Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy.

Aciclovir (acyclovir) is a nucleoside analogue with antiviral activity in vitro against the herpes simplex viruses (HSV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6). Topical, oral or intravenous aciclovir is well established in the treatment of ophthalmic, mucocutaneous and other HSV infections, with intravenous aciclovir the accepted treatment of choice in herpes simplex encephalitis. The efficacy of aciclovir is increased with early (preferably during the prodromal period) initiation of treatment but, despite significant clinical benefit, viral latency is not eradicated, and pretreatment frequencies of recurrence usually continue after episodic acute treatment is completed. Intravenous administration has also shown benefit in the treatment of severe complications of HSV infection in pregnancy, and neonatal HSV infections. Recurrence of HSV has been completely prevented or significantly reduced during suppressive therapy with oral aciclovir in immunocompetent patients. Use of oral aciclovir is effective but controversial in the treatment of otherwise healthy individuals with varicella (chickenpox), and in some countries it has been recommended for use only in cases which may be potentially severe. The development of rash and pain associated with herpes zoster (shingles) is attenuated with oral or intravenous aciclovir therapy, ocular involvement is prevented, and post-herpetic neuralgia appears to be decreased. Similarly, in a few patients with zoster ophthalmicus, oral aciclovir has reduced the frequency and severity of long term ocular complications and post-herpetic neuralgia, and herpes zoster oticus is improved with intravenous aciclovir. Oral aciclovir has prevented recurrence of HSV genital or orofacial infections during suppressive therapy in > 70% of immunocompetent patients in most clinical trials. Suppression of latent HSV, VZV and CMV infections has been achieved in many immunocompromised patients receiving the oral or intravenous formulations. Aciclovir also appears to offer partial protection from invasive CMV disease in CMV-seropositive bone marrow transplant recipients. The few comparative trials published have shown aciclovir to be at least as effective as other investigated antivirals in the treatment of HSV infections in immunocompetent patients, and more effective than inosine pranobex in the prophylaxis of genital herpes. Similarly, in isolated clinical trials, oral aciclovir appears as effective as topical idoxuridine and oral brivudine in some parameters in immunocompetent patients with VZV infections, and the intravenous formulation appears at least as effective as oral brivudine and intravenous vidarabine in treating these infections in immunocompromised patients.(ABSTRACT TRUNCATED AT 400 WORDS)