{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T03:14:18Z","timestamp":1782702858119,"version":"3.54.5"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia"},{"DOI":"10.13039\/501100006506","name":"Brazilian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>No specific therapy is approved for human T-cell lymphotropic virus type 1 (HTLV-1) infection. We tested the effect of dolutegravir (DTG) on clinical outcomes and on HTLV-1 proviral load (PVL) in adults with HTLV-1 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an open-label, randomized controlled phase 2 trial in Salvador, Brazil. Symptomatic adults with HTLV-1 infection were randomized 1:1 to DTG 50 mg once daily or vitamin C (VTC) 500 mg once daily for 48 weeks. We evaluated changes in gait performance (timed 10-meter walk test [T10MWT]). Key secondary endpoints included change in PVL and prespecified neurofunctional and urinary outcomes. Primary analyses emphasized intragroup and between-group comparisons; exploratory per-protocol analyses were performed for neurofunctional measures. Asymptomatic participants were included for PVL and immunological evaluations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-three participants (53 symptomatic) were randomized (DTG, n = 43; VTC, n = 40). At week 48, there was no between-group difference in T10MWT. However, DTG use significantly reduced PVL over 48 weeks compared with VTC (P &amp;lt; .001). Exploratory per-protocol analyses found significant improvements associated with DTG use in lower limb spasticity (P &amp;lt; .001), sensory function (light touch, P = .035; pinprick, P = .001), and median nocturia frequency (P = .012). Network analysis of cytokine expression showed a change in the DTG group from baseline to week 48, with loss of negative correlations and a more balanced pattern. DTG was well tolerated, with no unexpected safety signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this pilot randomized trial, DTG use was associated with significantly reduced PVL and improvement in neurofunctional and immunological characteristics of participants in exploratory analyses. These findings provide evidence supporting the use of integrase inhibitors for HTLV-1 infection.<\/jats:p>\n                    <jats:p>Clinical Trials Registration. Brazilian Clinical Trial Register (ReBEC), code RBR-5x7ccxp.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag163","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:40:49Z","timestamp":1772800849000},"page":"e910-e920","source":"Crossref","is-referenced-by-count":4,"title":["Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4673-6991","authenticated-orcid":false,"given":"Carlos","family":"Brites","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine, Federal University of Bahia , Salvador ,","place":["Brazil"]},{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Monta\u00f1o-Castellon","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-8422","authenticated-orcid":false,"given":"Mar\u00eda B","family":"Arriaga","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleyde","family":"Marconi","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Federal University of Bahia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Mayoral","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Luz","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila A","family":"Figueredo","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias da Saude, Federal University of Bahia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca S D","family":"Fiuza","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias da Saude, Federal University of Bahia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo M","family":"Netto","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Federal University of Bahia , Salvador ,","place":["Brazil"]},{"name":"Funda\u00e7\u00e3o Bahiana de Infectologia , Salvador ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"2026052019274038200_ciag163-B1","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1038\/sj.onc.1208968","article-title":"Global epidemiology of HTLV-I infection and associated diseases","volume":"24","author":"Proietti","year":"2005","journal-title":"Oncogene"},{"key":"2026052019274038200_ciag163-B2","doi-asserted-by":"crossref","first-page":"e0171303","DOI":"10.1371\/journal.pone.0171303","article-title":"HTLV-1 is predominantly sexually transmitted in Salvador, the city with the highest HTLV-1 prevalence in Brazil","volume":"12","author":"Nunes","year":"2017","journal-title":"PLoS One"},{"key":"2026052019274038200_ciag163-B3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S1473-3099(07)70081-6","article-title":"Human T-lymphotropic virus 1: recent knowledge about an ancient infection","volume":"7","author":"Verdonck","year":"2007","journal-title":"Lancet Infect Dis"},{"key":"2026052019274038200_ciag163-B4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S1473-3099(19)30402-5","article-title":"Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies","volume":"20","author":"Schierhout","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026052019274038200_ciag163-B5","doi-asserted-by":"crossref","first-page":"e400","DOI":"10.1016\/S2666-5247(23)00359-2","article-title":"Human T-lymphotropic virus type 1 and antiretroviral therapy: practical considerations for pre-exposure and post-exposure prophylaxis, transmission prevention, and mitigation of severe disease","volume":"5","author":"O\u2019Donnell","year":"2024","journal-title":"Lancet Microbe"},{"key":"2026052019274038200_ciag163-B6","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3390\/pathogens13070553","article-title":"High HTLV-1 proviral load predates and predicts HTLV-1-associated disease. Literature review and the London experience","volume":"13","author":"Taylor","year":"2024","journal-title":"Pathogens"},{"key":"2026052019274038200_ciag163-B7","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/phar.1386","article-title":"Dolutegravir: a new integrase strand transfer inhibitor for the treatment of HIV","volume":"34","author":"Shah","year":"2014","journal-title":"Pharmacotherapy"},{"key":"2026052019274038200_ciag163-B8","doi-asserted-by":"crossref","first-page":"e0262739","DOI":"10.1371\/journal.pone.0262739","article-title":"Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM\/TSP)","volume":"17","author":"Zarei Ghobadi","year":"2022","journal-title":"PLoS One"},{"key":"2026052019274038200_ciag163-B9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12977-019-0508-8","article-title":"An