Prevention of genital HSV infections 
Short review 
IS IT POSSIBLE TO PREVENT 
THE CLINICAL MANIFESTATIONS OF 
GENITAL HERPES SIMPLEX VIRUS INFECTIONS? 
J. Drinovec and M. Mejač 
SUMMARY 
The paper reports about genital herpes simplex virus (HSV) infections, especially recurrences of genital 
herpes and their pharmacological management. Some clinical studies with acyclovir and its important results 
for the management of genital herpes are reviewed. 
KEY WORDS 
genital HSV infections, pharmacological management, prevention, suppression 
INTRODUCTION 
The incidence of genital herpes simplex virus 
(HSV) infection is increasing (1), particularly in 
industrial developed countries. It is caused in 70 to 
95% by herpes simplex virus type 2 (HSV-2). It can 
also be caused by herpes simplex virus · type 1 
(HSV-1). Clinical manifestations of genital HSV 
infection are divided into initial and recurrent episodes, 
which can be asymptomatic or symptomatic. The 
virus stays in the host for the whole Iife. 
PHARMACOLOGICAL MANAGE:MENT 
OF GENITAL HSV INFECTIONS 
The acyclic nucleoside analogue acyclovir with 
high affinity and selectivity for herpesviruses is a 
first-Iine therapy in the management of genital herpes 
(1). But it cannot eradicate the virus. 
acta dennatovenerologica A.P A. Vol 4, 95, No 3 
Recommended treatment for initial genital HSV 
infection is oral acyclovir 200 mg 5 times daily for 
5 days and intravenous therapy for severe cases. A 
topical formulation is less effective. No preparation 
prevents the onset of recurrent episodes. Oral acyclovir 
is also recommended for recurrent genital herpes. 
Mild and rare episodes are treated episodically 
(episodic therapy). Patients with frequent (more 
than 6 attacks per year) and/or more severe 
recurrences and those who are very troubled by 
recurrences should be given continuous daily acyclovir 
(suppressive therapy) for severa! months to 1 year. 
After one year's therapy it is evaluated if suppressive 
therapy should be continued (Fig. 1 ). 
Several studies have demonstrated that acyclovir 
significantly reduces the number of recurrent episodes 
of genital herpes compared with placebo (2, 3). 
A study of 5 years of suppressive therapy '"'.ith 
acyclovir found a progressive decrease in the frequency 
155 
Prevention of genital HSV infections 
Tab. l. Mean annual recurrence rates (4). 
Therapy group Baseline Year 1 Year 2 Year 3 Year 4 Year 5 
E1S4 (n=179) 120 12.5 1.6 1.2 1.0 0.8 
s5 (n=210) 12.9 1.7 1.3 1.0 0.9 0.8 
P-value 0.0001 0.02 0.05 0.2 0.3 
E
1
S4: episodic therapy year 1, suppressive therapy 
S5: suppressive therapy years 1 through 5. 
of recurrences over the 5-year period of continuous 
acyclovir therapy ( 4 ). (Tab. 1 ). 
A progressive decrease in the percentage of patients 
reporting recurrences was also seen with years on 
therapy. By the 5th year of the study, approximately 
70% of patients reported a year free of genital 
herpes, and 20% of the patients had been recurrence-
free for the entire study period (5). (Fig. 2). 
Table 2. Effects of oral suppressive and intermittent 
acyclovir therapy and placebo on genital herpes 
recurrence ( 6) 
Treatment group 
Placebo 
Intermittent 
Suppressive 
P-value 
Median tirne to first 
recurrence ( days) 
23 
28 
250 
0.001 
A study of 156 patients with 6 or more recurrences 
of genital herpes a year compared the efficacy and 
300 
250 
III u 
C: 
f 200 
:i 
u-
111 1/l 
.:: iu° 150 
f 'C ·---,S 100 
50 
o 
• acyclovir 
D placebo 
years 2 through 5. 
safety of suppressive acyclovir therapy versus episodic 
treatment of recurrences. It was shown that daily 
suppressive acyclovir therapy significantly reduced 
the median recurrence rate, compared with episodic 
treatment (6). If a recurrence occurred during 
suppressive therapy, the duration of the attack was 
shorter than was observed with episodic therapy. 
Time to first recurrence in days was statistically 
significant longer (p 0,001) in the suppressive group 
than in patients on episodic therapy (28 days). 
(Tab. 2). 
It was shown that the safety profile of acyclovir 
was similar whether treatment was used episodically 
or continuously. There was no loss of efficacy over 
tirne and no emergence of resistant virus. 
Pregnancy 
Recurrent episodes of genital herpes during 
pregnancy are not thought to be harmful to the 
fetus, but a recurrence or primary episode close to 
term does pose the risk of neonatal infection during 
delivery. In such a case a caesarian section is 
necessary. In this moment acyclovir is administered 
n=143, n=58, n=88, n=1146, n=261, 
5 x 200 mg, 4 x 200 mg, 4 x 200 mg, 2 x 400 mg, 2 x 400 mg, 
4 months 84 days 84 days 1 year 1 year 
Figure l. Controlled trials using suppressive acyclovir therapy in patients with freq_uently recurring genital herpes (2, 3) 
156 acta dermatovenerologica A.PA. Vol 4, 95, No 3 
Prevention of genital HSV infections 
1M~------- - ----- --- - - --, 
80 
~ ., 
i 60 
C. 
o ., 
"' ., 
C 40 
~ 
&! 
20 
o E,S, (n=179) 
• S, (n=210) 
s year 
E
1
S
4
: Episod ic therapy year 1, suppressive therapy 
years 2 to 5, n= 179. 
S
5
: Suppressive therapy years 1-5, n=21 O. 
Figure 2. Annual percentage of patients recurrence-
free (5) 
during pregnancy only in life-threatening herpes 
diseases (7). It is currently under investigation for 
potential use in genital HSV infection in last weeks 
of pregnancy. Prepartal therapy with acyclovir should 
decrease the rate of caesarian section and prevent 
neonatal HSV infection during delivery. 
Immunocompromised patients 
Patients with immunological deficit resulting from 
human immunodeficiency virus (HIV) infection or 
immunosuppressive therapy for organ transplant reci-
pients or malignancy are at particular risk of reacti-
vation of HSV infection, also genital. Intravenous or 
oral acyclovir provides effective prophylaxis against 
HSV infection in immunocompromised patients (8,9) . 
CONCLUSIONS 
After primary genital HSV infection the virus can 
not be removed from the organism. Clinical manife-
stations of genital herpes are treated according to 
the intensity of clinical manifestations of the disease. 
The frequency of genital herpes recurrences can 
be significantly reduced by a suppressive therapy. 
Patients are treated with 800 mg acyclovir orally in 
2 or 4 doses daily for up to 1 year. After one 
year's therapy it is evaluated if suppressive therapy 
should be continued. 
Prepartal therapy with acyclovir should prevent 
neonatal HSV infection during delivery and decrease 
the rate of caesarian section. 
On the whole, prophylaxis with acyclovir in 
immunocompromised persons is effective and reasonable. 
REFERENCES 
l. De Ruiter A, Thin RN. Genital herpes, a guide 
to pharmacological therapy. Drugs 1994; 47 (2): 
297-304. 
2. Kaplowitz LG, Baker D, Gelb L, et al. Prolonged 
continuous acyclovir treatment of normal adults with 
frequently recurring genital herpes simplex infection. 
Jama 1991; 265: 747-751. 
3. Mertz GJ, Jones CC, Mills J, et al. Long-term 
acyclovir suppression of frequently recurring genital 
herpes simplex infection. A multicentre double-blind 
trial. Jama 1988; 260 (2): 201-206. 
4. Goldberg LH, Kaufman R, Kurtz TO, Conant 
MA, Eron L, et al. Long-term suppression of recurrent 
genital herpes with acyclovir: a 5-year benchmark. 
Archives of Dermatology 1993; 129: 582-587. 
5. Goldberg LH, Kaufman RH, Kurtz TO, Conant 
MA, Eron LJ, Batenhorst RL, Boone GS, and the 
Acyclovir Study Group. Continuous five-year treatment 
of patients with frequently recurring genital herpes 
simplex virus infection with acyclovir. J Med Virol 
1993; (suppl 1): 45-50. 
6. Mattison HR, Reichman RC, Benedetti J, Bolgiano 
D, Davis LG, et al. Double-blind, placebo-controlled 
trial comparing long-term suppressive with short-
term oral acyclovir therapy for management of 
recurrent genital herpes. Amer J Med 1988; 85 
(suppl 2A): 20-25. 
7. Dwyer DE, Cunningham AL. Herpes simplex 
virus infection in pregnancy. Bailliere žs clinical 
obstetrics and gynaecology 1993; 7: 75-105. 
8. Saral R, Burns WH, Laskin 01, et al. Acyclovir 
prophylaxis of herpes simplexvirus infections. A 
randomized, double-blind, controlled trial in bone-
marrow-transplant recipients. N Engl J Med 1981; 
305: 63-66. 
9. Wade JC, Newton B, Flournoy N, et al. Oral 
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reactivation after marrow transplantation. Ann Intern 
Med 1984; 100: 823-828. 
AUTHORS' ADDRESSES 
Jože Drinovec MD, PhD, Krka p.o., Novo mesto, Slovenia, Dunajska 65, 61000 Ljubljana, Slovenia 
Maja Mejač MD, Krka p.o ., Novo mesto, Slovenia, Dunajska 65, 61000 Ljubljana, Slovenia 
acta dermatovenerologica A.P A . Vol 4, 95, No 3 157