{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:37:40Z","timestamp":1791571060143,"version":"4.3.4"},"reference-count":135,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Women in Science for the Developing World (OWSD) and Swedish International Development Cooperation Agency (SIDA)","award":["3240314457"],"award-info":[{"award-number":["3240314457"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Inflammation is a crucial component of the immune response essential for host defense and tissue repair. However, when the immune response becomes dysregulated, it can contribute to the pathogenesis of chronic diseases. While acute inflammation is a short-lived, protective response, chronic inflammation is sustained over time and can lead to immune dysfunction, tissue damage, and disease progression. The chronic inflammation theory of disease suggests that persistent immune activation\/inflammation underlies both infectious and non-infectious conditions and serves as a unifying mechanism across distinct pathological states. In this review article, we argue that human immunodeficiency virus (HIV) infection represents a prime model for studying chronic inflammation, and that despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) exhibit persistent immune activation, systemic inflammation, and an increased risk of cardiovascular, metabolic, and neurodegenerative diseases. Here, the interplay between microbial translocation, immune dysregulation, and metabolic reprogramming fuels a state of chronic inflammation that accelerates disease progression beyond HIV itself. Key factors such as T-cell exhaustion, persistent monocyte\/macrophage activation, and immunometabolic dysfunction contribute to such a sustained inflammatory state. This review explores the molecular and cellular mechanisms driving chronic inflammation in HIV infection with a focus on immunometabolism and its implications for broader inflammatory diseases. By understanding such pathways, we can identify novel therapeutic targets to mitigate inflammation-driven disease progression not only in HIV but across a spectrum of chronic inflammatory conditions.<\/jats:p>","DOI":"10.3390\/v17060839","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T03:59:17Z","timestamp":1749700757000},"page":"839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["HIV, Inflammation, and Immunometabolism: A Model of the Inflammatory Theory of Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Eman","family":"Teer","sequence":"first","affiliation":[{"name":"Centre for Cardio-Metabolic Research in Africa, Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7600, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4916-0171","authenticated-orcid":false,"given":"Nyasha C.","family":"Mukonowenzou","sequence":"additional","affiliation":[{"name":"Centre for Cardio-Metabolic Research in Africa, Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7600, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-4294","authenticated-orcid":false,"given":"M. Faadiel","family":"Essop","sequence":"additional","affiliation":[{"name":"Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abudukelimu, A., Barberis, M., Redegeld, F.A., Sahin, N., and Westerhoff, H.V. (2018). Predictable Irreversible Switching Between Acute and Chronic Inflammation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01596"},{"key":"ref_3","unstructured":"Pahwa, R., Goyal, A., and Jialal, I. (2025). Chronic Inflammation. StatPearls, StatPearls Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s12250-020-00332-0","article-title":"Monocyte\/Macrophage-Mediated Innate Immunity in HIV-1 Infection: From Early Response to Late Dysregulation and Links to Cardiovascular Diseases Onset","volume":"36","author":"Teer","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Antar, S.A., Ashour, N.A., Marawan, M.E., and Al-Karmalawy, A.A. (2023). Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044004"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/embor.2012.142","article-title":"The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment","volume":"13","author":"Hunter","year":"2012","journal-title":"EMBO Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S375","DOI":"10.1093\/infdis\/jis200","article-title":"Immunologic basis of cardiovascular disease in HIV-infected adults","volume":"205","author":"Hsue","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zicari, S., Sessa, L., Cotugno, N., Ruggiero, A., Morrocchi, E., Concato, C., Rocca, S., Zangari, P., Manno, E.C., and Palma, P. (2019). Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART. Viruses, 11.","DOI":"10.3390\/v11030200"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/WCO.0b013e32834695fb","article-title":"Current understanding of HIV-associated neurocognitive disorders pathogenesis","volume":"24","author":"Gannon","year":"2011","journal-title":"Curr. Opin. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mu, W., Patankar, V., Kitchen, S., and Zhen, A. (2024). Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection. Viruses, 16.","DOI":"10.3390\/v16020219"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.tim.2012.09.001","article-title":"Microbial translocation, immune activation, and HIV disease","volume":"21","author":"Klatt","year":"2013","journal-title":"Trends Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Raehtz, K.D., Barrenas, F., Xu, C., Busman-Sahay, K., Valentine, A., Law, L., Ma, D., Policicchio, B.B., Wijewardana, V., and Brocca-Cofano, E. (2020). African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008333"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.4049\/jimmunol.179.5.3035","article-title":"Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence","volume":"179","author":"Pandrea","year":"2007","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1089\/aid.2011.0213","article-title":"Immune activation in the pathogenesis of treated chronic HIV disease: A workshop summary","volume":"28","author":"Plaeger","year":"2012","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.4049\/jimmunol.180.9.5771","article-title":"IL-10: The master regulator of immunity to infection","volume":"180","author":"Couper","year":"2008","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1615\/CritRevImmunol.v32.i1.30","article-title":"Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease","volume":"32","author":"Iyer","year":"2012","journal-title":"Crit. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/imr.12079","article-title":"HIV-associated chronic immune activation","volume":"254","author":"Paiardini","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.10.001","article-title":"Systemic effects of inflammation on health during chronic HIV infection","volume":"39","author":"Deeks","year":"2013","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/nm1511","article-title":"Microbial translocation is a cause of systemic immune activation in chronic HIV infection","volume":"12","author":"Brenchley","year":"2006","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1182\/blood-2003-09-3333","article-title":"Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load","volume":"104","author":"Deeks","year":"2004","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1742-4690-7-54","article-title":"Innate immune recognition and activation during HIV infection","volume":"7","author":"Mogensen","year":"2010","journal-title":"Retrovirology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/COH.0000000000000242","article-title":"Role of immune activation in progression to AIDS","volume":"11","author":"Utay","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11904-017-0356-x","article-title":"Inflammation, Immune Activation, and Antiretroviral Therapy in HIV","volume":"14","author":"Hileman","year":"2017","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies","volume":"27","author":"Cohn","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.18683\/germs.2021.1242","article-title":"Exhaustion and senescence of CD4 and CD8 T cells that express co-stimulatory molecules CD27 and CD28 in subjects that acquired HIV by drug use or by sexual route","volume":"11","author":"Banica","year":"2021","journal-title":"Germs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12981-018-0194-y","article-title":"Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells","volume":"15","author":"Nabatanzi","year":"2018","journal-title":"AIDS Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kuller, L.H., Tracy, R., Belloso, W., De Wit, S., Drummond, F., Lane, H.C., Ledergerber, B., Lundgren, J., Neuhaus, J., and Nixon, D. (2008). Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050203"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1161\/CIRCULATIONAHA.122.057443","article-title":"Cardiovascular Disease Among Persons Living with HIV: New Insights into Pathogenesis and Clinical Manifestations in a Global Context","volume":"147","author":"Ntsekhe","year":"2023","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/QAI.0000000000001964","article-title":"Metabolic Syndrome and Neurocognitive Deficits in HIV Infection","volume":"81","author":"Yu","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/s41423-024-01167-5","article-title":"The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond","volume":"21","author":"Ngo","year":"2024","journal-title":"Cell. Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10262","DOI":"10.1128\/JVI.00993-12","article-title":"Homeostasis and function of regulatory T cells in HIV\/SIV infection","volume":"86","author":"Presicce","year":"2012","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S2055-6640(20)30305-8","article-title":"Regulatory T cells: The ultimate HIV reservoir?","volume":"4","author":"Rocco","year":"2018","journal-title":"J. Virus Erad."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11904-013-0171-y","article-title":"HIV and neurocognitive dysfunction","volume":"10","author":"Spudich","year":"2013","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Saikh, K.U., Anam, K., Sultana, H., Ahmed, R., Kumar, S., Srinivasan, S., and Ahmed, H. (2024). Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158421"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8180","DOI":"10.1128\/JVI.00421-07","article-title":"MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands","volume":"81","author":"Meier","year":"2007","journal-title":"J. Virol."},{"key":"ref_37","first-page":"128","article-title":"Immune activation, HIV persistence, and the cure","volume":"21","author":"Douek","year":"2016","journal-title":"Top. Antivir. