HIV reservoir size is related to CD4+ and CD8+ T-cell differentiation in HCV/HIV-coinfected individuals treated with direct acting antivirals (DAAs).

GHIGLIONE, YANINA; POLO, MARÍA LAURA; TRIFONE, CÉSAR ARIEL; URIOSTE, ALEJANDRA; SALIDO, JIMENA; RHODES, AJANTHA; POBLETE, GABRIELA; PEREZ, HECTOR; SALOMON H; MARIA FLORENCIA QUIROGA; TURK, GABRIELA; LEWIN, SHARON R; LAUFER, NATALIA

Congreso; IAS 2019; 2019

Background: The dynamics of the HIV reservoir is shaped by the T-cell differentiation and activation. We aimed to determine the relationship between phenotypic immune markers and HIV persistence in HCV/HIV co-infected individuals following HCV treatment with direct acting antivirals (DAAs).Methods: In a prospective longitudinal observational study, HIV/HCV-coinfected individuals on suppressive cART (n=19) received sofosbuvir/daclatasvir±ribavirin. All achieved sustained virological response. Blood samples were obtained at enrollment (baseline sample, BSL); at end-of-HCV treatment (EOT) and at 12-month after EOT (12MPT). T-cell differentiation (CD45RO, CCR7, CD95, CD28), exhaustion (PD-1) and activation (HLA-DR, CD38, CD25) markers were quantified on CD4+ and CD8+ T-cells, by flow cytometry. Plasma cytokines were evaluated by ELISA. Cell-associated HIV DNA (total, HIV-integrated) and unspliced (US) RNA were quantified by real-time PCR. Data was analyzed using non-parametric statistics.Results: At enrollment, the median CD4+ T-cell count was 291 (IQR: 231-776) cells/ml. For CD4+ T-cells, the proportions of central and transitional memory cells (defined as CCR7+/CD45RO+/CD95+/CD28+ and CCR7-/CD45RO+/CD95+/CD28+) were higher than terminal effectors (TE, CCR7-/CD45RO-/CD95+/CD28-) at BSL and post-HCV clearance. In contrast, for CD8+ T-cells there were higher proportions of effector memory(EM, CCR7-/CD45RO+/CD95+/CD28-) and TE cells at all time points evaluated.At 12MPT compared to BSL, HLA-DR, CD38/HLA-DR and PD-1 expression on CD4+ T-cells and CD8+ T-cells significantly declined (p=0.0137, p=0.0371, p=0.0371 for CD4 and p=0.001, p=0.0186, p=0.0020 for CD8, respectively). Plasma ICAM-1 (Intercellular Adhesion Molecule 1); CXCL10 (IP-10) and IL-8 were reduced after HCV clearance (EOT: all p< 0.002; 12MPT: all p< 0.01).Spearman''s correlations showed that the proportion of BSL naïve CD4+ T-cells inversely correlated with levels of total and HIV-integrated DNA measured at EOT samples (total: r=-0.7337, p=0.0008; HIV-integrated: r=-0.6583, p=0.0056). On the CD8 compartment, higher proportion of BSL EM T-cells correlated with higher levels of HIV DNA at EOT and 12MPT (EOT: r=0.5882, p=0.0147 and 12MPT: r=0.5874 p=0.0489).Conclusions: Cellular and plasma markers of immune activation were significantly reduced after treatment with DAAs. Moreover, preservation of a less differentiated memory panel (before DAA treatment) was related with a smaller HIV reservoir, post-HCV clearance. This data might contribute to elucidate the immune mechanisms involved in HIV persistence in coinfected subjects.