New therapeutic approaches to the alphaHerpes virus infections.

The character of diseases caused by alphaHerpes viruses has changed over the last decade. The severity of disease and the frequency of Acyclovir / Aciclovir resistance has increased with the increase in the number of immunocompromised patients. Compounding the trend towards more virulent herpes disease is the current emphasis towards outpatient management of many diseases. Much of the current antiviral research focuses on providing drugs with (i) improved oral bioavailability and pharmacokinetics which permit less frequent oral or topical dosing for suppressive treatment of herpes simplex virus (HSV) infections, (ii) different mechanisms of action for synergic effects in treating resistant HSV infections in the immunocompromised host and (iii) improved efficacy. Future antiviral agents will probably target enzymes or viral factors essential for infection or will inhibit other steps in the viral infection cycle, such as viral entry, protein synthesis or capsid assembly. Medications that augment the immune response constitute another pathway for combating herpes viral infections. Many of the newer experimental agents target essential processes unique to Herpes virus replication and, therefore, potentially have high selectivity.

Comparison of effects of Famciclovir ( Famvir ) and valAcyclovir / Aciclovir on pathogenesis of herpes simplex virus type 2 in a murine infection model.

The effects of Famciclovir ( Famvir ) (FCV) and valAcyclovir / Aciclovir (VACV) were compared in a cutaneous infection model for herpes simplex virus type 2 (HSV-2). The compounds were administered orally from day 1 to day 5 postinfection. Both compounds reduced local inflammation and virus replication in the skin. FCV markedly reduced mortality and virus replication in the nervous system. On the cessation of therapy after 5 days, when the levels of infectious virus in the tissues were reduced to below the level of detection, there followed a rebound of virus replication in the ganglia and brain stems of mice that had been treated with VACV. The recurrence of infection in the brain stem occurred on three separate occasions. No such recurrences were observed following FCV treatment. When ganglia were explanted from survivors 6 weeks later, latent virus was shown to be reactivated in all 10 of 10 control, untreated mice. The number of mice whose ganglia yielded virus was reduced to 60% in mice that had been treated with VACV, whereas no mice that had been treated with FCV had evidence of latent infection by this test.

Detection of ganciclovir resistance after Valacyclovir ( Valtrex )-prophylaxis in renal transplant recipients with active cytomegalovirus infection.

Whether valAcyclovir / Aciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received Valacyclovir ( Valtrex ) prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.

ValAcyclovir / Aciclovir for chronic hepatitis B virus infection after lung transplantation.

We report on a chronic asymptomatic hepatitis B surface antigen (HBsAg) carrier who developed an increase in aminotransferase and HBsAg levels 1 year after lung transplantation. During treatment for cutaneous herpes simplex virus (HSV) infection with oral valAcyclovir / Aciclovir there was a marked decrease in replicating hepatitis B virus (HBV)-DNA and aminotransferase levels, which was sustained for 9 months by continuing low-dose valAcyclovir / Aciclovir. A second rise in aminotransferase levels again responded to a valAcyclovir / Aciclovir dose increase and the HBV-DNA levels declined further. Although we cannot exclude a spontaneous variation of the serologic parameters, our observation suggests that valAcyclovir / Aciclovir may represent a valuable therapeutic option in the treatment of chronic hepatitis B after lung transplantation.