. Addressing these patient-centered factors and logistical barriers may support the successful integration of long-acting therapies into routine HIV care. Future longer-interval agents may improve patient-centered acceptability. Full article

Regional HIV-1 epidemics are evolving with distinct patterns in transmission routes, subtype distribution, and molecular transmission cluster (MTCs) characteristics. We analyzed 9500 HIV-1 cases diagnosed over 30 years using phylogenetic and network methods, integrating molecular, epidemiological, demographic, and behavioral data. Subtype A6 remains dominant nationally (80.6%), followed by 63_02A6 (7.9%), subtype B (5.6%), 02_AG_FSU (1.2%), 03_A6B (0.7%), and 14/73_BG (0.6%). Non-A6 infections were more common among males (OR 1.51) and men who have sex with men (OR 7.33). Network analysis identified 421 MTCs, with 256 active clusters. Clustering was more likely among young individuals (OR: 1.31), those not receiving antiretroviral therapy (OR: 2.70), and injecting drug users (OR: 1.28). Non-A6 subtypes showed a higher likelihood of clustering. Phylogenetic analysis revealed that local clusters of the major subtypes originated between the late 1970s (subtype B) and the mid-2000s (63_02A6) with links to populations in Eastern Europe, Central Asia (subtypes A6, 63_02A6, 02_AG_FSU, 03_A6B), and Western Europe and the Americas (subtype B, 14/73_BG). These findings indicate a complex, evolving regional epidemic transitioning from subtype A6 dominance to a more diverse mix of subtypes. The ability of non-A6 subtypes to form active MTCs suggests their establishment in the local population. Full article

The HIV-1 aspartic protease is an effective target for the treatment of HIV/AIDS. Current therapy utilizes a selection of nine protease inhibitors (PIs) in combination with other classes of antiretroviral drugs. Although PIs were originally developed based on the knowledge of the HIV-1 subtype B protease, the existence of other HIV-1 subtypes and the effects of drug resistance on currently available PIs have become a major challenge in the treatment of HIV/AIDS. Specifically, the HIV-1 subtype C accounts for more than half of the global HIV infections. Considering the importance and relevance of the subtype C virus, in this timely review we discuss the effect of polymorphisms in the HIV-1 subtype C protease on drug resistance, flap flexibility, and hinge region dynamics. We discuss novel paradigms of protease inhibition that attempt to overcome the limitations of currently available inhibitors which fall short considering genetic diversity and resistance mutations. Full article

Background/Objectives: The timely initiation of antiretroviral therapy (ART) in persons living with HIV (PLWH) can improve clinical outcomes. However, ART commencement is often delayed. Portugal, despite having one of the highest new HIV diagnosis rates within the European Union, has limited available national-level data. Prior evidence from 2017 to 2018 suggests that the average time to ART initiation exceeds the recommendations for optimal patient benefits. This study aimed to determine the number of days from the first hospital appointment to the commencement of ART among newly diagnosed PLWH in Portugal between 2017 and 2022 at the national level and across different hospitals. It was hypothesized that newly diagnosed PLWH in Portugal experience a delay in ART initiation beyond the recommended timeframe. Methods: A retrospective analysis of records from Portuguese public tertiary care hospitals, which manage most HIV patients, was conducted. Descriptive statistics (measures of central tendency, dispersion, and frequency) were applied, along with association tests and a binary logistic regression model to examine factors influencing the timing of ART initiation. Results: A total of 2229 cases (out of 3434 received) from 19 hospitals were considered eligible. The median time interval between the first hospital appointment and ART initiation was 29.00 days, with a decreasing tendency between 2017 and 2022. Patients initiating therapy after 14 days had higher CD4 levels and lower viral loads compared to those starting within 14 days, with statistical significance. Conclusions: Continuous and regular monitoring of key indicators, such as the time to ART initiation, is pivotal for assessing the effectiveness of HIV treatment programs and pinpointing areas in need of improvement. Full article