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100193","DOI":"10.1016\/j.cellin.2024.100193","article-title":"Role of the CARD8 inflammasome in HIV pathogenesis","volume":"3","author":"Wang","year":"2024","journal-title":"Cell Insight"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.cell.2024.01.048","article-title":"The CARD8 inflammasome dictates HIV\/SIV pathogenesis and disease progression","volume":"187","author":"Wang","year":"2024","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/imr.12082","article-title":"Dendritic cell dysregulation during HIV-1 infection","volume":"254","author":"Miller","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cytogfr.2018.03.003","article-title":"Type I interferon and HIV: Subtle balance between antiviral activity, immunopathogenesis and the microbiome","volume":"40","author":"Scagnolari","year":"2018","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1054-3589(07)55002-7","article-title":"Structure and function of the HIV envelope glycoprotein as entry mediator, vaccine immunogen, and target for inhibitors","volume":"55","author":"Prabakaran","year":"2007","journal-title":"Adv. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.tim.2019.06.002","article-title":"Molecular Mechanism of HIV-1 Entry","volume":"27","author":"Chen","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"124420131251","DOI":"10.1128\/CVI.00066-10","article-title":"Characterization of immune responses to capsid protein p24 of human immunodeficiency virus type 1 and implications for detection","volume":"17","author":"Tang","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12977-018-0398-1","article-title":"Episomal HIV-1 DNA and its relationship to other markers of HIV-1 persistence","volume":"15","author":"Zurakowski","year":"2018","journal-title":"Retrovirology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yin, X., Langer, S., Zhang, Z., Herbert, K.M., Yoh, S., Konig, R., and Chanda, S.K. (2020). Sensor Sensibility-HIV-1 and the Innate Immune Response. Cells, 9.","DOI":"10.3390\/cells9010254"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e143940","DOI":"10.1172\/jci.insight.143940","article-title":"HIV-1 integration sites in CD4+ T cells during primary, chronic, and late presentation of HIV-1 infection","volume":"6","author":"Kok","year":"2021","journal-title":"JCI Insight"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12058","DOI":"10.1128\/JVI.01471-15","article-title":"Interaction between Reverse Transcriptase and Integrase Is Required for Reverse Transcription during HIV-1 Replication","volume":"89","author":"Tekeste","year":"2015","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/JVI.01322-19","article-title":"How HIV Nef Proteins Hijack Membrane Traffic to Promote Infection","volume":"93","author":"Buffalo","year":"2019","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/B978-0-12-385987-7.00005-1","article-title":"HIV immune evasion disruption of antigen presentation by the HIV Nef protein","volume":"80","author":"Wonderlich","year":"2011","journal-title":"Adv. Virus Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"913","DOI":"10.18632\/aging.100390","article-title":"Deciphering the role of nuclear factor-kappaB in cellular senescence","volume":"3","author":"Vaughan","year":"2011","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s13365-022-01061-8","article-title":"Human immunodeficiency virus-1 Tat exerts its neurotoxic effects by downregulating Sonic hedgehog signaling","volume":"28","author":"Khan","year":"2022","journal-title":"J. Neurovirol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101471","DOI":"10.1016\/j.smim.2021.101471","article-title":"Residual immune dysfunction under antiretroviral therapy","volume":"51","author":"Cai","year":"2021","journal-title":"Semin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1097\/QAD.0000000000001109","article-title":"Inflammation, immune activation, and cardiovascular disease in HIV","volume":"30","author":"Nou","year":"2016","journal-title":"AIDS"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., Feehan, J., and Apostolopoulos, V. (2024). Inflammation: The Cause of All Diseases. Cells, 13.","DOI":"10.3390\/cells13221906"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mazzuti, L., Turriziani, O., and Mezzaroma, I. (2023). The Many Faces of Immune Activation in HIV-1 Infection: A Multifactorial Interconnection. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010159"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wiertsema, S.P., van Bergenhenegouwen, J., Garssen, J., and Knippels, L.M.J. (2021). The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients, 13.","DOI":"10.3390\/nu13030886"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hunt, P.W., Landay, A.L., Sinclair, E., Martinson, J.A., Hatano, H., Emu, B., Norris, P.J., Busch, M.P., Martin, J.N., and Brooks, C. (2011). A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015924"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Caruso, M.P., Falivene, J., Holgado, M.P., Zurita, D.H., Laufer, N., Castro, C., Nico, A., Maeto, C., Salido, J., and Perez, H. (2019). Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-38547-1"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Omenetti, S., and Pizarro, T.T. (2015). The Treg\/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00639"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/s41423-023-01036-7","article-title":"Intricacies of TGF-beta signaling in Treg and Th17 cell biology","volume":"20","author":"Wang","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"103866","DOI":"10.1016\/j.bjid.2024.103866","article-title":"The role of T regulatory cells in the immunopathogenesis of HIV: Clinical implications","volume":"28","author":"Mohammadi","year":"2024","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Atehortua, L., Baig, M., Morris, J., Trentman, S., Davidson, W.S., Fichtenbaum, C.J., and Chougnet, C.A. (2023). Impaired response of memory Treg to high density lipoproteins is associated with intermediate\/high cardiovascular disease risk in persons with HIV. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1146624"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrneurol.2016.27","article-title":"HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment","volume":"12","author":"Saylor","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.4049\/jimmunol.174.7.4407","article-title":"Depletion of regulatory T cells in HIV infection is associated with immune activation","volume":"174","author":"Eggena","year":"2005","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2217\/hiv.09.8","article-title":"Type I interferon in HIV treatment: From antiviral drug to therapeutic target","volume":"3","author":"Boasso","year":"2009","journal-title":"HIV Ther."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Teer, E., Mukonowenzou, N.C., and Essop, M.F. (2025). The Role of Sustained Type I Interferon Secretion in Chronic HIV Pathogenicity: Implications for Viral Persistence, Immune Activation, and Immunometabolism. Viruses, 17.","DOI":"10.3390\/v17020139"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.virol.2014.12.033","article-title":"T cell exhaustion during persistent viral infections","volume":"479\u2013480","author":"Kahan","year":"2015","journal-title":"Virology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.coph.2009.04.008","article-title":"Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity","volume":"9","author":"Sanjabi","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/cei.12814","article-title":"Ageing and inflammation in patients with HIV infection","volume":"187","author":"Nasi","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1093\/infdis\/jis236","article-title":"Preserved function of regulatory T cells in chronic HIV-1 infection despite decreased numbers in blood and tissue","volume":"205","author":"Angin","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.arr.2016.12.004","article-title":"HIV-associated cellular senescence: A contributor to accelerated aging","volume":"36","author":"Cohen","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11904-009-0038-4","article-title":"Early immune senescence in HIV disease","volume":"7","author":"Desai","year":"2010","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Soper, A., Kimura, I., Nagaoka, S., Konno, Y., Yamamoto, K., Koyanagi, Y., and Sato, K. (2017). Type I Interferon Responses by HIV-1 Infection: Association with Disease Progression and Control. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01823"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Apetroaei, M.-M., Baliou, S., Ioannou, P., Fragkiadaki, P., \u0218tefan, G., Nedea, M.I., Burcea-Dragomiroiu, G.-T.-A., Velescu, B.\u0218., Docea, A.O., and Udeanu, D.I. (2025). The Hallmarks of Ageing in Human Immunodeficiency Virus Infection and the Impact of Antiretroviral Therapy on Telomeres: A Molecular Perspective. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040273"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijid.2016.10.004","article-title":"HIV and aging","volume":"53","author":"Wing","year":"2016","journal-title":"Int. J. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41423-022-00840-x","article-title":"Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology","volume":"19","author":"Chi","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s12250-021-00386-8","article-title":"Expansion of GARP-Expressing CD4+CD25\u2212FoxP3+ T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa","volume":"36","author":"Teer","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chan, Y.T., Cheong, H.C., Tang, T.F., Rajasuriar, R., Cheng, K.K., Looi, C.Y., Wong, W.F., and Kamarulzaman, A. (2022). Immune Checkpoint Molecules and Glucose Metabolism in HIV-Induced T Cell Exhaustion. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112809"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ebiom.2016.02.012","article-title":"Glucose Metabolism in T Cells and Monocytes: New Perspectives in HIV Pathogenesis","volume":"6","author":"Palmer","year":"2016","journal-title":"eBioMedicine"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1365-2567.2010.03255.x","article-title":"T-cell exhaustion: Characteristics, causes and conversion","volume":"129","author":"Yi","year":"2010","journal-title":"Immunology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev-immunol-041015-055318","article-title":"CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer","volume":"37","author":"McLane","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/imr.12823","article-title":"T-cell exhaustion in HIV infection","volume":"292","author":"Fenwick","year":"2019","journal-title":"Immunol. