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J Antimicrob Chemother. 2015;70(6):1833-42. doi: 10.1093/jac/dkv046. Epub 2015 Feb 26.

Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1.

Author information

1
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain 'Lluita contra la Sida' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain.
2
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
3
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain.
4
Hospital Gregorio Marañón, Madrid, Spain.
5
AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid, Spain.
6
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain.
7
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
8
Hospital Reina Sofía, Córdoba, Spain.
9
Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Barcelona, Madrid, Spain.
10
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
11
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain fgarcia@clinic.ub.es.

Abstract

OBJECTIVES:

The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed.

METHODS:

HIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466.

RESULTS:

MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/10(6) PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P = 0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment.

CONCLUSIONS:

MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1-infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram.

KEYWORDS:

disulfiram; functional cure; poxvirus; reservoir

PMID:
25724985
DOI:
10.1093/jac/dkv046
[Indexed for MEDLINE]

Publication types, MeSH terms, Substances, Secondary source ID

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