In this rural Ugandan population, over a two decades study period we found that individuals infected with HIV-1 subtype D, the most prevalent subtype, had a significantly faster disease progression to CD4 cell counts ≤250 cells/mm3 than those infected with subtype A. Although non-significant, HIV-1 subtype D cases also had a faster disease progression to AIDS and to death than subtype A cases. Here, CD4 is linked to AIDS.