Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naïve patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especially in those patients with CD4<200cells/mm(3), who lost positive selective immune pressure in the HVR-1 region. Differences in immune regulation of HCV quasispecies in HIV coinfected individuals deserve further exploration to clarify the different outcomes of chronic hepatitis C noted between the immunocompromised and the immunocompetent host.