Current HIV Research最新文献

Introduction/objective: "Immunological non-responders" (INRs) are individuals living with HIV who are undergoing Highly Active Antiretroviral Therapy (HAART) but fail to restore their CD4⁺ T-cells count despite effective viral control. The incomplete immune restoration in INRs is often associated with the low-productive proliferation of memory CD4⁺ T lymphocytes. The ability of CD4⁺ T cells to divide is critically dependent on the glycolytic pathway, which supplies the necessary energy and building blocks for cell division. We hypothesize that impaired glycolytic activity in the memory CD4⁺ T cells of INRs contributes to their ineffective proliferation, ultimately limiting immune restoration.

Methods: This study involved two groups of HIV-infected HAART-treated subjects: INR and Immunological Responders (IR). A third group consisted of healthy controls, comprising uninfected volunteers. To identify the metabolic factors contributing to immunological non-response to therapy, glucose uptake, and lactate production were measured in the memory CD4⁺ T cells from all three groups.

Results: INR had the highest activation level in memory CD4+ T cells and the greatest glucose uptake. However, both groups of HIV-infected patients had significantly reduced lactate production compared to the healthy donors. Short-term phytohemagglutinin stimulation provoked an increase in lactate production in memory CD4+ T lymphocytes. Nevertheless, we found significantly reduced lactate production levels in activated memory CD4+ Т cells of INR an IR.

Conclusion: In INRs, there is a discrepancy between the highly activated phenotype of memory CD4⁺ T lymphocytes and their glycolytic activity. This reduced glycolysis may explain the lowproductive proliferation of memory CD4⁺ T lymphocytes in INRs.

Anti-Retroviral Therapy (ART) is a fundamental principle in the management of Human immunodeficiency virus (HIV) infection, significantly improving the quality of life for individuals living with the virus. However, the success of ART crucially depends on patient adherence to complex medication regimens that come with the therapy. Patients must meticulously adhere to their prescribed treatment plans to maintain viral suppression and prevent the progression of HIV. Medication adherence, a multifaceted challenge in healthcare, becomes particularly entangled within the realm of ART. Patients are often prescribed a combination of antiretroviral medications, each with unique dosing schedules and dietary requirements as instructed by the physician. For individuals with varying levels of health literacy, language proficiency, and cultural backgrounds, comprehending and adhering to these regimens can be overwhelming and challenging. Non-adherence to these medications can result in treatment failure, drug resistance, and compromised health outcomes that burden the healthcare systems. In that perspective, the role of pictograms as visual aids emerges as part and parcel of patient education and counseling within healthcare systems. Pictograms are graphical representations of concepts or actions designed to transcend linguistic and literacy barriers. When used in conjunction with ART, they simplify complex medication instructions, empower patients with knowledge, and improve adherence. Generally, the role of pictograms in supporting medication adherence and patient counseling in antiretroviral therapy is a powerful testament that serves a purpose in bridging communication and literacy gaps within the healthcare systems. By simplifying complex medication regimens, empowering patients with knowledge, and fostering adherence, pictograms contribute to better health outcomes and the overall success of ART. As healthcare providers and systems continue to harness the potential of pictograms, patient education and adherence in the management of HIV and other chronic conditions stand to be greatly enhanced.

Aims: The Human Immunodeficiency Virus (HIV) is a significant global health concern that affects millions of people worldwide. This virus targets the immune system, specifically CD4 cells, weakening the body's ability to combat infections and diseases.

Background: Scutellaria baicalensis, a plant of the genus Lamiaceae, and its root is the main part used in medicine. Pharmacological studies have shown that Scutellaria baicalensis has various activities such as anti-inflammatory, anti-viral, anti-bacterial, anti-tumor, antioxidant effects, etc. Objective: To investigate the anti-HIV activity of Scutellaria baicalensis against the HIV coreceptor CXCR4.

Methods: We conducted in-silico studies using bioinformatics tools like SWISS ADME, ProTox- II, PyRx, and Biovia Discovery Studio. Ligand structures were retrieved from the PubChem database, and the crystal structure of the target protein CXCR4 Chemokine receptor (PDB ID: 3ODU) with a resolution of 2.50 Å was retrieved from the Protein data bank.

Results: From the results, we filtered out 19 compounds with the highest binding affinity compared to the native ligand (-7.9 kcal/mol), which ranges from -10.1 kcal/mol to -8.0 kcal/mol. For the 19 compounds, we conducted ADME and Toxicity studies. From the studies, Baicalin, Wogonoside, and Oroxylin A-7-O-Glucuronide possess binding affinity of -10.1 kcal/mol, -9.6 kcal/mol, and -9.2 kcal/mol, which is greater than the native ligand (-7.9 kcal/mol).

