Current HIV Research最新文献

{"title":"Genotypic Diversity and Pre-Treatment Resistance Characteristic Analysis Among Newly Diagnosed HIV-1-Positive MSM from 2020-2022 in Jiaxing City, China.","authors":"Xiaofei Zhang, Ganglin Ren, Zhijian Ge, Shencong Lv, Ping Li, Yin Song, Miaomiao Jia, Yamei Zhou, Yong Yan, Guoying Zhu","doi":"10.2174/011570162X373907250607024902","DOIUrl":"10.2174/011570162X373907250607024902","url":null,"abstract":"<p><strong>Background: </strong>Since the first recorded HIV-1 infection in 1998, Jiaxing City has seen increasing HIV infections among men who have sex with men (MSM), necessitating targeted research to understand HIV-1 subtypes and drug resistance patterns to improve prevention and treatment strategies.</p><p><strong>Objectives: </strong>The study aimed to assess the variety of HIV-1 subtypes, the pre-treatment drug re-sistance (PDR) among MSM in Jiaxing, China, and transmission dynamics of drug-resistant strains. The findings may contribute to the development of targeted HIV prevention and control strategies for the MSM population.</p><p><strong>Methods: </strong>Plasma samples from all newly reported cases of HIV-1 transmitted through male-to-male sexual contact in Jiaxing City from 2020 to 2022 were retrospectively analyzed. Demo-graphic and epidemiological data were collected. Partial pol gene regions were amplified, se-quenced, and analyzed for drug resistance mutations (DRMs) using the Stanford HIV Drug Re-sistance Database. The Calibrated Population Resistance (CPR) program was utilised to identify Surveillance Drug Resistance Mutation (SDRM). A molecular transmission network was con-structed to investigate the scale of transmitted drug resistance (TDR) strains.</p><p><strong>Results: </strong>We obtained a total of 298 eligible genetic sequences, revealing a diverse distribution of HIV-1 subtypes, with CRF07_BC, CRF01_AE, and CRF55_01B as the most prevalent. Pretreat-ment DRMs were detected in 91 cases (30.5%), yielding an overall PDR prevalence of 11.0%. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) was most frequent (5.4% each). TDR prevalence reached 7.0%, showing an increasing trend (2020-2022). The molecular network analysis indicated sporadic dissemination of drug-resistant cases rather than large-scale transmission chains.</p><p><strong>Conclusion: </strong>The convergence of high HIV-1 subtype diversity, elevated PDR prevalence, rising TDR rates, and sporadic resistant strain transmission within MSM networks necessitates the sus-tained resistance surveillance and precision public health interventions.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332625","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}

{"title":"Assessment of Brain Volume and Cortical Thickness in People with HIV and Major Depressive Disorder.","authors":"Kadir Aşçıbaşı, Sabri Atalay, Hazal Albayrak Uçak, Birce Begüm Burhanoğlu","doi":"10.2174/011570162X378166250605034405","DOIUrl":"10.2174/011570162X378166250605034405","url":null,"abstract":"<p><strong>Objective: </strong>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 symp-tomatology in PWH.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The PWH Dep+ group exhibited increased gray matter volume in the left anterior cin-gulate 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-.</p><p><strong>Conclusions: </strong>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 un-derlying depression in PWH. The findings should be interpreted with caution, given the relatively small sample size and the exclusion of female participants.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332624","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}

{"title":"Impact of the COVID-19 Pandemic on the Clinical Management of People Living with HIV: A Retrospective Study of 246 Patients at a Single Center.","authors":"Selva Ala Selek, Aysun Benli, Seniha Başaran, Arif Atahan Çağatay, Halit Özsüt","doi":"10.2174/011570162X360947250605052248","DOIUrl":"https://doi.org/10.2174/011570162X360947250605052248","url":null,"abstract":"<p><strong>Introduction: </strong>The COVID-19 pandemic caused disruptions in the diagnosis, follow-up and treatment of non-COVID-19 patients due to the burden on the healthcare system. This may lead to missed early diagnosis opportunities in people living with HIV (PLWH). This study aimed to investigate the effects of the COVID-19 pandemic on the demographic characteristics, clinical and laboratory findings, diagnosis, follow-up, and treatment processes of PLWH, and the frequency of opportunistic infections (OIs), AIDS-defining malignancies (ADMs), and late diagnosis (LD).</p><p><strong>Methods: </strong>Our study was designed as a retrospective cohort study. Individuals over the age of 18 years who were newly diagnosed with HIV infection in our hospital between 2018 and 2023 were included in the study. In this study, 246 PLWH were identified. During the pandemic period, the mean age of PLWH was lower (p=0.025), the use of 2 nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI/r) decreased (p=0.026) and antiretroviral therapy (ART) adherence was higher (p=0.015). LD (48.8% vs. 47.5%) was similar for the two periods, OIs rate (22.6% vs. 18.5%) was lower and ADMs rate (4.8% vs. 6.2%) was higher in the pandemic period.</p><p><strong>Results: </strong>During the quarantine period, OIs rate (p=0.008) and hospitalization (p=0.002) decreased significantly. Compared to the pre-pandemic period, there was a decrease in primary school graduates (p=0.043) and Centers for Disease Control and Prevention (CDC) category C applicants (p=0.029) and an increase in university graduates (p=0.027) in the quarantine period. After the quarantine period, there was an increase in hospitalization (p=0.002), CDC category C admissions (p=0.021) and ART adherence (p=0.016). Other data were similar for the three periods.</p><p><strong>Conclusion: </strong>In summary, while the COVID-19 pandemic led to notable changes in patients' characteristics and HIV-related clinical characteristics and treatment, the incidence of LD, OIs and ADMs did not increase significantly. Continued monitoring and adaptation of healthcare services are crucial to managing PLWH effectively in the context of global health crises.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324657","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}

