Genital herpes and its management

P Sen, consultant1 and S E Barton, consultant and clinical director,2

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Introduction
Genital herpes is an important public health disease and is the leading cause of genital
ulcer disease worldwide. We present the latest evidence based guidelines from the
British Association for Sexual Health and HIV (BASHH), the Centers for Disease
Control and Prevention (CDC), and other expert committees to provide an up to date
account of genital infection with herpes simplex virus (HSV), its clinical features and
diagnosis, and a practical approach to management of affected patients. Treatment
regimens have largely been based on evidence obtained from randomised controlled
trials, while certain new diagnostic tests are limited by lower levels of evidence
obtained only from descriptive or case studies.

Summary points

Genital herpes is the leading cause of genital ulcer disease worldwide

Most patients with genital herpes have no symptoms and shed virus intermittently
in the genital tract
Counselling of patients and their sexual partners is critical in the management of
genital herpes
Caesarean section is recommended for all pregnant women presenting with a first
episode of genital herpes after 34 weeks' gestation
Genital herpes caused by HSV-2 infection has been shown to double the risk of
becoming infected with HIV through sexual transmission
Suppressive antiviral therapy for genital herpes should be routinely offered to
people with both HSV and HIV

Sources and selection criteria

We searched PubMed (1966-2006) for relevant studies using keywords and text terms
for genital herpes. We accessed the WHO and Health Protection Agency (United
Kingdom) website to assess the disease burden of genital herpes and consulted
guidelines on genital herpes from the British Association for Sexual Health and HIV
(2001) and the Centers for Disease Control and Prevention (CDC, 2006). Additional
data and references were obtained from International Union against Sexually
Transmitted Infections (IUSTI) meetings, BASHH meetings, the International Herpes
Management Forum (IHMF), the World STI/HIV congress, and a personal archive of
references.
What causes genital herpes and how is infection
acquired?
Genital herpes is caused by infection with herpes simplex virus (HSV), commonly by
HSV type 2 and now increasingly by type 1. Both HSV-1 and HSV-2 infections are
acquired from contact with infectious secretions on oral, genital, or anal mucosal
surfaces. Genital herpes can also be acquired from contact with lesions from other
anatomical sites such as the eyes and non-mucosal surfaces such as herpetic whitlow
on fingers or from lesions on the buttocks and trunk.

What is the prevalence of genital herpes in the UK

and worldwide?
In the UK, there was a 15% increase in the number of diagnoses of first attack of
genital herpes from 16479 cases in 1995 to 19180 cases in 2004.1 In the United
States, an estimated 40-60 million people are infected with HSV-2, with an incidence
of 1-2 million infections and 600000-800000 clinical cases a year.2 The prevalence of
genital herpes in developing countries varies from 2-74% according to the country. In
some African countries that are experiencing HIV epidemics, HSV-2 is highly
prevalent (70%), and there is evidence that genital HSV increases the risk of HIV
infection and that people with both are more likely to transmit HIV infection.3

How do patients present?

First (initial) episode of genital herpes

The initial episode is the first episode of genital infection with either HSV-1 or HSV-2
(box 1). Primary genital herpes is the first episode in an individual with no pre-
existing antibodies to either HSV type. A non-primary first episode is the first
infection in an individual with pre-existing antibodies to the other HSV type.4 5

Box 1 Presentation of first episode of genital herpes

Often severe
Multiple grouped vesicles that rupture easily leaving painful erosions and ulcers
In men, the lesions occur mainly on the prepuce and subpreputial areas of the
penis
In women, the lesions occur on the vulva, vagina, and cervix
There may be associated systemic symptoms such as fever and myalgia
Healing of uncomplicated lesions takes two to four weeks
Severe complications are rare but can include autonomic neuropathy with urinary
retention and aseptic meningitis

Recurrent genital herpes

Groups of vesicles or ulcers develop in a single anatomical site and heal within 10
days. For the first two years patients may experience an average of five clinical
episodes a year, which may reduce in frequency thereafter. Genital HSV caused by
type 1 infection recurs less often, and thus typing of infection may inform patient
counselling.

Asymptomatic HSV infection

Most people with HSV infection have mild unrecognised or subclinical disease and
are unaware of their infection. They may shed the virus intermittently in the genital
tract and thus transmit the infection to their sexual partners entirely unknowingly.
Subclinical shedding occurs most commonly in the first year of infection in patients
with genital HSV-2 infection and in individuals with frequent symptomatic
recurrences. Perianal shedding is common in HIV negative, HSV-2 seropositive men
who have sex with men and are asymptomatic.w1 Most infections of genital herpes are
transmitted by people who are unaware that they are infected or who have no
symptoms when transmission occurs

How do I make a diagnosis of genital herpes?

