Genital herpes: a lifelong condition

Case Scenario

Justin, a 25-year-old male, presents to your pharmacy to fill a repeat prescription for valaciclovir 500 mg tablets, which he uses for episodic management of genital herpes. As you are counselling him, he reports that he has experienced six episodes so far this year.

He finds the symptoms to be quite severe, and it is beginning to have a negative impact on his overall health.

Justin wonders why he is experiencing so many episodes and asks you if there is anything else that he can do.

Already read the CPD in the journal? Scroll to the bottom to SUBMIT ANSWERS.

Introduction 

Genital herpes is a common sexually transmitted infection (STI) caused by the herpes simplex virus (HSV).¹ It is the most frequent cause of genital ulceration worldwide and is a significant risk factor for HIV infection.¹ Data from 2016 suggests that approximately 13% of the world’s population aged 15–49 are infected with genital herpes.² Currently, there is no cure or vaccine for genital herpes, and treatment is focused on improving symptoms, decreasing risk of complications and reducing transmission risk.³

Given infection is lifelong, the pharmacist has an important role in helping patients manage their condition with the use of both pharmacological and non-pharmacological therapies and by providing advice on the risk of transmission.⁴  

There are two strains of HSV: HSV type 1 (HSV-1), which usually infects the lips and mouth, and HSV type 2 (HSV-2), which commonly affects the genital and anal regions.⁵ Each strain, however, has the ability to infect the other area of the body.⁵ Approximately 75% of Australian adults are estimated to be infected by HSV-1, and 12% with HSV-2 presenting as genital herpes.⁶

Many adults with genital herpes are undiagnosed, therefore true prevalence is likely higher.⁷ Females are more likely to be infected with HSV-2 than men, as the rate of male to female transmission is almost twice that of female to male.¹ Initial HSV-1 infection usually occurs early in life, whereas HSV-2 infection often coincides with the onset of sexual activity and is most common in women aged 35–44 years.^4,6 HSV is transmitted through either direct contact with active lesions or via viral shedding.⁴  

Viral shedding is the process whereby the virus is shed intermittently at a peripheral site, mucosal surfaces of the genitals or in secretions.⁴ It usually begins during the first phase of infection, which may be several hours or days before any signs or symptoms appear. Viral shedding is also common in asymptomatic infections, and as a result, patients can be unaware they are infectious and able to transmit HSV.¹  

HSV-2 genital herpes is usually acquired through sexual intercourse (vaginal or anorectal), whereas HSV-1 genital herpes is due to transmission during mouth to genital contact.⁷ Genital herpes caused by HSV-2 is usually more severe and prone to more recurrent episodes and asymptomatic viral shedding.⁵

There are 5 distinct stages in the HSV infection cycle, which explain the clinical presentation of genital herpes⁵:

• primary mucocutaneous infection
• sacral dorsal root ganglia infection
• virus latency
• reactivation of the virus
• recurrent (episodic) infection.

Latent infections can reactivate periodically, causing recurrent episodes.⁵ The risk of reactivation is dependent on a number of physical and environmental stimuli, including stress, trauma, UV light and immune status.⁴ Approximately 38% of patients experience at least six recurrent episodes, and 20% have 10 or more recurrences.⁴  

Recurrences are more common in the first year of infection and the frequency of episodes usually decreases over time. Unfortunately, some patients can experience outbreaks for many years.⁴ HSV infection can be transmitted from expectant mother to child, resulting in neonatal herpes.⁵  

Neonatal herpes is a serious systemic infection with a high morbidity and mortality rate.⁸ Transmission usually occurs while the baby is travelling through an infected birth canal during delivery, and a caesarean section is recommended if the mother presents with either active genital lesions or asymptomatic HSV-2 cervicitis.⁴ The risk of transmission is greatest if the mother is infected with HSV-2 late in pregnancy, a the levels of HSV-2 in the genital tract are highest early in infection.²

Symptoms

A variety of factors, such as previous HSV exposure, HSV type, patient specifics (age, infection site, immune status, etc.) and initial versus recurrent episode, all influence presenting signs and symptoms of genital herpes.⁵

Initial infection and first episode

Early identification of genital herpes is difficult as the majority of initial or primary infections are either asymptomatic or minimally symptomatic.^5,7 Asymptomatic infection can result in the infection going unnoticed, further facilitating transmission.² A person can first experience symptoms of HSV either at the time of initial or primary infection, or, as in most cases, in a subsequent reactivation after previously having an asymptomatic primary infection.^3,7 

