Overview of Herpesvirus Infections: Herpesviruses: Merck Manual Professional

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Herpesviruses

Overview of Herpesvirus Infections

Drug Treatment of Herpesviruses

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Overview of Herpesvirus Infections

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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 or be shed. 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 people can transmit infection. Epstein-Barr virus (EBV) and human herpesvirus type 8 (HHV-8), also known as Kaposi's sarcoma–associated herpesvirus (KSHV), are tightly linked with cancer.

Table 1

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Herpesviruses That Infect Humans
Common Name	Other Name	Typical Manifestations
Herpes simplex virus type 1	Human herpesvirus 1	Gingivostomatitis, keratoconjunctivitis, cutaneous herpes, genital herpes, encephalitis, herpes labialis, esophagitis, pneumonia, hepatitis*^,†
Herpes simplex virus type 2	Human herpesvirus 2	Genital herpes, cutaneous herpes, gingivostomatitis, neonatal herpes, aseptic meningitis, disseminated infection, hepatitis^,†
Varicella-zoster virus	Human herpesvirus 3	Chickenpox, herpes zoster, disseminated herpes zoster*
Epstein-Barr virus	Human herpesvirus 4	Infectious mononucleosis, hepatitis, encephalitis, nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt's lymphoma, lymphoproliferative syndromes, oral hairy leukoplakia
Cytomegalovirus	Human herpesvirus 5	Infectious mononucleosis, hepatitis, congenital cytomegalic inclusion disease, hepatitis, retinitis, pneumonia, colitis
Human herpesvirus 6	—	Roseola infantum, otitis media with fever; encephalitis
Human herpesvirus 7	—	Roseola infantum
Human herpesvirus 8	Kaposi's sarcoma–associated herpesvirus	Not a known cause of acute illness but has a causative role in Kaposi's sarcoma (see Cancers of the Skin: Kaposi's 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
*In immunocompromised hosts.
^†Uncommonly causes fulminant hepatitis without cutaneous lesions in immunocompetent hosts.

Drug Treatment of Herpesviruses

Drugs that have activity against herpesviruses include acyclovirSome Trade Names
ZOVIRAX
Click for Drug Monograph
, cidofovirSome Trade Names
VISTIDE
Click for Drug Monograph
, famciclovirSome Trade Names
FAMVIR
Click for Drug Monograph
, fomivirsenSome Trade Names
VITRAVENE

, foscarnetSome Trade Names
FOSCAVIR
Click for Drug Monograph
, ganciclovirSome Trade Names
CYTOVENE
Click for Drug Monograph
, idoxuridine, penciclovirSome Trade Names
DENAVIR
Click for Drug Monograph
, trifluridineSome Trade Names
VIROPTIC
Click for Drug Monograph
, valacyclovirSome Trade Names
VALTREX
Click for Drug Monograph
, valganciclovirSome Trade Names
VALCYTE
Click for Drug Monograph
, and vidarabine (see Table 2: Herpesviruses: Drugs Used to Treat Herpesvirus Infections).

