Abstract
The frequency and clinical significance of drug-resistant herpes viruses occurring in clinical settings requires thorough investigation. We have studied over 100 HSV isolates from a variety of sources and have found one group, from a 15 month boy with adenosine deaminase deficient type of severe combined immunodeficiency, which was resistant to both ACV and IUDR. During a 6 week hospitalization he received topical ophthalmic, parenteral and oral ACV for treatment of herpetic keratitis and cutaneous lesions involving face, hands and perirectal areas. Early treatment courses resulted in dramatic clinical improvement but later recurrences were characterized by chronic lesions unresponsive to ACV despite serum levels up to 6 mcg/ml. After death from Pseudomonas sepsis and pneumonia, postmortem tissues, although HSV-positive, showed no evidence of viral cytopathic effect. A 100-fold decrease in sensitivity to ACV was noted between early and late isolates. Thymidine kinase activity was normal in sensitive but absent in resistant isolates. Reduced apparent pathogenicity in man was paralleled by a 100-1000-fold decrease of these isolates in their virulence (as determined by PFU/LD50 and PFU/MID50 ratios) in normal, hairless and nude mice by intracerebral and cutaneous innoculation. Cutaneous infection caused by the resistant virus was less severe or produced low-grade, chronic, lesions rather than acutely fatal infections. Antiviral resistance can occur in selected clinical situations but diminished sensitivity may be associated with diminished virulence.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sibrack, C., Gutman, L., Wilfert, C. et al. 1072 ALTERED PATHOGENICITY OF ACYCLOVIR (ACV) RESISTANT HSV FROM AN IMMUNODEFICIENT CHILD. Pediatr Res 15 (Suppl 4), 621 (1981). https://doi.org/10.1203/00006450-198104001-01098
Issue Date:
DOI: https://doi.org/10.1203/00006450-198104001-01098