EFFECT OF THE SYNTHETIC IMMUNOMODULATOR ADAMANTYLAMIDE DIPEPTIDE ON REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS ALONE AND IN COMBINATION WITH AZIDOTHYMIDINE

Adamantylamide dipeptide (AdDP) is a novel immunomodulator combining, in a single molecule, antiviral 1-aminoadamantane and the essential mo iety of the adjuvant-active muramyl dipeptide L-alanyl-D-isoglutamine. The effect of AdDP, alone and in combination with sub-optimal doses o f the specific antiretroviral drug azidothymidine (AZT), to modulate H IV-1 infection in vitro was investigated. Cultures of lymphocytic KE37 /1 cells infected with HIV and treated with AdDP or AZT inhibited the production of various HIV antigens by 78% and 68% respectively on day 7 after infection, as reflected by sensitive antigen capture ELISAs. P ersistently HIV-infected KE37/1 cells cocultured with uninfected cells treated with AdDP or AZT resulted in 37% and 56% inhibition respectiv ely of p24 antigen production on day 3. Anti-HIV inhibition decreased to 11% by day 6 in cultures containing AZT-pretreated cells, but remai ned stable at 38% in the presence of AdDP-pretreated cells. Inactive a mounts of AdDP and AZT in the lymphocytic Hg cell-line exhibited a sig nificant synergistic effect of 60% reduction of HIV antigen production when both agents were used in combination. Treatment of monocytoid U9 37 cells with an inactive dose of AdDP and a dose of AZT capable of in ducing a 60% reduction further increased the inhibition of HIV p24 ant igen production to 92%. These results make AdDP a worthy candidate war ranting further investigation.