Sir,- Adenine arabinoside, its monophosphate ester, and human leucocyte interferon are the only antiviral agents that have been shown to inhibit hepatitis B viral (HBV) replication in vivo Acyclovir (acycloguanosine) inhibits herpes simplex virus in vitro and in vivo, its action being dependent on phosphorylation by a virus-coded thymidene kinase. Varicella zoster virus has a similar enzyme but is less sinsitive to acyclovir. In vitro studies have also shown some activity against cytomegalovirus and Epstein-Barr virus but at much higher drug concentrations. There is no satisfactory in vitro model for studying HBV infection.
Four HBsAg, DNA polymerase (DNAp), and HBeAg positive males aged 21-36 with chronic liver disease were given acyclovir 5, 7.5, or 10 mg/kg as an i.v. bolus or 15 mg i.v. as an infusion in 200 ml dextrose/saline over 1 h, 8-hourly for 5-7 days. There was no decrease in HBV-DNAp in the two patients treated with 5 and 7-5 mg/kg doses. In contrast, the 10 mg/kg and 15 mg/kg doses produced a decrease in HBV-DNAp and serum HBV-DNA (measured by molecular hybridisation with P-cloned HBV-DNA), most marked with the higher dose. A transient increase in urea and creatinine was seen in case 3 treated with 10 mg/kg 8-hourly as an i.v. bolus whereas no effect was seen in case 4 treated with 15 mg/kg-8 hourly as an i.v. infusion over 1 h. A more detailed description of the patients, methods, complications of therapy, and antiviral activity related toplasma levels of acyclovir will be reported elsewhere.
The decrease in HBV-DNAp and HBV-DNA in the patients treated with 10 or 15 mg/kg 8 hourly suggests that acyclovir inhibits the production of complete virus particles. As far as is known, HBV does not induce specific thymidine kinase activity in the infected cell so that the action of the drug in this infection is currently unknown. More prolonged inhibition of HBV replication with HBeAg to anti-HBe seroconversion and permanent loss of DNAp is seen with longer courses of antiviral therapy. Animal work suggests that renal impairment may be caused by a transient crystal nephropathy which occurs when the concentration of acyclovir in the collecting duct esceeds the drug solubility, and a review of patients suggest that this is more common following i.v. bolus injection than i.v. infusion. Further study with acyclovir at 15 mg/kg 8 hourly given as an i.v. infusion for longer periods is warranted.