We studied repeated measurements of CD4 cell counts on 5739 HIV-1-infected individuals with reliably estimated dates of seroconversion (SC) aged > or =15 years at SC prior to initiation of highly active antiretroviral therapy (HAART) or AIDS using random effects models. Estimated CD4 cell count at SC differed significantly by sex, exposure group, and age, being higher in women, hemophilic men, and injection drug users (IDUs) as well as in those aged >40 years at SC. The rate of CD4 cell count decline did not differ significantly by sex; thus, differences between men and women were stable throughout the HIV-1 incubation period. There was a monotonic relationship between CD4 slopes and age at SC, with steeper slopes in older subjects. At 5 years after SC, the median difference in CD4 cell counts between the oldest (>40 years at SC) and youngest (16-20 years at SC) subjects was around 90 cells/microL. Mean rate of CD4 decline was significantly steeper in subjects diagnosed during acute infection. There was no evidence of a faster loss of CD4 cells in subjects who seroconverted after 1994. Apart from hemophilic men, who tended to have a steeper rate of CD4 decline on average, mean CD4 slopes did not differ by exposure category. These results suggest that before the initiation of HAART or other interventions based on immune status, consideration of demographic factors may be worthwhile.