{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:14:32Z","timestamp":1779138872860,"version":"3.51.4"},"reference-count":92,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R61 DA047038,R33 DA047038,P30AI042853,P30AI060354,UL1TR002541"],"award-info":[{"award-number":["R61 DA047038,R33 DA047038,P30AI042853,P30AI060354,UL1TR002541"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:p>\n                    Opioid use may affect the HIV-1 reservoir and its reversal from latency. We studied 47 virally suppressed people with HIV (PWH) and observed that lower concentration of HIV-1 latency reversal agents (LRAs), used with small molecules that did not reverse latency, synergistically increased the magnitude of HIV-1 reactivation ex vivo, regardless of opioid use. This LRA boosting, which combined a second mitochondria-derived activator of caspases mimetic or low-dose PKC agonist with histone deacetylase inhibitors, generated more unspliced HIV-1 transcription than PMA with ionomycin (PMAi), the maximal known HIV-1 reactivator. LRA boosting associated with greater histone acetylation, modulated surface activation-induced markers, and altered T cell production of TNF-\u03b1, IL-2, and IFN-\u03b3. HIV-1 reservoirs in PWH contained unspliced and polyadenylated virus mRNA, the ratios of which were greater in resting than total CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and corrected to 1:1 with PMAi exposure. We characterized treated suppressed HIV-1 infection as a period of inefficient, not absent, virus transcription. Multiply spliced HIV-1 transcripts and virion production did not consistently increase with LRA boosting, suggesting the presence of a persistent posttranscriptional block. LRA boosting can be leveraged to probe mechanisms of an effective cellular HIV-1 latency reversal program.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.185480","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T12:00:32Z","timestamp":1730203232000},"source":"Crossref","is-referenced-by-count":2,"title":["HIV-1 latency reversal agent boosting is not limited by opioid use"],"prefix":"10.1172","volume":"9","author":[{"given":"Tyler","family":"Lilie","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Bouzy","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Archana","family":"Asundi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA."},{"name":"Grayken Center for Addiction, Boston Medical Center, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Roche","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-3213","authenticated-orcid":true,"given":"Alex","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendyll","family":"Coxen","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Corry","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Jordan","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiera","family":"Clayton","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts T.H. 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