Two　kinds　of　chitosan-stavudine　(d4T)　conjugates,　chitosan-O-isopropyl-5＇-O-d4T　monophosphate　conjugate　(Cs-P-d4T)　with　a　phosphoramide　linkage　and　chitosan-5＇-O-succinyl-d4T　conjugate　(Cs-S-d4T)　with　a　succinic　spacer,　were　synthesized　using　an　Atherton-Todd　reaction　and　carbodiimide　coupling　reaction,　respectively,　and　then　structurally　characterized.　Their　in　vitro　drug　release　behaviors　and　anti-human　immunodeficiency　virus　(HIV)　activity　were　investigated　and　compared.　Both　of　the　chitosan-d4T　conjugates　more　strongly　prefer　to　release　corresponding　d4T　derivatives　rather　than　free　d4T　in　a　prolonged　manner　but　have　different　hydrolysis　routes.　The　anti-HIV　activity　and　cytotoxicity　evaluated　in　the　MT4　cell　line　revealed　that　the　anti-HIV　selectivity　index　was　in　the　following　order:　Cs-P-d4T　＞　d4T　＞＞　Cs-S-d4T　since　the　released　d4T-5＇-(O-isopropyl)　monophosphate　from　Cs-P-d4T　can　bypass　the　rate-limiting　bottleneck　of　nucleoside　phosphorylation,　while　the　released　5＇-O-succinyl-d4T　from　Cs-S-d4T　has　to　be　hydrolyzed　to　d4T　and　then　successively　phosphorylated　to　its　active　form　to　exert　antiviral　activity.　The　results　suggested　that　constructing　a　chitosan-nucleoside　reverse　transcriptase　inhibitor　(NRTI)　conjugate　with　a　phosphoramide　linkage　may　be　an　efficient　approach　for　improving　NRTI　therapy　efficacy　in　antiretroviral　treatment.