Current HIV Research最新文献

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Immunoinformatics Analysis of Potent Therapeutic Formulations for the Development of HIV-1 Nefmut-Carrying Engineered Exosomes. HIV-1携带nefmut的工程外泌体开发的有效治疗配方的免疫信息学分析。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-05-21 DOI: 10.2174/011570162X361821250512115612
Parisa Moradi Pordanjani, Azam Bolhassani, Fatemeh Heidarnejad, Elnaz Agi
{"title":"Immunoinformatics Analysis of Potent Therapeutic Formulations for the Development of HIV-1 Nefmut-Carrying Engineered Exosomes.","authors":"Parisa Moradi Pordanjani, Azam Bolhassani, Fatemeh Heidarnejad, Elnaz Agi","doi":"10.2174/011570162X361821250512115612","DOIUrl":"https://doi.org/10.2174/011570162X361821250512115612","url":null,"abstract":"<p><strong>Background: </strong>The concept of designer exosomes involves developing engineered ex-osomes to overcome the limitations of natural exosomes in targeted drug delivery and vaccine development.</p><p><strong>Methods: </strong>In this study, the multiepitope constructs were designed based on immunogenic regions of mutant Nef protein of Human Immunodeficiency Virus-1 (HIV-1 Nefmut) that were prone to high Post-Translational Modifications (PTMs), such as palmitoylation and myristoylation. These constructs with high scores in PTMs were selected for interactions with molecules involved in exosome biogenesis, anchoring of a protein in membranes, and enzymes involved in PTMs (e.g., the mutant enzyme ZDHHC21 p.T209S). Moreover, the selected multiepitope construct with the highest PTM score and stable linkage with these molecules was fused to the first exon of the HIV-1 Tat protein as an antigen candidate, and to GFP as a tracking tool for evaluating their effects on the PTM scores and affinity binding with various molecules.</p><p><strong>Results: </strong>Our data demonstrated that the multiepitope construct No.13 had better scores for incor-poration into exosomes compared to the whole sequences of Nefmut and wild-type Nef protein (Nefwt). Furthermore, the linkage of Tat protein to construct No. 13 did not hinder its loading in exosomes compared to GFP, suggesting the use of this construct in vaccine development.</p><p><strong>Conclusion: </strong>The multiepitope construct No.13 harboring potent Nef mut epitopes can be applied for linkage with other viral antigens, enhancing their delivery into exosomes for therapeutic ap-plications.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ferroptosis and Dysfunction of CD3+CD4-CD8- T Cells are Associated with Poor Immune Reconstitution in HIV Patients. 铁凋亡和CD3+CD4-CD8- T细胞功能障碍与HIV患者免疫重建不良相关
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-05-20 DOI: 10.2174/011570162X366300250509112302
Xi Quan, Qing Xiao, Junli Luo, Chaoyu Wang, Yixing Zhou, Chensi Zeng, Xiaomei Zhang, Jieping Li, Dehong Huang, Chongling Hu, Bingling Guo, Shuang Chen, Zailin Yang, Xiaohong Deng, Yao Liu
{"title":"Ferroptosis and Dysfunction of CD3+CD4-CD8- T Cells are Associated with Poor Immune Reconstitution in HIV Patients.","authors":"Xi Quan, Qing Xiao, Junli Luo, Chaoyu Wang, Yixing Zhou, Chensi Zeng, Xiaomei Zhang, Jieping Li, Dehong Huang, Chongling Hu, Bingling Guo, Shuang Chen, Zailin Yang, Xiaohong Deng, Yao Liu","doi":"10.2174/011570162X366300250509112302","DOIUrl":"https://doi.org/10.2174/011570162X366300250509112302","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Some HIV patients stay in an immune unresponsive state after antiretroviral therapy (ART), with a notably higher risk of AIDS-related and non-AIDS-related complications. Double-negative T cells (DNT) can compensate for immunity and prevent immune overactivation in HIV patients. Also, immune non-responders (INRs) have fewer DNT cells than immune responders (IRs). HIV infection and ART can change the dynamic function of cell mitochondria, which are crucial in ferroptosis. Ferroptosis is a form of cell death marked by the accumulation of reactive oxygen species (ROS) and iron-dependent lipid peroxidation. Yet, the changes in DNT cell function in INRs and the impact of ferroptosis on immune reconstitution remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Our study focused on the expression level of DNT cells in HIV immune non-responders. Then, we detected markers of ferroptosis, cell activation, proliferation, killing function, and inflammatory