Background:  Activation of CD4⁺ T cells facilitates HIV infection. Despite an increased frequency of several markers of T cell activation during HIV infection, the effect of the expression of these markers on the infection of CD4⁺ T cells by HIV has not been characterized.

Methods:  We used polychromatic flow cytometry to characterize the frequency of CD38, Ki67, HLA DR, and CCR5 expressing CD4⁺ T cells and the maturational phenotypes of these cells in 7 HIV-infected and 8 HIV-uninfected individuals. Viral loads in the HIV-infected individuals were 2,680 to 188,000 (median 21,900) copies/mL and CD4⁺ T cells counts were 145 to 829 (median 609) cells/mL. In 6 of these individuals, we sorted memory (CD45RO⁺ and CD45RO^–CD27^–) CD4⁺ T cells into populations expressing the following markers of activation: CD38^-HLA DR^-, CD38⁺HLA DR^– and CD38⁺HLA DR⁺; CD38^–Ki67^–, CD38⁺Ki67^– and CD38⁺Ki67⁺; and CCR5^–DR^–, CCR5⁺DR^– and CCR5⁺ DR⁺ and then determined the frequency of infection of these cells using real-time polymerase chain reaction (RT-PCR) to quantify the amount of HIV Gag DNA per cell.

Results:  The frequency of CD38⁺ (p <0.01) memory CD4⁺ T cells was higher in HIV-infected individuals (median 12.5, range 6.1 to 25.3%) than in HIV-uninfected individuals (median 3.3, range 1.6 to 10.6%). Ki67 was also expressed more frequently in memory CD4⁺ T cells (p <0.05) from HIV-infected individuals (median 5.9, range 2.4 to 11.3%) than from HIV-uninfected individuals (median 3.6, range 1.4 to 5.4%). Frequencies of CD38, and Ki67 expressing CD4⁺ T cells were similar in CD45R0⁺CD27⁺, CD45RO⁺CD27^– and CD45RO^–CD27^– populations from these HIV-infected individuals. The frequency of Gag DNA containing memory CD4⁺ T cells from HIV-infected individuals was not significantly higher in any of the activated populations as judged by expression of CD38, Ki67, HLA DR, or CCR5. In all cases the median frequency of infection of activated CD4⁺ T cells was less than 2-fold higher than was found in the non-activated populations.

Conclusions:  The absence of any significant increase in the rate of infections of activated CD4⁺ T cells is surprising considering the importance of activation in HIV infection in vivo and suggests that more than expression of markers of activation is required to assure preferential infection of CD4⁺ T cells.