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11904-010-0066-0","article-title":"Revisiting immune exhaustion during HIV infection","volume":"8","author":"Khaitan","year":"2011","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.ebiom.2019.07.027","article-title":"Inflammatory and immunometabolic consequences of gut dysfunction in HIV: Parallels with IBD and implications for reservoir persistence and non-AIDS comorbidities","volume":"46","author":"Alzahrani","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1111\/febs.15327","article-title":"Glycolysis\u2014A key player in the inflammatory response","volume":"287","author":"Oller","year":"2020","journal-title":"FEBS J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11904-020-00484-4","article-title":"Dysfunctional Immunometabolism in HIV Infection: Contributing Factors and Implications for Age-Related Comorbid Diseases","volume":"17","author":"Butterfield","year":"2020","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.immuni.2021.12.013","article-title":"Inflammation in obesity, diabetes, and related disorders","volume":"55","author":"Rohm","year":"2022","journal-title":"Immunity"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Patergnani, S., Bouhamida, E., Leo, S., Pinton, P., and Rimessi, A. (2021). Mitochondrial Oxidative Stress and \u201cMito-Inflammation\u201d: Actors in the Diseases. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020216"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6238978","DOI":"10.1155\/2018\/6238978","article-title":"Examining Relationships between Metabolism and Persistent Inflammation in HIV Patients on Antiretroviral Therapy","volume":"2018","author":"Ahmed","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_93","unstructured":"Chaudhry, R., and Varacallo, M.A. (2025). Biochemistry, Glycolysis. StatPearls, StatPearls Publishing."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1007\/s00125-017-4526-6","article-title":"Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses","volume":"61","author":"Boutens","year":"2018","journal-title":"Diabetologia"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7570\/jomes24030","article-title":"Dynamic Roles and Expanding Diversity of Adipose Tissue Macrophages in Obesity","volume":"33","author":"Soedono","year":"2024","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.immuni.2014.09.008","article-title":"HIF transcription factors, inflammation, and immunity","volume":"41","author":"Palazon","year":"2014","journal-title":"Immunity"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41392-024-01954-6","article-title":"Metabolic regulation of the immune system in health and diseases: Mechanisms and interventions","volume":"9","author":"Hu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nri3520","article-title":"Macrophages in atherosclerosis: A dynamic balance","volume":"13","author":"Moore","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/MOL.0000000000000634","article-title":"Monocytes and macrophages in atherogenesis","volume":"30","author":"Amengual","year":"2019","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Meyers, A.K., and Zhu, X. (2020). The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging. Cells, 9.","DOI":"10.3390\/cells9081808"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular Smooth Muscle Cells in Atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.cmet.2010.03.014","article-title":"Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner","volume":"11","author":"Kalender","year":"2010","journal-title":"Cell Metab."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Zhao, X., An, X., Yang, C., Sun, W., Ji, H., and Lian, F. (2023). The crucial role and mechanism of insulin resistance in metabolic disease. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1149239"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/COH.0000000000000755","article-title":"HIV and cardiovascular disease: The role of inflammation","volume":"17","author":"Funderburg","year":"2022","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"107734","DOI":"10.1016\/j.jdiacomp.2020.107734","article-title":"Role of ceramides in the pathogenesis of diabetes mellitus and its complications","volume":"35","author":"Mandal","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s11904-016-0321-0","article-title":"Lipid Abnormalities and Inflammation in HIV Inflection","volume":"13","author":"Funderburg","year":"2016","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cca.2021.12.010","article-title":"Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry","volume":"526","author":"Zhang","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/mi.2007.1","article-title":"HIV infection and the gastrointestinal immune system","volume":"1","author":"Brenchley","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Moretti, S., Schietroma, I., Sberna, G., Maggiorella, M.T., Sernicola, L., Farcomeni, S., Giovanetti, M., Ciccozzi, M., and Borsetti, A. (2023). HIV-1-Host Interaction in Gut-Associated Lymphoid Tissue (GALT): Effects on Local Environment and Comorbidities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512193"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrmicro2848","article-title":"Microbial translocation in HIV infection: Causes, consequences and treatment opportunities","volume":"10","author":"Sandler","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/COH.0000000000000234","article-title":"Microbial translocation and microbiome dysbiosis in HIV-associated immune activation","volume":"11","author":"Zevin","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/MIB.0000000000000750","article-title":"Current Understanding of Dysbiosis in Disease in Human and Animal Models","volume":"22","author":"DeGruttola","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"113336","DOI":"10.1016\/j.celrep.2023.113336","article-title":"Impaired gut microbiota-mediated short-chain fatty acid production precedes morbidity and mortality in people with HIV","volume":"42","author":"Sereti","year":"2023","journal-title":"Cell Rep."