Aims:　Tat　protein　plays　a　pivotal　role　in　both　the　human　immunodeficiency　virus　type　1　(HIV-1)　replication　cycle　and　the　pathogenesis　of　HIV-1　infection.　Sirtuins　1　(SIRT1)　is　a　possible　candidate　for　redox　modulation　because　its　activity　is　regulated　by　nicotinamide　adenine　dinucleotide　(NAD(+))　or　NAD(+)/NADH　ratio.　The　aim　of　the　present　study　was　to　determine　whether　the　redox　status　and　SIRT1　expression　are　related　to　HIV-1　Tat　protein-induced　transactivation.　Main　methods:　HeLa-CD4-long　terminal　repeat　(LTR)-beta-gal　(MAGI)　cells　were　transfected　with　Tat　plasmid.　Tat-induced　HIV-1　LTR　transactivation　was　determined　by　MAGI　cell　assay.　The　NAD(+)　or　NADH　levels　and　SIRT1　activity　were　measured.　In　addition,　the　protein　expression　of　SIRT1　was　assayed　by　western　blotting.　Key　findings:　Pretreatment　with　resveratrol　increased　intracellular　NAD(+)　levels　and　SIRT1　protein　expression　after　Tat　plasmid　transfection　in　a　concentration-dependent　manner.　Pretreatment　with　resveratrol　attenuated　Tat-induced　HIV-1　transactivation　in　MAGI　cells.　These　effects　of　resveratrol　were　largely　abolished　by　knockdown　of　SIRT1　by　short　interfering　RNA　(siRNA).　Pretreatment　with　nicotinamide,　a　SIRT1　inhibitor,　potentiated　Tat-induced　HiV-1　transactivation　in　MAGI　cells,　and　overexpression　of　SIRT1　attenuated　Tat-induced　HIV-1　transcription　in　MAGI　cells.　Significance:　Inhibition　of　SIRT1　activity　by　Tat　is　considered　a　critical　step　of　Tat　transactivation.　Resveratrol　and　related　compounds　represent　potential　candidates　for　novel　anti-HIV　therapeutics.　(C)　2009　Elsevier　Inc.　All　rights　reserved.