RESUMEN
BACKGROUNDWe 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 α4ß7 on the HIV-1 reservoir size.METHODSParticipants 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.RESULTSVedolizumab 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, α4ß7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4ß7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where α4ß7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA.CONCLUSIONOur findings support α4ß7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4ß7 blockade in tissue as a promising tool for HIV-cure combination strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT03577782.FUNDINGThis 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.
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Anticuerpos Monoclonales Humanizados , Infecciones por VIH , VIH-1 , Carga Viral , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Linfocitos T CD4-Positivos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Íleon/metabolismo , Íleon/virología , Integrinas/metabolismo , ARN Viral/sangre , Carga Viral/efectos de los fármacosRESUMEN
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Asunto(s)
Humanos , Masculino , Adulto , Insuficiencia Renal Crónica/cirugía , Hiperparatiroidismo Secundario/cirugía , Glomerulonefritis/cirugía , Trasplante de Riñón , SíndromeRESUMEN
No disponible