RECOMMENDATION 3
For adults and adolescents with a recurrent clinical episode of genital HSV infection, the WHO STI guideline suggests treatment over no treatment.
Conditional recommendation, moderate quality evidence
Remarks: Treatment should be given within the first 24 hours of the onset of symptoms or during the prodromal phase. This recommendation also applies to people living with HIV, people who are immunocompromised and pregnant women.
RECOMMENDATION 4
For adults and adolescents with a recurrent clinical episode of genital HSV infection, the WHO STI guideline suggests the use of aciclovir over valaciclovir or famciclovir.
Conditional recommendation, moderate quality evidence
Dosages for adults, adolescents and pregnant women:
aciclovir 400 mg orally thrice daily for 5 days, 800 mg twice daily for 5 days, or 800 mg thrice daily for 2 days
valaciclovir 500 mg orally twice daily for 3 days
famciclovir 250 mg twice daily for 5 days
Dosages for people living with HIV and people who are immunocompromised:
aciclovir 400 mg orally thrice daily for 5 days
valaciclovir 500 mg orally twice daily for 5 days
famciclovir 500 mg orally twice daily for 5 days
Remarks: Although the benefits of the medicines are probably similar, the costs of valaciclovir and famciclovir are higher than aciclovir, and therefore aciclovir is preferred. The choice of dosage may depend on compliance considerations. Treatment should be given within the first 24 hours of the onset of symptoms or during the prodromal phase.
SUMMARY OF THE EVIDENCE
The evidence for treatment of recurrent clinical episodes of genital HSV infection that are not frequent compared to no treatment is of moderate quality, due to unclear randomization methods and/or unclear loss to follow-up in the trials. Data from 16 randomized controlled trials were reported in 13 articles, relating to the use of aciclovir (9 trials), valaciclovir (3 trials) and famciclovir (5 trials). The findings indicate that aciclovir in various dosages for 2–5 days probably reduces the duration of viral shedding (MD: 1.32 fewer days; 95% CI: 1.36–1.27), symptoms (MD: 2.02 fewer days; 95% CI: 3.27–0.77) and lesions (MD: 1.07 fewer days; 95% CI: 1.3–1.0) when compared to placebo. Valaciclovir in various dosages probably reduces the duration of viral shedding by a median of 2 days, and lesions and symptoms by 1–2 days when compared to placebo. Famciclovir in various dosages probably reduces the duration of viral shedding, lesions and symptoms by a median of 1–2 days when compared to placebo. The GDG agreed that the differences in benefits were small and the differences in harms were trivial between the medicines and no treatment. In most trials, quality of life, compliance, pain, genital HSV transmission, and HIV transmission and acquisition were not measured.
Aciclovir, valaciclovir and famciclovir were compared. Two trials compared aciclovir and valaciclovir and found that there is probably little to no difference between the two medicines in terms of duration of viral shedding, lesions and symptoms, and risk of adverse events (moderate quality evidence). One trial compared aciclovir to famciclovir and found that there may be little to no difference in the same outcomes (low quality evidence). Another trial compared famciclovir to valaciclovir and found that there is probably little to no difference in outcomes (moderate quality evidence). The GDG agreed that there were only trivial differences in benefits and harms between the medicines.
Different dosages of aciclovir were compared in two trials (200 mg five times daily for 5 days versus alternatives). The findings indicate that there may be little to no difference between the various doses in terms of duration of symptoms, lesions and viral shedding, and adverse events. Different dosages of valaciclovir were compared in four trials (500 mg twice daily for 5 days versus the same for 3 days, and versus 1000 mg twice daily for 5 days). Again findings indicate there is probably little to no difference in outcomes between the doses. Famciclovir at doses of 125, 250 or 500 mg twice daily for 5 days were compared and there may be little to no difference in outcomes across these different dosages.
There were data providing moderate to low quality evidence from three studies that compared aciclovir to placebo in people living with HIV, and two studies that compared different doses of aciclovir, valaciclovir and famciclovir. The effects were inconsistent across different doses, but most doses were provided for 5 days and generally resulted in benefits and few harms.
The GDG agreed that there would be little variability in patient values and preferences relating to the different medicines and treatment regimens. However, higher value is likely to be placed on reducing the number and frequency of tablets taken. Research relating to other conditions indicates that adherence to treatment regimens may be improved with simpler regimens, although when compliance was measured in the studies included for HSV treatments, compliance was similar between different medicines and treatment regimens. Overall, it was agreed that the different regimens and medicines are probably acceptable to most people. Since the comparisons of different dosages of medicines compared to placebo and to each other showed few differences, the GDG agreed to recommend the dosages and regimens requiring fewer days of treatment and fewer tablets per day. Both valaciclovir and famciclovir are more expensive than aciclovir, and famciclovir is more expensive than valaciclovir. Where the medicines are a direct cost to people with HSV, the more expensive medicines would probably reduce equity if recommended.
In summary, there are probably small benefits and trivial side-effects of episodic therapy over no treatment, and moderate additional costs of providing episodic treatment versus no treatment. There may be trivial differences in benefits and side-effects between the different medicines and dosages. Although there is probably no important uncertainty or variability in the values patients place on reducing the duration of lesions and other symptoms, acceptability of episodic therapy may depend on the individual. All medicines are feasible to provide, but aciclovir costs less than famciclovir or valaciclovir.