Acyclovir-resistant herpes simplex virus type 1 in intra-ocular fluid samples of herpetic uveitis patients

BACKGROUND: Acyclovir (ACV) is the antiviral drug of choice to treat patients with herpes simplex virus type 1 (HSV-1) uveitis. The prevalence of intra-ocular ACV-resistant (ACV(R)) HSV-1 in herpetic uveitis is unknown and may have clinical consequences. In addition to its predictive value on ACV susceptibility, the polymorphic HSV-1 thymidine kinase (TK) gene facilitates differentiation between HSV-1 strains.

OBJECTIVES: The objective of this study was to determine the genetic composition and ACV susceptibility of the causative virus in intra-ocular fluid samples (IOF) of HSV-1 uveitis patients.

STUDY DESIGN: The intra-ocular HSV-1 pool from 11 HSV-1 uveitis patients was determined by sequencing IOF-derived viral TK genes. The ACV susceptibility profile of the cloned intra-ocular TK variants was defined by mass spectrometry. In addition, the ganciclovir (GCV) susceptibility of the ACV(R) HSV-1 TK variants was defined.

RESULTS: Intra-ocular fluid samples of HSV-1 uveitis patients contain HSV-1 quasispecies, principally consisting of one major and multiple genetically related minor patient-specific TK variants. Four of 10 patients analyzed had an intra-ocular ACV(R) HSV-1 of which 3 were cross-resistant to GCV. The ACV(R) profile of intra-ocular HSV-1 did not correlate with symptomatic ACV treatment.

CONCLUSIONS: Affected eyes of HSV-1 uveitis patients are commonly infected with a patient-specific HSV-1 quasispecies, including one major and multiple genetically related minor variants. A relatively high prevalence of intra-ocular ACV(R) HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients.