Immunomodulation as a treatment strategy for genital herpes: review of the evidence.

In this review, we discuss the ongoing development of a new treatment option for genital herpes (GH), the disease caused by herpes simplex virus (HSV) types I and II. Following infection, the virus establishes a latent infection in peripheral neurons, which periodically activates to cause recurrent skin lesions or asymptomatic shedding in the anogenital area. A new class of drugs, the immune response modifiers (IRMs), modulates the immune system against viral infection. This approach is currently being tested as a treatment for GH. We first review the effectiveness of treatment of other viral diseases with imiquimod, the first IRM to be licensed (Aldara, imiquimod 5% cream), and one used for the treatment of external anogenital warts. We then focus on resiquimod, an analog of imiquimod, which shows early promise as a new treatment option for GH. The evidence from in vitro and in vivo studies, in particular the guinea pig model of GH, describing the effectiveness and mode of action of this novel immunopharmacological agent is presented. Resiquimod stimulates specific cells of the innate immune system (including monocytes/macrophages, dendritic cells (DC) and B lymphocytes) to produce cytokines (in particular IFN-alpha, IL-12, TNF-alpha and IFN-gamma) that initiate and drive the development of the Th1 acquired immune response against HSV-infected cells. Recent results from clinical trials and in vivo studies in animal models are consistent with the hypothesis that the development of HSV-specific cell-mediated immunity may prove to be the key in providing a long-lasting protection against GH recurrences.