Description: Background.  Liver disease is common during human immunodeficiency virus (HIV) infection, but valid serum fibrosis markers are lacking. We hypothesize that HIV monoinfection and HIV/hepatitis C virus (HCV) coinfection is associated with an enhanced liver fibrosis (ELF) score higher than that for uninfected controls and examine whether this association is affected by factors other than liver injury. Methods.  The association of HIV and HIV/HCV coinfection with the ELF score was evaluated using multivariable regression after controlling for transient elastography–measured liver stiffness and traditional and HIV-related factors in a cross-sectional analysis of 297 women. Results.  HIV/HCV-coinfected and HIV-monoinfected women had higher median ELF scores than controls (9.6, 8.5, and 8.2, respectively). After adjustment for demographic, behavioral, and metabolic factors and for inflammatory markers, HIV/HCV coinfection remained associated with a 9% higher ELF score (95% confidence interval [CI], 5%–13%), while the association of HIV monoinfection was substantially attenuated (1% higher ELF score; 95% CI, –2% to 4%). After further adjustment for liver stiffness, HIV/HCV coinfection remained associated with 6% higher levels (95% CI, 3%–10%). In HIV/HCV-coinfected and HIV-monoinfected women, higher liver stiffness values were associated with higher ELF scores, as were older age and a nadir CD4 + T-cell count of 〈200 cells/mm 3 . Conclusions.  Our findings suggest that the ELF score can be used to assess liver fibrosis severity in HIV-infected women. However, higher ELF scores may reflect extrahepatic fibrosis in HIV-infected patients with a history of severe immunosuppression or advanced age.