Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 70, Issue 6, Pages 1833-1842Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkv046
Keywords
poxvirus; disulfiram; reservoir; functional cure
Funding
- RIS [Red Tematica Cooperativa de Grupos de Investigacion en Sida del Fondo de Investigacion Sanitaria (FIS)], HIVACAT (Catalan Programme for the Development of HIV-1 Vaccines) [EC10-153, TRA-094, FIS PI10/02984, FIS PS09/01297, FIPSE-360731-09, SAF2006-26667-E, SAF2008-02036, FIS PI050058,]
- ICREA Funding Source: Custom
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available