Based on the assumption that the rate of CD4 cell count loss in treatment-naïve patients is correlated with the virulence of HIV-1, we evaluated 4616 patients. Patients who entered a German national database between 1985 and 1995 had a median annual CD4 cell count loss of 48 cells/μl, whereas those registered between 1999 and 2009 had a median annual CD4 cell count loss of 68 cells/μl (P < 0.001). This suggests that HIV-1 virulence has increased over the course of the epidemic.