{"title":"Germline-targeting Strategies to Induce bNAbs against HIV-1.","authors":"Tugba Atabey, Rogier W Sanders, Yoann Aldon","doi":"10.2174/011570162X365229250527111140","DOIUrl":"https://doi.org/10.2174/011570162X365229250527111140","url":null,"abstract":"<p><p>Developing an effective HIV-1 vaccine remains a critical global health challenge, hin-dered by the virus's high genetic diversity, immune evasion strategies, and structural complexity of its Envelope (Env) glycoprotein. Broadly neutralizing antibodies (bNAbs), capable of targeting conserved Env epitopes, offer a promising path for vaccine design. Germline-targeting (GT) strat-egies have emerged as a promising approach to engage naive B cell precursors that have the po-tential to mature into bNAb-producing cells. Advances in GT have enabled the design of immu-nogens capable of recruiting specific bNAb precursors in animal models and early clinical trials. Despite these successes, achieving neutralization breadth requires sequential immunizations with tailored boosting strategies to guide B cell maturation. Studies underscore the importance of using immunogens that mimic native Env structures while modulating glycosylation patterns to focus immune responses. Emerging approaches, such as membrane-bound presentation and mRNA de-livery, hold the potential for enhancing immunogen effectiveness and rapid pre-clinical and in human screening to identify combinations of immunogens that foster bNAb lineages. This review seeks to synthesize key developments in GT strategies for HIV-1 vaccines, highlighting the de-sign and implementation of immunogens that drive bNAb precursor maturation. It aims to under-score the importance of integrating structural insights, immunogen sequence design, and delivery methods to enhance the induction of bNAbs, offering direction for future research to address ex-isting gaps and optimize vaccine efficacy.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282813","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}

{"title":"Predictive Model for the Detection of Subclinical Atherosclerosis in HIV Patients on Antiretroviral Treatment.","authors":"César Gálvez-Barrón, Sara Gamarra-Calvo, José Ramón Blanco Ramos, Isabel Sanjoaquín Conde, Carlos Pérez-López, Antonio Miñarro, Guillermo Verdejo-Muñoz","doi":"10.2174/011570162X373384250529110832","DOIUrl":"https://doi.org/10.2174/011570162X373384250529110832","url":null,"abstract":"<p><strong>Objective: </strong>Patients living with HIV (PLHIV) have a higher cardiovascular risk than others, which is why the early detection of atherosclerosis in this population is important. The present study reports predictive models of subclinical atherosclerosis for this population of patients, made up of variables that are easily collected in the clinic.</p><p><strong>Methods: </strong>The study design is a cross-sectional observational study. PLHIV without established cardiovascular disease were recruited for this study. Predictive models of subclinical atherosclerosis (Doppler ultrasound) were developed by testing sociodemographic variables, pathological history, data related to HIV infection, laboratory parameters, and capillaroscopy as potential predictors. Logistic regression with internal validation (bootstrapping) and machine learning techniques were used to develop the models.</p><p><strong>Results: </strong>Data from 96 HIV patients were analysed, 19 (19.8%) of whom had subclinical atherosclerosis. The predictors that went into both machine learning models and the regression model were hypertension, dyslipidaemia, protease inhibitors, triglycerides, fibrinogen, and alkaline phosphatase. Age and C-reactive protein were also part of the machine learning models. The logistic regression model had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.84-0.99), which became 0.80 after internal validation by bootstrapping. The ma-chine learning techniques produced models with AUCs ranging from 0.73 to 0.86.</p><p><strong>Conclusion: </strong>We report predictive models for subclinical atherosclerosis in PLHIV, demonstrating relevant predictive performance based on easily accessible parameters, making them potentially useful as a screening tool. However, given the study's limitations-primarily the sample size-external validation in larger cohorts is warranted.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257545","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}

