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Michele Reyes, PhD; Nazerah S. Shaik, MPH; Judith M. Graber, MS; Rosane Nisenbaum, PhD; Neal T. Wetherall, PhD; Keiji Fukuda, MD; William C. Reeves, MD; for the Task Force on Herpes Simplex Virus Resistance

Arch Intern Med. 2003;163:76-80.

Background  Genital herpes is epidemic in the United States; long-term acyclovir therapy is common; and long-term use of antimicrobials in suppressive doses favors development of resistance.

Objective  To determine the prevalence of and risk factors for acyclovir-resistant genital herpes.

Methods  We identified and attempted to enroll all patients 18 years or older with suspected genital herpes who attended 22 sexually transmitted disease and human immunodeficiency virus (HIV) clinics in the United States between October 1996 and April 1998. We conducted standardized interviews of all consenting patients. Lesions were cultured, and isolates were typed as herpes simplex virus (HSV) 1 or HSV-2 and tested for acyclovir sensitivity (using a 50% inhibitory concentration of 2 µg/mL) by plaque reduction, which was independently confirmed.

Results  Herpes simplex virus was isolated from 2088 of 3602 patients, and 90.2% of isolates were HSV-2. Fifteen isolates, all HSV-2, were acyclovir resistant. Three (0.18%) of 1644 HIV-negative patients had acyclovir-resistant isolates (95% confidence interval [CI], 0.04%-0.5%); resistance was associated with oral (P<.006) and topical (P<.001) acyclovir use. Twelve (5.3%) of 226 HIV-positive patients yielded resistant HSV isolates (95% CI, 2.8%-9.1%); resistance was associated with oral acyclovir use (P<.001), duration of the current episode (P<.001), history of recurrent genital herpes (P<.01), and low CD4 cell count (P<.05).

Conclusions  In the 15 years following licensure of acyclovir, resistance to the drug remains low among immunocompetent patients. However, 5% of HIV-positive patients had resistant HSV-2 isolates. Continued surveillance is essential to monitor changes in acyclovir resistance and to characterize the clinical and public health importance of acyclovir-resistant HSV.

From the Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Reyes, Shaik, Graber, Nisenbaum, Fukuda, and Reeves); ViroMed Laboratories Inc, Minneapolis, Minn (Dr Wetherall). Dr Wetherall is employed by ViroMed Laboratories, Minneapolis, Minn, which has had contractual arrangements with Glaxo Wellcome unrelated to this study. Dr Davis was an employee of Glaxo Wellcome at the time of this study, and Drs Kern, Corey, Crumpacker, Darby, and Sacks have served as paid consultants to Glaxo Wellcome.

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