Valaciclovir - A review of its long term utility in the management of genital herpes simplex virus and cytomegalovirus infections

Valaciclovir is an aciclovir prodrug used to treat infections caused by her pes simplex virus (HSV) and varicella tester virus, and for prophylaxis aga inst cytomegalovirus (CMV), Oral valaciclovir provides significantly better oral bio availability than oral aciclovir itself, contributing to the need for less frequent administration. Several studies have demonstrated the efficacy of long term (> 90 days) the rapy with valaciclovir for the suppression of genital HSV disease in otherw ise healthy individuals with HSV infection. In 1 randomised, double-blind t rial, once daily valaciclovir (1000mg, 500mg and 250mg) produced statistica lly significant suppression of disease recurrence, as did twice daily valac iclovir 250mg and aciclovir 400mg. Valaciclovir dosages of greater than or equal to 500mg daily are recommended for suppression of genital herpes recu rrences in immunocompetent individuals. This disease occurs frequently in p atients with human immunodeficiency virus (HIV) infection and, in a single randomised double-blind trial, prophylactic valaciclovir (1000mg once daily or 500mg twice daily) and aciclovir (400mg twice daily) were found to be o f similar efficacy in the suppression of genital herpes, However, a higher than expected dropout rate indicated that more studies of valaciclovir in p atients with HIV are required. In a randomised trial of patients undergoing renal transplant, valaciclovir 2g 4 times daily for 90 days significantly reduced the incidence and delay ed the onset of CMV disease: the incidence in valaciclovir-treated patients who were CMV-seronegative at baseline, and recieived a kidney from a CMV-s eropositive donor, was 3% versus 45% for placebo after 90 days of treatment . Acute graft rejection was also reduced in the valaciclovir-treated group. A small study in heart transplant patients compared valaciclovir (2g 4 tim es daily) with aciclovir (200mg 4 times daily) and found a significant redu ction in CMV antigenaemia favouring valacilovir at the end of the treatment period. Additional reductions in other indices of CMV in those given valac iclovir compared with aciclovir were also noted. In a preliminary study of prophylaxis for CMV disease in bone marrow transplant recipients valaciclov ir (2g 4 times daily) was superior to aciclovir (800mg 4 times daily) in te rms of time to CMV viraemia or viruria, Although valaciclovir (8 g/day for approximate to 30 weeks) reduced the incidence and time to CMV disease comp ared with aciclovir (3.2 g/day) in patients with advanced HIV disease, vala ciclovir was associated with more gastrointestinal complaints and an increa sed risk of death, leading to premature termination of the study. As yet, no trials comparing the efficacy of valaciclovir with famciclovir ( the oral prodrug for penciclovir) in the suppression of recurrent episodes of genital herpes have been published, nor have direct comparisons been mad e between valaciclovir with ganciclovir in patients with CMV disease. Valaciclovir is well tolerated at dosages used to suppress recurrent episod es of genital herpes (500 to 1000 mg/day) in immunocompetent and HIV seropo sitive individuals, with headache being reported most often. However, a pot entially fatal thrombotic microangiopathy (TMA)-like syndrome has been repo rted in some immunocompromised patients receiving high-dose prophylactic va laciclovir therapy (8 g/day) for CMV disease for prolonged periods, and the risk of this syndrome appears to be higher in patients with advanced HIV d isease. While the clinical benefits of valaciclovir in some immunocompromis ed patients may outweigh the risk of TMA, close monitoring for symptoms of TMA is indicated in all immunocompromised patients receiving high-dose vala ciclovir. Conclusion: Oral valaciclovir is an effective drug for the suppression of r ecurrent episodes of genital herpes in immunocompetent and immunocompromise d individuals. It is as effective as oral aciclovir and has a similar toler ability profile, but in the recommended dosage requires less frequent admin istration in imnmunocompetent patients which may improve compliance in this group. Whether the possible compliance advantage will result in valaciclov ir replacing aciclovir for this indication probably depends on pharmacoecon omic factors. In patients who have undergone renal transplantation, valacic lovir has demonstrated efficacy as prophylactic therapy for CMV infection a nd disease. There is also preliminary evidence supporting the use of valaci clovir to prevent CMV disease in heart and bone marrow transplant recipient s. Valaciclovir is likely to become a valuable component of therapy in the management of renal transplant recipients. Further studies are required to establish the value of valaciclovir in the prevention of CMV disease in oth er transplant settings and in patients with HIV disease, and its efficacy r elative to therapies other than aciclovir in these indications.