{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:47:26Z","timestamp":1782971246124,"version":"3.54.5"},"reference-count":175,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973840"],"award-info":[{"award-number":["81973840"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>People living with HIV (PLWH) are at increased risk for depression, anxiety, and other comorbid psychiatric disorders. HIV-associated depression involves complex neurobiological disturbances, including chronic neuroinflammation. This includes microglial activation, elevated levels of pro-inflammatory cytokines and mediators, and altered brain metabolites. Additionally, there is dysregulation of monoaminergic neurotransmission, particularly impaired serotonergic signaling. Prolonged hyperactivation of the hypothalamic-pituitary-adrenal axis, indicated by abnormally high cortisol levels, is also observed. Together, these pathological processes contribute to persistent brain inflammation and metabolic imbalance. Under prolonged inflammatory conditions, activated microglia release factors such as tumor necrosis factor-alpha. These factors can induce oligodendrocyte apoptosis and demyelination, exacerbating neural injury. Psychosocial stressors\u2014such as stigma, death-related anxiety, and internalized shame\u2014may amplify these pathways through immune-neural crosstalk. Our primary focus, however, is on pharmacological targeting. We propose a three-tiered intervention framework: 1) Targeted neuropharmacological interventions (e.g., SSRIs and anti-inflammatory agents); 2) Optimized ART regimens; 3) Integrated psychosocial support. While further research is needed to establish long-term efficacy and personalized treatment options, this multidimensional approach may reduce the progression of HIV-associated depression and improve clinical outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1645991","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:34:14Z","timestamp":1756964054000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["HIV-associated depression: a translational framework targeting neuroimmune inflammation and psychosocial stress modulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Fei","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"B1","unstructured":"Global HIV & AIDS statistics \u2014 Fact sheet\n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e25997","DOI":"10.1002\/jia2.25997","article-title":"Growing older with HIV in the treat-all era","volume":"25","author":"Rajasuriar","year":"2022","journal-title":"J Int AIDS Soc"},{"key":"B3","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/COH.0000000000000298","article-title":"Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population","volume":"11","author":"Wandeler","year":"2016","journal-title":"Curr Opin HIV AIDS"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30358-1","article-title":"Estimated life expectancy gains with antiretroviral therapy among adults with HIV in Latin America and the Caribbean: a multisite retrospective cohort study","volume":"8","author":"Smiley","year":"2021","journal-title":"Lancet HIV"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2022.11.061","article-title":"Global prevalence of suicide in patients living with HIV\/AIDS: A systematic review and meta-analysis","volume":"323","author":"Rafiei","year":"2023","journal-title":"J Affect Disord"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(21)00319-2","article-title":"The risk of mental illness in people living with HIV in the UK: a propensity score-matched cohort study","volume":"9","author":"Gooden","year":"2022","journal-title":"Lancet HIV"},{"key":"B7","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12916-016-0640-4","article-title":"Beyond viral suppression of HIV-the new quality of life frontier","volume":"14","author":"Lazarus","year":"2016","journal-title":"BMC Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1111\/pcn.12097","article-title":"HIV infection and depression","volume":"68","author":"Arseniou","year":"2014","journal-title":"Psychiatry Clin Neurosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjspcare-2019-001952","article-title":"Global prevalence of depression in HIV\/AIDS: a systematic review and meta-analysis","volume":"9","author":"Rezaei","year":"2019","journal-title":"BMJ Support Palliat Care"},{"key":"B10","unstructured":"Depressive disorder (depression)\n          \n          2025"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-019-02613-6","article-title":"Depression prevalence, antidepressant treatment status, and association with sustained HIV viral suppression among adults living with HIV in care in the United States, 2009-2014","volume":"23","author":"Gokhale","year":"2019","journal-title":"AIDS Behav"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000002286","article-title":"Medical Monitoring Project. 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