University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In neonates diagnosed with herpes simplex virus (HSV) infection, does treatment with oral acyclovir as suppressive therapy, as compared to no suppressive therapy, prevent HSV recurrence?

Clinical Bottom Lines

1. Administration of oral acyclovir can prevent cutaneous recurrence of HSV in neonates after cutaneous (skin, eyes, mouth) disease.
2. The effects of HSV recurrences on neurological outcome are the subject of ongoing research.
3. Prescribing oral acyclovir suppression therapy is not without risk of side effects (e.g. transient neutropenia).
4. More investigation is necessary before oral acyclovir suppressive therapy is used routinely.

Summary of Key Evidence

1. This was a phase I/II clinical trial examining the safety and toxicity, efficacy, and pharmacokinetics of oral acyclovir.¹
2. Study enrolled 26 infants less than one month of age with virologically confirmed HSV-2 infection of the skin, eyes, or mouth. Inclusion criteria included gestational age greater than 34 weeks, birth weight greater than 2000g, and normal CSF and neuroimaging at initiation and completion of IV acyclovir.
3. 18 infants in the efficacy portion of the study received 10 days of IV acyclovir following by 6 months of oral acyclovir as suppressive therapy. 16 patients received 300mg/m2 divided TID while 2 received 300mg/m2 divided BID.
4. 13 of 16 infants receiving TID dosing had no recurrences of HSV while both infants receiving BID dosing experienced recurrences. Caregivers of 2 of the 3 infants experiencing recurrences on TID dosing reported poor compliance with the suppressive therapy in follow-up interviews.
5. 12 of 26 infants in the clinical trial developed transient neutropenia with ANC<1000cells/mm3 on at least one evaluation during the six months of oral acyclovir.

Additional Comments

• A previous Collaborative Antiviral Study group found only 54% of infants have no cutaneous recurrences in the six months after resolution of cutaneous disease if untreated with suppressive therap.²
• A 2006 case study reports the development of HSV encephalitis in a 3-month-old female on oral acyclovir suppressive therapy. The study warns against masking CNS disease with suppressive therapy.³
• Phase III clinical trials examining the use of oral acyclovir suppressive therapy in infants with cutaneous and CNS disease have been ongoing since 1997.³
  

Citation

1. Kimberlin D, Powell D, Gruber W, et al. Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial. Pediatr Infect Dis J. 1996; 15:247-54.
2. Whitley RJ, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. N Eng J Med. 1991;324:444-9.
3. Fonseca-Aten M. Messina AF, Jafri HS, Sanchez PJ. Herpes simplex virus encephalitis during suppressive therapy with acyclovir in a premature infant. Pediatrics. 2005; 115:804-9.

CAT Author: Kerri Randall, MD

CAT Appraisers: John Frohna, MD

Date appraised: October 25, 2006