Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

Détails

Ressource 1Télécharger: 28970080_BIB_CB6E21477314.pdf (2218.10 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_CB6E21477314
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.
Périodique
EBioMedicine
Auteur(s)
Huang Y., Pantaleo G., Tapia G., Sanchez B., Zhang L., Trondsen M., Hovden A.O., Pollard R., Rockstroh J., Ökvist M., Sommerfelt M.A.
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Statut éditorial
Publié
Date de publication
10/2017
Peer-reviewed
Oui
Volume
24
Pages
195-204
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Controlled Clinical Trial ; Journal Article
Publication Status: ppublish
Résumé
In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24 <sup>Gag</sup> vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI.
All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log <sub>10</sub> -transformed VL (VE <sup>VL</sup> ) or CD4 count (VE <sup>CD4</sup> ).
A lower fold-change of CD4+ T-cell proliferation was associated with VE <sup>CD4</sup> at week 48 (p=0.036, multiplicity adjusted q=0.036) and week 52 (p=0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VE <sup>VL</sup> at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VE <sup>VL</sup> at week 44 (p=0.045, q=0.070), week 48 (p=0.028, q=0.070), and week 52 (p=0.037, q=0.074). A higher fold-change of IL-6 was associated with VE <sup>VL</sup> at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VE <sup>CD4</sup> at week 48 (p=0.009, q=0.009).
These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.
Mots-clé
AIDS Vaccines/administration & dosage, AIDS Vaccines/pharmacology, Adult, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/drug effects, Cell Proliferation/drug effects, Female, HIV Infections/drug therapy, HIV Infections/immunology, HIV-1/immunology, HIV-1/physiology, Humans, Immunity, Cellular, Interleukin-6/metabolism, Male, Middle Aged, Treatment Outcome, Tumor Necrosis Factor-alpha/metabolism, Viral Load/drug effects, Young Adult, Analytical treatment interruption (ATI), CD4, HIV, Immune predictors, Therapeutic vaccine, Viral load
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/10/2017 14:36
Dernière modification de la notice
09/05/2019 1:18
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