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We determined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activities of various dideoxy-nucleoside analogs by using phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBMs) and resting PBMs (R-PBMs) as target cells. The comparative order of anti-HIV-1 activity in PHA-PBMs was azidothymidine (AZT) &gt; dideoxycytidine (ddC) &gt; dideoxythymidinene (d4T) &gt; dideoxyinosine (ddI) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) &gt; 2'-beta-fluoro-dideoxyadenosine (F-ara-ddA), while that in R-PBMs was ddC &gt; ddI, PMEA, and F-ara-ddA, &gt;&gt; AZT and d4T. A pronucleotide, bis-(S-acetylthioethanol)phosphotriester-ddAMP, which bypasses the anabolic monophosphorylation step for the intracellular delivery of ddAMP, was highly active both in PHA-PBMs and R-PBMs. These data may have basic and clinical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy with dideoxynucleosides, and in the development of active pronucleotides.

antimicrobial agents and chemotherapy

Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells