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


Valaciclovir accelerated healing in recurrent herpes genitalis

ACP J Club. 1997 Mar-Apr;126:41. doi:10.7326/ACPJC-1997-126-2-041

Source Citation

Spruance SL, Tyring SK, DeGregorio B, Miller C, Beutner K, and the Valaciclovir HSV Study Group. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Arch Intern Med. 1996 Aug 12/26;156: 1729-35.



To evaluate the effectiveness of peroral valaciclovir in the treatment of 1 acute episode of recurrent herpes genitalis.


Randomized, double-blind, placebo-controlled trial with a minimum 7-day follow-up.


Academic, private, and public medical facilities in the United States.


987 healthy volunteers (median age 34 y, 62% women) who had ≥ 4 recurrences of genital herpes within the past 12 months. Exclusion criteria included other significant medical conditions or allergies and pregnancy or lactation.


Patients were allocated to 1 of 3 treatment groups: valaciclovir, 1000 mg twice daily for 5 days (n = 368); valaciclovir, 500 mg twice daily for 5 days (n = 360); or placebo, twice daily for 5 days (n = 259). Patients were instructed to self-initiate treatment within 24 hours of the first signs or symptoms of a recurrence.

Main outcome measures

Length of episode, time to healing, duration and severity of pain, time to cessation of viral shedding, and adverse events.

Main results

In an intention-to-treat analysis, both dosages were effective; no statistically significant differences were seen. In patients receiving the lower dosage, the median episode length was 4.0 days compared with 5.9 days in patients receiving placebo (hazard ratio [HR] 1.94, CI 1.64 to 2.31, P < 0.001). Patients receiving the lower dosage also had a shorter time to lesion healing than did patients reveiving placebo (4.1 d vs 6.0 d, HR 1.94, CI 1.59 to 2.36, P < 0.001). Both valaciclovir dosages reduced the percentage of patients with episodes {69% for the lower dose vs 79% for placebo, P = 0.005}*. {This absolute risk reduction of 10% means that 10 patients would need to be treated with 500 mg of valaciclovir (compared with placebo) to prevent 1 additional episode, 95% CI 6 to 33; the relative risk reduction was 13%, CI 4% to 21%.}* Valaciclovir accelerated the resolution of pain (HR 1.81, CI 1.53 to 2.14) and the cessation of viral shedding (HR 2.8%, CI 2.12 to 3.94). Adverse effects were similar among all treatment groups.


Valaciclovir given within 24 hours after onset of an episode of herpes genitalis accelerated the time to resolution of the episode and lesion healing.

Source of funding: In part, Burroughs Wellcome Co.

For article reprint: Dr. S.L. Spruance, Health Sciences AIDS Center, School of Medicine, Room 4B322, University of Utah, 50 North Medical Drive, Salt Lake City, UT 84132, USA. FAX 801-585-6422.

*Numbers calculated from data in article.


Many patients with genital herpes subsequently develop chronic recurrent infections. Although no cure for herpes genitalis currently exists, effective treatments are available that can reduce the number, intensity, and duration of episodes. Until recently, standard therapy for recurrent genital herpes was limited to acyclovir taken 5 times/d continuously or on a per-episode basis. Although 2 trials (1, 2) have shown the effectiveness of continuous therapy for preventing recurrences, little evidence supports the benefits of per-episode treatment with acyclovir.

Two new drugs, valaciclovir and famciclovir, have recently been approved by the U.S. Food and Drug Administration for the treatment of herpes. Both drugs have a higher bioavailability than does acyclovir; thus, they have a more user-friendly dosing schedule (twice daily) (3). Valaciclovir is a pro-drug of acyclovir, whereas famciclovir is an oral form of penciclovir and may prove to be a good alternative for patients whose infection is resistant to acyclovir.

The results of the study by Spruance and colleagues show that per-episode treatment with valaciclovir is effective. Famciclovir was also recently evaluated in a well-designed randomized controlled trial (4) that showed similar results.

Clinicians are faced with 3 medications (acyclovir, famciclovir, and valaciclovir) and 2 treatment strategies (per-episode and continuous therapy) for their patients with recurrent genital herpes. For patients with very frequent episodes (e.g., > 10 episodes per year), continuous therapy with acyclovir (400 mg twice daily) is probably indicated. However, per-episode therapy with famciclovir or valaciclovir is now an acceptable alternative for patients with less frequent episodes. Until a trial comparing these 2 new drugs is done, either agent is indicated and cost may be the deciding factor.

Thomas McGinn, MD
Montefiore Medical CenterBronx, New York, USA


1. Rooney JF, Straus SE, Mannix ML, et al. Ann Intern Med. 1993;118:268-72.

2. Goldberg LH, Kaufman R, Kurtz TO, et al. Arch Dermatol. 1993;129:582-7.

3. Rolan P. Clin Pharmacokinet. 1995;29: 333-40.

4. Sacks SL, Aoki FY, Diaz-Mitoma F, Sellors J, Shafran SD. JAMA. 1996;276:44-9.