Small molecule inhibitor of HIV-1 nuclear import suppresses HIV-1 replication in human lymphoid tissue ex vivo: a potential addition to current anti-HIV drug repertoire

Despite recent progress in anti-HIV therapy, which has to do mainly with in troduction of protease inhibitors into clinical practice, drug toxicity and emergence of drug-resistant isolates during the long-term treatment of the patients necessitates search for new drugs that can be added to currently used components of a multi-drug cocktail in highly active anti-retroviral t herapy (HAART). Recently, we described a class of arylene bis(methylketone) compounds that inhibit nuclear import of HIV-1 pre-integration complexes a nd suppress viral replication in macrophages and PBMC in vitro. In this rep ort, we demonstrate that one of these compounds, CNI-H1194, inhibited HIV-1 replication in primary lymphoid tissue ex vivo. The compound did not antag onize the activity of currently used anti-HIV drugs that inhibit viral reve rse transcriptase or protease. These results suggest that arylene bis(methy lketone) compounds might be a valuable addition to HAART. (C) 2000 Elsevier Science B.V. All rights reserved.