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Brief description/objective

Objectives
The impact of the CD4 nadir reflecting the timing of ART initiation on the immune functionality to recall antigens in the long-term is not yet well understood. A preserved polyfunctional CD4 T-cell profile characterised by double / triple cytokine secreting CD4 cells is thought to be of advantage.
Methods
In a proof-of-principle pilot study we evaluated the influenza A-specific polyfunctional CD4 T-cell profile (IFN-g, TNF-a, IL-2) in 3 HIV-positive patients on HAART with a high (>500/ul) and low (<50/ul) CD4 nadir each compared to 3 healthy HIV-negative controls before (BL) and 2 weeks (w2) after seasonal 2010/11 influenza immunisation as a model of recall-antigen exposure. The functional cytokine profile of CD4 T-cell responses (sample minus neg. control +2SD) were evaluated in duplicates by FACS.
Results
Baseline characteristics (age, time on ART, CD4 cell count at time of immunisation, % CD38+/HLA-DR+ and % PD-1 expressing CD4 T-cells) between HIV-pos. patients with a high or low CD4 nadir were not significantly different, although we observed a trend towards a higher number activated CD4 T-cells (CD38+ or HLA-DR+) in patients with a low CD4 nadir. The mean increase in the number of influenza A-specific CD4 T-cells / Mio. PBMC after immunisation was not different in HIV-pos. compared to HIV-neg. patients (delta % 2.2 versus 1.8, p=0.68). The changes BL-w2 of the percentage of single and multiple cytokine pos. cells / total influenza-specific CD4 T-cells in HIV-neg. controls and HIV-pos. patients with a CD4 nadir >500/ul were similar with a significant decrease of single cytokine pos. in favour of an increase of multiple cytokine pos. CD4 T-cells, with a dominant increase of IL-2 pos. secreting CD4 cells (p=.002 and .036 resp.). In contrast, HIV-pos. patients with a low CD4 nadir showed no quantitative changes of single / multiple cytokine positive CD4 T-cells (p=.65). The patterns of the cytokine expression changes (delta BL-w2) were similar in controls and HIV pos. patients with a high CD4 nadir compared to HIV pos. patients with a low CD4 nadir (see fig.).
Conclusion
A low CD4 nadir is associated with an functional impaired influenza A-specific CD4 T-cell response after immunisation despite absolute CD4 T-cell recovery under HAART compared to healthy controls and HIV-pos. patients on HAART with a CD4 nadir >500. These preliminary findings need to be verified in a lager cohort, but argue for a substantial benefit of an early HAART initiation.