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Eight types of herpesviruses infect humans (see Table 1: Herpesviruses: Herpesviruses That Infect Humans ). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently reactivate. Herpesviruses do not survive long outside a host; thus, transmission usually requires intimate contact, although varicella-zoster virus (VZV) may spread by aerosol. In people with latent infection, the virus can reactivate without causing symptoms; in such cases, asymptomatic shedding occurs and people can transmit infection. Epstein-Barr virus (EBV) and human herpesvirus type 8 (HHV-8), also known as Kaposi sarcoma–associated herpesvirus (KSHV), can cause certain cancers. Roseola infantum, a childhood disease caused by herpesvirus 6 (and sometimes 7) is discussed elsewhere (see Miscellaneous Viral Infections in Infants and Children: Roseola Infantum).
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Table 1
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| Herpesviruses That Infect Humans |
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Common Name
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Other Name
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Typical Manifestations
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Herpes simplex virus type 1
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Human herpesvirus 1
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Gingivostomatitis, keratoconjunctivitis, cutaneous herpes, genital herpes, encephalitis, herpes labialis, esophagitis*, pneumonia*, hepatitis*,†
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Herpes simplex virus type 2
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Human herpesvirus 2
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Genital herpes, cutaneous herpes, gingivostomatitis, neonatal herpes, aseptic meningitis, disseminated infection*, hepatitis*,†
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Varicella-zoster virus
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Human herpesvirus 3
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Chickenpox, herpes zoster, disseminated herpes zoster*
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Epstein-Barr virus
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Human herpesvirus 4
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Infectious mononucleosis, hepatitis, encephalitis, nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, lymphoproliferative syndromes*, oral hairy leukoplakia*
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Cytomegalovirus
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Human herpesvirus 5
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Infectious mononucleosis, hepatitis, congenital cytomegalic inclusion disease, hepatitis*, retinitis*, pneumonia*, colitis*
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Human herpesvirus 6
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—
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Roseola infantum, otitis media with fever; encephalitis
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Human herpesvirus 7
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—
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Roseola infantum
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Kaposi sarcoma–associated herpesvirus
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Human herpesvirus 8
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Not a known cause of acute illness but has a causative role in Kaposi sarcoma (see Cancers of the Skin: Kaposi Sarcoma)* and AIDS-related non-Hodgkin lymphomas that grow primarily in the pleural, pericardial, or abdominal cavities as lymphomatous effusions
Also linked with multicentric Castleman disease
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*In immunocompromised hosts.
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†Uncommonly causes fulminant hepatitis without cutaneous lesions in immunocompetent hosts.
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Drug Treatment of Herpesviruses
Drugs that have activity against herpesviruses include acyclovir, cidofovir, famciclovir, fomivirsen, foscarnet, ganciclovir, idoxuridine, penciclovir, trifluridine, valacyclovir, valganciclovir, and vidarabine (see Table 2: Herpesviruses: Drugs Used to Treat Herpesvirus Infections).
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Table 2
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| Drugs Used to Treat Herpesvirus Infections |
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Drug
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Activity
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Uses
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Adverse Effects
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Acyclovir
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Active against (in order of potency) HSV type 1 (HSV-1), HSV-2, VZV, and EBV
Minimal activity against CMV
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Oral or IV (IV indicated when a higher serum drug level is required, as for herpes simplex encephalitis)
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Oral: Infrequent
IV: Rarely, renal toxicity due to precipitation of acyclovir crystals; in immunocompromised patients, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)
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Cidofovir
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In vitro inhibition of a broad spectrum of viruses, including HSV-1, HSV-2, VZV, CMV, EBV, KSHV, adenovirus, HPV, and human polyomavirus
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Generally used for CMV, but use limited by renal toxicity
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Significant renal toxicity
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Famciclovir (prodrug of penciclovir)
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Antiviral spectrum similar to acyclovir (strains resistant to acyclovir also resistant to famciclovir)
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As effective as acyclovir for genital herpes and herpes zoster and more bioavailable than acyclovir after oral administration (which is theoretically important for VZV infection)
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Infrequent
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Fomivirsen
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Potent activity against CMV (antisense oligonucleotide inhibits CMV protein synthesis)
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Intravitreal injection: For patients with HIV infection and CMV retinitis that is resistant to other therapies
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Increased intraocular pressure, corticosteroid-responsive uveitis
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Foscarnet
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Active against EBV, KSHV, human herpesvirus 6, acyclovir-resistant (and acyclovir-susceptible) HSV and VZV, and ganciclovir-resistant (and ganciclovir-susceptible) CMV
Some anti-HIV activity
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Efficacy similar to that of ganciclovir for treating and delaying progression of CMV retinitis
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Renal toxicity in up to one third of patients if foscarnet is given without adequate hydration, electrolyte imbalances
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Ganciclovir
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In vitro activity against all herpesviruses, including CMV, but HSV strains that are resistant to acyclovir also cross-resistant to ganciclovir
Used in patients with both HIV and CMV retinitis
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IV form most common
Oral: Only 6 to 9% bioavailable; requires 12 capsules/day for a standard dose (1 g tid), limiting its usefulness
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Primarily, bone marrow suppression, particularly neutropenia, which sometimes requires treatment*
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Idoxuridine
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Active against HSV-1, HSV-2, VZV, vaccinia, and CMV
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Topical: Because of its high systemic toxicity, limited to topical ophthalmic treatment of herpes simplex keratoconjunctivitis
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Systemic toxicity
Irritation, pain, photophobia, pruritus, inflammation or edema of the eyelids
Rarely, allergic reactions
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Penciclovir
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Active against HSV-1, HSV-2, VZV, CMV, and EBV
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Topical (cream): Used to treat recurrent herpes labialis in adults
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Erythema
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Trifluridine (trifluorothymidine)
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Active against HSV-1 and HSV-2
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Topical: Ophthalmic treatment of primary keratoconjunctivitis and recurrent keratitis or ulceration caused by HSV-1 and HSV-2
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Bone marrow suppression (which precludes systemic use), ocular stinging, palpebral edema
Less commonly, punctate keratitis, allergic reactions
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Valacyclovir (prodrug of acyclovir)
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Antiviral spectrum similar to that of acyclovir
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3–5 times more bioavailable than acyclovir
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Similar to those of acyclovir
TTP/HUS in some patients with advanced HIV and in transplant recipients who received valacyclovir in higher doses than currently recommended†
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Valganciclovir
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Similar to ganciclovir
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Oral: Taken as two 450-mg tablets once/day or q 12 h (more bioavailable than oral ganciclovir)
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Similar to ganciclovir
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Vidarabine (adenine arabinoside, ara-A)
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For HSV infections
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IV form not used anymore because of neurotoxicity
Ophthalmic preparations: Effective for acute keratoconjunctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2
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Superficial punctate keratitis with tearing, irritation, pain, and photophobia
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*Severe neutropenia (< 500 neutrophils/μL) may require bone marrow stimulation with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, or ganciclovir may be stopped, or the dose may be reduced.
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†
Valacyclovir should be used with caution in patients with advanced HIV and in transplant recipients.
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CMV = cytomegalovirus; EBV = Epstein-Barr virus; HPV = human papillomavirus; HSV = herpes simplex virus; KSHV = Kaposi sarcoma–associated herpesvirus; VZV = varicella-zoster virus.
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Last full review/revision April 2013 by Kenneth M. Kaye, MD
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