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 core-ceptor 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 Ao 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.

Robust assay technologies and reference reagents are essential components in efforts to develop safe and effective antibody-mediated prevention strategies for HIV-1. Here, we de-scribe current approaches used to conduct standardized assessments of neutralizing, binding, and Fc receptor-mediated effector functions of vaccine-elicited antibodies, with an emphasis on recent developments that enable early precursors and intermediates of broadly neutralizing antibodies (bnAbs) to be monitored. We also describe how these assay technologies were adapted to facili-tate clinical evaluations of passively delivered bnAbs for HIV-1 prevention.

Controversy exists around the relative merits of Fc functions in controlling or prevent-ing HIV-1 infection. Proponents point to general correlations of Fc functions with control of HIV, indicating that non-neutralizing antibodies could force immune escape, as observed in the early experiments with Fc mutants of the b12-neutralizing monoclonal antibody. Nay-sayers point to the primary role of neutralization in the control of HIV, the general failure of vaccine trials in-cluding antibodies with Fc functions, and the lack of additional benefit with newer broadly neu-tralizing monoclonal antibodies, such as PGT121. The truth may lie somewhere in between and there are lessons to be learned from the utility of Fc functions in other viral infections. In general, however, the additional benefit of Fc function over and above robust anti-HIV neutralizing anti-bodies may be modest. The intense primary research focus on delivering and inducing potent and broadly neutralizing antibodies, regardless of their Fc function potential, is justified.

Background: Modern Anti-retroviral Therapy (ART) prevents disease progression in people living with HIV. Due to the increasing age of people living with HIV, the detection and management of comorbidities has become more important.

Objective: In this study, we aimed to detect the prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and associated risk factors among people living with HIV followed up in our center.

Methods: This single-center, cross-sectional study included people living with HIV, on ART for ≥1 year and virologic suppression for ≥6 months, presenting for routine follow-up between October 1, 2021, and April 1, 2022. Participants with a concurrent etiology for hepatic steatosis were excluded. Transient elastography (TE) was performed. NAFLD was defined as a controlled attenuation parameter (CAP) ≥248 dB/m; significant fibrosis (≥F2) was defined as liver stiffness measurement ≥7.1 kPa.

Results: A total of 102 people living with HIV (84% men; median age, 39 years [IQR 33-52.5]) were enrolled. The treatment regimen of all participants included a nucleos(t)ide reverse transcriptase inhibitor and an integrase strand transfer inhibitor. TE analysis indicated NAFLD in 28 (27.5%) and fibrosis in 9 (8.8%; 6 with NAFLD) participants. In multivariable analysis, type two diabetes (OR:5.7 [95% CI 1.4-22.2], p=0.013), larger waist circumference (OR:1.1 [95% CI 1.03-1.16], p=0.007), higher alanine aminotransferase (OR:1.05 [95% CI 1.01-1.09], p=0.018), and higher thyroid stimulating hormone (OR:3.1 [95% CI 1.4-6.8], p=0.005] were independently associated with NAFLD.

Conclusion: We observed a significant prevalence of NAFLD among people living with HIV followed up in our center. The high prevalence of NAFLD in our sample mirrors that of the general population, likely due to rising rates of metabolic dysfunction. Our findings highlight the importance of timely screening and implementation of management strategies for NAFLD in this population.

An effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glyco-protein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These 'germline-targeting' Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the mat-uration of germline-precursor BCRs into their broadly neutralizing forms.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, often becomes a comorbidity in individuals infected with Human Immunodeficiency Virus (HIV), the cause of Acquired Immunodeficiency Syndrome (AIDS). HIV-positive individuals have a 30-fold higher risk of contracting TB compared to non-HIV individuals. Assessment of HIV-TB disease progression commonly relies on measuring CD4 cell counts. However, in areas with limited access, the World Health Organization (WHO) recommends using Total Lymphocyte Count (TLC) ≤ 1200 cells/μL as an alternative. Additionally, chest X-rays, a widely accessible radio-logical method, aid in diagnosing TB in HIV-positive patients, complementing TLC in assessing disease progression in limited facilities.

Objective: The objective of this study was to analyze the differences in the location and characteristics of TB lesions based on HIV status and TLC levels.

Methods: A case-control study was conducted at Adam Malik Central Hospital on pulmonary TB patients from December 2021 to December 2022, meeting inclusion criteria. Evaluation of TB lesion locations and characteristics was performed by two researchers, while HIV status and TLC data were extracted from medical records.

Results: The study involved 154 subjects, including 77 HIV-positive and 77 non-HIV individuals. The percentage of male participants was 81.8%, with a mean age of 43.4 ± 14.4 years. The significant differences in the characteristics and locations of lesions (cavities, miliary lesions, fibro-sis, atelectasis, and upper and lower lung) were revealed in HIV-positive and HIV-negative patients. Similarly, significant differences in the characteristics and locations of lesions (cavities, miliary lesions, fibrosis, atelectasis, and upper and lower lung) were revealed in a patient with TLC ≤ 1200 and TLC > 1200.

Conclusion: The study highlights significant differences in the characteristics and locations of tuberculosis lesions about HIV status and total lymphocyte count levels among pulmonary TB patients. HIV-positive individuals exhibited distinct patterns of TB lesions compared to their HIV-negative counterparts, indicating the impact of HIV on TB disease progression. Furthermore, variations in lesion characteristics were also observed based on TLC levels, with notable differences between patients with TLC ≤ 1200 cells/μL and those with TLC > 1200 cells/μL. These findings underscore the importance of considering both HIV status and TLC in the assessment and management of TB in affected individuals. TLC can serve as an alternative to CD4 measurement in situations where access to CD4 testing is limited.

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: 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 LTBI-positive 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.

Background: The increased risk of metabolic 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 re-ferral 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 be-tween 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.

Human Immunodeficiency Virus (HIV) remains a significant global health challenge, necessitating rapid, sensitive, and accessible diagnostic tools. We examined recent advancements in electrochemical sensors for HIV gene detection, focusing on various sensing strategies, nanomaterial integration, and novel platform designs. Electrochemical sensors have demonstrated remarkable progress in HIV detection, offering high sensitivity and specificity. DNA/RNA-based sensors, aptamer approaches, and nanostructured platforms have detection limits as low as attomolar concentrations. Innovative signal amplification techniques, such as branched DNA amplification and toehold strand displacement reactions, have further enhanced sensitivity. Multiplexed detection systems enable simultaneous quantification of multiple HIV targets and related biomarkers. Integration of microfluidic technologies has improved sample processing and detection efficiency. Paper-based sensors show promise for low-cost, disposable testing platforms suit-able for resource-limited settings. While challenges remain in terms of selectivity in complex biological samples and point-of-care applicability, electrochemical sensors hold great potential for revolutionizing HIV diagnostics. Future developments in recognition elements, artificial intelligence integration, and combined sensing modalities are expected to address current limitations and expand the capabilities of these sensors, ultimately contributing to improved HIV management and epidemic control strategies.