Please use this identifier to cite or link to this item:
Title: Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B
Author: Rosas Umbert, Miriam
Mothe, Beatriz
Noguera Julian, Marc
Bellido, Rocío
Puertas, María C.
Carrillo, Jorge
Rodriguez, C.
Pérez Álvarez, Núria
Cobarsi, Patricia
Gómez, Carmen E.
Esteban, Mariano
Jímenez, José Luis
García Alcaide, Felipe
Blanco, Julià
Martínez Picado, Javier
Paredes, Roger
Brander, Christian
Keywords: Infeccions per VIH
Vacunes antivíriques
Cèl·lules T
HIV infections
Viral vaccines
T cells
Issue Date: 27-Sep-2017
Publisher: Public Library of Science (PLoS)
Abstract: The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2017, vol. 12, num. 9, p. e0184929
Related resource:
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Files in This Item:
File Description SizeFormat 
693516.pdf2.61 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons