Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Topical acyclovir is of limited or no benefit to patients with recurrent herpes labialis

ACP J Club. 1991 July-Aug;115:6. doi:10.7326/ACPJC-1991-115-1-006

Source Citation

Worrall G. Topical acyclovir for recurrent herpes labialis in primary care. Can Fam Physician. 1991 Jan;37:92-8.



To determine whether topical acyclovir is effective in the treatment of recurrent herpes labialis.

Data sources

A MEDLINE search was done for English and French language articles published since 1980, and hand searches were done of reference lists from review articles and from major infectious diseases texts.

Study selection

13 original articles and 9 review articles were identified. 6 articles were selected that included nonimmunocompromised patients and in which acyclovir ointment or cream was used in a commercially available formulation.

Data extraction

Each study was reviewed by the author and assessed for validity and generalizability using 9 criteria.

Main results

All 6 trials were randomized and double-blinded, and all tested a 5% ointment or cream applied for 5 to 10 days. The number of patients for whom data were available ranged from 13 to 208; the number of episodes of herpes labialis ranged from 31 to 208. Outcomes evaluated included duration and degree of pain, time to crusting and loss of crust, time to complete healing, size of lesion, and number of aborted lesions. In the 2 largest trials (n = 208 and n = 60 patients) no clinical benefit was found with acyclovir use, although both trials had sufficient power to detect small differences. In 3 other trials, patients were specifically asked to begin applying cream or ointment as soon as possible after the start of symptoms. No clinical benefit was found in 1 of these studies (51 patients). Times from onset of symptoms to crust formation and to complete healing were reduced by 1 to 2 days with acyclovir use in 2 of these studies (n = 49 and n = 13 patients) among compliant patients. Among 30 patients with complete data in 1 other trial, mean duration of vesiculation and days to complete healing were significantly reduced by 0.9 and 2.6 days, respectively, with acyclovir use.


The available evidence suggests that acyclovir in the form of a 5% cream or ointment is of limited or no benefit for patients with recurrent herpes labialis.

Source of funding: Not stated.

Address for article reprint: Dr. G. Worrall, District Medical Officer, Glovertown, Newfoundland A0G 2L0, Canada.


It is estimated that approximately 100 million episodes of recurrent herpes labialis occur annually in the United States. Most cases are caused by herpes simplex virus-1 (HSV-1), but HSV-2 may also have a causal role; HSV-2 has only rarely been isolated from recurrent lesions. The nucleoside analog, acyclovir, selectively inhibits viral replication and is marketed in topical, oral, and intravenous formulations, having successively increasing efficacies.

This review by Worrall was generally well done. It did not, however, provide assurance that study selection and the extraction of data were reproducible and free from bias. The same commercially available 5% topical medication was used in each study, and it appears that most patients had established lesions at the time treatment was started. In these patients no benefit was observed. If topical acyclovir is to be of use in the treatment of herpes labialis, early application in the prodromal phase and frequent, regular use will likely be the only circumstance for a beneficial response. Unfortunately, the results of this overview do not answer the question of efficacy of treatment at this early stage. Although in 3 studies statistically significant differences in outcomes (time to crust formation, duration of vesiculation, and time to complete healing) were reported, these differences were probably clinically unimportant.

Although patients who present with an episode of recurrent herpes labialis recognize that the infection is minor, treatment is often requested. Physicians may prescribe topical acyclovir, acknowledging that the infection is not serious enough to warrant oral acyclovir. On the basis of evidence summarized in this review, however, physicians can be confident that in most circumstances specific treatment is unnecessary—and that topical acyclovir does not provide important clinical benefits.

J. C. Niederman, MD
Yale UniversityNew Haven, Connecticut, USA
F. Smaill, MB, ChB
McMaster UniversityHamilton, Ontario, Canada