Conclusion: Thus, Baicalin may possess the most potential activity against HIV. Moreover, further in-vitro and in-vivo studies are needed to evaluate their biological potential, and this work may help scientists in their future studies.

Objective: This study aims to examine neuroanatomical differences associated with depressive symptoms in people with HIV (PWH) by comparing three groups: depressed PWH (PWH Dep+), non-depressed PWH (PWH Dep-), and HIV-negative controls. The primary goal is to explore specific alterations in brain volume and cortical thickness linked to depressive symptomatology in PWH.

Methods: A total of 61 male participants (28 PWH, 33 controls) underwent psychiatric evaluation and high-resolution structural MRI scanning. Voxel-based morphometry (VBM) and cortical thickness analyses were conducted, with age and education considered as covariates. Participants were classified into PWH Dep+ and PWH Dep- based on depression scales.

Results: The PWH Dep+ group exhibited increased gray matter volume in the left anterior cingulate cortex and decreased cortical thickness in the left frontal pole compared to controls. In contrast, PWH Dep- participants showed increased cortical thickness in the bilateral postcentral gyrus and posterior cingulate gyrus. Additionally, volume reductions in the middle occipital and middle temporal gyri distinguished PWH Dep+ from PWH Dep-.

Conclusions: Depression in PWH is associated with structural brain changes, particularly in frontal and occipital regions. Although causality cannot be inferred due to the cross-sectional design, these results may enhance our understanding of the neuropathological mechanisms underlying depression in PWH. The findings should be interpreted with caution, given the relatively small sample size and the exclusion of female participants.

Introduction: Human immunodeficiency virus (HIV) is a primary health concern that leads to Acquired immunodeficiency syndrome (AIDS), with more than 39.9 million people living with HIV globally. Dolutegravir sodium is a lipophilic compound with a log P value of 2.2. The current research aimed at augmenting the solubility, dissolution, and therapeutic benefits of Dolutegravir sodium through Solid lipid nanoparticles.

Methods: The solid lipid nanoparticles (SLN) of Dolutegravir sodium were developed using highspeed homogenization and probe sonication methods. The solid lipid and surfactant were scrutinized for the development of SLN. The optimization of SLN was established using the Box- Behnken design model. The effects of lipid, surfactant, and homogenization speed on particle size and entrapment efficiency were evaluated. The colloidal dispersion was lyophilized, and accelerated stability was assessed.

Results: Fourier Transform Infrared Spectroscopy (FTIR) confirmed the interactions between the drug excipients. The thermal behavior and crystalline nature were checked with Differential Scanning Calorimetry (DSC). Among the several tested solid lipids, the highest solubility was observed in glyceryl monostearate (GMS). The colloidal dispersion was stabilized by the Tween 20.

Discussion: Accordingly, the Box-Behnken design model and the analysis of variance (ANOVA) model were applied. The p-values for the particle size and entrapment efficiency were 0.0050 and 0.0010, respectively. The optimized batch D5 showed a particle size of 189 nm, zeta potential (ZP) of -24.6 mV, entrapment efficiency of 85.94%, and drug release of 87.02%. The optimized batch D5 was further lyophilized and analyzed with scanning electron microscopy (SEM), which confirmed the nanoscale range for SLN of Dolutegravir sodium.

Conclusion: A significant enhancement in solubility and dissolution was achieved with the solid lipid nanoparticles. The sustained delivery of 24 hours reduces the dosage frequency and minimizes the viral load for the effective therapy of HIV, thereby improving patients' comfort and compliance.

Introduction: The enduring presence of HIV reservoirs represents an important obstacle to clinical management. Extensive research has been conducted in this field, but there are no bibliometric analyses focusing on HIV reservoir research.

Aim: This study aimed to present the current status and global trends in HIV reservoir research through bibliometric analysis.

Methods: Studies on HIV reservoirs published from 1 January 1994 to 31 December 2023 were included in the Web of Science Core Collection database, and annual publication numbers, institutions, countries, and authors were analysed using CiteSpace bibliometric software. Furthermore, popular research topics and trends were analysed using co-cited references and keywords. From 1994 to 2023, 5778 publications on HIV reservoirs were included, with the United States producing the most publications, citations, and research funding. The most productive individual author was Nicolas Chomont. Cell was the journal publishing the most publications, while Nat Med had the best total link strength. The University of California System was the institution that made the greatest contribution. Keyword clustering analysis of the extracted publications indicated that the research areas over the past three decades have primarily focused on "central nervous system," "histone deacetylase," "multiple Epstein‒Barr virus infection," and "dendritic cell."

