Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.
AIDS
; 28(12): 1769-81, 2014 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-24911353
ABSTRACT
OBJECTIVE:
Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART.DESIGN:
A randomized, observer-blind, controlled trial (NCT00707967).METHODS:
HIV-infected adults on cART in Switzerland were randomized 3ââ1ââ1 to receive two doses, 1 month apart, of M72/AS01, AS01 or 0.9% physiological saline (Nâ=â22, Nâ=â8 and Nâ=â7, respectively) and were followed up to 6 months postdose 2 (D210). Individuals with CD4⺠cell counts below 200 cells/µl were excluded. Adverse events (AEs) including HIV-specific and laboratory safety parameters were recorded. Cell-mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1 month after each dose (D30, D60) and D210.RESULTS:
Thirty-seven individuals [interquartile range (IQR) CD4⺠cell counts at screening 438-872 cells/µl; undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01 recipients, no vaccine-related serious AEs or cART-regimen adjustments were recorded, and there were no clinically relevant effects on laboratory safety parameters, HIV-1 viral loads or CD4⺠cell counts. M72/AS01 was immunogenic, inducing persistent and polyfunctional M72-specific CD4⺠T-cell responses [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210, predominantly CD40LâºIL-2âºTNF-αâº, CD40LâºIL-2⺠and CD40LâºIL-2âºTNF-αâºIFN-γâº]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second vaccination until study end.CONCLUSION:
M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
/
Tuberculose
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Infecções por HIV
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Vacinas contra a Tuberculose
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Antirretrovirais
/
Lipídeo A
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
AIDS
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2014
Tipo de documento:
Article