{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:03:51Z","timestamp":1780074231760,"version":"3.54.0"},"reference-count":123,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Combined antiretroviral therapy (cART) has transformed HIV into a manageable chronic disease. However, people living with HIV (PLWH) experience a 16-year reduction in comorbidity-free life expectancy compared to HIV-negative individuals, driven by persistent chronic immune activation despite virological suppression. Serious non-AIDS events (SNAEs)\u2014including cardiovascular disease, metabolic disorders, and malignancies\u2014now represent the predominant cause of morbidity. This narrative review provides a clinician-oriented synthesis of immunopathophysiological mechanisms driving chronic inflammation in treated HIV infection, focusing on the gut\u2013immune axis, restriction factors, trained immunity, biomarker-guided risk stratification, and therapeutic strategies. We searched PubMed\/MEDLINE, Embase, and Web of Science through April 2026 using terms related to HIV chronic immune activation, gut-associated lymphoid tissue, microbial translocation, inflammaging, restriction factors, trained immunity, and biomarkers. This review followed the SANRA checklist. Irreversible destruction of gut-associated lymphoid tissue (GALT), intestinal barrier dysfunction, microbial translocation, maladaptive trained immunity, persistent myeloid activation with NLRP3 inflammasome signaling and cellular senescence, and viral reservoir persistence collectively perpetuate systemic inflammation. Biomarkers, including sCD14, IL-6, and suPAR, independently predict mortality but are not pathogen-specific. The REPRIEVE trial demonstrated a 36% reduction in cardiovascular risk with pitavastatin (HR 0.64, 95% CI 0.48\u20130.84), validating inflammation as a therapeutic target. Integration of early cART, statin therapy, optimal antiretroviral selection, and emerging strategies\u2014including GLP-1 receptor agonists and gut-directed therapies\u2014offers a practical framework for reducing inflammation-associated comorbidities in virologically suppressed PLWH.<\/jats:p>","DOI":"10.3390\/microorganisms14061229","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:57:18Z","timestamp":1780070238000},"page":"1229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Gut\u2013Immune Axis in Treated HIV Infection: From Mucosal Damage to Chronic Inflammation and Therapeutic Opportunities\u2014A Clinician-Oriented Narrative Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-1317","authenticated-orcid":false,"given":"Thomas N.","family":"Nitsotolis","sequence":"first","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-3681","authenticated-orcid":false,"given":"Stelios F.","family":"Assimakopoulos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8900-0212","authenticated-orcid":false,"given":"Maria","family":"Lagadinou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Papalexandrou","sequence":"additional","affiliation":[{"name":"Ionian Nephrology Center, 18450 Piraeus, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Krikis","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios","family":"Kourtidis","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Christaki","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-2266","authenticated-orcid":false,"given":"Haralampos","family":"Milionis","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.6189183","article-title":"Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)","volume":"220","author":"Chermann","year":"1983","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1126\/science.6200936","article-title":"Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS","volume":"224","author":"Gallo","year":"1984","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/S0140-6736(13)61809-7","article-title":"The end of AIDS: HIV infection as a chronic disease","volume":"382","author":"Deeks","year":"2013","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41572-023-00452-3","article-title":"HIV infection","volume":"9","author":"Bekker","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1093\/infdis\/jiw275","article-title":"Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection","volume":"214","author":"Hunt","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-med-042909-093756","article-title":"HIV infection, inflammation, immunosenescence, and aging","volume":"62","author":"Deeks","year":"2011","journal-title":"Annu. Rev. Med."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/path.2276","article-title":"Immune activation and inflammation in HIV-1 infection: Causes and consequences","volume":"214","author":"Appay","year":"2008","journal-title":"J. Pathol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"e207954","DOI":"10.1001\/jamanetworkopen.2020.7954","article-title":"Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000\u20132016","volume":"3","author":"Marcus","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e349","DOI":"10.1016\/S2352-3018(17)30066-8","article-title":"Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: A collaborative analysis of cohort studies","volume":"4","author":"Trickey","year":"2017","journal-title":"Lancet HIV"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1001\/jamainternmed.2013.3728","article-title":"HIV infection and the risk of acute myocardial infarction","volume":"173","author":"Freiberg","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1161\/CIRCULATIONAHA.117.033369","article-title":"Global Burden of Atherosclerotic Cardiovascular Disease in People Living with HIV: Systematic Review and Meta-Analysis","volume":"138","author":"Shah","year":"2018","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Okine, T., Hill, E., Sheran, K., and Swartz, T.H. (2025). Beyond viral suppression: Decoding the mitochondrial-immune axis in HIV-associated inflammation and immune dysfunction. