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iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy

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dc.contributor.author de Jong, W. en_US
dc.contributor.author Aerts, J. en_US
dc.contributor.author Allard, S. en_US
dc.contributor.author Brander, C. en_US
dc.contributor.author Buyze, J. en_US
dc.contributor.author Florence, E. en_US
dc.contributor.author van Gorp, E. en_US
dc.contributor.author Vanham, G. en_US
dc.contributor.author Leal, L. en_US
dc.contributor.author Mothe, B. en_US
dc.contributor.author Thielemans, K. en_US
dc.contributor.author Plana, M. en_US
dc.contributor.author Garcia, F. en_US
dc.contributor.author Gruters, R. en_US
dc.date.accessioned 2020-08-25T09:54:53Z
dc.date.available 2020-08-25T09:54:53Z
dc.date.issued 2019 en_US
dc.identifier.issn 1745-6215 en_US
dc.identifier.doi http://dx.doi.org/10.1186/s13063-019-3409-1 en_US
dc.identifier.other http://lib.itg.be/pdf/itg/2019/2019tria0361.pdf en_US
dc.identifier.other 10 pp. en_US
dc.identifier.other 29 en_US
dc.identifier.other ITG-C5A; ITG-C6A; ITG-B8A; MULTI; DCS; U-CTU; U-HIVCLI; DBM; U-VIROL; JIF; DOI; PDF; PMC; Abstract; ITMPUB; DSPACE68 en_US
dc.identifier.uri http://hdl.handle.net/10390/11082
dc.description.abstract BACKGROUND: HIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro. METHODS/DESIGN: This is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNgamma ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes. DISCUSSION: This trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection. TRIAL REGISTRATION: EudraCT 2016-002724-83 (22 September 2016); ClinicalTrials.gov, ID: NCT02888756 . Registered on 23 August 2016. en_US
dc.language English en_US
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/31208472 en_US
dc.subject HIV en_US
dc.subject Viral diseases en_US
dc.subject Treatment en_US
dc.subject Antiretroviral therapy en_US
dc.subject Vaccines en_US
dc.subject iHIVARNA en_US
dc.subject Evaluation en_US
dc.subject Clinical trials en_US
dc.title iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy en_US
dc.type Article en_US
dc.citation.issue 1 en_US
dc.citation.jtitle Trials en_US
dc.citation.volume 20 en_US
dc.citation.pages 361 en_US
dc.citation.abbreviation Trials en_US


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