{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:58:41Z","timestamp":1778770721417,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009060","name":"SIDACTION","doi-asserted-by":"publisher","award":["16-1-AAE-10663"],"award-info":[{"award-number":["16-1-AAE-10663"]}],"id":[{"id":"10.13039\/100009060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>To better understand why about 15% of people with human immunodeficiency virus-1 (PWH) on highly active antiretroviral therapy do not restore their CD4 count, we explored the link previously reported between glutamate plasma level and CD4 count.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We recruited 44 adults with HIV-1 aviremic under antiretroviral therapy. Their peripheral blood concentrations in glutamate and \u03b3-aminobutyric acid (GABA) were determined by ELISA. Flow cytometry was used to detect GABA receptor, reactive oxygen species (ROS) produced by monocytes, and programmed T-cell death. DNA-dependent protein kinase (DNA-PK) and p53 phosphorylation were analyzed by western blot. DNA damage was quantified by immunofluorescence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We show that (1) some virologic responders present high plasma levels of glutamate and of its derivative, GABA; (2) monocytes express the GABA receptor GABA-B1; (3) GABA-B1 stimulation induces monocytic ROS production; (4) monocytes of PWH with high plasma levels of GABA release high amounts of ROS; and (5) monocyte-derived ROS oxidize the DNA of CD4+ T cells, creating double-strand breaks that activate DNA-PK and p53, and finally apoptosis. The intensity of this cascade of events is inversely correlated with the slope of CD4+ T-cell recovery in treated PWH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We propose that DNA damage resulting from ROS produced by GABA-activated monocytes plays a key role in impaired immune restoration. Consequently, GABA-B1 antagonists and\/or ROS inhibitors might be a promising therapy for nonimmunologic responders. Furthermore, the same mechanism could be involved in CD4 loss in the natural course of the infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT04028882.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf058","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T17:34:08Z","timestamp":1738690448000},"page":"1246-1257","source":"Crossref","is-referenced-by-count":2,"title":["\u03b3-Aminobutyric Acid-Induced Monocytic Reactive Oxygen Species Impair CD4 Restoration in Treated Adults With HIV-1"],"prefix":"10.1093","volume":"231","author":[{"given":"Mehwish","family":"Younas","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, UMR9002, Centre National de la Recherche Scientifique and Montpellier University , Montpellier 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,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5891-0822","authenticated-orcid":false,"given":"Philippe","family":"Pasero","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, UMR9002, Centre National de la Recherche Scientifique and Montpellier University , Montpellier ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Rondard","sequence":"additional","affiliation":[{"name":"Institute of Functional Genetics, UMR5203, Centre National de la Recherche Scientifique, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, and Montpellier University , Montpellier ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina K","family":"Psomas","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, UMR9002, Centre National de la Recherche Scientifique and Montpellier 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