HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: safety, immunogenicity and effect on the viral reservoir (Study BCN02)

HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: safety, immunogenicity and effect on the viral reservoir (Study BCN02)

Fecha de publicación online: 05/06/2020 Revista: Frontiers in Immunology

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.

Autores: 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

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