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

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. Copyright © 2020 Mothe, Rosás-Umbert, Coll, Manzardo, Puertas, Morón-López, Llano, Miranda, Cedeño, López, Alarcón-Soto, Melis, Langohr, Barriocanal, Toro, Ruiz, Rovira, Carrillo, Meulbroek, Crook, Wee, Miró, Clotet, Valle, Martinez-Picado, Hanke, Brander, Moltó and the BCN02 Study Investigators.

Citation

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, BCN02 Study Investigators. HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02). Frontiers in immunology. 2020;11:823

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PMID: 32435247

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