Th17 and Tregs at Early HIV Infection Influence Disease Progression and HIV Specific CD8+ Responses

JULIANA FALIVENE ; YANINA A. GHIGLIONE; NATALIA L. LAUFER; MARÍA E. SOCÍAS; MARÍA J. RUIZ; PEDRO CAHN; OMAR SUED; HORACIO SALOMÓN; GABRIELA TURK; MARÍA M. GHERARDI

Boston

Conferencia; CROI 2014; 2014

International Antiviral Society

Background: Th17 and Treg subsets have been related to HIV/SIV disease progression. Their role and direct relation with specific HIV-adaptive T cell responses during primary HIV infection (PHI) are unexplored topics. Aim: To analyze the frequency and balance of Th17 and Treg subsets and the correlation with clinical parameters, immune activation and HIV-specific responses during early infection. Methodology: PBMCs were obtained from 6 healthy donors (HDs) and 28 HIV infected subjects: 6 elite controllers (ECs), 5 chronics (Chs) and 17 PHIs within 6 months post-infection (mpi)). Th17 and Treg cells (baseline and 12 mpi samples) were identified as CD3+/CD4+ IL-17+ or CD25+/FoxP3+ (respectively). Data was compared inter/intragroups and correlated to clinical parameters (viral load (VL), CD4 counts), CD4+ or CD8+ CD38+/HLA-DR+ activated T cells and HIV-specific CD8+ responses (specifically a viral inhibitory activity (VIA) assay and intracellular cytokine staining (ICS) for IFN-gamma production and CD107a/b cytotoxicity markers) measured at baseline, 6 and 12 mpi, using parametric and nonparametric statistics. Results: Chs had lower % of Th17 cells compared to HDs and ECs (p=0.006 and 0.021 respectively), among which frequencies were similar (median 0.14 vs 0.11 respectively). In PHI group, CD4 counts at 6 mpi directly correlated with baseline Th17 counts (p=0.048, r=0.5). Moreover, VL at 12 mpi inversely correlated with baseline % of Th17 (p=0.041, r=-0.596). Th17/Tregs ratio was higher for HDs compared to any HIV+ group (p