Limited evidence finds modest benefit in favour of antivirals for the prevention of cold sores

shutterstock_53580727 - cold sore

Recurrent herpes labialis (cold sores) is a common infection of the lip. The usual cause is the herpes simplex virus type 1 (HSV-1) although HSV-2 is been increasingly implicated. It is estimated that 90% of the population have been exposed to HSV-1. 20-30% of those infected experience outbreaks of  small blisters or sores on or around the mouth with frequencies ranges from monthly to annually. Triggers include sunlight, trauma, fever, stress, and dental treatment.  They are self limiting but can cause significant discomfort.

The aim of this review was to the effectiveness of antiviral agents in the prevention of Recurrent herpes labialis (RHL).

What did they do

An extensive literature search was conducted that included Cochrane Central Register of Controlled Trials, Medline, and Embase  databases and a wide range of other resources. No language restrictions were applied, and all relevant non–English-language papers were translated. Only randomised controlled trials were included, quality assessment and data synthesis followed methods  described in the Cochrane handbook.

They found

  • 10 studies matched the inclusion criteria, only 1 paper had a low risk of bias, 5 an  unclear risk and  4 papers a high risk of bias.
  • A significant difference in favour of antiviral agents when all 10 trials were pooled (RR 0.70, 95% CI 0.55-0.89). However, the pooled trials showed evidence of statistical heterogeneity (I2 = 61%; P = .004).
  • Oral acyclovir (800-1,600 mg daily) and valacyclovir (500 mg daily for 4 months) were shown to be effective in the prevention of RHL when taken prior to the appearance of any symptoms or exposure to triggers.


While this review found support for the use of systemic acyclovir and valacyclovir for the prevention of RHL. The findings from this review should be interpreted with caution because of the methodological quality of the studies.

 Rahimi H,T Mara T,Costella J,Speechley M,Bohay R. Effectiveness of antiviral agents for the prevention of recurrent herpes labialis: a systematic review and meta-analysis. Oral Surgery, Oral Medicine, Oral Pathology,


This is a well conducted systematic review  that has found a modest benefit in favour of antivirals. However, as the authors themselves note there are quality concerns with the majority of the studies and variation regarding the treatment protocols and the triggers to which the patients were exposed . These are good reasons to interpret the findings with caution.   The authors also searched for  ongoing trials and noted that 8 studies ( 6 of acyclovir, 1 of valacyclovir, and 1 of famciclovir) are currently registered hopefully these will help provide more definitive conclusions.

It is also worth noting that a Cochrane review protocol ( Lee et al ) for treatments for herpes simplex labialis  was registered towards the end of last year.

Lee C, Chi CC, Hsieh SC, Chang CJ, Delamere FM, Peters MC, Kanjirath PP, Anderson PF. Interventions for treatment of herpes simplex labialis (cold sores on the lips) (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD009375. DOI: 10.1002/14651858.CD009375.



Share on Facebook Tweet this on Twitter Share on LinkedIn Share on Google+