Taken together, our study sheds light on how chronic inflammation—as defined by aberrantly elevated plasma markers—and an altered subsets composition of the T cell compartment could together deteriorate antigen-specific CD4 T cell responses in ART-treated HIV infection and highlights mechanisms that may be relevant for the maintenance of vaccine-induced immunity in other conditions driving chronic inflammation such as aging, auto-immune diseases or cancer. Here, CD4 is linked to HIV infectious disease.