Acyclovir (ACV) has been used for more than 15 years in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey was undertaken to assess the level of ACV resistance in the population. More than 2,000 HSV isolates from both immunocompetent and immunocompromised patients in northwest England were collected over a 2-year period and tested for sensitivity to ACV. These studies suggested a prevalence of resistance of approximately 0.1 to 0.6% in immunocompetent individuals, with no apparent difference in prevalence between treated and untreated groups. In line with previous studies, the prevalence of resistance in treated immunocompromised individuals was approximately 6%.
A detailed study was made of herpes simplex virus type 1 (HSV-1) isolates from an immunocompromised patient whose infection became resistant to acyclovir (ACV) during a prolonged course of oral treatment. Three HSV isolates and 33 virus clones derived from them were characterised. The development of clinical resistance correlated with the emergence of thymidine kinase (TK) defective strains. The ACV-sensitive strains studied contained a small proportion of insensitive virus. The resistant isolate contained 0.6% of TK-positive virus which was sensitive to a relatively low concentration of ACV.
Herpes simplex virus strains, isolated from three immunocompromised patients whose infections showed clinical resistance to acyclovir, were studied as treatment progressed. Virus isolated from two patients remained sensitive to acyclovir throughout. Isolates from the third patient, who had received a prolonged course of oral acyclovir, showed a sharp decrease in drug sensitivity which corresponded to loss of thymidine kinase activity. No changes in restriction endonuclease profiles were observed in isolates from the same patient as treatment with acyclovir progressed.
Opportunistic viral infections were investigated in 156 adult patients admitted over one year to a medical oncology service: 35% of the total group and 65% of those with acute leukaemia experienced viral infections, 79% of which were with viruses of the herpes group. Surprisingly few enteric viruses were recovered. Reactivation of herpes simplex virus in the brains of these immunosuppressed patients was suggested by the demonstration by nucleic acid hybridization of herpes simplex virus DNA sequences in neurones and endothelial cells in patients with evidence of past infection with virus. Acyclovir was effective in therapy and prophylaxis. Twenty-three strains from 7 patients were tested for sensitivity to this antiviral: in 3 instances clinical resistance was observed but the strains were fully sensitive in vitro, as were all other strains tested.
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