Prodromal signs, such as tingling, itching and paraesthesia, are usually the first symptoms of genital herpes and generally begin approximately 1 week after initial exposure.⁴ This phase can last anywhere between a few hours and several days.⁷ The prodromal phase is followed by the formation of painful, bilateral pustular or ulcerative lesions on external genitalia over 7–10 days.⁷  

Lesions are usually reported as appearing on the vulva and vagina in females, and less commonly on the cervical and perianal regions. Areas around the glans or the shaft of the penis are the usual reported sites of lesions.⁹ Lesions can also be reported around the anal region.⁹  

Genital lesions usually heal within 2–4 weeks, and viral shedding stops after approximately 11–12 days.⁵ Flu-like symptoms, such as fever, headache and malaise, can be experienced in the first few days of the lesions.⁵ Patients may also experience other symptoms, including local itching, pain or discomfort, vaginal or urethral discharge, paraesthesia, and urinary retention.⁴ Symptoms are usually more severe in females, the immunocompromised, and those experiencing a symptomatic primary infection.³

Recurrent infections and clinical episodes

Recurrent episodes are caused by reactivation of the virus.⁴ During these episodes, patients can experience outbreaks of increased viral shedding, blisters and ulcer formation. Approximately 50% of patients experience prodromal symptoms before lesions appear in a recurrent episode.^4,5 Recurrent infections are usually less severe, characterised by fewer unilateral lesions, milder symptoms, and are shorter.⁵ On average, active lesions usually heal in 7 days, and viral shedding lasts 4 days.⁵

Approximately 20% of patients, may experience symptoms outside of the genital area, including lesions on the lumbosacral back, buttocks and legs.¹⁰  

Complications

While genital herpes may be an asymptomatic infection for many, it can have serious complications. Potential rare complications include meningitis, encephalitis, and secondary infection of ulcerated skin.⁵ Immunocompromised patients are at greater risk of complications and experience more severe infections.² A meta-analysis found HSV-2 infection to be a statistically significant risk factor for contracting HIV, with patients seropositive for HSV-2 approximately 3 times more likely to become infected with HIV.¹¹ Furthermore, patients with both HIV and HSV-2 are more likely to infect others with HIV.⁷

Given genital herpes is a lifelong condition characterised by frequent symptomatic recurrences, for many patients, its diagnosis can cause emotional distress, instigating feelings of anxiety, guilt and isolation.^1,7 This psychological distress can impact both a patient’s quality of life and sexual relationships.²

Diagnosis and management of genital herpes

Recognition and clinical diagnosis of genital herpes are the first steps in its effective management.¹² The presence of characteristic genital lesions, combined with a history of similar lesions, or recent sexual contact with an individual with similar lesions, is often the basis of a clinical diagnosis.⁵ Laboratory testing is required for confirmation of diagnosis.⁵ Before commencing treatment, a swab should be taken from either the base of the lesion or deroofed vesicle for HSV type-specific testing.¹³  

Treatment should commence prior to laboratory confirmation.¹³ Therapeutic Guidelines also recommend screening for other sexually transmitted diseases. Contact tracing is not required.¹³

Genital herpes treatment is focused on symptom relief, as well as reducing transmission risk and the frequency, severity and duration of recurrent episodes.³ It is not curative, and response to treatment is dependent on the timing of antiviral medication initiation relative to the onset of symptoms; it is most effective if initiated within 72 hours of symptom onset.¹³

Australian guidelines recommend the guanine analogues aciclovir, famciclovir or valaciclovir for the treatment of genital herpes.¹³ Duration of therapy and dosage are determined by the type of episode. 

Therapeutic Guidelines recommendations are outlined in Table 1. All three medicines are usually well tolerated and have few adverse effects.¹⁴ Dosage adjustments are required in renal impairment due to the increased risk of nephrotoxicity and neurological adverse effects.¹⁴  

Table 1: Management of genital herpes

Initial infection

Treatment is most effective when commenced at the first signs or symptoms of infection. The World Health Organization (WHO) guidelines for genital herpes treatment suggest there is moderate quality evidence to support antiviral treatment of an initial clinical episode of genital herpes in adults or adolescents.⁷ Aciclovir, famciclovir and valaciclovir are all effective in reducing viral shedding, symptom duration, and lesion healing time.⁵  

