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HERPES SIMPLEX VIRUS AND OTHER HUMAN HERPES VIRUSES

The human herpes viruses (HHV) are double-stranded linear DNA viruses that cause a variety of different cutaneous manifestations. Included in the herpes family are herpes simplex virus type 1 and type 2, known to cause cold sores and genital lesions, respectively, although both types of lesions can be caused by either virus. These two subtypes have also been known to cause gingivostomatitis, herpes gladiatorum, eczema herpeticum, herpes whitlow, neonatal herpes, lumbosacral herpes, herpetic keratoconjunctivitis, herpes encephalitis, and cervicitis, and are a leading cause of erythema multiforme.

Human herpes virus type 3 (varicella zoster) presents in its primary form as chickenpox, and in a recurrent form as herpes zoster or shingles. Epstein-Barr virus (EBV) (HHV4) is commonly known to cause infectious mononucleosis.

Human herpes virus type 5 is more commonly known as cytomegalovirus (CMV) and is the leading cause of blindness in AIDS patients and a leading infectious cause of fetal abnormalities. Human herpes virus type 6 (HHV 6) is recognized as the cause of exanthem subitum (roseola infantum), which was known as "sixth disease."

Human herpes virus type 8 (HHV8) is associated with Kaposi's sarcoma (KS) in HIV-infected persons as well as with classic KS. Herpesvirus simiae, also known as B virus.

Ten drugs are FDA-approved for treatment of herpes virus infections. Idoxuridine, trifluridine, and vidarabine are ophthalmic preparations used for herpes keratitis and keratoconjunctivitis.

The most widely used form of acyclovir (ACV) is the oral form. Oral ACV is used for the therapy of oral, genital, and other HSV infections. For first episode genital herpes, the usual dose of ACV is 200 mg.

Because of the low bioavailability of oral ACV and the frequent dosing schedule, two additional drugs were approved for treatment of herpes. Both of these new drugs provide more convenient dosing and greater bioavailability than does oral acyclovir. Famciclovir (FCV) is the oral prodrug form of the acyclic nucleoside penciclovir, which must be phosphorylated like acyclovir to be active. Penciclovir triphosphate has a much longer intracellular half life than does acyclovir triphosphate (i.e., the T1/2 of penciclovir).

Valacyclovir (VACV) is a 1-valyl ester of ACV. This drug has a five times greater bioavailability than oral ACV, reaching plasma levels of ACV similar to the level attained.

Sorivudine (1-B-D-arabinofuranosyl-E-5-2-bromovinyl) uracil (BV-ara-U) is a synthetic deoxythymidine nucleoside analogue that is 1000 times.

Three drugs are approved for CMV retinitis and other CMV infections: foscarnet, ganciclovir, and cidofovir, all of which are given intravenously.

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