states of DNT cells in INRs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The study involved 88 PLHIVs who had received antiretroviral therapy for over 4 years and tested virus-negative. These patients were classified into two groups: 28 INRs (CD4 &lt; 350/μl) and 60 IRs (CD4 ≥350/μl). Additionally, 25 sex- and age-matched HCs were included. Flow cytometry was used to detect ferroptosis markers (JC-1, Lipid ROS, lipid peroxidation), cell proliferation, and cell activation. Transmission electron microscopy (TEM) was applied to observe mitochondrial morphology. Finally, statistical analysis was performed on the detection results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After long-term antiretroviral therapy, we found that INRs had a lower DNT cell count than IRs. Regarding proliferation and activation, our results showed higher CD38/HLA-DR co-expression and Ki67 expression in INRs' DNT cells than in IRs', indicating over-activation of DNT cells in INRs. In terms of killing function, the perforin and granzyme B levels in INRs' DNT cells were lower than those in IRs', suggesting impaired killing function of DNT cells in INRs. For ferroptosis, the proportion of DNT cells with decreased MMP in INRs was higher than in IRs and HCs. INRs' DNT cells also had higher levels of lipid ROS and lipid peroxidation compared to those in IRs and HCs. TEM revealed that the mitochondria of INRs' DNT cells had typical morphological features. Moreover, INRs' DNT cells had a greater degree of inflammation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study centered on the proliferation, activation, ferroptosis, killing function, and inflammatory status of DNT cells in INRs. We found that DNT cells in INRs had more active proliferation and activation, weakened killing function, mitochondrial function with typical ferroptosis features, and increased TNF-αlevels. Correlation analysis indicated that DNT cell overactivation (Ki-67+, CD38+HLA-DR+), MMP reduction ratio, and TNF-αexpression were negatively related to immune reconstitution in P","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Compromised Glycolysis in Memory CD4+ T cells Derived from HIV-infected Immunological Non-Responders to Highly Active Antiretroviral Therapy. 对高活性抗逆转录病毒治疗无应答的hiv感染者的记忆性CD4+ T细胞糖酵解受损
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-05-06 DOI: 10.2174/011570162X361238250421120542
Violetta V Vlasova, Larisa B Korolevskaya, Evgeniya V Saidakova, Konstantin V Shmagel
{"title":"Compromised Glycolysis in Memory CD4+ T cells Derived from HIV-infected Immunological Non-Responders to Highly Active Antiretroviral Therapy.","authors":"Violetta V Vlasova, Larisa B Korolevskaya, Evgeniya V Saidakova, Konstantin V Shmagel","doi":"10.2174/011570162X361238250421120542","DOIUrl":"https://doi.org/10.2174/011570162X361238250421120542","url":null,"abstract":"<p><p>HAART-treated HIV-infected individuals, known as «immunological non-responders» (INR), fail to restore CD4+ T cell counts despite effective viral control. Incomplete immune restoration in INR is usually linked to low-productive proliferation of memory CD4+ T lymphocytes. Given that CD4+ T cell ability to divide critically depends on the glycolytic pathway, we aimed to determine the levels of glucose uptake and glycolysis in memory CD4+ T cells of INR. Two groups of HIV-infected HAART-treated subjects were studied: INR and immunological responders, with a healthy controls group comprising uninfected volunteers. The results showed that INR had the highest activation level in memory CD4+ T cells and the greatest glucose uptake. Short-term phytohemagglutinin stimulation provoked an increase in aerobic glycolysis in memory CD4+ T lymphocytes. Nevertheless, we found significantly reduced aerobic glycolysis in activated memory CD4+ Т cells of INR. Hence in INR, there is a discrepancy between the highly activated phenotype of memory CD4+ T lymphocytes and their glycolytic activity.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Healthcare Providers' Perspectives on Same-Day Antiretroviral Initiation in Ethiopian Healthcare Facilities. 卫生保健提供者对埃塞俄比亚卫生保健设施当日开始抗逆转录病毒治疗的看法。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-05-06 DOI: 10.2174/011570162X354534250414010350
Kidanu Hurisa Chachu, Kefiloe Adolphina Maboe
