Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

Miriam Rosás-Umbert, Beatriz Mothe, Marc Noguera-Julian, Rocío Bellido, Maria C. Puertas, Jorge Carrillo, C. Rodriguez, Núria Perez-Alvarez, Patricia Cobarsí, Carmen E. Gomez, Mariano Esteban, Jose Luis Jímenez, Felipe García, Julià Blanco, Javier Martinez-Picado, Roger Paredes, Christian Brander

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    Abstract

    © 2017 Rosás-Umbert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
    Original languageEnglish
    Article numbere0184929
    JournalPLoS ONE
    Volume12
    Issue number9
    DOIs
    Publication statusPublished - 1 Sep 2017

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