insight to HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis","volume":"16","author":"Mozhgani","year":"2019","journal-title":"Retrovirology"},{"key":"2026052019274038200_ciag163-B10","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1002\/acn3.51437","article-title":"Clinical trial of raltegravir, an integrase inhibitor, in HAM\/TSP","volume":"8","author":"Enose-Akahata","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"key":"2026052019274038200_ciag163-B11","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.3389\/fmicb.2019.01877","article-title":"Inhibition of HTLV-1 infection by HIV-1 first- and second-generation integrase strand transfer inhibitors","volume":"10","author":"Barski","year":"2019","journal-title":"Front Microbiol"},{"key":"2026052019274038200_ciag163-B12","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/ptj\/67.2.206","article-title":"Interrater reliability of a modified Ashworth scale of muscle spasticity","volume":"67","author":"Bohannon","year":"1987","journal-title":"Phys Ther"},{"key":"2026052019274038200_ciag163-B13","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s11999-016-5133-4","article-title":"Classifications in brief: American Spinal Injury Association (ASIA) impairment scale","volume":"475","author":"Roberts","year":"2017","journal-title":"Clin Orthop Relat Res"},{"key":"2026052019274038200_ciag163-B14","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1177\/1545968307301880","article-title":"Validity of the walking scale for spinal cord injury and other domains of function in a multicenter clinical trial","volume":"21","author":"Ditunno","year":"2007","journal-title":"Neurorehabil Neural Repair"},{"key":"2026052019274038200_ciag163-B15","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.3389\/fmicb.2018.01651","article-title":"Proposal of classification criteria for HTLV-1-associated myelopathy\/tropical spastic paraparesis disease activity","volume":"9","author":"Sato","year":"2018","journal-title":"Front Microbiol"},{"key":"2026052019274038200_ciag163-B16","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/sj.sc.3101677","article-title":"Disability profile of patients with HTLV-I-associated myelopathy\/tropical spastic paraparesis using the Functional Independence Measure (FIM)","volume":"43","author":"Franzoi","year":"2005","journal-title":"Spinal Cord"},{"key":"2026052019274038200_ciag163-B17","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.jpain.2009.09.014","article-title":"Translation to Portuguese and validation of the Douleur Neuropathique 4 questionnaire","volume":"11","author":"Santos","year":"2010","journal-title":"J Pain"},{"key":"2026052019274038200_ciag163-B18","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1590\/S0037-86822006000600007","article-title":"HTLV-1 and HTLV-2 proviral load: a simple method using quantitative real-time PCR","volume":"39","author":"Tamegao-Lopes","year":"2006","journal-title":"Rev Soc Bras Med Trop"},{"key":"2026052019274038200_ciag163-B19","doi-asserted-by":"crossref","first-page":"e0157132","DOI":"10.1371\/journal.pone.0157132","article-title":"Assessing walking ability in people with HTLV-1-associated myelopathy using the 10 meter timed walk and the 6 minute walk test","volume":"11","author":"Adonis","year":"2016","journal-title":"PLoS One"},{"key":"2026052019274038200_ciag163-B20","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1590\/0004-282x20190169","article-title":"The effect of home exercise on the posture and mobility of people with HAM\/TSP: a randomized clinical trial","volume":"78","author":"Mota","year":"2020","journal-title":"Arq Neuropsiquiatr"},{"key":"2026052019274038200_ciag163-B21","doi-asserted-by":"crossref","first-page":"e1010774","DOI":"10.1371\/journal.ppat.1010774","article-title":"Dynamics and consequences of the HTLV-1 proviral plus-strand burst","volume":"18","author":"Ramanayake","year":"2022","journal-title":"PLoS Pathog"},{"key":"2026052019274038200_ciag163-B22","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/S1473-3099(20)30328-5","article-title":"Human T-cell lymphotropic virus type-1: a lifelong persistent infection, yet never truly silent","volume":"21","author":"Hirons","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2026052019274038200_ciag163-B23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12977-019-0504-z","article-title":"Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes","volume":"16","author":"Afonso","year":"2019","journal-title":"Retrovirology"},{"key":"2026052019274038200_ciag163-B24","doi-asserted-by":"crossref","first-page":"106343","DOI":"10.1016\/j.ijantimicag.2021.106343","article-title":"HIV-1 integrase strand transfer inhibitors: a review of current drugs, recent advances and drug resistance","volume":"57","author":"Mbhele","year":"2021","journal-title":"Int J Antimicrob Agents"},{"key":"2026052019274038200_ciag163-B25","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.1016\/j.cell.2025.06.023","article-title":"Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo","volume":"188","author":"Cooney","year":"2025","journal-title":"Cell"},{"key":"2026052019274038200_ciag163-B26","doi-asserted-by":"crossref","first-page":"e1006861","DOI":"10.1371\/journal.ppat.1006861","article-title":"Switching and loss of cellular cytokine producing capacity characterize in vivo viral infection and malignant transformation in human T-lymphotropic virus type 1 infection","volume":"14","author":"Kagdi","year":"2018","journal-title":"PLoS Pathog"},{"key":"2026052019274038200_ciag163-B27","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3390\/v10120691","article-title":"Cytokine networks dysregulation during HTLV-1 infection and associated diseases","volume":"10","author":"Futsch","year":"2018","journal-title":"Viruses"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciag163\/67365924\/ciag163.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/82\/5\/e910\/67365924\/ciag163.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/82\/5\/e910\/67365924\/ciag163.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:27:49Z","timestamp":1779319669000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/82\/5\/e910\/8524593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3,9]]},"published-print":{"date-parts":[[2026,5,20]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciag163","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5,15]]},"published":{"date-parts":[[2026,3,9]]}}}