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

Front Immunol. 2020 May 6;11:823. doi: 10.3389/fimmu.2020.00823. eCollection 2020.

Abstract

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: HDAC inhibitor; HIVconsv; early-treatment; kick&kill strategy; romidepsin.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Adult
  • Antiviral Agents / therapeutic use*
  • Depsipeptides / therapeutic use*
  • Disease Reservoirs
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Viral Load
  • Viremia
  • Virus Latency

Substances

  • AIDS Vaccines
  • Antiviral Agents
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • romidepsin