Although global attention is correctly focused on addressing the newly arrived COVID-19, a perennial challenge remains from herpes simplex virus (HSV), which has been with us since ancient times. Over 2000 years ago, Hippocrates described spreading skin lesions, and Greek scholars defined the word herpes ‘to creep or crawl’. The ancient Greek historian Herodotus defined the association of mouth ulcers with fever as ‘herpes febralis’, and by the 18th century, the king of France's physician, Astruc, had described the lesions associated with genital herpes (Whitley and Gnann, 1993).
HSV type 1 (HSV-1) most commonly affects the mouth and lips (Whitley and Gnann, 1993). Gottlieb et al (2017) noted that more than 500 million people globally have genital HSV infection, and HSV type 2 (HSV-2) is the leading cause of genital ulcer disease worldwide. Further, the latent nature of all herpes virus infections presents a challenge in terms of treatment and management.
The revolution in antiviral therapy began in 1977, with the launch of acyclovir (now aciclovir) as Zovirax, a safe, specific anti-herpes agent (Brigden et al, 1981). Although the standard treatment for orofacial herpes is typically aciclovir, current products have a reduced ability to promote drug skin penetration and tend to leak from the application site, a problem that has been addressed by Costa et al (2019). They have shown how aciclovir-impregnated dressings, constructed from a fibrous matrix, have the potential to enhance the topical treatment of orofacial herpes by providing a sustained release of aciclovir, while improving the skin permeability of the drug (Costa et al, 2019).
However, as Piret and Boivin (2016) indicate, not only can the long-term administration of aciclovir for the treatment of severe infections in immunocompromised patients promote the development of drug resistance, but the prevalence of aciclovir-resistant HSV isolates among immunocompetent individuals can range from 0.1 to 0.7%, and has reached 6.4% in immunocompetent patients with herpetic keratitis.
This raises the question of a vaccine against HSV, which Gottlieb et al (2019) acknowledge as an important global goal for sexual and reproductive health. It was encouraging when Bernstein et al (2017) reported that a vaccine trial of 134 individuals with genital HSV-2 ‘was shown to have an acceptable safety profile, reduce viral shedding, reduce the frequency of genital lesions, and boost the humoral and cellular immune responses to HSV-2’. Similarly, Dropulic et al (2019) found that their ‘first-in-human study of the replication-defective HSV vaccine HSV529 was safe and well-tolerated, with evidence of immunogenicity in HSV-naive and previously infected subjects’.
The apparent readiness with which individuals with genital herpes are willing to participate in trials of antiviral agents and possible vaccines may stem from the association of genital herpes with profound psychological distress, which, as Oseso et al (2016) point out, may be more burdensome to a patient than the discomfort of recurrent genital lesions. Perhaps it is such eagerness to participate in finding an effective treatment or cure that helps explain how patients were recruited into a criminal enterprise, reported by Dyer (2018). Dyer's report describes how the United States Food and Drug Administration investigated a microbiologist who had conducted an experimental live HSV-2 vaccine trial ‘in Illinois hotel rooms, with no apparent safety oversight, consent forms, or ethics approval’.
‘The apparent readiness with which individuals with genital herpes are willing to participate in trials of antiviral agents and possible vaccines may stem from the association of genital herpes with profound psychological distress’
Leaving aside acts of criminality, there are diverse ethical aspects to the management of patients with recurrent genital herpes, and pharmacists offering advice on sexual health might benefit from a heightened awareness of what they might include. For example, Krantz et al (2004) consider serology screening tests for HSV-2 infection, which is mostly asymptomatic and incurable. They balance patient autonomy against public health concerns and conclude that such screening cannot be ethically justified. And Dunphy (2014) reflects on the moral question of whether a person with genital herpes who is shedding virus ought to be sexually active, noting that ‘the decision does not relate to the health of that individual but to his or her propensity to inflict avoidable harm on others’. Dunphy (2014) also points out that 2011 saw the first successful criminal prosecution in the UK in relation to the transmission of genital herpes from one person to another.
It seems that despite the ancient origins of HSV and progress in the management of its infections, HSV will continue to pose ethical challenges for healthcare professionals.