Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro

Thalidomide is currently being evaluated for efficacy in alleviating some manifestations of HIV-I infection, To determine whether thalidomide has any direct effects on HIV-1 infection, we investigated the effect of thalidomide and also of three structural analogs of thalidomide on HIV-1 replication in vitro in human monocyte-derived macrophages, The thalidomide analogs were previously shown to inhibit TNF-alpha production in vitro at much lower concentrations than thalidomide. In HIV-l-infected macrophages treated with thalidomide or thalidomide analogs, viral replication was reduced by 60 to 80% as determined by measuring viral RT activity in the culture supernatants. In all experiments the analogs inhibited HIV-1 replication more efficiently than did thalidomide, The drugs also reduced HIV-1 gag mRNA expression. Furthermore, the drugs caused a decrease in NF-kappa B-binding activity in nuclear extracts of HIV-l-infected macrophages. The role of NF-kappa B in the drug-induced inhibition of HIV-1 replication was confirmed using an NF-kappa B-defective mutant virus to infect macrophages.