Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam.

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 CD38HLA-DR, PD1, and TIGIT CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all  < .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 PD1TIGIT 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.