2026-04-14T02:36:39Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2157502025-12-05T12:45:56Zcom_2072_1057col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Jiménez León, María Reyes author Gasca Capote, Carmen author Roca Oporto, Cristina author Espinosa, Nuria author Sobrino, Salvador author Fontillón Alberdi, Maria author Gao, Ce author Roseto, Isabelle author Gladkov, Gregory author Rivas Jeremías, Inmaculada author Neukam, Karin author Sánchez Hernández, José Germán author Rigo Bonnin, Raúl author Cervera Barajas, Antonio J. author Mesones, Rosario author García, Federico author Álvarez Rios, Ana Isabel author Bachiller, Sara author Vitalle, Joana author Pérez Gómez, Alberto author Camacho Sojo, María Inés author Gallego, Isabel author Brander, Christian author Mcgowan, Ian author Mothe, Beatriz author Viciana, Pompeyo author Yu, Xu author Lichterfeld, Mathias author López Cortés, Luis F. author Ruiz Mateos, Ezequiel author 2024-10-14T13:32:58Z 2024-10-14T13:32:58Z 2024-07-09 2024-10-03T15:11:47Z BACKGROUND. We evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the effect of alpha 4 beta 7 on the HIV-1 reservoir size. METHODS. Participants started ART with monthly vedolizumab infusions, and ATI was performed at week 24. Biopsies were obtained from ileum and cecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry, and cell-sorting and antibody competition experiments were assayed. RESULTS. Vedolizumab was safe and well tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve more than 1,000 HIV-1 RNA copies/mL and the proportion of participants off ART was observed, being higher in the vedolizumab group compared with historical controls. Just before ATI, alpha 4 beta 7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of alpha 4 beta 7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where alpha 4 beta 7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA. CONCLUSION. Our findings support alpha 4 beta 7 as an important determinant in HIV-1 reservoir size, suggesting the complete alpha 4 beta 7 blockade in tissue as a promising tool for HIV-cure combination strategies. TRIAL REGISTRATION. ClinicalTrials.gov NCT03577782. FUNDING. This work was supported by the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, a way to make Europe, research contracts FI17/00186 and FI19/00083 and research projects PI18/01532, PI19/01127, PI22/01796), Conserjer & iacute;a de Econom & iacute;a, Conocimiento, Empresas y Universidad, Junta de Andaluc & iacute;a (research projects P20/00906), the Red Tem & aacute;tica de Investigaci & oacute;n Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council. Infeccions per VIH Immunoteràpia HIV infections Immunotheraphy Vedolizumab and ART in recent HIV-1 infection unveil the role of α4β7 in reservoir size