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1686785"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Teer, E., Mukonowenzou, N.C., and Essop, M.F. (2025). HIV, Inflammation, and Immunometabolism: A Model of the Inflammatory Theory of Disease. Viruses, 17.","DOI":"10.3390\/v17060839"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1161\/CIRCRESAHA.124.323891","article-title":"Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease","volume":"134","author":"Obare","year":"2024","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.biochem.67.1.1","article-title":"HIV-1: Fifteen proteins and an RNA","volume":"67","author":"Frankel","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jmbi.1998.2354","article-title":"Structural biology of HIV","volume":"285","author":"Turner","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.chom.2008.04.008","article-title":"HIV-1 accessory proteins\u2014Ensuring viral survival in a hostile environment","volume":"3","author":"Malim","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40875","DOI":"10.1074\/jbc.R112.416925","article-title":"The restriction factors of human immunodeficiency virus","volume":"287","author":"Harris","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nature06553","article-title":"Tetherin inhibits retrovirus release and is antagonized by the HIV-1 Vpu protein","volume":"451","author":"Neil","year":"2008","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/nar\/28.3.663","article-title":"A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter","volume":"28","author":"Pereira","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.virol.2014.02.008","article-title":"Transcriptional control of HIV latency: Cellular signaling pathways, epigenetics, happenstance and the hope for a cure","volume":"454\u2013455","author":"Mbonye","year":"2014","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Colomer-Lluch, M., Ruiz, A., Moris, A., and Prado, J.G. (2018). Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02876"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.chom.2010.06.004","article-title":"Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses","volume":"8","author":"Kirchhoff","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.immuni.2012.08.013","article-title":"Intrinsic cellular defenses against human immunodeficiency viruses","volume":"37","author":"Venkatesh","year":"2012","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature15399","article-title":"HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation","volume":"526","author":"Rosa","year":"2015","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nature15400","article-title":"SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef","volume":"526","author":"Usami","year":"2015","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1038\/nm.3956","article-title":"MARCH8 inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins","volume":"21","author":"Tada","year":"2015","journal-title":"Nat. Med."},{"key":"ref_30","unstructured":"Coffin, J.M., Hughes, S.H., and Varmus, H.E. (1997). Retroviruses, Cold Spring Harbor Laboratory Press."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nature10117","article-title":"SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx","volume":"474","author":"Laguette","year":"2011","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ni.2236","article-title":"SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates","volume":"13","author":"Lahouassa","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/COH.0000000000000233","article-title":"HIV replication: A game of hide and sense","volume":"11","author":"Sauter","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e145928","DOI":"10.1172\/jci.insight.145928","article-title":"Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells","volume":"6","author":"Keramati","year":"2021","journal-title":"JCI Insight"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nature02343","article-title":"The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys","volume":"427","author":"Stremlau","year":"2004","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature12542","article-title":"Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection","volume":"502","author":"Goujon","year":"2013","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nature12653","article-title":"MX2 is an interferon-induced inhibitor of HIV-1 infection","volume":"502","author":"Kane","year":"2013","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dubrovsky, L., Pushkarsky, T., Brichacek, B., Bastin, A., Roberts, A., Lucar, J., Ruiz, M.E., Semeniuk, O., Siegel, M., and Sviridov, D. (2026). Maladaptive Trained Immunity Drives Persistent IL-6 Production and Enhanced TLR Responsiveness in Monocyte-Derived Macrophages from People Living with HIV. Microorganisms, 14.","DOI":"10.3390\/microorganisms14020355"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1097\/QAD.0000000000001441","article-title":"Basic science and pathogenesis of ageing with HIV: Potential mechanisms and biomarkers","volume":"31","author":"Lagathu","year":"2017","journal-title":"AIDS"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tedeschi, V., Paldino, G., Kunkl, M., Paroli, M., Sorrentino, R., Tuosto, L., and Fiorillo, M.T. (2022). CD8 T Cell Senescence: Lights and Shadows in Viral Infections, Autoimmune Disorders and Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063374"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1084\/jem.20041196","article-title":"Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract","volume":"200","author":"Mehandru","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1084\/jem.20040874","article-title":"CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract","volume":"200","author":"Brenchley","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1182\/blood-2008-05-159301","article-title":"Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections","volume":"112","author":"Brenchley","year":"2008","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nazli, A., Chan, O., Dobson-Belaire, W.N., Ouellet, M., Tremblay, M.J., Gray-Owen, S.D., Arsenault, A.L., and Kaushic, C. (2010). Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000852"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5666","DOI":"10.1016\/j.cell.2025.08.024","article-title":"Immunometabolic defects of CD8+ T cells disrupt gut barrier integrity in people with HIV","volume":"188","author":"Froehle","year":"2025","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1056\/NEJMoa072761","article-title":"Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes","volume":"356","author":"Nissen","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1503\/cmaj.080486","article-title":"Long-term use of thiazolidinediones and fractures in type 2 diabetes: A meta-analysis","volume":"180","author":"Loke","year":"2009","journal-title":"CMAJ"},{"key":"ref_50","first-page":"193ra91","article-title":"Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism","volume":"5","author":"Dunham","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/mi.2013.116","article-title":"An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia","volume":"7","author":"Dillon","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"803185","DOI":"10.1155\/2014\/803185","article-title":"Gut Microbiota in HIV Infection: Implication for Disease Progression and Management","volume":"2014","author":"Nwosu","year":"2014","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_53","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_54","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/s41564-025-02253-8","article-title":"Human immunodeficiency virus-associated gut microbiome impacts systemic immunodeficiency and susceptibility to opportunistic gut infection","volume":"11","author":"Bashiardes","year":"2026","journal-title":"Nat. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ebiom.2016.01.032","article-title":"Gut Microbiota Linked to Sexual Preference and HIV Infection","volume":"5","author":"Rocafort","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","unstructured":"Grund, B., Baker, J.V., Deeks, S.G., Wolfson, J., Wentworth, D., Cozzi-Lepri, A., Cohen, C.J., Phillips, A., Lundgren, J.D., and Neaton, J.D. (2016). Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death Among HIV-Positive Adults on Suppressive Antiretroviral Therapy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155100"},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1089\/aid.2013.0280","article-title":"Microbial translocation and cardiometabolic risk factors in HIV infection","volume":"30","author":"Manner","year":"2014","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/QAI.0000000000000954","article-title":"Do biomarkers of inflammation, monocyte activation, and altered coagulation explain excess mortality between HIV infected and uninfected people?","volume":"72","author":"Tate","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1086\/652749","article-title":"Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection","volume":"201","author":"Neuhaus","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/infdis\/jir214","article-title":"Soluble CD163 made by monocyte\/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after antiretroviral therapy","volume":"204","author":"Burdo","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1001\/jamacardio.2023.5661","article-title":"Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial","volume":"9","author":"Lu","year":"2024","journal-title":"JAMA Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ouyang, J., Yan, J., Zhou, X., Isnard, S., Harypursat, V., Cui, H., Routy, J.-P., and Chen, Y. (2023). Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1173956"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1093\/infdis\/jiq118","article-title":"Plasma levels of soluble CD14 independently predict mortality in HIV infection","volume":"203","author":"Sandler","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/cid\/ciy966","article-title":"Soluble Urokinase Plasminogen Activator Receptor Is Predictive of Non-AIDS Events During Antiretroviral Therapy-mediated Viral Suppression","volume":"69","author":"Hoenigl","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/infdis\/jiu238","article-title":"Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection","volume":"210","author":"Hunt","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.micinf.2005.10.006","article-title":"The role of lipopolysaccharide-binding protein in modulating the innate immune response","volume":"8","author":"Zweigner","year":"2006","journal-title":"Microbes Infect."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1093\/gerona\/gls178","article-title":"Lipopolysaccharide-binding protein, a surrogate marker of microbial translocation, is associated with physical function in healthy older adults","volume":"67","author":"Stehle","year":"2012","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/hiv.12015","article-title":"Markers of microbial translocation predict hypertension in HIV-infected individuals","volume":"14","author":"Manner","year":"2013","journal-title":"HIV Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1093\/infdis\/jiu254","article-title":"Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment","volume":"210","author":"Tenorio","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.exger.2016.02.005","article-title":"Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: A systematic review","volume":"77","author":"Weltevrede","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41590-018-0049-7","article-title":"Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors","volume":"19","author":"Patin","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/hiv.12357","article-title":"Systemic