Notably, TGF-β signaling (TGFB1-TGFBR1-TGFBR2) was extinguished during HIV-mono infection yet reappeared in co-infection, whereas IL16-CD4 and CD40LG-(ITGAM/ITGB2) interactions disappeared with HIV-mono and did not recover, underscoring stage-specific rewiring of T-cell communication networks. Here, CD40LG is linked to infection.