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A high proviral load (PVL) is one of the main risk factors for HAM\/TSP. Recently, it was shown that raltegravir could inhibit cell\u2010free and cell\u2010to\u2010cell transmission of HTLV\u20101 in\u00a0vitro. Given the substantial clinical experience in human immunodeficiency virus infection and its excellent safety profile, this agent may be an attractive therapeutic option for HAM\/TSP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen subjects with HAM\/TSP received raltegravir 400\u00a0mg orally twice daily in an initial 6\u2010month treatment phase, followed by a 9\u2010month post\u2010treatment phase. HTLV\u20101 PVLs were assessed using droplet digital PCR from the PBMCs every 3\u00a0months, and from the CSF at baseline, month 6, and month 15. We also evaluated the ability of raltegravir to regulate abnormal immune responses in HAM\/TSP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While a downward trend was observed in PBMC and\/or CSF PVLs of some patients, raltegravir overall did not have any impact on the PVL in this HAM\/TSP patient cohort. Clinically, all patients\u2019 neurological scores and objective measurements remained relatively stable, with some expected variability. Immunologic studies showed alterations in the immune profiles of a subset of patients including decreased CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells and spontaneous lymphoproliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Raltegravir was generally well tolerated in this HAM\/TSP patient cohort. A subset of patients exhibited a mild decrease in PVL as well as variations in their immune profiles after taking raltegravir. These findings suggest that raltegravir may be a therapeutic option in select HAM\/TSP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration Number<\/jats:title><jats:p>NCT01867320.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51437","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T12:47:00Z","timestamp":1632574020000},"page":"1970-1985","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Clinical trial of raltegravir, an integrase inhibitor, in HAM\/TSP"],"prefix":"10.1002","volume":"8","author":[{"given":"Yoshimi","family":"Enose\u2010Akahata","sequence":"first","affiliation":[{"name":"Viral Immunology Section, National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland 20892 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridgette 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