ObjectiveTo determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1in vitro.DesignA sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides.MethodsActivity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIbcells. Inhibition of virus adsorption to the host cells was measured by a p24antigen capture enzyme-linked immunosorbent assay.ResultsDS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIBstrain) in MT-4 cells was 0.7μg/ml. The compound was not cytoxic at concentrations ≤ 100 μg/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152.ConclusionDS-4152 has the potential, from thesein vitrostudies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24serum levels and CD4+cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.