Search Results (1,302)

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

Super-resolution microscopy (SRM) has revolutionized our understanding of subcellular structures, including cell organelles and viruses. For human immunodeficiency virus (HIV), SRM has significantly advanced knowledge of viral structural biology and assembly dynamics. This review analyzes how SRM techniques (particularly PALM, STORM, STED, and SIM) have been applied over the past decade to study HIV structural components and assembly. By categorizing and comparing studies based on SRM methods, HIV components, and labeling strategies, we assess the strengths and limitations of each approach. Our analysis shows that PALM is most commonly used for live-cell imaging of HIV Gag, while STED is primarily used to study the viral envelope (Env). STORM and SIM have been applied to visualize various components, including Env, capsid, and matrix. Antibody labeling is prevalent in PALM and STORM studies, targeting Env and capsid, whereas fluorescent protein labeling is mainly associated with PALM and focused on Gag. A recent emphasis on Gag and Env points to deeper investigation into HIV assembly and viral membrane dynamics. Insights from SRM studies of HIV not only enhance virological understanding but also inform future research in therapeutic strategies and delivery systems, including extracellular vesicles. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Diabetic sensorimotor polyneuropathy (DSPN) is the most prevalent complication of diabetes, affecting nearly half of all persons with diabetes. It is characterized by nerve degeneration, progressive sensory loss and pain, with increased risk of ulceration and amputation. Despite its high prevalence, disease-modifying treatments for DSPN do not exist. Mitochondrial dysfunction and Ca²⁺ dyshomeostasis are key contributors to the pathophysiology of DSPN, disrupting neuronal energy homeostasis and initiating axonal degeneration. Recent findings have demonstrated that antagonism of the muscarinic acetylcholine type 1 receptor (M₁R) promotes restoration of mitochondrial function and axon repair in various neuropathies, including DSPN, chemotherapy-induced peripheral neuropathy (CIPN) and HIV-associated neuropathy. Pirenzepine, a selective M₁R antagonist with a well-established safety profile, is currently under clinical investigation for its potential to reverse neuropathy. The transient receptor potential melastatin-3 (TRPM3) channel, a Ca²⁺-permeable ion channel, has recently emerged as a downstream effector of G protein-coupled receptor (GPCR) pathways, including M₁R. TRPM3 activation enhanced mitochondrial Ca²⁺ uptake and bioenergetics, promoting axonal sprouting. This review highlights mitochondrial and Ca²⁺ signaling imbalances in DSPN and presents M₁R antagonism and TRPM3 activation as promising neuro-regenerative strategies that shift treatment from symptom control to nerve restoration in diabetic and other peripheral neuropathies. Full article

Artificial intelligence (AI) techniques—ranging from hybrid mechanistic–machine learning (ML) ensembles to gradient-boosted decision trees, support-vector machines, and deep neural networks—are transforming the management of seasonal influenza, respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptom-based triage models using eXtreme Gradient Boosting (XGBoost) and Random Forests, as well as imaging classifiers built on convolutional neural networks (CNNs), have improved diagnostic accuracy across respiratory infections. Transformer-based architectures and social media surveillance pipelines have enabled real-time monitoring of COVID-19. In HIV research, support-vector machines (SVMs), logistic regression, and deep neural network (DNN) frameworks advance viral-protein classification and drug-resistance mapping, accelerating antiviral and vaccine discovery. Despite these successes, persistent challenges remain—data heterogeneity, limited model interpretability, hallucinations in large language models (LLMs), and infrastructure gaps in low-resource settings. We recommend standardized open-access data pipelines and integration of explainable-AI methodologies to ensure safe, equitable deployment of AI-driven interventions in future viral-outbreak responses. Full article

Although ART leads to viral suppression, people living with HIV (PLWH) still face an increased risk of comorbidities, such as cancer. The HIV-1 Tat protein may contribute to the promotion of chronic inflammation, oxidative stress, and genomic instability. While the presence of anti-Tat antibodies has been associated with slower disease progression, their potential role in modulating DNA damage remains unclear. Assess the effect of anti-Tat antibodies on cytotoxic and DNA damage in PLWH. A cross-sectional study was conducted in 178 PLWH. Serum anti-Tat IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity and DNA damage were assessed via serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nuclear anomalies (Micronucleus cytome assay) in 2000 buccal cells. Statistical significance was considered at p < 0.05. Anti-Tat antibodies were found in 24.2% of participants. Positive individuals had lower CD4+ T cell counts (p = 0.045) and higher levels of pyknosis (p = 0.0001). No differences in 8-OHdG were found, but 8-OHdG correlated positively with CD4+ counts (rho = 0.334, p = 0.006). Pyknosis negatively correlated with CD4+ counts (rho = −0.272, p = 0.027). Anti-Tat antibodies may not prevent DNA damage but could be related to cytotoxic effects in PLWH. Full article

