Acyclovir susceptibilities of herpes simplex virus strains isolated from solid organ transplant recipients after acyclovir or ganciclovir prophylaxis

Abstract

We determined the acyclovir (ACV) susceptibilities of herpes simplex virus (HSV) isolates (n = 18) recovered from solid organ transplant patients after antiviral prophylaxis with ACV or ganciclovir. All isolates tested were susceptible to ACV (50%Yo inhibitory concentration, <1 FLM). A clinical review of patients with HSV disease showed that all improved with specific anti-HSV therapy, and no recurrences were reported.Recurrent infections with herpes simplex virus (HSV) are a major cause of morbidity in patients with bone marrow transplants (BMTs), solid organ transplants (SOTs), and AIDS (7,8,15,20). Acyclovir (ACV), an acyclic guanosine derivative with excellent in vitro and in vivo activities against HSV, has been shown to reduce the risk of HSV infections and HSV-related diseases in BMT and renal transplant recipients (13,16,18,20). In these studies, the administration of ACV (intravenously [i.v.] or orally) for 3 to 12 weeks posttransplantation significantly reduced the incidence of HSV infections from 50 to 80% to less than 10%. Despite its poor in vitro activity against cytomegalovirus (CMV), ACV has been successfully used to prevent CMV infection in kidney transplant and BMT recipients (2, 12). A potential risk associated with the prolonged use of ACV is the emergence of resistant HSV strains; resistant isolates are increasingly being found in persons with AIDS and less commonly in other immunocompromised patients (3,10,14,15). Such infections could lead to progressive disease and death (7,10,15). The effect that prolonged exposure to ACV could have in selecting resistant HSV isolates in patients with a lesser degree of immunosuppression (such as transplant recipients) is not well defined. Although a few studies have examined HSV susceptibilities in BMT patients receiving ACV prophylaxis (5, 17), systematic monitoring of ACV susceptibilities has not been done in SOT patients who excrete HSV during or after antiviral prophylaxis. In a large prophylactic trial of ACV for CMV infection conducted at our institution, 2 (3.8%) of 53 kidney transplant recipients randomized to receive ACV developed mucocutaneous HSV infections (2), but the ACV susceptibilities of those HSV isolates were not determined. In the present study, we analyzed the susceptibilities to ACV of HSV isolates from SOT patients with active HSV infections after prophylaxis with ACV or ganciclovir (GCV).(This study was presented in part at the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, Calif., 10 to 14 October 1992.)Frozen HSV isolates recovered from SOT patients who had received CMV prophylaxis with ACV or GCV at our institution were used in the ACV susceptibility studies. * Corresponding author.Initial viral cultures were performed only for isolates from patients with lesions suggestive of HSV infection or at the physician's request. ACV susceptibilities were determined by using a commercially available DNA-DNA hybridization assay (HSV Antiviral Susceptibility Test Kit; Diagnostic Hybrids Inc., Athens, Ohi...

Efficient gene delivery and selective transduction of astrocytes in the mammalian brain using viral vectors

“…Thymidine kinase is a phosphotransferase enzyme that incorporates dGTP analogs in the presence of ganciclovir instead of cellular dGTP and leads to the blockade of cellular replication (Boivin et al, 1993). But the low transduction efficiency neither improved tumor progression nor the overall survival time (Ram et al, 1993 1994; Gunzburg et al, 1995).…”

Infections in solid-organ transplant recipients

“…Acyclovir resistance may arise from mutations in the genes for thymidine kinase or DNA polymerase (453). Acyclovir-resistant isolates have been associated with progressive and severe disease in immunocompromised patients, particularly those with AIDS, and it is possible that resistance will become a problem for transplant recipients in years ahead (187), although this has not occurred to date (61).…”

"The end of innocence" revisited: resistance of herpesviruses to antiviral drugs.

“…Ljungman et al (84) described three bone marrow transplant patients who developed severe pneumonia due to ACV-resistant HSV that emerged during the course of ACV treatment. By contrast, Boivin et al (12) recently showed that, for solid organ transplant patients, prophylaxis with ACV or GCV did not result in emergence of ACV-resistant HSV variants and that HSVrelated disease in these patients responded to antiviral therapy without subsequent recurrences. These authors suggest that the relatively lower degree of immunosuppression in these patients compared with AIDS and bone marrow transplant patients, and the relatively high-dose ACV regimen used in prophylaxis, may explain the lack of resistance development.…”