Reasons for the accelerated progression of liver fibrosis in HIV-1/HCV coinfection are not well defined. Increased microbial translocation and/or immune activation may play a role. The aim of this research was to investigate the relationship between Th17 and Th22 cells with microbial translocation, immune activation and liver fibrosis in HIV-1/HCV coinfection. HIV-1 infection led to a preferential reduction in peripheral Th17 and Th22 cells and a reduction in Th17:Treg and Th22:Treg cell ratios. There was a negative correlation between Th17 and Th22 frequencies, Th17:Treg and Th22:Treg ratios with markers of microbial translocation and immune activation. In addition we found significant increases in the activity of the enzyme IDO, which promotes CD4 Treg development at the expense of Th17 cells. Alterations in the distribution of Th17, Th22 and Treg cells may be a mechanism through which immune activation promotes fibrogenesis. HIV-1/HCV coinfection led to increased immune activation and microbial translocation. There was a more marked depletion of Th17 cells than in HIV-1 monoinfection, and reduced Th22 cells, Th17:Treg ratio and Th22:Treg ratio, which were not seen in HCV monoinfection. Unlike HCV monoinfection there was no increase in Th1 cells in HIV-1/HCV coinfection. There was a stronger association between reduction in Th17:Treg, Th22:Treg ratios and markers of immune activation and microbial translocation in patients with HIV-1/HCV coinfection compared to HCV monoinfection. Th1 cells displayed robust negative correlations with immune activation in HIV-1/HCV coinfection, but not in HCV monoinfection. There was no association between alterations in CD4 T cell subsets and liver fibrosis in HCV monoinfection. In HIV-1/HCV coinfection reduced Th17 cell and depleted Th1 responses were associated with liver fibrosis. Our research implicates HIV-1 driven depletion of Th1 and Th17 cells in the development of liver fibrosis in HIV-1/HCV co-infection.