Factors associated with the occurrence of severe liver fibrosis in HIV/HCV (hepatitis C virus) coinfected patients remain poorly understood. We thus questioned which factors influenced the occurrence of fibrosis in a cohort of HIV/HCV coinfected intravenous drug user patients. HIV/HCV coinfected intravenous drug user patients naive of anti-HCV therapy for whom a liver biopsy was performed between 1996 and 2003 were retrospectively studied in three University hospitals in Paris and the Parisian region. One hundred and fifty two patients (131 men and 21 women; mean age 39.3+/-4.9 years) were studied. Most of them (62%) were treated with HAART. HCV genotypes included type 1 (N=78), type 2 (N=1), type 3 (N=38) and type 4 (N=35). Mean duration of HCV infection was 19.0+/-5.2 years. Sixty-six percent had minimal to moderate fibrosis (F0/F1/F2) and 34% severe fibrosis (F3/F4). Multivariate analysis retained METAVIR activity score (OR=2.60, 95%CI [1.46-4.64]; P=0.001), mixed pattern of steatosis (OR=3.29, 95%CI [1.24-8.71]; P=0.017) and a CD4 cell count<200/mm3 (OR=4.04, 9%CI [1.47-11.12]; P=0.007) as independent factors associated with severe fibrosis. HAART did not influence the occurrence of liver fibrosis. In this cohort of HIV/HCV coinfected intravenous drug user patients, METAVIR activity score, mixed steatosis and a low CD4 cell count were independent factors associated with severe liver fibrosis.