{"title":"Healthcare Providers' Perspectives on Same-Day Antiretroviral Initiation in Ethiopian Healthcare Facilities.","authors":"Kidanu Hurisa Chachu, Kefiloe Adolphina Maboe","doi":"10.2174/011570162X354534250414010350","DOIUrl":"https://doi.org/10.2174/011570162X354534250414010350","url":null,"abstract":"<p><strong>Background: </strong>The concept of same-day antiretroviral therapy (ART) initiation entails initiating HIV treatment promptly upon diagnosis, ideally during the initial clinic visit or even on the same day as diagnosis. This study explores the factors leading to patient loss to follow-up after same-day ART initiation and the benefits and challenges associated with this approach.</p><p><strong>Methods: </strong>A qualitative research design was employed to investigate healthcare providers' perspectives regarding same-day ART initiation and its contribution to patient loss to follow-up following same-day ART initiation, benefits, and challenges. It is a qualitative study conducted in the form of in-depth cell phone interviews with physicians and nurses who are providing ART services within healthcare facilities in Ethiopia. Data collection was conducted from April 30, 2021, to March 22, 2022.</p><p><strong>Results: </strong>The findings revealed that same-day ART initiation offers both advantages and drawbacks. Findings show benefits such as shifts in perceptions and attitudes towards HIV, reduced transmission rates, enhanced service utilization, and viral suppression. However, disadvantages included its inappropriateness for critically ill patients' refusal to accept results and suboptimal adherence, leading to increased risk of patient loss to follow-up.</p><p><strong>Conclusion: </strong>Same-day ART initiation presents a dual nature, offering immediate benefits in HIV management and transmission reduction, yet facing challenges regarding suitability for critically ill patients and adherence issues. The authors recommend addressing factors such as patient education, stigma reduction, and tailored interventions, which are crucial in optimizing the effectiveness of this approach and minimizing patient loss to follow-up.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2. 导航COVID-19治疗前景:当前治疗SARS-CoV-2的疗效和副作用。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-05-06 DOI: 10.2174/011570162X338375250414114957
Sachin Parwani, Shobha Upreti, Chandan Kumar Mishra, Ashutosh Tripathi, Surajit Chakraborty, Sameer Tiwari
{"title":"Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2.","authors":"Sachin Parwani, Shobha Upreti, Chandan Kumar Mishra, Ashutosh Tripathi, Surajit Chakraborty, Sameer Tiwari","doi":"10.2174/011570162X338375250414114957","DOIUrl":"https://doi.org/10.2174/011570162X338375250414114957","url":null,"abstract":"<p><p>Coronavirus Disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China. Des-ignated as an epidemic by the World Health Organization (WHO) on January 30, 2020, the virus quickly escalated to a global emergency, officially declared a pandemic in March 2020. With over 6 million recorded deaths and more than 200 identified symptoms in diverse individuals, the impact of COVID-19 is substantial. COVID-19 poses a greater risk to individuals with advanced HIV, while those with well-managed HIV are not at increased risk. Although COVID-19 vaccines are generally effective for people with HIV, some may experience reduced vaccine effectiveness and breakthrough infections due to suboptimal immune responses. Long COVID, affecting at least 65 million individuals, adds a layer of complexity. The virus's rapid mutation has led to diverse symptomatology, prompting adjustments in treatment guidelines. This review compre-hensively examines repurposed antiviral drug candidates against COVID-19, explores immune responses across different age groups, delves into the mechanisms of COVID-19 vaccines, and discusses potential immunosuppressants. Additionally, the focus extends to Intravenous Immu-noglobulin (IVIG), steroids, and anti-cytokine therapy as promising avenues to address cytokine release syndrome (CRS), a critical condition in COVID-19 patients.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Visualizing and Analyzing Global Trends and Frontier Research in HIV Reservoirs: A Bibliometric Study from 1994 to 2023. 艾滋病病毒库的全球趋势和前沿研究的可视化分析:1994 - 2023年文献计量学研究。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-05-02 DOI: 10.2174/011570162X360028250418095855
