Abstract
The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected 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 with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p < .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 PD1(+), TIGIT(+), and dual PD1(+)TIGIT(+) CD8 T cells. A nonsignificant tendency toward more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared with EFV-based therapy. The initiation of ART in HIV/HCV-coinfected 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.