The clinical diagnosis of genital HSV infection has a low sensitivity and specificity;
laboratory confirmation of infection and typing of HSV is essential as it influences the
management, prognosis, and counselling of patients.

Detection of HSV in clinical lesionsTable 1 compares the methods of detection.

detection. Take swabs from the base of the lesion or fluid from a vesicle. For culture
tests it is essential that the cold chain (4C) is maintained and appropriate media are
used. Polymerase chain reaction (PCR) is the most useful test as less meticulous
handling of specimens is required.

Table1
Comparison of detection methods for HSV in clinical lesions

SerologyCommercial tests that use complement fixation are not type specific.
Seroconversion from a zero baseline is usually diagnostic of a primary infection. In
the case of recurrent infection, an immune response from a non-zero baseline may be
detected. These tests cannot distinguish between initial and recurrent infections,
however, and have been replaced by sensitive tests such as enzyme linked
immunosorbent assay (ELISA) and radioimmunoassay (RIA). Type specific serology
tests (TSSTs), which detect glycoprotein G2 specific to HSV-2 and glycoprotein G1
specific to HSV-1 infection, are the only commercially available diagnostic tools
available to identify those with asymptomatic HSV infection and can effectively
distinguish the two types with high sensitivity (80-98%) and specificity ( 96%).8
Case control studies have shown that there are certain clinical settings when these
tests may help the diagnosis of HSV infection9w2-4 (boxes 2 and 3).
Box 2 When type specific serology testing can be useful 9w2-w4

The patient's partner has genital herpes and patient wants to know if he or she has
been infected
The patient presents with recurrent genital or atypical ulcers and results of culture
or polymerase chain reaction tests are negative
Screening of individuals at high risk of sexually transmitted infections
Testing of pregnant women with undiagnosed genital herpes

Box 3 When type specific serology testing is not useful and should not
be used9w2-w4

To differentiate oral from genital HSV-1 infection

During the 2 to 12 weeks after infection as it is not known how long after
infection the test results remain positive as antibody levels serorevert to normal
over time
In children aged <14 years as it has a low sensitivity and specificity
In medicolegal cases as viral culture is the ideal test for genital herpes

How do I manage patients with genital herpes?

First episode of genital herpes

General measures (evidence level IV, grade C, table 2) for treating patients with a first
episode include cleaning affected areas with normal saline, giving analgesia (systemic
or local, such as lidocaine gel), and treating any secondary bacterial infection.
infection.

Table 2
Details of grade of recommendation and equivalent evidence level

Specific antiviral therapy

Aciclovir has a good record of safety and efficacy and is available in generic
formulations. Other drugs, such as valaciclovir and famciclovir, have less frequent
dosing regimens compared with aciclovir (box 4) but are more expensive.
Randomised control trials have shown that all three drugs reduce the severity and
duration of clinical attacks.10w5 None of these drugs eradicate the infection or latent
virus.
Box 4 Recommended regimens for first episode of genital herpes (1b,
A)3 4

Aciclovir 200 mg orally five times a day for 5-10 days or

Aciclovir 400 mg orally three times a day for 5-10 days or
Valaciclovir 500 mg to 1 g orally twice a day for 5-10 days or
Famciclovir 250 mg orally three times a day for 5-10 days

There is no evidence of benefit from courses of treatment longer than five days.
BASHH guidelines, however, recommend that treatment should be continued beyond
five days if new lesions continue to form, if symptoms and signs are severe, or if the
patient also has HIV. The guidelines also state that combined oral and topical
treatment is of no additional benefit. Numerous over the counter and internet based
topical and oral herbal cures are available. There is no scientific evidence for the
use of essential oils, plant extracts, zinc, and L-lysine, and they have no place in the
management of genital herpes.

Our preferred treatment is aciclovir 400 mg orally three times a day for seven days
because it is effective, low cost, and patients comply with treatment.

Recurrent genital herpes

Treatment of recurrent attacks includes supportive therapy, episodic antiviral therapy,

or suppressive antiviral therapy. Most recurrent attacks are mild and self limiting
however, and can be managed with supportive therapy only. General measures for
treating patients include cleaning the affected areas with normal saline, giving
analgesia (systemic or local such as lidocaine gel), and treating secondary bacterial
infection.

Supportive therapySupportive therapy includes saline bathing, the use of analgesia,

and counselling of sexual behaviour and can be instituted when recurrences are mild
and self limiting.

