Trip Answers

Question answered:26/06/06 Warning! this question is over two years old.

Clinical Evidence contains a chapter on herpes labialis (1) in which the authors discuss interventions aimed at preventing recurrent attacks of herpes labialis, this states:

 

“Six RCTs found limited evidence suggesting that prophylactic oral antiviral agents may reduce the frequency and severity of attacks compared with placebo, but the optimal timing and duration of treatment is uncertain. We found no RCTs on the effects of topical antiviral agents used as prophylaxis.

 

We found no systematic review. Topical antiviral agents versus placebo: We found no good quality RCTs comparing topical antiviral agents versus placebo or no treatment. Oral antiviral agents versus placebo: We found four RCTs and one pooled analysis of two further RCTs. The first RCT (147 American skiers with a history of herpes labialisprecipitated by ultraviolet light) found that prophylactic oral aciclovir (400 mg twice daily, beginning 12 hours before ultraviolet exposure) reduced the frequency of attacks and duration of symptoms compared with placebo (P < 0.05). The second RCT (239 Canadian skiers with a history of recurrent herpes labialis) found no significant difference in lesion occurrence between those who took aciclovir (800 mg twice daily, starting on the day before exposure to ultraviolet light for a minimum of 3 days to a maximum of 7 days) and those who took placebo (21/93 [23%] with aciclovir v 21/102 [21%] with placebo; P = 0.92). The third RCT (20 people with recurrent herpes labialis) found that aciclovir (400 mg twice daily for 4 months) led to 53% fewer clinical recurrences than placebo (P = 0.05). The fourth RCT (248 adults with a history of sun-induced recurrent herpes labialis) compared three different dosages of famciclovir (125, 250, and 500 mg) versus placebo. Treatment was given three times daily for 5 days, beginning 48 hours after exposure to artificial ultraviolet light. The RCT found no significant difference in the number of lesions among the four groups (number of lesions reported as non-significant; P value not reported). However, it found that increasing the dose of famciclovir significantly reduced the size and duration of lesions, in a dose–response relation. Compared with placebo, the 500 mg dose, but not the other doses, significantly reduced the mean size of lesions and reduced the mean time to healing by 2 days (mean size of lesions: P = 0.04; mean time to healing: P = 0.01; absolute healing times not reported). The pooled analysis of two further RCTs (98 adults with a history of four or more attacks in the previous year) found that oral valaciclovir 500 mg daily significantly decreased the chance of recurrence within 4 months, and significantly increased the time to recurrence compared with placebo (no recurrence within 4 months: 62% with oral valaciclovir v 40% with placebo; P = 0.041; mean time to recurrence: 13.1 weeks with oral valaciclovir v 9.6 weeks with placebo; P = 0.016).”

 

On harms the authors note:

 

“Topical antiviral agents versus placebo: See also harms under the effects of antiviral treatments for the first attack. Oral antiviral agents versus placebo: The first RCT found no significant difference in mild to moderate central nervous system or gastrointestinal tract adverse events between treatment groups (7/77 [10%] with aciclovir v 3/76 [4%] with placebo; P = 0.34). Similarly, the second RCT found no significant difference between rates of adverse events between treatments (58/115 [50%] with aciclovir v 59/124 [48%] with placebo; P = 0.68). Headache and nausea were the most common adverse effects to be reported. The RCT reported five severe adverse events (knee throbbing, constipation, cold sore discomfort, stomach ache, and depression) with aciclovir, and six severe adverse events (insomnia, diarrhoea, and four people with headache) with placebo. The third RCT gave no information on adverse events. The fourth RCT found no significant difference in headache or nausea, the most common adverse events, between treatments (no data reported). It found no severe adverse events within 30 days of the last dose of famciclovir. The pooled analysis of two further RCTs found slightly fewer adverse events, most commonly mild headache, with valaciclovir compared with placebo (22 events in 33% of people taking valaciclovir v 29 events in 39% of people taking placebo). However, none of the adverse events with valaciclovir and only three with placebo were certainly attributable to study medication. See also harms under the effects of antiviral treatments for the first attack.”

 

Finally the authors comment:

 

“All participants in the second RCT were allowed to use paracetamol (acetaminophen) and encouraged to use sunscreen.”

 

Prodigy has also produced a guideline on herpes simplex (2). This is freely available and can be viewed in full by following the link in the reference section.

 

We have been unable to locate information from our usual sources on investigations for recurrent cold sores

 

1. http://www.clinicalevidence.com/ceweb/conditionpdf/1704.pdf
2. http://www.prodigy.nhs.uk/herpes_simplex_oral

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