Data from eight randomised controlled trials comparing treatment with aciclovir versus no treatment found that aciclovir treatment decreased the duration of symptoms and lesions by 2 days; pain was decreased by 2 or more days; and viral shedding was reduced by 9 or more days.⁷ The few trials directly comparing aciclovir, famciclovir and valaciclovir found only ‘trivial’ differences in relation to their adverse event profile and efficacy.⁷  

Choice of medicine is dependent on practical considerations that may impact compliance, such as dose frequency, tablet burden and cost.¹³  

Episodic management 

Treatment should be initiated either during the prodromal phase or within the first 24 hours of symptom onset.⁷ Episodic treatment courses are shorter than those required to treat initial infections, as viral replication in recurrent infection is short-lived.¹³

Suppressive or prophylactic treatment

The WHO recommends that suppressive or prophylactic, rather than episodic management, be considered in patients who experience either frequent recurrences (4–6 times annually) or severe episodes, or in instances where recurrences cause distress.⁷ Suppressive therapy reduces the frequency of genital herpes recurrences by 70–80% in patients who experience frequent episodes and reduces viral shedding.¹⁵  

Studies have also shown suppressive therapy is associated with increased treatment satisfaction compared to episodic therapy.¹⁵ Prior to treatment initiation, recurrent episodes should be monitored for a few months to determine a frequency and severity, and the need for ongoing suppressive therapy should be assessed after 1 year.⁷  

If patients continue to experience recurrent episodes despite suppressive therapy, and after reconfirming the diagnosis is correct, guidelines recommend changing suppressive therapy to valaciclovir 500 mg twice daily.¹³ The Australian Medicines Handbook (AMH) recommends either aciclovir or valaciclovir for suppressive treatment for patients also diagnosed with HIV.¹⁸

Prescribing suppressive therapy to women with recurrent genital herpes late in their pregnancy reduces the risk of active disease during delivery and increases the chance of a vaginal delivery.¹³ 

In preparation for delivery, an increased prophylactic dose may be prescribed after 36 weeks’ gestation. Guidelines recommend either aciclovir 400 mg 8-hourly or valaciclovir 500 mg 12-hourly until delivery.¹³ Frequent severe episodes in an immunocompromised patient can suggest the development of drug-resistant genital herpes.¹³ 

Immunocompromised patients are at greater risk of drug resistance, possibly due to their weakened immune system, which allows the virus to survive in conditions it wouldn’t normally, and often leads to prolonged, more severe recurrent episodes.¹⁶ 

Up to 10% of immunocompromised patients have drug-resistant genital herpes, and patients not responding to standard treatment should be referred for specialist investigation.^13,16

Emerging treatments

Given there is currently no cure for genital herpes, prevention via vaccination would dramatically reduce its prevalence and impact.¹⁷ To date, several subunit or replication-deficient vaccine candidates have been trialled in humans and have failed to produce a strong immune response.¹⁷ The success of a live-attenuated vaccine in the prevention of varicella zoster virus, however, sets precedent for a development of a live-attenuated HSV-2 vaccine.¹⁷

Knowledge to practice

Pharmacists are in an ideal position to provide reassurance that, while not curable, genital herpes is a manageable chronic condition. The risk of transmission is minimised by avoiding sexual contact from the first signs of infection or recurrence, until the lesions have fully healed, using barrier protection methods (e.g. condoms) at all times, even when no lesions are present, and by taking medication as prescribed.^1,4 Pharmacists must reiterate the importance of having immediate access to antiviral medications to allow for early and successful treatment.⁴

Non-pharmacological therapies also play an important role. Wearing loose clothing, ensuring the area is kept dry, avoiding soap on the area, and bathing the area in salt water are lifestyle measures that can help during an episode.¹⁸ If the patient experiences severe dysuria, passing urine in a bath may lessen the pain.¹ Simple analgesics, such as paracetamol or ibuprofen may also be of benefit.¹ A healthy diet, sufficient rest and sleep, and stress management are also important factors in managing genital herpes.¹⁸

Initial diagnosis can trigger feelings of embarrassment and shame, as well as concerns over the impact on overall health, sex life and relationships.^1,7 Referral to either a psychologist or counsellor experienced in genital herpes may be of benefit. Sexual Health Australia provides counselling and support for newly diagnosed patients and/or their partners.^1,19 There are also numerous self-help groups and government websites, such as Healthdirect, which can provide further information.²⁰

While topical aciclovir is indicated for the treatment of oral HSV-1 infections, it is not recommended for genital herpes.⁴ It is therefore important for over- the-counter purchases of topical aciclovir to be adequately assessed and any potential genital herpes infections referred to a medical practitioner.