Episodic antiviral therapy (1a, A)Initiate episodic antiviral therapy during the
prodrome or early in an attack (box 5).w6 Oral aciclovir, valaciclovir,11 and
famciclovirw7 reduce the severity and duration by a median of one to two days.w6 w8 w9
Topical antiviral therapy is less effective than systemic therapy.4w10 Randomised
controlled trials have shown all these regimens to be effective. Our preferred
treatment is aciclovir 400 mg orally three times a day for five days because it is
effective and low cost.

Box 5 Recommended regimens for episodic therapy (1a, A)3 4

Aciclovir 200 mg orally five times a day for 5 days or

Aciclovir 400 mg orally three times a day for 5 days or
Aciclovir 800 mg orally twice a day for 5 days or
Aciclovir 800 mg orally three times a day for 2 days or
Valaciclovir 500 mg orally twice a day for 3-5 days or
 Valaciclovir 1 g orally once a day for 5 days or
Famciclovir 125 mg orally twice a day for 5 days or
Famciclovir 1 g orally twice a day for 1 day

Suppressive antiviral therapy (1a, A)Meta-analyses of randomised controlled trials

have shown that suppressive antiviral therapy can significantly reduce (by 70 to 80%)
the number of recurrences in patients with frequently recurring (6 recurrences a
year) genital herpes.12w11 Box 6 shows the recommended regimen. Patients should
discontinue treatment after 12 months to assess the ongoing frequency of recurrences.
The timing of this should be agreed with the patient, and recurrences should be
treated.

Box 6 Recommended regimens for suppressive therapy (1a, A)3 4

Aciclovir 400 mg orally twice a day or

Valaciclovir 250 mg orally twice a day or
Valaciclovir 500 mg once daily or
Valaciclovir 1 g once daily or
Famciclovir 250 mg orally twice a day

How do I manage patients with asymptomatic HSV

infection?
A landmark study by Corey et al found that daily suppressive treatment with
valaciclovir can reduce HSV-2 transmission among HSV-2 discordant heterosexual
couples by 75% for clinical disease and reduce acquisition (measured by serology) by
48%.13 Other antiviral drugs may be effective but have not been investigated.14

What are the important points to discuss when

counselling patients?
Counselling infected people and their sexual partners is integral to the successful
management of genital herpes.w12 Physicians should provide counselling to help
patients cope with infection and prevent sexual and perinatal transmission.15

We have summarised the various points that physicians need to consider and discuss
when counselling patients (box 7). This guide comes from personal practices and
guidance from the British Association for Sexual Health and HIV (BASHH), the
Centers for Disease Control and Prevention (CDC), and the International Herpes
Management Forum. Educational reading material16 and access to web based literature
on genital herpes should be provided as part of the counselling process.
Box 7 Points to discuss during counselling5 16

Information on the natural course of the disease, the potential for recurrent
attacks, and the role of asymptomatic shedding in sexual transmission. Patients
should be informed that asymptomatic viral shedding is more common in genital
HSV-2 than HSV-1 infection and is most frequent in the first 12 months after the
infection is acquired.

Patients with a first episode of genital herpes should be told that this does not
necessarily indicate recent infection and that genital symptoms may develop
several years after the infection is acquired.

Information on antiretroviral treatments available and their impact on infectivity.

Episodic as well as suppressive therapy should be discussed with patients in
respect to recurrent episodes of infection.

Patients in a stable long term relationship where one partner is not infected may
remain discordant for several years despite potential repeated exposure; they
should be told that the risk of sexual transmission of HSV-2 can be reduced by
the daily use of valaciclovir by the infected partner.

Abstention from sexual activity during prodromal symptoms or when lesions are
present.

Advice to inform current and new sexual partners before initiating a sexual
relationship.

Use of condoms with new or uninfected partners, particularly in the 12 months

after the first attack.

Sexual partners of infected patients should be advised that they may be infected
even if they have no symptoms. Type specific serological testing should be
offered to them to determine whether they are at risk of HSV acquisition.

Asymptomatic people who test positive for HSV-2 infection on type specific
serology testing should be counselled in the same way as those with symptoms
and taught to recognise the clinical manifestations of infection.

Women with a history of genital herpes or with male partners with a history of
genital herpes should inform their doctors early in any pregnancy to prevent the
risk of neonatal infections.

Pregnant women who are not infected with HSV-2 should avoid sexual
intercourse with their male infected partners during the third trimester. Pregnant
women who are not infected with HSV-1 should also avoid genital exposure to
HSV-1 during the third trimester (such as oral sex with a partner with oral herpes
and vaginal intercourse with a partner with genital HSV-1 infection).
How do I manage genital herpes in a pregnant
woman?
Data from the aciclovir pregnancy registry on the use of aciclovir in pregnancy does
not show any increase in the number of birth defects.w13

First episode of genital herpes

For women who acquire the infection in the first and second trimester treat with oral
or intravenous aciclovir in standard doses and plan for vaginal delivery. For women in
who vaginal delivery is planned, continuous aciclovir in the last four weeks of
pregnancy will reduce the risk of clinical recurrence at term delivery by caesarean
section (1b, A).17

All women presenting with the first episode of genital herpes after 34 weeks' gestation
should be delivered by caesarean section. If vaginal delivery is unavoidable, treat the
mother and baby with aciclovir.

