Data_Sheet_1_HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (S.docx (8.48 MB)

Data_Sheet_1_HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02).docx

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posted on 06.05.2020 by Beatriz Mothe, 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, Jessica Toro, Irene Ruiz, Cristina Rovira, Antonio Carrillo, Michael Meulbroek, Alison Crook, Edmund G. Wee, Jose M. Miró, Bonaventura Clotet, Marta Valle, Javier Martinez-Picado, Tomáš Hanke, Christian Brander, José Moltó, The BCN02 Study Investigators

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.

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