Hypothetical fate of CD45RA⁺/CD4⁺ (RA) and CD45RO⁺/CD4⁺ (RO) lymphocyte subsets in vivo during HIV-1 infection. (1) Infected thymic/precursor emigrants allow fewer cells into the peripheral circulation, resulting in a lower RA population. (2) A lower RA population leads to less differentiation into RO cells, resulting in a reduced RO population. (3) Infected RO cells are lost and cytokine feedback to stimulate RA proliferation is decreased, resulting in both lower RA and RO populations.