{"title":"Access to Language Lnterpretation Services at Health Care Facilities Providing Care to Adults Diagnosed with HIV in the United States, 2019.","authors":"Mabel Padilla, Linda Beer, Ruth E Luna-Gierke, Tracy Tie, Jen-Feng Lu, John Weiser","doi":"10.2174/011570162X362664250527051957","DOIUrl":"https://doi.org/10.2174/011570162X362664250527051957","url":null,"abstract":"<p><strong>Introduction: </strong>People with limited English proficiency (LEP) experience barriers to healthcare access and optimal outcomes. Language interpretation services can facilitate clear communication-which is key to effective HIV care and treatment.</p><p><strong>Methods: </strong>We analyzed weighted data from the 2019 cycle of the Medical Monitoring Project (MMP), a cross-sectional, complex sample survey of U.S. adults with diagnosed HIV, and data from the 2021 MMP Facility Survey, a survey of facilities providing care to 2019 MMP respond-ents. We estimated the percentage of people with HIV (PWH) with LEP who received care at facilities offering language interpretation services and facilities providing language interpretation services, overall and by selected characteristics.</p><p><strong>Results: </strong>Overall, 89.9% of PWH with LEP received care at a facility with language interpretation services, and 83.6% of facilities provided language interpretation services. PWH with LEP who were unemployed were less likely than those who were employed to receive care at a facility with language interpretation services. Facilities that were Federally Qualified Health Centers, were not private practices, received Ryan White HIV/AIDS Program funding, and accepted public health care coverage were more likely to provide language interpretation services than facilities without these characteristics.</p><p><strong>Conclusion: </strong>Our findings demonstrate that most HIV care facilities are providing access to lan-guage services to PWH with LEP in the United States.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224651","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}

{"title":"Funding Strategies to Foster Enabling Basic Science Research in the Development of an HIV Vaccine.","authors":"Stuart Z Shapiro","doi":"10.2174/011570162X360804250527065110","DOIUrl":"https://doi.org/10.2174/011570162X360804250527065110","url":null,"abstract":"<p><p>Despite recent advances in other prevention strategies, an effective vaccine is still needed to guarantee a sustained end to the HIV/AIDS pandemic. However, the traditional ap-proaches of vaccinology have thus far failed to produce an effective vaccine. More basic research may be needed to enhance our understanding of HIV immunity and the immunological principles behind vaccination and to leverage advanced technologies before applied research activities can be successfully used to develop a distributable HIV vaccine. US Government funding plays a crucial role in promoting, enabling, and advising independent scientists and experts to perform such research. This article was written to provide, to the broader scientific community, detail about the tools NIAID uses for research funding, how and why they were used for HIV vaccine development, and how they have been helpful; it is written from the perspective of a Program Officer's experiences while working for more than 25 years in the Division of AIDS (DAIDS) of NIAID at the NIH (the US National Institutes of Health). Several types of funding activities pro-mote HIV vaccine development efforts, but three types of such activities and their impact on HIV vaccine development will be discussed in more detail.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215207","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}

{"title":"Correlation between Antiretroviral Therapy Responses and Resistance to First-Line Reverse Transcriptase Inhibitors in People Living with HIV-1 Experiencing Virological Failure in South Sulawesi, Indonesia.","authors":"Nurjannah -, Francisca Srioetami Tanoehardjo, Risna Halim Mubin, Sri Jayanti, Haerani Rasyid, Agussalim Bukhari, Andi Kurnia Bintang, Khairuddin Djawad, Budiman Bella, Burhanuddin Bahar, Caecilia Hapsari Ceriapuri Sukowati, Muhammad Nasrum Massi","doi":"10.2174/011570162X336531250517171339","DOIUrl":"https://doi.org/10.2174/011570162X336531250517171339","url":null,"abstract":"<p><strong>Introduction: </strong>The effectiveness of antiretroviral therapy (ART) in treating HIV is in-fluenced by the clinical response of patients, which, in turn, impacts the development of drug resistance. This study aimed to assess the correlation between clinical treatment response and resistance to first-line reverse transcriptase inhibitors in HIV patients receiving treatment for ≤12 and >12 months in South Sulawesi, a province in Indonesia.</p><p><strong>Methods: </strong>In this cross-sectional study, 36 people living with HIV (PLHIV) experiencing viro-logical failure (VF) were sampled from HIV services in the province from August 2022 to January 2023. HIV-1 viral RNAs were extracted, sequenced, and analyzed for drug sensitivity and re-sistance classification using the Stanford University HIV Drug Resistance Database (HIVdb) ac-cording to World Health Organization (WHO) recommendations, determining resistance levels and HIV subtypes. Phylogenetic analysis of PR-RT sequences (~1200 base pairs) was performed using the Muscle program and MEGA11 software, utilizing the neighbor-joining method with the Kimura two-parameter model.</p><p><strong>Results: </strong>Genotyping of plasma samples revealed that a significant proportion of patients exhib-ited mutations associated with resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) (48.6% and 51.4%, respectively). Clinical response indica-tors, such as initial body mass index and occurrence of opportunistic infections, were found to correlate with specific drug resistance, highlighting the importance of monitoring treatment re-sponse. Moreover, virologic response showed strong associations with resistance to specific drugs, suggesting the need for tailored therapeutic approaches. Patient behaviors related to trans-mission risk factors were also found to be linked to resistance levels, underscoring the multifac-torial nature of resistance development.</p><p><strong>Conclusion: </strong>Overall, this study underscores the importance of considering treatment response in managing HIV and suggests implications for optimizing therapy regimens to mitigate resistance emergence.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179998","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}

{"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}

{"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}