Genital herpes: oral antiviral treatments


General background | Focus of the review | Comments on evidence | Search and appraisal summary | Substantive changes at this update | Abstract | Cite as


General background

Genital herpes simplex infection can be caused by either herpes simplex virus (HSV) type 1 (HSV-1) or HSV type 2 (HSV-2) and is one of the most common sexually transmitted diseases. Common symptoms include recurrent painful genital ulcerations. Asymptomatic shedding is frequent, especially in the first year after a primary episode, and probably represents the major source of sexual transmission. The herpes virus has a characteristic protein coat and each of the types has identifiable proteins. Glycoprotein G2 is associated with HSV-2 and glycoprotein G1 is associated with HSV-1 Type-specific antibodies to the viral proteins develop within the first several weeks of infection and persist. Detection of these specific antibodies, in addition to direct detection of the virus, is important in making an accurate diagnosis. There is no cure for HSV infection. In repeated randomised clinical trials, the use of antiviral agents compared to placebo for individuals with a first episode of genital HSV significantly reduces the duration of symptoms and speeds healing. The use of antiviral medications is also shown to reduce the frequency and duration of recurrent outbreaks and to reduce the frequency of asymptomatic shedding. Oral antiviral treatment of someone who is seropositive for HSV is effective in reducing transmission to a previously uninfected sexual partner. Genital herpes, like other genital ulcer diseases, is a significant risk factor for acquiring HIV for both men and women. People with HIV can have severe herpes outbreaks, and this may help facilitate transmission of both herpes and HIV infections to others.


Focus of the review

This update to a previously published review focuses on specific questions for which evidence was insufficient to identify the best treatment. There is now a preponderance of evidence supporting the role of antiviral treatment in treatment of the initial episode of genital herpes. However selecting the most appropriate antiviral treatment remains a challenge and, therefore, this review focuses on the effects of different oral antiviral treatments in two select populations: HIV-negative individuals with a first episode of genital herpes and treatment of both first episode and recurrences for HIV-positive individuals. These populations were selected because evidence from clinical trials was limited at the time of the last systematic review, and an update in these areas could provide clinicians with information on best therapies.


Comments on evidence

We found eight studies that met our inclusion criteria. In regards to the question of the effects of different oral antiviral treatments versus each other for a first episode of genital herpes in the HIV-negative individual, we found high grade evidence from one randomised controlled trial comparing oral valaciclovir and acyclovir. Both treatments were equally effective in treating the first episode by decreasing symptoms with similar rates of adverse effects; however, this evidence is from a single study. For the question regarding treatment of recurrent infections in HIV-positive individuals, we found moderate to very low grade evidence from seven trials. Studies for HIV positive individuals were only included if the majority of subjects in the study were HIV positive. In particular, we found moderate evidence that the recurrence rates of HSV are lower for HIV-positive individuals on valaciclovir compared to placebo, and the recurrence rates are similar between those on acyclovir when compared to valaciclovir. While studies indicated that HIV-positive individuals on acyclovir as compared to placebo had lower recurrence rates and less viral shedding, these studies had several methodological issues.


Search and appraisal summary

The update literature search for this review was carried out from the date of the last search, January 2010, to October 2013. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 62 studies. After deduplication and removal of conference abstracts, 48 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 28 studies and the further review of 20 full publications. Of the 20 full articles evaluated, no systematic reviews and one RCT was added at this update.


Additional information

In this review we found no randomised controlled trials of sufficient quality comparing famiciclovir with other antiviral therapies. Famciclovir is an oral pro-drug of penciclovir with increased bio-availability and a longer half-life than acyclovir and, therefore, is considered a treatment option for primary genital herpes outbreak. There are studies comparing famciclovir with placebo, showing favourable results.


Substantive changes at this update

Daily oral antiviral treatment (aciclovir, valaciclovir, famciclovir) for preventing recurrence of genital herpes in HIV-positive people One RCT added.[24] Categorisation unchanged (beneficial).


INTRODUCTION: Genital herpes is an infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), and is among the most common sexually transmitted diseases. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different oral antiviral treatments versus each other for a first episode of genital herpes in HIV-negative people? What are the effects of different antiviral treatments for genital herpes in HIV-positive people? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found eight studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir, famciclovir, and valaciclovir.

Cite as

Hollier LM, Eppes C. Genital herpes: oral antiviral treatments. Systematic review 1603. BMJ Clinical Evidence. . 2015 April. Accessed [date].

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