Results: Moreover, keyword emergence analysis indicates that "provirus" and "identification" are likely to become central themes in future research. Future investigations should prioritize elucidating the specific mechanisms underlying proviral persistence and the identification of novel biomarkers in HIV reservoirs. Additionally, exploring the role of proviral dynamics in therapeutic development and reservoir targeting could offer new insights into potential treatment strategies.

Conclusion: This study makes a significant contribution to the understanding of HIV reservoirs, shedding light on key characteristics and emerging trends while also pointing to future research directions.

Human Immunodeficiency Virus (HIV) damages or interferes with immune cell function and remains a serious worldwide public health concern. Many researchers have studied the virus since its discovery in an effort to better understand its immunopathogenesis and neuropathogenesis. For those who have access to efficient HIV prevention, diagnosis, treatment, and care, HIV infection has now evolved into a chronic illness that can be controlled. Despite a decrease in HIV prevalence in the general population, certain subpopulations continue to exhibit higher-risk behaviors. This work aims to uncover research gaps in HIV gene expression studies, which is crucial in finding a cure. For instance, blood samples are used for most of the gene expression experiments for HIV. However, since there are very few HIV latent reservoir cells in the blood, it can be difficult to identify and quantify them. Furthermore, blood cell populations might not accurately represent the features of reservoir cells found throughout the body. Using HIV reservoir cells from distinct tissue types in gene expression research projects could help us pinpoint the main cause of the latent HIV resilience. Gene expression studies using potential repurposed drug candidates, as well as alternative experimental setups with combinations of antiretroviral therapies, can be utilized in future studies as well. Additionally, large-sample research designs that specifically investigate intestinal disruption in individuals with HIV and associated comorbidities may help us better understand the processes behind HIV.

Introduction: The rapid increase in incidences of drug resistance and off-target toxicity in the case of Human Immunodeficiency Virus (HIV) has increased the demand for drugs with fewer side effects. HIV-1 Integrase (IN) is a promising target that helps integrate viral DNA with human DNA. It acts as a target for strand transfer inhibitors. However, the emergence of resistant mutations in the proteins necessitates the exploration of potent allosteric drugs. The allosteric integrase inhibitors (ALLINI) that interrupt the association of the integrase binding domain of the lens epithelium growth factor (LEDGF/p75) and LEDGF/p75 binding site of the IN are more promising as they hinder site specificity and viral replication.

Objective: In this study, a 3D-QSAR, molecular docking, and ADMET were carried out to investigate the binding of the C2-pyrazolopyrimidine amides and amide isosteres.

Method: The 3D-QSAR model was developed using a series of 24 C-2 substituted pyrazolopyrimidine and amide isosteres. A statistically significant model was constructed, showing the determination coefficient (r2) and five-fold cross-validation (q2) at 0.946 and 0.506, respectively. Furthermore, the contour maps of the electrostatic potential and van der Waals coefficient provided structural modifications in the features to improve the inhibitory activity.

Result: A molecular docking study was also performed to check the binding of the compounds to the LEDGF/p75 binding site of the IN, along with ADMET evaluation.

Conclusion: The outcome of the study will help to prepare the potent molecules with enhanced allosteric inhibitory activity.

Background: The increased risk ofmetabolic syndrome (MetS) and its subcomponents among people living with HIV/AIDS, especially in developing countries, is well documented with the global pooled prevalence of the related risk factors in this population.

Objective: This study aimed to explore the prevalence of MetS among Iranian People living with HIV according to the ATP III and Iranian criteria.

Methods: The cross-sectional study was conducted on consecutive patients who visited THE referral centre for AIDS/HIV between May to December 2023. A total of 130 participants (n=83; 63.8%male) were investigated based on the inclusion criteria, which included having a minimum age of 25 and a maximum of 65 years and following a stable ART treatment regimen for at least six months. A Chi-square test was used to determine the relationship between the categorical variables. Uni/Multi-variable linear regression analysis was used to quantify the associations between MetS and HIV by the independent variables.

Results: The incidence of MetS according to ATP III and Iranian criteria were 42 (32.3%) and 45 (34.6%), which was higher in older patients (p=0.001) and those with more duration since HIV diagnosis (p=0.02). Around 33.1% and 16.1% were overweight and obese, respectively. Among the components of MetS, the highest prevalence (50.8%) was related to low HDL, and the lowest was related to fasting blood sugar (21.5%). The average body fat mass, protein mass, Soft lean mass, and percentage body fat were 18.54 ± 9.46 kg, 10.91 ± 2.17 kg, 51.31 ± 9.61 kg, and 24.86±10.25% that were higher in MetS group (p<0.05).

Conclusion: Our study points out the high prevalence of MetS in an Iranian population living with HIV, especially those suffering from the underlying disease for a longer time. Conducting multi-centric studies with larger sample sizes is needed to confirm our results and determine the most effective measures.