CD4(+)CD38(+) central memory T cells contribute to HIV persistence in HIV-infected individuals on long-term ART

BACKGROUND: Despite the effective antiretroviral treatment (ART) of HIV-infected individuals, HIV persists in a small pool. Central memory CD4(+) T cells (Tcm) make a major contribution to HIV persistence. We found that unlike HLA-DR, CD38 is highly expressed on the Tcm of HIV-infected subjects receiving ART for > 5 years. It has been reported that the half-life of total and episomal HIV DNA in the CD4(+)CD38(+) T cell subset, exhibits lower decay rates at 12 weeks of ART. Whether CD38 contributes to HIV latency in HIV-infected individuals receiving long-term ART is yet to be addressed. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of HIV-infected subjects receiving suppressive ART. The immunophenotyping, proliferation and apoptosis of CD4(+) T cell subpopulations were detected by flow cytometry, and the level of CD38 mRNA and total HIV DNA were measured using real-time PCR and digital droplet PCR, respectively. A negative binomial regression model was used to determine the correlation between CD4(+)CD38(+) Tcm and total HIV DNA in CD4(+) T cells. RESULTS: CD38 was highly expressed on CD4(+) Tcm cells from HIV infected individuals on long-term ART. Comparing with HLA-DR(−)Tcm and CD4(+)HLA-DR(+) T cells, CD4(+)CD38(+) Tcm cells displayed lower levels of activation (CD25 and CD69) and higher levels of CD127 expression. The proportion of CD38(+) Tcm, but not CD38(−) Tcm cells can predict the total HIV DNA in the CD4(+) T cells and the CD38(+) Tcm subset harbored higher total HIV DNA copy numbers than the CD38(−) Tcm subset. After transfected with CD38 si-RNA in CD4(+) T cells, the proliferation of CD4(+) T cells was inhibited. CONCLUSION: The current date indicates that CD4(+)CD38(+) Tcm cells contribute to HIV persistence in HIV-infected individuals on long-term ART. Our study provides a potential target to resolve HIV persistence.