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

PLoS One. 2017 Sep 27;12(9):e0184929. doi: 10.1371/journal.pone.0184929. eCollection 2017.

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.

Publication types

  • Clinical Trial

MeSH terms

  • AIDS Vaccines / immunology*
  • DNA, Viral / metabolism
  • HIV Infections / immunology*
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • Humans
  • Immunity, Humoral
  • Treatment Outcome
  • Vaccination*
  • Viral Load / immunology

Substances

  • AIDS Vaccines
  • DNA, Viral

Grants and funding

This study was partially supported by grants: amfAR, The Foundation for AIDS Research (US) grant number 108532-53-RGRL, EC10-153, TRA-094, RIS [Red Temática Cooperativa de Grupos de Investigación en Sida del Fondo de Investigación Sanitaria (FIS)], HIVACAT (Catalan Programme for the Development of HIV-1 Vaccines, by grant MTM2015-64465-C2-1-R from the Ministerio de Economía y Competitividad del Gobierno de España and by 2014 SGR 464 from the Departament d’Economia i Coneixement de la Generalitat de Catalunya. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.