inflammation and liver damage in HIV\/hepatitis C virus coinfection","volume":"17","author":"Shmagel","year":"2016","journal-title":"HIV Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/hep.29170","article-title":"Hepatitis C virus-induced CCL5 secretion from macrophages activates hepatic stellate cells","volume":"66","author":"Sasaki","year":"2017","journal-title":"Hepatology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1177\/09680519050110040701","article-title":"Modulatory effects of sCD14 and LBP on LPS-host cell interactions","volume":"11","author":"Kitchens","year":"2005","journal-title":"J. Endotoxin Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000505099","article-title":"Interleukin-6: A Masterplayer in the Cytokine Network","volume":"98","author":"Uciechowski","year":"2020","journal-title":"Oncology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"a028415","DOI":"10.1101\/cshperspect.a028415","article-title":"Interleukin-6 Family Cytokines","volume":"10","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0009-9120(03)00096-1","article-title":"Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility","volume":"36","author":"Pelsers","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"ofy288","DOI":"10.1093\/ofid\/ofy288","article-title":"I-FABP Is Higher in People with Chronic HIV Than Elite Controllers","volume":"5","author":"Cheru","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1073\/pnas.1318249111","article-title":"Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues","volume":"111","author":"Fletcher","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Maidji, E., Somsouk, M., Rivera, J.M., Hunt, P.W., and Stoddart, C.A. (2017). Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006202"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nature16933","article-title":"Persistent HIV-1 replication maintains the tissue reservoir during therapy","volume":"530","author":"Fryer","year":"2016","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1172\/JCI45157","article-title":"Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections","volume":"121","author":"Zeng","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1172\/JCI0216413","article-title":"Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis","volume":"110","author":"Schacker","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1056\/NEJMc2400870","article-title":"Trial Update of Pitavastatin to Prevent Cardiovascular Events in HIV Infection","volume":"390","author":"Grinspoon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1093\/infdis\/jiv277","article-title":"HIV-1 Infection Accelerates Age According to the Epigenetic Clock","volume":"212","author":"Horvath","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"104488","DOI":"10.1016\/j.isci.2022.104488","article-title":"Accelerated aging with HIV begins at the time of initial HIV infection","volume":"25","author":"Breen","year":"2022","journal-title":"iScience"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e13998","DOI":"10.1111\/acel.13998","article-title":"Can statin preventative treatment inform geroscience-guided therapeutics?","volume":"22","author":"Guaraldi","year":"2023","journal-title":"Aging Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e560","DOI":"10.1093\/cid\/ciaf247","article-title":"Effect of Pitavastatin on Epigenetic Aging Biomarkers in People with HIV: Pilot Substudy of the REPRIEVE Trial","volume":"81","author":"Corley","year":"2026","journal-title":"Clin. Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e180075","DOI":"10.1172\/JCI180075","article-title":"The impact of sex on HIV immunopathogenesis and therapeutic interventions","volume":"134","author":"Mihealsick","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_95","unstructured":"UNAIDS (2025). Fact Sheet 2025\u2014Global HIV Statistics, Joint United Nations Programme on HIV\/AIDS. Available online: https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/UNAIDS_FactSheet_en.pdf."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chen, Y., Ding, X., Ray, S., Thirugnanam, S., Blair, R.V., Saied, A., Sukhanov, S., Kolls, J.K., Kim, W.-K., and Delafontaine, P. (2026). Persistent activation of monocytes\/macrophages and cell senescence in SIV-infected macaques on ART. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1788994"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1097\/QAD.0000000000002833","article-title":"Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals","volume":"35","author":"Leal","year":"2021","journal-title":"AIDS"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1097\/QAD.0000000000004204","article-title":"Senescence-related cytokine levels are associated with HIV-1 serostatus and persistence","volume":"39","author":"Li","year":"2025","journal-title":"AIDS"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1001\/jamacardio.2024.4115","article-title":"Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients with HIV: A Secondary Analysis of the REPRIEVE Randomized Clinical Trial","volume":"10","author":"Schnittman","year":"2025","journal-title":"JAMA Cardiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e284","DOI":"10.1016\/S2352-3018(17)30075-9","article-title":"Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial","volume":"4","author":"Aberg","year":"2017","journal-title":"Lancet HIV"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa1506816","article-title":"Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection","volume":"373","author":"Lundgren","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1056\/NEJMoa1507198","article-title":"A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa","volume":"373","author":"Danel","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/mi.2014.50","article-title":"Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients","volume":"8","author":"Hocqueloux","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Nitsotolis, T., Kyriakoulis, K.G., Kollias, A., Papalexandrou, A., Kalampoka, H., Mastrogianni, E., Basoulis, D., and