Table 2

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Drugs Used to Treat Herpesvirus Infections
Drug	Activity	Uses	Some Adverse Effects
AcyclovirSome Trade Names ZOVIRAX Click for Drug Monograph	Active against (in order of potency) HSV type 1 (HSV-1), HSV-2, VZV, and EBV Minimal activity against CMV	Oral or IV (IV indicated when a higher serum drug level is required, as for herpes simplex encephalitis)	Oral: Infrequent; IV: Renal toxicity; in immunocompromised patients, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)
CidofovirSome Trade Names VISTIDE Click for Drug Monograph	In vitro inhibition of a broad spectrum of viruses, including HSV-1, HSV-2, VZV, CMV, EBV, KSHV, adenovirus, HPV, and human polyomavirus	Generally used for CMV, but use limited by renal toxicity	Significant renal toxicity
FamciclovirSome Trade Names FAMVIR Click for Drug Monograph	Antiviral spectrum similar to acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph (strains resistant to acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph also resistant to famciclovirSome Trade Names FAMVIR Click for Drug Monograph )	As effective as acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph for genital herpes and herpes zoster and more bioavailable after oral administration (which is theoretically important for VZV infection)	Infrequent
FomivirsenSome Trade Names VITRAVENE (prodrug of penciclovirSome Trade Names DENAVIR Click for Drug Monograph )	Potent activity against CMV (inhibits CMV protein synthesis)	Intravitreal injection: For patients with HIV infection and CMV retinitis that is resistant to other therapies	Increased intraocular pressure, corticosteroid-responsive uveitis
FoscarnetSome Trade Names FOSCAVIR Click for Drug Monograph	Active against EBV, KSHV, human herpesvirus 6, acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph -resistant (and acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph -susceptible) HSV and VZV, and ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph -resistant (and ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph -susceptible) CMV Some anti-HIV activity	Efficacy similar to that of ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph for treating and delaying progression of CMV retinitis	Renal toxicity, electrolyte imbalances
GanciclovirSome Trade Names CYTOVENE Click for Drug Monograph	In vitro activity against all herpesviruses, including CMV, but HSV strains that are resistant to acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph also cross-resistant to ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph Used in patients with both HIV and CMV retinitis	IV form most common Oral: Only 6 to 9% bioavailable; requires 12 capsules/day for a standard dose (1 g tid), limiting its usefulness	Primarily, bone marrow suppression, particularly neutropenia, which sometimes requires treatment*
Idoxuridine	Active against HSV-1, HSV-2, VZV, vaccinia, and CMV	Topical: Because of its high systemic toxicity, limited to topical ophthalmic treatment of herpes simplex keratoconjunctivitis	Systemic toxicity Irritation, pain, photophobia, pruritus, inflammation or edema of the eyelids Rarely, allergic reactions
PenciclovirSome Trade Names DENAVIR Click for Drug Monograph	Active against HSV-1, HSV-2, VZV, CMV, and EBV	Topical (cream): Used to treat recurrent herpes labialis in adults	Erythema
TrifluridineSome Trade Names VIROPTIC Click for Drug Monograph (trifluorothymidine)	Active against HSV-1 and HSV-2	Topical: Ophthalmic treatment of primary keratoconjunctivitis and recurrent keratitis or ulceration caused by HSV-1 and HSV-2 As effective as vidarabine and possibly effective in patients who have not responded to idoxuridine or vidarabine	Bone marrow suppression (which precludes systemic use), ocular stinging, palpebral edema Less commonly, punctate keratitis, allergic reactions
ValacyclovirSome Trade Names VALTREX Click for Drug Monograph (prodrug of acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph )	Antiviral spectrum similar to that of acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph	3–5 times more bioavailable than acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph	Similar to those of acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph TTP/HUS in some patients with advanced HIV and in transplant recipients who received valacyclovirSome Trade Names VALTREX Click for Drug Monograph in higher doses than currently recommended^†
ValganciclovirSome Trade Names VALCYTE Click for Drug Monograph	Similar to ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph	Oral: Taken as two 450-mg tablets once/day or bid (more bioavailable than ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph )	Similar to ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph
Vidarabine (adenine arabinoside, ara-A)	For HSV infections Appears less susceptible to development of drug resistance than idoxuridine	IV form not used anymore Ophthalmic preparations: Effective for acute keratoconjunctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2	Neurotoxicity limiting IV use Superficial punctate keratitis with tearing, irritation, pain, and photophobia
*Severe neutropenia (< 500 neutrophils/μL) may require bone marrow stimulation with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, or ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph may be stopped. ^† ValacyclovirSome Trade Names VALTREX Click for Drug Monograph should be used with caution in patients with advanced HIV and in transplant recipients.
CMV = cytomegalovirus; EBV = Epstein-Barr virus; HPV = human papillomavirus; HSV = herpes simplex virus; KSHV = Kaposi's sarcoma–associated herpesvirus; VZV = varicella-zoster virus.