Pregnancy introduces significant physiological changes that alter the pharmacokinetics (PK) of antiretroviral therapy (ART), impacting its safety and efficacy in HIV-positive women. Optimizing ART during pregnancy is critical to maintaining maternal virological suppression and preventing mother-to-child transmission (MTCT) of HIV. This review evaluates the impact of pregnancy-induced PK changes on ART and proposes strategies for tailored regimens to improve outcomes. A comprehensive review of published literature was conducted, focusing on PK adaptations during pregnancy and their implications for different ART classes, including protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and nucleoside reverse transcriptase inhibitors (NRTIs). Key studies were analyzed to assess drug exposure, efficacy, and safety. Pregnancy significantly alters the PK of antiretrovirals, with increased hepatic metabolism, renal clearance, and changes in plasma protein binding leading to reduced drug exposure. For example, drugs like lopinavir and atazanavir require dose adjustments, while dolutegravir maintains efficacy despite reduced plasma levels. Integrase inhibitors demonstrate favorable virological suppression, although cobicistat-boosted regimens show subtherapeutic levels. Tailored approaches, such as therapeutic drug monitoring (TDM), optimize ART efficacy while minimizing toxicity. Pregnancy-specific PK changes necessitate evidence-based ART adjustments to ensure virological suppression and reduce MTCT risk. Incorporating TDM, leveraging pharmacogenomic insights, and prioritizing maternal and neonatal safety are critical for personalized ART management. Further research into long-acting formulations and global guideline harmonization is needed to address disparities in care and improve outcomes for HIV-positive pregnant women. Full article

Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. This ongoing inflammation contributes to the development of HIV-associated neurocognitive disorders (HANDs), including dementia and Alzheimer’s disease-like pathology. These complications are particularly prevalent among the aging population with HIV. This review aims to provide a comprehensive overview of HAND, with a focus on the contribution of oxidative stress induced by HIV-mediated reactive oxygen species (ROS) production through viral proteins such as gp120, Tat, Nef, Vpr, and reverse transcriptase. In addition, we discuss current and emerging therapeutic interventions targeting HAND, including antioxidant strategies and poly (ADP-ribose) polymerase (PARP) inhibitors. These are potential adjunctive approaches to mitigate neuroinflammation and oxidative damage in the CNS. Full article

HIV-associated lymphoma (HAL) is a heterogeneous and highly aggressive group of malignancies. Although antiretroviral therapy (ART) has significantly prolonged the survival of people living with HIV (PLWH), the risk of malignancy secondary to HIV infection remains higher than in HIV-negative individuals, with HAL being among the most frequent. The pathogenesis of HAL is complex, involving multifactorial interactions. In current clinical practice, HAL faces a double challenge: the lack of effective biological risk warning systems and the lack of precise prognostic stratification tools. In recent years, the construction of multidimensional biomarker systems has shown critical value in the comprehensive management of HAL. This review aims to systematically summarize recent advances in circulating biomarkers for HAL, focusing on the potential applications of immune environment indicators, such as inflammatory cytokine profiles and microbial translocation markers, as well as serum protein profiles, lymphocyte subsets, extracellular vesicles (EVs), circulating microRNAs (miRNAs), and viral biomarkers. These biomarkers offer promising avenues for early risk prediction, therapeutic monitoring, and prognostic evaluation. Developing an assessment system based on multidimensional biomarkers will optimize early risk stratification, enable precise prognostic classification, and support personalized therapeutic strategies, thereby providing a novel theoretical basis and practical direction for the clinical management of HAL. Full article

In the era of combined antiretroviral therapy, around 50% of chronic HIV (+) individuals show varying degrees of memory and cognitive deficiency (NeuroHIV), a phenomenon of accelerated brain aging. HIV protein transactivator of transcription (TAT) has been well-accepted as a risk factor contributing to NeuroHIV through dysregulating microglia (Mg) functions. Previous studies have demonstrated that HIV-TAT can affect lipid metabolism, immune responses, autophagy, and senescence in rodent Mg. However, due to the significant species differences between rodent and human Mg (hMg), it is essential to take caution when interpreting the results obtained from rodent models into human conditions. For the unanswered questions, we generated hMg from human inducible pluripotent stem cells (iPSCs) and exposed them to HIV-TAT. The results obtained from Flow analysis and immunostaining experiments reveal that TAT can induce LD accumulation and increase perilipin-2 (Plin2) levels in hMg. Meanwhile, HIV-TAT can upregulate autophagosome formation and p53 levels. Through human immune array assay, we showed that TAT can increase the expression of multiple pro-inflammatory mediators, cytokines, and chemokines in hMg. Extensive bioinformatic analysis shows that HIV-TAT can affect multiple neuroimmune signaling pathways and indicates that microRNAs (miRNAs) are coherently involved in such dysregulation. Overall, our findings provide direct evidence showing that HIV-TAT can affect lipid metabolism, autophagy, senescence signaling, and multiple neuroimmune-related pathways in hMg and indicate the roles of novel miRNAs on NeuroHIV pathogenesis, which deserves further investigations. Full article

