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| Página principal > Artículos > Artículos publicados > Vedolizumab and ART in recent HIV-1 infection unveil the role of α4β7 in reservoir size |
(Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Institut d'Investigació Biomèdica de Bellvitge) (AELIX Therapeutics S.L.) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia)) (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
| Fecha: | 2024 |
| Resumen: | 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 α4β7 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, α4β7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4β7 was observed on peripheral CD4 T cells but not in gut (ileum and cecum), where α4β7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA. CONCLUSION. Our findings support α4β7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4β7 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), Conserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (research projects P20/00906), the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council. |
| Ayudas: | Instituto de Salud Carlos III PI17/00186 Instituto de Salud Carlos III PI19/00083 Instituto de Salud Carlos III PI18/01532 Instituto de Salud Carlos III PI19/01127 Instituto de Salud Carlos III PI22/01796 Ministerio de Economía y Competitividad RD16/0025/0020 |
| Nota: | Altres ajuts: Junta de Andalucía (research projects P20/00906) |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Publicado en: | JCI insight, Vol. 9 Núm. 16 (July 2024) , ISSN 2379-3708 |
