A total of 100 herpes simplex viruses isolated from lesions not responding to acyclovir (ACV) therapy were recovered from 51 patients infected with human immunodeficiency virus. In vitro analysis of these isolates included testing their susceptibility to ACV and determining their thymidine kinase (TK) phenotypes. Of the 100 isolates evaluated, 23 were ACV sensitive and 77 were ACV resistant. Seventy-four of these ACV-resistant isolates were of the TK-deficient or low-TK-producer phenotype and three were of the TK-altered phenotype. The TKs of isolates that represented each of the different autoradiographic phenotypes were further characterized by enzyme kinetics. The ability of selected isolates to cause disease in vivo was evaluated-by using several mouse virulence models. Cutaneous virulence in normal and immunocompromised mice was evaluated, and neurovirulence in normal mice was determined. Latent infections were assayed by the cocultivation of trigeminal ganglia recovered from mice that had survived acute infection. These reactivated viruses were evaluated in vitro and compared with the original infecting isolate. The mechanisms of resistance and pathogenicity of these herpes simplex virus isolates recovered from patients positive for human immunodeficiency virus are similar to those reported for isolates recovered from normal and immunocompromised patients without AIDS.
The sensitivity to acyclovir of more than 800 herpes simplex virus (HSV) isolates from over 300 patients were tested by the dye-uptake method. While a broad spectrum of sensitivity was found, approximately 90% of the isolates were inhibited by less than 1 mg/l of acyclovir. Therapy usually did not significantly alter the sensitivity of HSV isolates except in a few severely immunocompromised patients in whom resistant viruses produced asymptomatic or indolent infections. The sensitivity of viruses isolated during subsequent recurrences was similar to that of the originally infecting virus, regardless of therapy. The requirement of convenient and standardized methods of virus sensitivity testing is emphasized so that additional data can be accumulated to allow more precise correlations between in-vitro virus sensitivity and clinical response to acyclovir therapy.
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