CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

598

Mucosal-Associated Invariant T (MAIT) Cells in HIV/HCV Coinfection Maddalena Cerrone 1 ; Esther Merlini; Bonnie vanWilgenburg 2 ; Leo Swadling 2 ; CamillaTincati 1 ; Stefania Cannizzo 1 ; Anna De Bona 1 ; Antonella d’Arminio Monforte 3 ; Paul Klenerman 2 ; Giulia Marchetti 4 1 Univ of Milan, Milan, Italy; 2 Univ of Oxford, Oxford, UK; 3 Infectious Diseases Clinic, San Paolo Hosp, Univ of Milan, Milan, Italy; 4 Clinic of Infectious Diseases, Univ of Milan, San Paolo Hosp, Milan, Italy Background: MAIT cells play a crucial role in the innate immunity. A substantial reduction in MAIT cells have been described in untreated HIV, that is not restored by cART, but little is known about the relationship of MAIT cells and HCV. We investigated the role of MAIT cells in the setting of HIV/HCV co-infection and the impact of anti-HCV therapy in a cohort of cART-treated HCV/HIV patients (pts). Methods: We enrolled 23 HIV/HCV+ cART treated pts with HIV-RNA<40cp/ml and median CD4 T-cell count of 527 cell/mmc (IQR 409-780); 15/23 started interferon-based anti-HCV regimen and 13 healthy controls (HC). Pts were stratified according to anti-HCV therapy outcome in sustained virological response (SVR) and non response (NR-relapser/ non responder). Flow cytometry analyses were performed (CD3/CD4/CD8/CD161/TCRVa7.2/CD39/CD69/IL18R/PD1/Granzyme B/Perforin). Severity of liver fibrosis was measured by FIB-4 score. Statistical analyses: Mann-Whitney, Wilcoxon, Spearman tests. Results: HIV/HCV pts displayed a significant contraction of total, CD8 and double-negative (DN) MAIT cells, compared to HC (Table 1). All MAIT cell subsets of HIV/HCV pts showed a trend towards higher CD39 expression, especially within the CD8 subset, and a lower CD69 expression (Table 1). No differences in PD-1, granzyme B and perforin expression were found. Following anti-HCV therapy, we found a non-significant increase in total (0.48vs0.63%), CD8+ (0.59vs0.76%) and DN (0.61vs1.19%) MAIT cells. Therapy and treatment outcome did not impact on MAIT cell frequency nor function. Interestingly, HIV/HCV pts displayed a positive correlation between CD8+MAIT frequency and AST (p=.004;r=0.62) and ALT (p=.01;r=0.56). In addition, CD69+CD8+MAIT directly correlated with HCV-RNA (p=.001; r=0.75) and inversely with the duration of both HIV (p=.002;r=-0.72) and HCV (p=.004;r=-0.7) infection. No significant correlation between the frequency of MAIT cells and severity of liver fibrosis was found. Conclusions: In HIV/HCV co-infected patients we show a profound contraction of the circulating MAIT cell compartment that is not recovered by anti-HCV treatment and virologically suppressive cART. The correlation between MAIT, HCV and hepatic necrosis enzymes, suggests an association between HCV-driven liver damage and the homeostasis of circulating MAIT cells via mechanisms that still need to be elucidated.

Poster Abstracts

240

CROI 2016