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Autophagy and mitophagy remove unwanted\/damaged material and mitochondria from the intracellular environment, respectively. Dysregulated autophagy in astrocytes, abundant CNS cells with crucial homeostatic functions, contributes to many neurodegenerative diseases. Few studies have examined effects of ART on autophagy in astrocytes. We treated primary human astrocytes with a common ART regimen and performed LC3B-II and p62 turnover assays. ART significantly inhibited both LC3B-II and p62 turnover. Since p62, one autophagy receptor that mediates mitophagy, autophagic clearance of mitochondria, turnover was inhibited, we also examined mitophagy. While ART decreased BNIP3L\/Nix homodimers, there were no changes in PINK1, Parkin, Mt-CO2, mitochondrial mass, or mitochondria\u2013lysosome colocalization, indicating that ART did not inhibit mitophagy. We show that antiretroviral drugs have distinct effects on autophagic processes in astrocytes, which represents an alteration in their homeostasis, a major function of autophagy. This likely contributes to HIV-NCI. Understanding these impacts is important for improving ART for PWH, who have, by necessity, ongoing ART exposure. It also facilitates development of therapies for HIV-NCI that may include modulation of autophagy.<\/jats:p>","DOI":"10.3390\/cells14231904","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"1904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiretroviral Drugs Impact Autophagy Differently in Primary Human Astrocytes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-5289","authenticated-orcid":false,"given":"Laura","family":"Cheney","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary","family":"Guzik","sequence":"additional","affiliation":[{"name":"Analytical Imaging Facility, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan W.","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.tins.2010.12.001","article-title":"Astrocyte-neuron metabolic relationships: For better and for worse","volume":"34","author":"Allaman","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/glia.1107","article-title":"Immune function of astrocytes","volume":"36","author":"Dong","year":"2001","journal-title":"Glia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nrn1870","article-title":"Astrocyte dysfunction in neurological disorders: A molecular perspective","volume":"7","author":"Seifert","year":"2006","journal-title":"Nat. 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