Current HIV Research最新文献

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.

Background/ Objective: Due to the impact of human immunodeficiency virus (HIV) infection on personal and social life, people living with HIV (PLWH) are faced with several challenges and issues. Therefore, PLWH requires psychological interventions. The study aims were to create a suitable platform for psychological structures that empower them to address their issues effectively. In this regard, we evaluated the effect of Mindfulness-based Cognitive Therapy (MBCT) and Silva-based Relaxation Therapy (SBRT) on Psychological Capital (PsyCap), Social Anxiety (SA), and CD4 count in PLWH.

Methods: This study employed an intervention-based semi-experimental design. The population consisted of 90 individuals infected with HIV. Participants were divided into two experimental groups receiving MBCT and SBRT, respectively, and one control group, selected randomly. Before and after the intervention, questionnaires and CD4+ tests were administered to the participants. Only two experimental groups received the intervention, while the control group received no training. The appropriate training for each group was conducted twice a week over eight sessions and each session lasted 90 minutes. In the intervention groups, all the people participated in all the group training sessions. No intervention was performed for the participants of the control group, and they only completed the questionnaires in the same period as the intervention groups. "Mindfulness-Based Cognitive Therapy" and "Mind Control" books were used for the implementation of MBCT and SBRT, respectively.

Results: It was revealed that a number of male participants constituted the majority with 58 (64.4%) compared to females. Regarding the means of transmission, sexual contact was the most common with 62 (68.8%) compared to other routes. The mean age of the participants was 40.5 ± 10.8 years. For the SBRT group, the mean CD4+ count was higher, with 599.5 ± 290.9 for pre-test and 563.2 ± 366.7 for post-test assessments, compared to other groups. After performing the linear regression analysis, it was found that the variables had no effect on the main outcome, which is CD4 count after the intervention (p-value= 0.27). For the MBCT group, the CD4+ count variable had a p-value = 0.10 (pretest: 447.2 ± 19.5, posttest: 411.9 ± 235.9), for the SBRT group, the CD4+ count variable had a p-value = 0.05 (pretest: 599.5 ± 290.9, posttest: 549 ± 259.9), and the control group, the CD4+ count variable had a p-value = 0.5 (pretest: 445 ± 222.7, posttest: 563.2 ± 366.7).

Conclusion: MBCT and SBRT may enhance the mental well-being of PLWH. Therefore, following the interventions, the mean level of SA decreased, and PsyCap increased. Thus, strategies to improve psychological support interventions may have a significant impact on improving the health status of individuals living with HIV, including indicators of SA and PsyCap.

Background: About 10% of individuals with latent tuberculosis infection (LTBI) develop tuberculosis (TB) disease during their lifetime. People living with HIV (PLWH) have a significantly higher risk of developing tuberculosis disease from latent tuberculosis infection (LTBI) compared to those without HIV. Many HIV treatment guidelines recommend screening and treating for LTBI.

Objective: This study aimed to investigate the LTBI screening frequency of PLWH and the rates of tuberculosis disease development during their follow-up.

Methods: A total of 483 PLWH were admitted to 3 research hospitals between January 2005 and April 2020. Patients who were 18 years and older, who did not have active TB disease, and who were followed up regularly were included in the study. Demographic characteristics and laboratory results of the patients, and tuberculin skin test (TST) and/or interferon gamma releasing assay (IGRA) results were recorded. Whether TB developed during the follow-up of the patients or not was recorded.

Results: A total of 482 PLWH were enrolled in the study, and 429 (89%) of them were male. The mean age of the patients was 37±13 years. The patients were followed for an average of 27.5 months (2-180 months). The mean CD4 count was 381±246/mm3 at the time of diagnosis. A total of 331 patients (68.7%) were screened for latent infection, and 62 (18.7%) of them were diagnosed with LTBI. During the follow-up of the patients, TB disease did not develop in anyone who was not screened for LTBI, while TB disease developed in 4 people who were screened. The mean age of PLWH who developed tuberculosis disease was 54±10 years, while those who did not develop it was 37±13 years, and the difference was statistically significant (p=0.009).

Conclusion: Screening for LTBI in PLWH and treating it when positive are recommended in the EACS guidelines. However, some local HIV guidelines recommend latent TB treatment according to ethnicity, CD4 count, and antiretroviral therapy use. Although the mean follow-up period was short, it was found that there was no difference in the development of TB disease in LTBIpositive and negative individuals in our study. For countries that are not on the list of high-burden countries for TB, it may be an option to give latent TB treatment only to selected patients who have lower CD4 counts.