The aim of this study was to investigate the early CD4+ T cell response among human immunodeficiency virus type 1 (HIV-1) seroconverters in relation to their year of seroconversion. Study participants were enrolled in the Swiss HIV Cohort Study between 1985 and 1995 and had not received antiretroviral treatment. The slope of the CD4+ T cell count within 2 years after seroconversion was significantly associated with the year of seroconversion, by sex and by use of injection drugs, when controlling for initial CD4+ cell count. These results show that the loss of CD4+ cells might be associated with the year of seroconversion, suggesting a change in the pathogenesis of HIV across the years. If these results are confirmed, they could have important implications for the pathogenesis of and therapeutic strategies for HIV-1 infection.