RNA viruses pose significant threats to global health, causing diseases such as COVID-19, HIV/AIDS, influenza, and dengue. These viruses are characterized by high mutation rates, rapid evolution, and the ability to evade traditional antiviral therapies, making effective treatment and prevention particularly challenging. In recent years, CRISPR/Cas13 has emerged as a promising antiviral tool due to its ability to specifically target and degrade viral RNA. Unlike conventional antiviral strategies, Cas13 functions at the RNA level, providing a broad-spectrum and programmable approach to combating RNA viruses. Its flexibility allows for rapid adaptation of guide RNAs to counteract emerging viral variants, making it particularly suitable for highly diverse viruses such as SARS-CoV-2 and HIV. This review discusses up-to-date applications of Cas13 in targeting a wide range of RNA viruses, including SARS-CoV-2, HIV, dengue, influenza, and other RNA viruses, focusing on its therapeutic potential. Preclinical studies have demonstrated Cas13’s efficacy in degrading viral RNA and inhibiting replication, with applications spanning prophylactic interventions to post-infection treatments. However, challenges such as collateral cleavage, inefficient delivery, potential immunogenicity, and the development of an appropriate ethical framework must be addressed before clinical translation. Future research should focus on optimizing crRNA design, improving delivery systems, and conducting rigorous preclinical evaluations to enhance specificity, safety, and therapeutic efficacy. With continued advancements, Cas13 holds great promise as a revolutionary antiviral strategy, offering novel solutions to combat some of the world’s most persistent viral threats. Full article

Acute myocardial infarction (AMI) in young adults, though less common than in older populations, is an emerging clinical concern with increasing incidence and diverse etiologies. Unlike classic atherosclerotic presentations, a significant proportion of AMI cases in individuals under 45 years are due to nonatherothrombotic mechanisms such as coronary vasospasm, spontaneous coronary artery dissection (SCAD), vasculitis, hypercoagulable states, and drug-induced coronary injury. This manuscript aims to explore the multifactorial nature of AMI in young adults through a focused review of current evidence and a series of illustrative clinical cases. We present and analyze four distinct cases of young patients with AMI, each demonstrating different pathophysiological mechanisms and risk profiles—including premature atherosclerosis, substance use, human immunodeficiency virus (HIV)-related coronary disease, and SCAD. Despite the heterogeneity of underlying causes, early diagnosis, individualized management, and aggressive secondary prevention were key to favorable outcomes. Advanced imaging, lipid profiling, and risk factor modification played a central role in guiding therapy. AMI in young adults requires heightened clinical suspicion and a comprehensive, multidisciplinary approach. Early intervention and recognition of nontraditional risk factors are essential to improving outcomes and preventing recurrent events in this vulnerable population. Full article

Background/Objective: Fentanyl plays a pivotal role in the opioid epidemic, defined by four waves of overdose deaths. To analyse fentanyl research trends, examining its links to mental health, pharmaceutical development, healthcare, diseases, and pathophysiology within the broader social and health context of the time. Methods: To understand the evolution of scientific publications on fentanyl and its relationship to the opioid crisis, a search using Web of Science Core Collection and PubMed was conducted. A total of 53,670 documents were retrieved related to opioid scientific production, among which 1423 articles (3%) focused specifically on fentanyl. The 21,546 MeSH terms identified in these documents were analysed by publication year and specific fields: Psychiatry and Psychology, Chemicals and Drugs, Healthcare, Diseases, and Phenomena and Processes. R-statistical/FactoMineR libraries were used for the correspondence analysis. Results: In the first overdose death wave, research focused on improving therapies and reducing side effects. The second wave emphasised detoxification methods with naltrexone, methadone, and behavioural therapies. The third wave addressed psychological treatments and HIV-syringe-sharing prevention. The fourth wave prioritised less addictive analogues and understanding consumer profiles to combat the epidemic. Conclusions: Fentanyl research has evolved alongside real-world challenges, reinforcing the connection between patients’ needs, healthcare professionals’ roles, illicit users, policymakers, and the research community’s contributions to addressing both therapeutic use and its broader societal impact. These findings highlight the necessity for an interdisciplinary approach to scientific research integrating prevention, treatment, education, legal reform, and social support, emphasising the need for public health policies and collaborative research to mitigate its impact. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article