Effects of 24-week Toll-like receptor 9 agonist treatment in HIV type 1+ individuals.
AIDS
; 33(8): 1315-1325, 2019 07 01.
Article
en En
| MEDLINE
| ID: mdl-30932955
ABSTRACT
DESIGN:
This was an exploratory, single-arm clinical trial that tested the immune enhancement effects of 24-weeks of Toll-like receptor 9 (TLR9) agonist (MGN1703; Lefitolimod; 60âmgâ×â2 weekly) therapy.METHODS:
We enrolled HIV-1-infected individuals on suppressive combination antiretroviral therapy. Safety was assessed throughout the study. The primary outcome was reduction in total CD4 T-cell viral DNA levels. Secondary outcomes included safety, detailed immunological and virological analyses, and time to viral rebound (viral load > 5000âcopies/ml) after randomization into an analytical treatment interruption (ATI).RESULTS:
A total of 12 individuals completed the treatment phase and nine completed the ATI. Adverse events were limited and consistent with previous reports for MGN1703. Although the dosing regimen led to potent T-cell activation and increased HIV-1-specific T-cell responses, there were no cohort-wide changes in persistent virus (total CD4 T cells viral DNA; Pâ=â0.34). No difference in time to rebound was observed between the ATI arms (log rank Pâ=â0.25). One of nine ATI participants, despite harboring a large replication-competent reservoir, controlled viremia for 150 days via both HIV-1-specific cellular and antibody-mediated immune responses.CONCLUSION:
A period of 24 weeks of MGN1703 treatment was safe and improved innate as well as HIV-1-specific adaptive immunity in HIV-1+ individuals. These findings support the incorporation of TLR9 agonism into combination HIV-1 cure strategies. TRIAL NAME AND REGISTRATION TLR9 Enhancement of antiviral immunity in chronic HIV-1 infection a phase 1B/2A trial; ClinicalTrials.gov NCT02443935.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
ADN
/
Linfocitos T CD4-Positivos
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Infecciones por VIH
/
VIH-1
/
Receptor Toll-Like 9
/
Factores Inmunológicos
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2019
Tipo del documento:
Article