Conclusion

Preventing genital herpes and controlling its transmission is challenging. While safe sex practices, education and antiviral therapies are effective measures, the ability to transmit the infection while asymptomatic makes it a complicated infection to manage. Couple this with treatment being suppressive, not curative, and it is clear that further preventive measures are required. 

Pharmacists can influence the clinical course of genital herpes by providing appropriate advice and reassurance to patients, which is critical to the effective management of the infection.

Key Points 

• Genital herpes is a lifelong infection characterised by recurrent symptomatic episodes. 
• Transmission can occur even when the patient is asymptomatic. 
• Treatment is focused on virus suppression with oral antiviral therapy and is not curative; aciclovir, famciclovir and valaciclovir are recommended options. 
• Different treatment regimens are required depending on the stage of infection, and immunocompromised patients are more likely to experience drug resistance.

If you do get an enrolment error, please click here

References

1. Azwa A, Barton SE. Aspects of herpes simplex virus: a clinical review.  J Fam Plann Reprod Health Care 2009; 35(4): 237-42.
2. World Health Organisation. Herpes simplex virus. 2022. At: who.int/news-room/fact-sheets/detail/herpes-simplex-virus
3. Heslop R, Roberts H, Flower D et al. Interventions for men and women with their first episode of genital herpes.  Cochrane Database of Systematic Reviews 2016, Issue 8. Art.No,:CD010684.
4. Alldredge BK, Corelli RL, Ernst ME et al. Applied Therapeutics: The clinical use of drugs. 10^th Philadelphia:Lippincott Williams& Wilkins; 2013. p.1641-1645.
5. DiPiro JT, Talbert RL, Yee GC et al. Pharmacotherapy: A pathophysiologic approach. 9^th New York: McGraw-Hill Education; 2014. p.1876-1878.
6. Cunningham AL, Taylor R, Taylor J et al. Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: a nationwide population-based survey.  Sex Transm infect. 2006;82(2):164-168.
7. World Health Organisation. WHO guidelines for the treatment of genital herpes simplex virus.  At: www.ncbi.nlm.nih.gov/books/NBK396232/pdf/Bookshelf_NBK396232.pdf
8. Kimberlin DW. Herpes simplex virus infections in the newborn. Semin Perinatol, 2007. 31(2): 19-25.
9. Jaishankar D, Shukla D. Genital herpes: Insights into sexually transmitted infectious disease. Microb Cell. 2016 Sep 5;3(9):438-450.
10. Vassantachart JM, Menter A. Recurrent lumbosacral herpes simplex virus infection. Proc (Bayl Univ Med Cent). 2016, 29:1, 48-49,
11. Freeman EE, Weiss HE, Glynn JR et al. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS: January 2, 2006;20(1):73-83
12. Singh A, Preiksaitis J, Ferenczy A et al. The laboratory diagnosis of herpes simplex virus infections. Can J Infect Dis Med Microbiol. 2005 Mar-Apr, 16(2): 92-98.
13. Genital Herpes (reviewed March 2020). In Therapeutic Guidelines [digital]. Melbourne: Therapeutic Guidelines Limited; 2021
14. Rossi S, ed. Australian medicines handbook. Adelaide: Australian Medicines Handbook; 2021.
15. Romanowski B, Marina RB, Roberts JN et al. Patients’ preference of valacyclovir once-daily suppressive therapy versus twice-daily episodic therapy for recurrent genital herpes: a randomised study. Sex Transm Dis. 2003 Mar;30(3):226-231
16. Piret J, Boivin G. Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence and management. Antimicrobial Agents and Chemotherapy Jan 2011, 55(2) 459-472
17. Joyce JD, Patel AK, Murphy B et al. Assessment of two novel live-attenuated vaccine candidates for herpes simplex virus 2 (HSV-2) in guinea pigs. Vaccines. 2021 9(258).
18. Queensland Government. Genital herpes. 2019.  At: http://conditions.health.qld.gov.au/HealthCondition/condition/14/188/62/Genital-Herpes
19. Sex therapy & counselling.  2020. At: www.sexualhealthaustralia.com.au/14.html
20. Healthdirect Australia. Genital herpes.    At: www.healthdirect.gov.au/genital-herpes

ELKE SMITH, BPharm, MHIthMgt is a pharmacist specialising in clinical governance and medication safety, with 15 years’ experience in providing safe, high-quality pharmacy services to aged care facilities.