期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.00823
关键词
romidepsin; HDAC inhibitor; kick&kill strategy; HIVconsv; early-treatment
类别
资金
- ISCIII [JR 13/00024, PI15/01188]
- European Union [681137-EAVI2020]
- NIH [P01-AI131568]
- Medical Research Council (MRC) UK
- UK Department for International Development (DFID) [G0701669]
- Departament de Salut de la Generalitat de Catalunya, Barcelona, Spain
- Ministerio de Economia y Competitividad [MTM2015-64465-C2-1-R]
- IDIBAPS, Barcelona, Spain
- HIVACAT Catalan research program for an HIV vaccine
- Fundacio Gloria Soler
- DGR [2013FI_B 00275]
- MRC [MR/N023668/1, G1001757, G0701669] Funding Source: UKRI
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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