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

• Published in: Frontiers in immunology Vol. 11; p. 823
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06.05.2020
• Subjects: Adult; AIDS Vaccines - immunology; Antiviral Agents - therapeutic use; Depsipeptides - therapeutic use; Disease Reservoirs; Drug Therapy, Combination; early-treatment; Female; HDAC inhibitor; Histone Deacetylase Inhibitors - therapeutic use; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - physiology; HIVconsv; Humans; Immunology; kick&kill strategy; Male; Middle Aged; Pilot Projects; romidepsin; Viral Load; Viremia; Virus Latency; HDAC inhibitor; early-treatment; kick&kill strategy; HIVconsv; romidepsin
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.00823

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.