Immunologic Change over 72 Weeks following Raltegravir- vs Efavirenz-based Therapy in HIV/HCV co-infected Individuals in Vietnam.
Academic Article
Overview
abstract
BACKGROUND: The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C (HCV)/ HIV co-infection is incompletely understood. METHODS: We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T-cell activation (HLA-DR, CD38) and immune exhaustion (PD-1,TIGIT) in HIV/HCV co-infected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- vs efavirenz (EFV)-based therapy when used as first time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared to those from ART-naïve HIV mono-infected and HIV sero-negative individuals. RESULTS: Prior to ART, HIV/HCV co-infected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38+HLA-DR+, PD1+ and TIGIT+ CD4 and CD8 T cells compared to ART-naive HIV mono-infected or HIV sero-negative individuals (all p< 0.01). Most parameters did not normalize despite 72 weeks of ART. In particular sCD163 persisted at high levels. Improvement over 72 weeks in fibrosis as assessed by FibroScan correlated with reductions in plasma sCD163 and in the frequencies of T cell activation, single PD-1+, TIGIT+ and dual PD-1+TIGIT+ CD8 T cells. A non-significant tendency towards more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared to EFV-based therapy. CONCLUSIONS: The initiation of ART in HIV/HCV co-infected individuals is associated with incomplete improvement in monocyte and T cell immune activation and exhaustion, which was associated with some corresponding improvement in liver fibrosis.
