Current recommendations for the treatment of genital herpes

Abstract

The incidence of genital herpes continues to increase in epidemic-like fashion. Aciclovir (acyclovir) has been the original gold standard of therapy. The recent addition of famciclovir and valaciclovir as antiherpes drugs has improved convenience as well as the efficacy of treatment. Although aciclovir remains a widely prescribed and reliable drug, its administration schedule falls short of the ease of usage that the newer nucleoside analogues offer, for both episodic and suppressive therapy. Suppression of symptomatic disease and asymptomatic shedding from the genitalia have both become popular approaches, if not the primary targets of antiviral therapy. Knowing that asymptomatic disease leads to most cases of transmission strongly suggests that suppression with antiviral agents could reduce transmission risk in discordant couples. Unfortunately, the role for antivirals in reducing transmission remains to be proven in clinical trials. Neonatal herpes is now successfully treated using aciclovir. Current randomised clinical trials are examining aciclovir and valaciclovir administration, as well as safety and efficacy for post-acute suppressive therapy. Prevention of recurrences in pregnancy is also a topic under investigation, with a view to reducing the medical need for Cesarean section, or alternatively (and far less likely to be accomplished) to protect the neonate. Although resistance is largely limited to the immunocompromised and a change in resistance patterns is not expected, several drugs are available for the treatment of aciclovir-resistant strains of herpes simplex. Foscarnet is the main alternative with proven efficacy in this setting. Unfortunately, administration of foscarnet requires intravenous therapy, although a single anecdote of topical foscarnet efficacy in this setting has been published. Alternatives include cidofovir gel, which is not commercially available but can be formulated locally from the intravenous preparation. Less effective alternatives include trifluridine and interferon. Future possibilities for treatment of genital herpes include a microparticle-based controlled-release formulation of aciclovir and resiquimod (VML-600; R-848). The search for an effective therapeutic vaccine for genital herpes has not been successful to date, although a live virus glycoprotein H-deficient (DISC) vaccine is currently in clinical trials. Recent data suggest that seronegative women are protected (albeit, not fully) by a glycoprotein D recombinant vaccine with adjuvant. Despite the established safety and convenience of current treatment options, better suppressive options and topical treatment options are much needed. Studies using existing agents as potential tools to avoid Cesarean section, or transmission to neonate or partner are ongoing. Both vaccines and antivirals may eventually play a role in prevention of infection.