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
Authors: Mothe Beatriz , Climent Nuria , Plana Montserrat , Rosàs Miriam , Jiménez José Luis , Muñoz-Fernández María Ángeles , Puertas María C. , Carrillo Jorge , Gonzalez Nuria , León Agathe , Pich Judit , Arnaiz Joan Albert , Gatell Jose M. , Clotet Bonaventura , Blanco Julià , Alcamí José , Martinez-Picado Javier , Alvarez-Fernández Carmen , Sánchez-Palomino Sonsoles , Guardo Alberto C. , Peña José , Benito José M. , Rallón Norma , Gómez Carmen E. , Perdiguero Beatriz , García-Arriaza Juan , Esteban Mariano , López Bernaldo de Quirós Juan Carlos , Brander Christian , García Felipe ,   on behalf of the RISVAC-03 Study Group, Mothe Beatriz , Cobarsi Patricia , Rosàs Miriam , Puertas María C. , Carrillo Jorge , Blanco Juliá , Martinez-Picado Javier , Clotet Bonaventura , Brander Christian , Climent Nuria , Plana Montserrat , Alvarez Carmen , Sánchez Sonsoles , León Agathe , Pich Judit , Arnaiz Joan Albert , Leal Lorna , Torres Berta , Lucero Constanza , Guardo Alberto C. , Gatell Jose M. , García Felipe , Jiménez José Luis , Muñoz-Fernández María Angeles , López Bernaldo de Quirós Juan Carlos , Esteban Mariano , Gómez Carmen Elena , Perdiguero Beatriz , García-Arriaza Juan , Cepeda Victoria , Sánchez-Sorzano Carlos Oscar , Gonzalez Nuria , Alcamí José , Jiménez Laura , Benito José M. , Rallón Norma , Peña José 
Published: March 2015

AbstractObjectivesThe 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.MethodsHIV-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.ResultsMVA-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/106 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.ConclusionsMVA-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.