We (1) unveil a role for TIGIT+ CD8+ T cells in HIV disease progression and demonstrate its relation to T cell exhaustion, (2) observe that TIGIT appears to associate with the cellular viral reservoir in CD4+ T cells, (3) we found that co-blockade of TIGIT and PD-L1 lead to a greater restoration of T cell function compared with a single blockade, and (4) by successfully cloning rhTIGIT (GenBank: KR534505) we reveal the similarities in expression and function of rhTIGIT on T cells in the non-human primate model of HIV/AIDS. Here, TIGIT is linked to AIDS.