Considerable　evidence　has　shown　that　autophagy　has　an　important　role　in　HIV-1　infection.　However,　it　is　still　unknown　whether　metabolism-regulated　autophagy　pathway　is　involved　in　Tat-mediated　HIV-1　transactivation.　This　study　demonstrated　that　treatment　of　Tat　in　TZM-bl　cells　significantly　down　regulated　protein　levels　of　Beclin-1,　Atg-5,　Atg-7,　and　LC3B-II　and　up-regulated　of　p62　levels.　Blockage　of　autophagy　enhanced　Tat-induced　HIV-1　transactivation　in　TZM-bl　cells.　Moreover,　we　found　that　Tat　activated　the　Akt/mTOR　and　inhibited　AMPK　signaling　pathway　that　was　related　to　its　up-regulation　of　PKM2　expression.　In　addition,　we　showed　that　PI3K/AKT　activation　and　AMPK　inhibtion　was　required　for　the　PKM2-mediated　inhibition　of　autophagy　in　Tat-treated　TZM-bl　cells.　In　conclusion,　our　data　reveals　that　PKM2-mediated　autophagy　inhibition　is　required　for　Tat-mediated　HIV-1　transactivation.　Metabolism-related　autophagic　pathway　may　act　as　a　promising　diagnostic　and　therapeutic　tool　for　HIV-1　infection　in　the　future.　(C)　2017　Elsevier　Inc.　All　rights　reserved.