Vpr, a virion-associated accessory virulence factor of HIV-1, promotes virus replication in both T cells and macrophages. Although Vpr’s early activity—antagonism of preintegration silencing and host restriction factors—has been documented, the relative contribution of virion-associated versus de novo expressed Vpr to HIV-1 replication fitness remains unclear. Here, we developed a T cell-based system that genetically separates early and late Vpr functions by combining tetracycline-inducible Vpr expression in CEM.SS T cells with vpr-deficient HIV-1 constructs and Gag p6 mutations that block Vpr packaging. CEM.SS T cells have been shown to recapitulate the positive effect of Vpr on HIV-1 replication observed in activated primary T cells. Using pairwise replication fitness assays under spreading infection conditions, we demonstrate that de novo synthesized Vpr exerts the dominant effect on HIV-1 replication in T cells, while virion-associated Vpr plays a lesser role. Somewhat unexpectedly, our findings reveal that antagonism of preintegration HIV-1 silencing by virion-associated Vpr is unlikely to be the major driver of enhanced HIV-1 replication in proliferating T cells. Instead, this function may play a more prominent role in the infection of non-dividing T cells and/or other cell types. Full article

In the current global health environment, the spread of the monkeypox virus (MPXV) and the persistent threat of human immunodeficiency virus (HIV) have become critical public health challenges. Since 2022, MPXV has rapidly disseminated worldwide, and nearly half of MPXV-infected individuals are co-infected with HIV. This complex situation calls for innovative preventive strategies. In this study, an innovative multi-epitope vaccine was designed using bioinformatics and immunoinformatic approaches. Ten HIV proteins and nine MPXV proteins were used to predict potential epitopes. Non-allergenic, highly antigenic, IFN-γ-inducible, and non-toxic epitopes were selected to construct the multi-epitope vaccine. It was found that the designed vaccine construct was highly antigenic, soluble, and had acceptable physicochemical properties. Based on molecular docking and molecular dynamics simulation (MDs) analyses, the vaccine construct demonstrated stable and robust interactions with Toll-like receptors (TLR2, TLR3, and TLR4). Although no actual animal experiments have been conducted to evaluate the vaccine’s effectiveness, immune simulations showed that the vaccine could elicit potent humoral and cell-mediated immune responses. Overall, this study provides a promising vaccine candidate against MPXV and HIV co-infection and emphasizes innovative strategies to interrupt the international transmission of these two viruses. Full article

Human cytomegalovirus (HCMV), a globally ubiquitous herpesvirus with the ability to carry out both lytic productive and lifelong latent infections, is a major cause of congenital infections, often leading to intellectual disabilities and neurological disorders. Moreover, HCMV is an opportunistic pathogen commonly found in immunocompromised individuals such as organ transplant recipients, HIV-positive individuals, and cancer patients, causing severe and life-threatening complications. While effective in inhibiting viral lytic infection, current FDA-approved compounds cannot eliminate the latent viral genome and have little effect on viral latent infection. Developing novel antiviral therapeutic approaches to eliminate HCMV lytic and latent infections is a major public health priority for controlling HCMV infection and preventing viral-associated diseases. The genome-editing technology based on the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) RNA-guided nuclease system represents a novel and promising antiviral approach through modifying or destroying the genetic material of human viruses. This review summarizes the recently published progress in using the CRISPR-Cas approach to study and inhibit HCMV infections and discusses prospects for developing the CRISPR-based genome-editing technology for therapeutic applications against HCMV infection and associated diseases. Full article

Momordica balsamina, a plant traditionally used in African medicine, contains a 30 kDa protein, MoMo30, previously identified by our group as an anti-HIV agent that binds glycan residues on the gp120 envelope protein, thereby acting as an entry inhibitor. In this study, we investigated whether prolonged exposure to MoMo30 exerts selective pressure on HIV-1 and induces mutations in the viral envelope (env) gene. T-lymphocyte cells were infected with HIV-1_NL4-3 and continuously treated with MoMo30 over a 24-day period. Viral RNA was isolated at regular intervals, and env genes were sequenced using the Illumina platform. RNA sequence variant calling was performed using iVar, which uses a frequency-based binomial test with a default allele frequency threshold of 3% and a minimum base quality of 20 and applies Bonferroni correction for multiple testing. The infectivity of the MoMo30-exposed virus was assessed using MAGI-CXCR4 cells, visualized by β-galactosidase staining, and compared to untreated controls. Statistical significance was determined via two-way ANOVA. MoMo30-treated HIV-1 exhibited multiple detrimental mutations in gp120 and gp41, including missense, nonsense, and frameshift changes. Notably, 32% of N-linked glycosylation sites were deleted in the treated virus, while no such changes were observed in controls. Functionally, the MoMo30-treated virus demonstrated a sixfold reduction in infectivity compared to untreated HIV-1_NL4-3. These findings suggest that MoMo30 imposes genetic pressure on HIV-1_NL4-3, selecting for mutations that reduce viral fitness. Full article

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article