Taken together, by analyzing changes in COX-2 expression, glycolysis level, and M1 polarization in the presence or absence of JNK inhibition, we found that phosphorylation of JNK promotes glycolysis enhancing, which is regulated by the COX-2/HIF-1α signaling axis, supporting M1 polarization of macrophages in HIV-1 infection. Here, HIF1A is linked to HIV-1 infection.