AUTHOR=Mothe Beatriz , Rosás-Umbert Miriam , Coll Pep , Manzardo Christian , Puertas Maria C. , Morón-López Sara , Llano Anuska , Miranda Cristina , Cedeño Samandhy , López Miriam , Alarcón-Soto Yovaninna , Melis Guadalupe Gómez , Langohr Klaus , Barriocanal Ana M. , Toro Jessica , Ruiz Irene , Rovira Cristina , Carrillo Antonio , Meulbroek Michael , Crook Alison , Wee Edmund G. , Miró Jose M. , Clotet Bonaventura , Valle Marta , Martinez-Picado Javier , Hanke Tomáš , Brander Christian , Moltó José , The BCN02 Study Investigators TITLE=HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02) JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00823 DOI=10.3389/fimmu.2020.00823 ISSN=1664-3224 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.