Activities of masked 2 ',3 '-dideoxynucleoside monophosphate derivatives against human immunodeficiency virus in resting macrophages

The anti-human immunodeficiency virus (HIV) activity of aryloxyphosphoramid ate protides of a number of anti-HIV nucleoside analogues was assessed in r esting primary monocyte-macrophages (MIM). While 2',3'-dideoxythymidine (d4 T), 2',3'-dideoxyadenosine (ddA), and 2',3'-dideoxy-2',3'-didehydroadenosin e (d4A) protides showed an anti-HIV activity that was 25- to 625-fold great er than the parent nucleotides d4T, ddA, and d4A, respectively, other arylo xyphosphoramidate protides showed similar or even lower anti-HIV activities than their parent compounds. This variable anti-HIV effect is most likely related to the different dynamics of intracellular nucleoside monophosphate release from the protides. Our results indicate the potential advantage of therapeutic use of this approach for some nucleotide analogues to affect H IV replication in M/M, one of the major reservoirs of HIV in vivo.