What is the difference between Herpes Simplex Virus (HSV) type 1 and Herpes Simplex Virus (HSV) type 2?

From the Guidelines

The primary distinction between HSV-1 and HSV-2 lies in their typical sites of infection, with HSV-1 commonly causing oral herpes and HSV-2 primarily causing genital herpes, although both types can infect either location through oral-genital contact. When considering management approaches, the goals are to prevent symptoms/recurrences, improve quality of life, and prevent transmission to sexual partners, with the recommended approaches differing based on the viral type (HSV-1 vs HSV-2) and the presence or absence of symptoms 1. Key differences between HSV-1 and HSV-2 include their prevalence, transmission modes, and recurrence rates, with HSV-1 being more common and often contracted non-sexually, while HSV-2 is mainly transmitted sexually and tends to cause more frequent recurrences in genital infections 1. Some of the key points to consider in the management of genital herpes include:

• The use of type-specific molecular or virologic tests for accurate diagnosis when genital ulcers are present, and type-specific serologic tests when lesions are not present 1.
• Management options such as episodic antiviral therapy for recurrent episodes or suppressive antiviral therapy to prevent recurrences and shedding, with medications like acyclovir, valacyclovir, or famciclovir being effective for both types 1.
• The importance of patient education on the natural history of the infection to combat stigma, and the consideration of the potential for extragenital manifestations and the impact on HIV acquisition and transmission 1. Given the lifelong nature of both infections and the potential for significant morbidity and impact on quality of life, a comprehensive approach to diagnosis, treatment, and prevention of transmission is crucial, taking into account the specific characteristics of each viral type and the individual patient's circumstances.

From the FDA Drug Label

Valacyclovir hydrochloride is rapidly converted to acyclovir, which has demonstrated antiviral activity against HSV types 1 (HSV‑1) and 2 (HSV‑2) and VZV both in cell culture and in vivo The quantitative relationship between the cell culture susceptibility of herpesviruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized Using plaque‑reduction assays, the EC 50 values against herpes simplex virus isolates range from 0.09 to 60 microM (0.02 to 13.5 mcg/mL) for HSV‑1 and from 0.04 to 44 microM (0.01 to 9. 9 mcg/mL) for HSV‑2 In cells infected with HSV-1, HSV-2 or VZV, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate The median EC50 values of penciclovir against laboratory and clinical isolates of HSV-1, and HSV-2, and VZV were 2 μM (range 1.2 to 2.4 μM, n = 7), and 2.6 μM (range 1.6 to 11 μM, n=6), respectively

Key Points:

• Both valacyclovir and famciclovir have antiviral activity against HSV-1 and HSV-2.
• The EC50 values for valacyclovir against HSV-1 and HSV-2 range from 0.09 to 60 microM and 0.04 to 44 microM, respectively.
• The EC50 values for famciclovir against HSV-1 and HSV-2 are 2 μM and 2.6 μM, respectively.
• Resistance to valacyclovir and famciclovir can occur due to mutations in the viral thymidine kinase and DNA polymerase genes.
• Cross-resistance has been observed among HSV isolates carrying frameshift mutations and resistance-associated substitutions. 2 3

From the Research

HSV 1 vs 2: Key Differences

• HSV-1 and HSV-2 are two types of herpes simplex virus, with HSV-1 traditionally associated with orofacial infections and HSV-2 with anogenital infections 4.
• However, HSV-1 is increasingly the cause of genital infections, highlighting the need for accurate diagnosis and treatment 4.
• Patients with HSV-2 have a higher risk of acquiring human immunodeficiency virus (HIV) infection 5.

Treatment and Management

• Current treatments, such as acyclovir, target viral DNA polymerase but have limited efficacy and are susceptible to resistance, especially in immunosuppressed populations 4.
• Valacyclovir, a prodrug of acyclovir, has been shown to be effective in suppressing recurrent episodes of genital herpes and reducing viral shedding 6, 7.
• Famciclovir, another antiviral drug, has also been shown to be effective in reducing symptomatic and asymptomatic reactivation of HSV-2, although valacyclovir may be somewhat better for suppression of genital herpes and associated shedding 8.

Epidemiology and Prevalence

• HSV-1 and HSV-2 are highly prevalent, infecting approximately 64% and 13% of the world's population, respectively 4.
• Genital herpes is a common sexually transmitted disease, affecting more than 400 million persons worldwide 5.
• The clinical spectrum of HSV disease ranges from mild cold sores to severe conditions such as encephalitis or systemic infection, particularly in immunocompromised individuals and neonates 4.