Psichogiou, M. (2024). Comparison of Integrase Strand Transfer Inhibitors (INSTIs) and Protease-Boosted Inhibitors (PIs) on the Reduction in Chronic Immune Activation in a Virally Suppressed, Mainly Male Population Living with HIV (PLWH). Medicina, 60.","DOI":"10.3390\/medicina60020331"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/cid\/civ327","article-title":"Changes in Inflammation and Immune Activation with Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s","volume":"61","author":"Kelesidis","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/cid\/ciz999","article-title":"Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials","volume":"71","author":"Sax","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1056\/NEJMoa1902824","article-title":"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV","volume":"381","author":"Venter","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"22603","DOI":"10.1038\/s41598-025-06500-0","article-title":"Associations between weight gain, integrase inhibitors antiretroviral agents, and gut microbiome in people living with HIV: A cross-sectional study","volume":"15","author":"Nguyen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_109","unstructured":"Koethe, J.R., Lake, J.E., Kantor, A., Smeaton, L., Erlandson, K.M., O\u2019Halloran, J.A., Campo, R.E., Debroy, P., Moran, L., and Belaunzaran-Zamudio, P.F. (2025, January 13\u201317). ACTG A5391 (DO-IT trial): Switching from INSTI-based regimens does not reduce weight in people with HIV. Presented at 13th International AIDS Society Conference on HIV Science (IAS 2025), Kigali, Rwanda. Abstract OAB0206LB."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nri2921","article-title":"Adipokines in inflammation and metabolic disease","volume":"11","author":"Ouchi","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/S2352-3018(19)30336-4","article-title":"Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial","volume":"7","author":"Molina","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Ascencio-Anastacio, A.M., Larios-Serrato, V., Mata-Mar\u00edn, J.A., Evaristo, M.R., N\u00fa\u00f1ez-Armend\u00e1riz, M., Cano-D\u00edaz, A.L., Chaparro-S\u00e1nchez, A., Salinas-Vel\u00e1zquez, G.E., Maldonado-Rodr\u00edguez, A., and Torres, J. (2025). Metabolomic Profile of Weight Gain of People Living with HIV Treated with Integrase Strand Transfer Inhibitor Regimens Reveals Dysregulated Lipid Metabolism and Mitochondrial Dysfunction. Metabolites, 15.","DOI":"10.3390\/metabo15110695"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"118831","DOI":"10.1016\/j.biopha.2025.118831","article-title":"Differential adipose tissue remodeling and metabolic effects of dolutegravir and bictegravir: Implications for HIV therapy","volume":"193","author":"Esplugues","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/mi.2016.122","article-title":"The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects","volume":"10","author":"Vallejo","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/cid\/ciy540","article-title":"Doravirine\/Lamivudine\/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz\/Emtricitabine\/Tenofovir Disoproxil Fumarate in Treatment-naive Adults with Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial","volume":"68","author":"Orkin","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S2213-8587(24)00150-5","article-title":"Once-weekly semaglutide in people with HIV-associated lipohypertrophy: A randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial","volume":"12","author":"Eckard","year":"2024","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Corley, M.J., Dwaraka, V., Pang, A.P.S., Labbato, D., Smith, R., Eckard, A.R., and McComsey, G.A. (2025). Semaglutide Slows Epigenetic Aging in People with HIV-associated Lipohypertrophy: Evidence from a Randomized Controlled Trial. medRxiv, preprint.","DOI":"10.1101\/2025.07.09.25331038"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1007\/s40262-018-0668-z","article-title":"Pharmacokinetics and clinical implications of semaglutide: A new glucagon-like peptide (GLP)-1 receptor agonist","volume":"57","author":"Hall","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1002\/jcph.107","article-title":"Impact of food and different meal types on the pharmacokinetics of rilpivirine","volume":"53","author":"Crauwels","year":"2013","journal-title":"J. Clin. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1592\/phco.26.3.341","article-title":"Inhibition of atazanavir oral absorption by lansoprazole gastric acid suppression in healthy volunteers","volume":"26","author":"Tomilo","year":"2006","journal-title":"Pharmacotherapy"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/QAI.0000000000001699","article-title":"Pharmacokinetics of tenofovir alafenamide when coadministered with other HIV antiretrovirals","volume":"78","author":"Begley","year":"2018","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/cid\/ciab212","article-title":"Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults with Human Immunodeficiency Virus","volume":"74","author":"Marconi","year":"2022","journal-title":"Clin. Infect. Dis."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/6\/1229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:07:14Z","timestamp":1780070834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/6\/1229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":123,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["microorganisms14061229"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14061229","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]}}}