Qingxin Gu, Fanrong Liang, Wenchuan Qi
{"title":"Visualizing and Analyzing Global Trends and Frontier Research in HIV Reservoirs: A Bibliometric Study from 1994 to 2023.","authors":"Qingxin Gu, Fanrong Liang, Wenchuan Qi","doi":"10.2174/011570162X360028250418095855","DOIUrl":"https://doi.org/10.2174/011570162X360028250418095855","url":null,"abstract":"<p><strong>Introduction: </strong>The enduring presence of HIV reservoirs represents an important obsta-cle to clinical management. Extensive research has been conducted in this field, but there are no bibliometric analyses focusing on HIV reservoir research.</p><p><strong>Aim: </strong>This study aimed to present the current status and global trends in HIV reservoir research through bibliometric analysis.</p><p><strong>Methods: </strong>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, insti-tutions, countries, and authors were analysed using CiteSpace bibliometric software. Further-more, 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 indi-cated that the research areas over the past three decades have primarily focused on \"central nerv-ous system,\" \"histone deacetylase,\" \"multiple Epstein‒Barr virus infection,\" and \"dendritic cell.\"</p><p><strong>Results: </strong>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 ther-apeutic development and reservoir targeting could offer new insights into potential treatment strategies.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The RV144 Trial Set Back HIV-1 Vaccine Development but Might Still Yield Useful Information. RV144试验阻碍了HIV-1疫苗的开发,但仍可能提供有用的信息。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-04-18 DOI: 10.2174/011570162X355671250402083527
John P Moore
{"title":"The RV144 Trial Set Back HIV-1 Vaccine Development but Might Still Yield Useful Information.","authors":"John P Moore","doi":"10.2174/011570162X355671250402083527","DOIUrl":"https://doi.org/10.2174/011570162X355671250402083527","url":null,"abstract":"<p><p>This article discusses how the RV144 Phase 3 HIV-1 vaccine trial conducted over 15 years ago impacted the subsequent direction of research intended to create and evaluate vaccines with potentially greater efficacy. Follow-on Phase 2b and Phase 3 trials directly or indirectly inspired by the modest efficacy reported for the RV144 trial have not shown any significant pro-tection against HIV-1 acquisition. No credibly protective new immunogens have emerged from the Correlates of Protection (CoP) or Risk (CoR) analyses conducted after RV144-inspired stud-ies in either humans or various macaque models. Notably, the RV144 trial did not induce neutral-izing antibodies (NAbs), only non-NAbs. However, only NAbs have been shown to be protective in macaque models. One possible but underappreciated explanation for the outcome of the RV144 trial could be trained innate immune responses against the non-HIV-1 canarypox virus vector antigens, considering the placebo group only received saline. In this article, the author outlines how monkey model research based directly or indirectly on the RV144 trial could still yield useful information on the possible role of trained immunity in short-term vaccine protection. However, non-human primate research, in general, should now focus on testing new immunogens that have a reasonable chance of inducing NAbs in humans, rather than expending more resources on CoP/CoR studies inspired by the RV144 trial and its follow-ups.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Virological Failure And HIV-1 Drug Resistance in Indian Adults and Adolescents on Protease Inhibitor Based Second-line Antiretroviral Therapy: A Five-year Follow-up Study. 基于蛋白酶抑制剂的二线抗逆转录病毒治疗在印度成人和青少年中的病毒学失败和HIV-1耐药性:一项为期五年的随访研究。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-04-14 DOI: 10.2174/011570162X344689250331081024
Sumit Arora, Kuldeep Ashta, Nishant Raman, Charu Mohan, N Kisenjang, Vikram Sharma, Anirudh Anilkumar
