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.
J Antimicrob Chemother
; 70(6): 1833-42, 2015.
Article
em En
| MEDLINE
| ID: mdl-25724985
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 (nâ=â20) or placebo (nâ=â10). 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; Pâ=â0.02 and Pâ=â0.04]. 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 (Pâ=â0.01). 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Vacinas contra a AIDS
/
Fármacos Anti-HIV
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2015
Tipo de documento:
Article