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In the pre\u2010ART era, severe forms such as HIV\u2010associated dementia (HAD) were prevalent and characterized by distinct neuropathological features, including multinucleated giant cells, microglial nodules, and extensive neuronal loss. In the ART era, milder forms of NCI are more frequent; however, the underlying histopathology remains poorly understood. These milder impairments are primarily associated with synaptodendritic damage and neuronal dysregulation, typically in the absence of productive infection in neurons. Instead, microglia and macrophages are implicated as key drivers of neuroinflammation and neuronal injury. In this study, we investigated the neuropathological features of brain tissue from PWH with and without symptomatic cognitive impairment. Immunohistochemical analysis revealed microglial nodules with active neuronal phagocytosis, which was associated with dendritic loss and neuronal damage. Complementary in vitro studies demonstrated that HIV\u2010infected microglia demonstrated enhanced phagocytic activity, supporting their direct role in neurodegeneration beyond cytokine\u2010mediated mechanisms. Together, these findings highlight microglial phagocytosis as one of the critical contributors of HIV\u2010associated NCI in the ART era.<\/jats:p>","DOI":"10.1111\/bpa.70064","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:44:03Z","timestamp":1767087843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Microglial reactivity and nodule formation are associated with Synaptodendritic damage in the brains of people with\n                    <scp>HIV<\/scp>\n                    \u20101"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5731-4065","authenticated-orcid":false,"given":"Roberta S.","family":"Dos Reis","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, School of Public Health University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6643-543X","authenticated-orcid":false,"given":"Lauren A.","family":"Ignatz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, School of Public Health University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-3111","authenticated-orcid":false,"given":"Sathish","family":"Selvam","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, School of Public Health University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-068X","authenticated-orcid":false,"given":"Marc C. 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