We recently observed that during early, untreated HIV-1 infection, the majority of activated (CD38+HLA-DR+) CD8+ T cells display a deficit in their ability to phosphorylate the extracellular signal-regulated kinases ERK1 and ERK2 (p-ERK1/2-refractory CD8+ T cells), while non-activated cells rarely displayed this signaling deficit [19]. Here, CD8A is linked to HIV-1 infection.