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

MARÍA LAURA POLO; JIMENA SALIDO; MARIA JOSE ROLON; FLORENCIA QUIROGA; LAUFER NATALIA; YANINA GHIGLIONE; ALEJANDRA URIOSTE; GABRIELA POBLETE; HORACIO SALOMON; SHARON LEWIN; CESAR TRIFONE; RHODES A; HECTOR PEREZ; GABRIELA TURK

México DC

Congreso; 10TH IAS CONFERENCE ON HIV SCIENCE (IAS 2019); 2019

IAS

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/l. 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