HIV-1　integrase　(IN)　is　an　important　drug　target　of　current　anti-AIDS　research　and　drug　development.　The　drug　resistance　mutations　(DRMs)　are　the　main　reason　of　integrase　inhibitor　therapy　failure,　but　the　drug　resistance　mechanism　remains　unclear.　We　introduced　mutations　artificially　into　HIV-1　integrase,　tested　the　activity　and　drug　resistance　of　individual　mutations,　and　analyzed　the　integrase　drug　resistance　mechanism　preliminarily.　The　mutations　involved　contain　two　single　mutations,　E92A　and　N155S,　and　a　double　mutation,　E92A/N155S.　These　mutations　were　obtained　using　genetic　engineering　methods,　and　these　recombinant　proteins　were　prepared　after　prokaryotic　expression　and　protein　purification.　The　strand-transfer　activity　of　the　integrases　was　tested　by　a　magnetic　beads　based　ELISA.　S-1360　and　Raltegravir　were　used　for　drug　resistance　testing.　Besides,　molecular　docking　was　performed　to　study　the　complex　of　S-1360　and　HIV-1　integrase　central　catalytic　domain　(including　wild　type　and　mutated　type)　using　Autodock.　The　main　results　are　as　follows:　N155S　mutation　decreases　about　80%　of　the　integrase　strand　transfer　activity,　while　E92A/N155S　only　decreases　about　42%.　It　indicates　that,　the　E92A　mutation　on　the　base　of　N155S　mutation　increased　the　integrase　activity　observably.　Besides,　E92A　and　E92A/N155S　mutations　exhibit　different　drug　resistance　to　different　inhibitors,　and　they　are　more　resistant　to　Raltegravir　than　to　S-1360.　A　mutation　could　cause　structural　change　of　the　integrase　catalytic　center　domain,　and　the　structural　change　eventually　influences　the　activity　and　drug　resistance.　As　to　E92A,　it　may　reduce　the　electrostatic　interaction　to　the　amino　acids　around　it,　and　influences　D64　and　D116　indirectly,　which　are　key　amino　acids　of　catalytic　center　domain.　This　may　give　a　rational　explanation　to　activity　recovery　of　N155S　caused　by　E92A.