Frontiers in Immunology (May 2020)

HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02)

  • Beatriz Mothe,
  • Beatriz Mothe,
  • Beatriz Mothe,
  • Miriam Rosás-Umbert,
  • Miriam Rosás-Umbert,
  • Pep Coll,
  • Christian Manzardo,
  • Maria C. Puertas,
  • Sara Morón-López,
  • Anuska Llano,
  • Cristina Miranda,
  • Samandhy Cedeño,
  • Miriam López,
  • Yovaninna Alarcón-Soto,
  • Guadalupe Gómez Melis,
  • Klaus Langohr,
  • Ana M. Barriocanal,
  • Ana M. Barriocanal,
  • Jessica Toro,
  • Irene Ruiz,
  • Cristina Rovira,
  • Antonio Carrillo,
  • Michael Meulbroek,
  • Alison Crook,
  • Edmund G. Wee,
  • Jose M. Miró,
  • Bonaventura Clotet,
  • Bonaventura Clotet,
  • Bonaventura Clotet,
  • Bonaventura Clotet,
  • Marta Valle,
  • Marta Valle,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Tomáš Hanke,
  • Tomáš Hanke,
  • Christian Brander,
  • Christian Brander,
  • Christian Brander,
  • José Moltó,
  • José Moltó,
  • The BCN02 Study Investigators

DOI
https://doi.org/10.3389/fimmu.2020.00823
Journal volume & issue
Vol. 11

Abstract

Read online

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control.

Keywords