HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis

Abstract

Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium stibogluconate is a drug of choice for the treatment of leishmaniasis. Because sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV-1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory-adapted and clinical strains of HIV-1, we report that sodium stibogluconate induces an increase in HIV- transcription and virus replication in primary CD4+ T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor-κB and activator protein 1, as well as the Syk, Jun, and mitogen-activated protein kinase/extracellular signal-related kinase signal-transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV-1-infected patients. © 2006 by the Infectious Diseases Society of America. All rights reserved.