Thalidomide and Thalidomide Analogs Reduce HIV Type 1 Replication in Human Macrophages in Vitro

Abstract

Thalidomide is currently being evaluated for efficacy in alleviating some manifestations of HIV-1 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-α production in vitro at much lower concentrations than thalidomide. In HIV-1-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-κB-binding activity in nuclear extracts of HIV-1-infected macrophages. The role of NF-κB in the drug-induced inhibition of HIV-1 replication was confirmed using an NF-κB-defective mutant virus to infect macrophages.