{"title":"Virological Failure And HIV-1 Drug Resistance in Indian Adults and Adolescents on Protease Inhibitor Based Second-line Antiretroviral Therapy: A Five-year Follow-up Study.","authors":"Sumit Arora, Kuldeep Ashta, Nishant Raman, Charu Mohan, N Kisenjang, Vikram Sharma, Anirudh Anilkumar","doi":"10.2174/011570162X344689250331081024","DOIUrl":"https://doi.org/10.2174/011570162X344689250331081024","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;In the changing HIV treatment landscape, the focus shifts to persons living with HIV (PLH) experiencing virological non-suppression on second-line antiretroviral therapy (ART). This includes understanding viral genetic profiles, antiretroviral susceptibility, and the effectiveness of protease inhibitors (PIs) amid evolving dolutegravir-based regimen recommendations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this retrospective study, PLH with first-line ART failure transitioned to second-line ART (dual NRTI + ritonavir-boosted PI) between September 2015 and October 2018. Eligible patients were ≥ 13 years old, with ≥ 9 months on first-line ART, and confirmed adherence at first-- line regimen failure. Conducted at a Northern Indian tertiary hospital, this 5 year follow-up examined virological outcomes and drug resistance. Follow-up included initial viral-load (VL) and CD4 testing at 6-months, subsequent VL testing every 6-12 months, clinical evaluations, and infection screenings. Data on demographics, treatment history, virological-failure (VF), and drug-resistance testing (DRT) (Viroseq HIV-1 genotyping-system) were analysed using Kaplan-Meier and Competing-risk analysis, with appropriate censoring and imputation for events like death, transfer-out, treatment discontinuation/ interruption, loss to follow-up (LTFU), or ART-regimen change.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;219 PLH shifted to ritonavir-boosted PI based second-line ART after 68 (median) months (IQR: 68) of first-line ART exposure and were followed up for 57 (median) months (IQR: 48), totalling 11,548 person-months (PM) of follow-up. Virological outcomes were assessed in 201 PLH. VF cumulative-incidence (Kaplan-Meier-analysis) ranged from 6.9% at 36 months to 15.9% at 60 months. Imputation scenarios showed a potential range, with worst-case incidences of 16.2% at 36 months and 29.4% at 60 months. Cumulative-incidence function (CIF) of VF (Competing-risk-analysis) ranged from 6.5% at 36 months to 12.7% at 60 months. Among 171 PLH with complete VL data, VF incidence was 2.7 per 1000 PM (n=29), with 94.7% achieving nadir VL &lt;1000 cp/mL. VF with PI-mutation (VF-M) analysis, including LTFU patients (n=183), showed CIF for VFM of 2.3% at 36 months and 4.9% at 60 months. DRT (n=23-sequences) revealed 17.4% lopinavir resistance, 34.8% atazanvir resistance, and darunavir (DRV) cross-resistance in three sequences. Overall, 26.1% had no significant drug-resistance mutations, 39.1% had NNRTI resistance, but no PI DRMs, and only 34.8% (of 23-PLH who underwent DRT) potentially required third-line ART.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This 5-year longitudinal study highlights the resilience of PIs in second-line ART. The incidence of VF with PI-resistance was notably low, indicating the ongoing effectiveness of PIs in managing PLH on second-line ART and the possibility of recycling PIs in subsequent ART regimens for these patients. Cross-resistance to DRV patients highlights","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular Docking Studies of Scutellaria Baicalensis Targeting HIV Co-Receptor CXCR4. 黄芩靶向HIV共受体CXCR4的分子对接研究
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-04-04 DOI: 10.2174/011570162X345178250316123743
Mohamed Akram Ali S, Thawfeeq Ahmad K Mf, Helina N, Rajamohamed H, Shobana A, Vinoth Kumar S
{"title":"Molecular Docking Studies of Scutellaria Baicalensis Targeting HIV Co-Receptor CXCR4.","authors":"Mohamed Akram Ali S, Thawfeeq Ahmad K Mf, Helina N, Rajamohamed H, Shobana A, Vinoth Kumar S","doi":"10.2174/011570162X345178250316123743","DOIUrl":"https://doi.org/10.2174/011570162X345178250316123743","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1. 在HIV-1抗体介导的预防策略的途径中,目前评估抗体的中和、结合和效应功能的方法。
IF 0.8 4区 医学
Current HIV Research Pub Date : 2025-03-27 DOI: 10.2174/011570162X363301250314034023
David C Montefiori, Guido Ferrari, Dieter Mielke, LaTonya D Williams, Georgia D Tomaras
{"title":"Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1.","authors":"David C Montefiori, Guido Ferrari, Dieter Mielke, LaTonya D Williams, Georgia D Tomaras","doi":"10.2174/011570162X363301250314034023","DOIUrl":"https://doi.org/10.2174/011570162X363301250314034023","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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