Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs - 22/11/17
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Summary |
Objectives |
The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir.
Methods |
This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm3 on cART. Six Vacc-4x (1.2 mg) intradermal immunizations using rhuGM-CSF (60 μg) as adjuvant were followed by 3 weekly intravenous infusions of romidepsin (5 mg/m2). Immune responses were determined by IFN-γ ELISpot, T-cell proliferation to p24 15-mer peptides covering the Vacc-4x region, intracellular cytokine staining (ICS) to the entire HIVGag and viral inhibition.
Results |
The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%)post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006; q = 0.183), post-latency reversal (p = 0.005; q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015; q = 0.254). Participants (40%) were defined as proliferation ‘Responders’ having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIVGag by ICS. There was a trend towards increased viral inhibition from baseline to post-vaccination (p = 0.08).
Conclusions |
In this ‘shock and kill’ approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.
Le texte complet de cet article est disponible en PDF.Highlights |
• | HIV ‘Shock & Kill’ approaches benefit from inclusion of an immune component. |
• | CD8+ T-cell proliferation is a functional immune assay to measure vaccine effect |
• | T-cell proliferation is sensitive to the influence of therapies on immune responses. |
• | T-cell proliferation can correlate with vaccine induced reductions in HIV reservoirs. |
Keywords : HIV, Vacc-4x, HDACi, Romidepsin, Latency reversal, Therapeutic vaccine, Immunotherapy
Plan
Vol 75 - N° 6
P. 555-571 - décembre 2017 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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