Drugs Used to Treat Herpesvirus Infections

Drug

Activity

Uses

Some Adverse Effects

AcyclovirSome Trade Names ZOVIRAX Click for Drug Monograph	Active against (in order of potency) HSV type 1 (HSV-1), HSV-2, VZV, and EBV Minimal activity against CMV	Oral or IV (IV indicated when a higher serum drug level is required, as for herpes simplex encephalitis)	Oral: Infrequent; IV: Renal toxicity; in immunocompromised patients, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)
CidofovirSome Trade Names VISTIDE Click for Drug Monograph	In vitro inhibition of a broad spectrum of viruses, including HSV-1, HSV-2, VZV, CMV, EBV, KSHV, adenovirus, HPV, and human polyomavirus	Generally used for CMV, but use limited by renal toxicity	Significant renal toxicity
FamciclovirSome Trade Names FAMVIR Click for Drug Monograph	Antiviral spectrum similar to acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph (strains resistant to acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph also resistant to famciclovirSome Trade Names FAMVIR Click for Drug Monograph )	As effective as acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph for genital herpes and herpes zoster and more bioavailable after oral administration (which is theoretically important for VZV infection)	Infrequent
FomivirsenSome Trade Names VITRAVENE (prodrug of penciclovirSome Trade Names DENAVIR Click for Drug Monograph )	Potent activity against CMV (inhibits CMV protein synthesis)	Intravitreal injection: For patients with HIV infection and CMV retinitis that is resistant to other therapies	Increased intraocular pressure, corticosteroid-responsive uveitis
FoscarnetSome Trade Names FOSCAVIR Click for Drug Monograph	Active against EBV, KSHV, human herpesvirus 6, acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph -resistant (and acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph -susceptible) HSV and VZV, and ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph -resistant (and ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph -susceptible) CMV Some anti-HIV activity	Efficacy similar to that of ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph for treating and delaying progression of CMV retinitis	Renal toxicity, electrolyte imbalances
GanciclovirSome Trade Names CYTOVENE Click for Drug Monograph	In vitro activity against all herpesviruses, including CMV, but HSV strains that are resistant to acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph also cross-resistant to ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph Used in patients with both HIV and CMV retinitis	IV form most common Oral: Only 6 to 9% bioavailable; requires 12 capsules/day for a standard dose (1 g tid), limiting its usefulness	Primarily, bone marrow suppression, particularly neutropenia, which sometimes requires treatment*
Idoxuridine	Active against HSV-1, HSV-2, VZV, vaccinia, and CMV	Topical: Because of its high systemic toxicity, limited to topical ophthalmic treatment of herpes simplex keratoconjunctivitis	Systemic toxicity Irritation, pain, photophobia, pruritus, inflammation or edema of the eyelids Rarely, allergic reactions
PenciclovirSome Trade Names DENAVIR Click for Drug Monograph	Active against HSV-1, HSV-2, VZV, CMV, and EBV	Topical (cream): Used to treat recurrent herpes labialis in adults	Erythema
TrifluridineSome Trade Names VIROPTIC Click for Drug Monograph (trifluorothymidine)	Active against HSV-1 and HSV-2	Topical: Ophthalmic treatment of primary keratoconjunctivitis and recurrent keratitis or ulceration caused by HSV-1 and HSV-2 As effective as vidarabine and possibly effective in patients who have not responded to idoxuridine or vidarabine	Bone marrow suppression (which precludes systemic use), ocular stinging, palpebral edema Less commonly, punctate keratitis, allergic reactions
ValacyclovirSome Trade Names VALTREX Click for Drug Monograph (prodrug of acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph )	Antiviral spectrum similar to that of acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph	3–5 times more bioavailable than acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph	Similar to those of acyclovirSome Trade Names ZOVIRAX Click for Drug Monograph TTP/HUS in some patients with advanced HIV and in transplant recipients who received valacyclovirSome Trade Names VALTREX Click for Drug Monograph in higher doses than currently recommended^†
ValganciclovirSome Trade Names VALCYTE Click for Drug Monograph	Similar to ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph	Oral: Taken as two 450-mg tablets once/day or bid (more bioavailable than ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph )	Similar to ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph
Vidarabine (adenine arabinoside, ara-A)	For HSV infections Appears less susceptible to development of drug resistance than idoxuridine	IV form not used anymore Ophthalmic preparations: Effective for acute keratoconjunctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2	Neurotoxicity limiting IV use Superficial punctate keratitis with tearing, irritation, pain, and photophobia
*Severe neutropenia (< 500 neutrophils/μL) may require bone marrow stimulation with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, or ganciclovirSome Trade Names CYTOVENE Click for Drug Monograph may be stopped. ^† ValacyclovirSome Trade Names VALTREX Click for Drug Monograph should be used with caution in patients with advanced HIV and in transplant recipients.
CMV = cytomegalovirus; EBV = Epstein-Barr virus; HPV = human papillomavirus; HSV = herpes simplex virus; KSHV = Kaposi's sarcoma–associated herpesvirus; VZV = varicella-zoster virus.

Last full review/revision December 2009 by Kenneth M. Kaye, MD

Content last modified February 2012

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