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Teer, E., Dominick, L., Mukonowenzou, N.C., and Essop, M.F. (2022). HIV-Related Myocardial Fibrosis: Inflammatory Hypothesis and Crucial Role of Immune Cells Dysregulation. Cells, 11.","DOI":"10.3390\/cells11182825"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Teer, E., Mukonowenzou, N.C., and Essop, M.F. (2022). The Role of Immunometabolism in HIV-1 Pathogenicity: Links to Immune Cell Responses. Viruses, 14.","DOI":"10.3390\/v14081813"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1152\/physiol.00028.2017","article-title":"HIV and Cardiovascular Disease: Role of Immunometabolic Perturbations","volume":"33","author":"Teer","year":"2018","journal-title":"Physiology"},{"key":"ref_119","unstructured":"Dominick, L.L. (2021). An Evaluation of the Role of Platelet Activation in HIV-Related Cardiovascular Diseases Onset. [Master\u2019s Thesis, Stellenbosch University]."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"H1146","DOI":"10.1152\/ajpheart.00797.2018","article-title":"HIV and cardiovascular diseases risk: Exploring the interplay between T-cell activation, coagulation, monocyte subsets, and lipid subclass alterations","volume":"316","author":"Teer","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"111855","DOI":"10.1016\/j.mad.2023.111855","article-title":"Role of cytokines and reactive oxygen species in brain aging","volume":"214","author":"MohanKumar","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1093\/infdis\/jiac370","article-title":"Biotypes of Central Nervous System Complications in People with Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology","volume":"227","author":"Joseph","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Lopez-Atalaya, J.P., and Bhojwani-Cabrera, A.M. (2025). Type I interferon signalling and interferon-responsive microglia in health and disease. FEBS J., 1\u201320.","DOI":"10.1111\/febs.70126"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11904-021-00570-1","article-title":"Advances in the Experimental Models of HIV-Associated Neurological Disorders","volume":"18","author":"Sil","year":"2021","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Fert, A., Richard, J., Marchand, L.R., Planas, D., Routy, J.P., Chomont, N., Finzi, A., and Ancuta, P. (2024). Metformin Enhances Antibody-Mediated Recognition of HIV-Infected CD4+ T-Cells by Decreasing Viral Release. bioRxiv.","DOI":"10.1101\/2024.02.15.580166"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41423-023-01064-3","article-title":"Regulation of CD8+ T memory and exhaustion by the mTOR signals","volume":"20","author":"Chen","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/COH.0000000000000752","article-title":"Statins for primary cardiovascular disease prevention among people with HIV: Emergent directions","volume":"17","author":"Fitch","year":"2022","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2174\/138161209787315684","article-title":"Statins and cardiovascular diseases: From cholesterol lowering to pleiotropy","volume":"15","author":"Zhou","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s11904-015-0273-9","article-title":"The role of statins in the setting of HIV infection","volume":"12","author":"Eckard","year":"2015","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Zivkovic, S., Maric, G., Cvetinovic, N., Lepojevic-Stefanovic, D., and Bozic Cvijan, B. (2023). Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review. Nutrients, 15.","DOI":"10.3390\/nu15061517"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1056\/NEJMoa2304146","article-title":"Pitavastatin to Prevent Cardiovascular Disease in HIV Infection","volume":"389","author":"Grinspoon","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"d\u2019Ettorre, G., Ceccarelli, G., Giustini, N., Serafino, S., Calantone, N., De Girolamo, G., Bianchi, L., Bellelli, V., Ascoli-Bartoli, T., and Marcellini, S. (2015). Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the \u201cProbio-HIV\u201d Clinical Trial. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137200"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Al-Habsi, N., Al-Khalili, M., Haque, S.A., Elias, M., Olqi, N.A., and Al Uraimi, T. (2024). Health Benefits of Prebiotics, Probiotics, Synbiotics, and Postbiotics. Nutrients, 16.","DOI":"10.3390\/nu16223955"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"D\u2019Angelo, C., Reale, M., and Costantini, E. (2017). Microbiota and Probiotics in Health and HIV Infection. Nutrients, 9.","DOI":"10.3390\/nu9060615"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/6\/839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:18Z","timestamp":1760032218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/6\/839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":135,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["v17060839"],"URL":"https:\/\/doi.org\/10.3390\/v17060839","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}