Recurrent genital herpes

In women with recurrent infection caesarean section should not be performed if there
are no genital lesions at the time of delivery. Daily suppressive aciclovir in the last
four weeks of pregnancy might prevent recurrences of genital herpes at term and
might be cost effective.18w14 If genital lesions are present at the onset of labour, experts
recommend delivery by caesarean section.19

What is the interaction between genital HSV-2 and

HIV?
Both HSV and HIV have reached epidemic proportions in certain developing
countries. Genital herpes caused by HSV-2 infection has been shown to double the
risk of becoming infected with HIV through sexual transmission.20 The ulcers and
breaks in the genital mucosa and skin caused by HSV-2 infection facilitate entry of
the HIV virus. These lesions contain large numbers of CD4 lymphocytes, which are
target cells for HIV. Transmission of HIV is more likely from people who also have
HSV-2,w15 possibly because of high titres of HIV in genital secretions during HSV-2
reactivation.w16

How do I manage genital herpes in HIV positive or

immunocompromised patients?
In patients with HIV or who are otherwise immunocompromised, episodes may be
prolonged, more severe, and require a longer duration of antiviral treatment (box 8). A
recent study found that treatment with valaciclovir at 1 g a day significantly reduced
HIV RNA genital shedding as well as the plasma viral load.21 These data support the
hypothesis that therapy for genital HSV infection in people with HIV reduces the risk
of their transmitting HIV and may affect the natural progression of HIV infection.
Further studies to investigate this are ongoing.

Box 8 Recommended regimens for daily suppressive therapy in people

with HIV (1b, A)4

Aciclovir 400-800 mg orally two to three times a day or

Valaciclovir 500 mg orally twice a day or

Famciclovir 500 mg orally twice a day

What about a vaccine?

To date the development of effective vaccines has not been promising. Difficulties
arise because of the complexity of the life cycle of the virus (latency) and the current
lack of understanding of the human mechanism of control of primary and recurrent
disease.22 A large scale study of a gD2-AS04 vaccine is being carried out to further
evaluate the protective effects in women as initial studies have shown differential
effects in men and women.

Conclusions
Genital herpes is an important public health disease that can cause substantial
morbidity if it is undiagnosed and untreated. Clinicians should suspect HSV infection
in all patients presenting with ulcers in the genital area. Genital HSV infection
increases the risk of HIV infection and people with both infections are more likely to
transmit HIV to their sexual partners.

Additional educational resources

World Health Organization

(www.who.int/topics/sexually_transmitted_infections/en/)offers factsheets and
latest publications and research on genital herpes

Centres for Disease Control And Prevention

(www.cdc.gov/std/Herpes/default.htm)offers factsheets on genital herpes

Sexually Transmitted Diseases Diagnostics Initiative

(www.who.int/std_diagnostics)

Kimberlin DW, Rouse DJ. Genital herpes. N Engl J Med 2004;350:1970-7.

Jones CA, Cunningham AL. Vaccination strategies to prevent genital herpes and
neonatal herpes simplex virus (HSV) disease. Herpes 2004;11:12-7.
Information resources for patients

International Herpes Management Forum

(www.ihmf.org/Patient/PatientResources.asp)this site offers information
leaflets for patients on genital herpes; the materials have been written in
collaboration with people who have genital herpes to help others with the
condition. The International Herpes Alliance offers support and information to
those with genital herpes, those helping to manage the disease, and national
patient support groups around the world

Australian Forum (www.herpes.com.au)

Herpes Health (Canadian site) (www.herpeshealth.com)

Association Herps Actualits (French site) (www.herpes.asso.fr)

Herpes Informatie Organisatie (Dutch site) (www.hiso.nl)

New Zealand Herpes Management Forum (www.herpes.org.nz)

British Association for Sexual Health and HIV

(www.bashh.org/guidelines/2002/hsv_0601.pdf)offers the latest UK
management guidelines on genital herpes

Centers for Disease Control and Prevention

(www.cdc.gov/std/Herpes/default.htm)offers facts, statistics, treatment
guidelines, and other resources on genital herpes

Notes
Contributors: Both authors contributed equally to the manuscript.

Competing interests: None declared.

Provenance and peer review: Commissioned, peer reviewed.

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