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” long before HHV type 6 was recognized. There is no specific disease linked to HHV type 7; however, this is a T-cell lymphotropic virus that has also serologically been associated with roseola. 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, is a nonhuman herpes virus that is of great importance to humans because of the high mortality rate from encephalomyelitis in persons infected with this 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. Vidarabine was previously approved for systemic use for herpes but was discontinued because its neurotoxicity and the advent of acyclovir, a safer agent. Acyclovir (9-2-hydroxyethoxymethyl guanine) is the most widely prescribed antiviral drug in the world. After its oral intake acyclovir becomes phosphorylated by a thymidine kinase (TK) specific for the herpes virus, resulting in a mono-phosphorylated form of acyclovir that must then be bi-and tri-phosphorylated by cellular enzymes. The triphosphate form inhibits viral DNA polymerase, resulting in chain termination. The herpesvirus-infected cells produce TK at a rate 100 times greater than that produced by uninfected cells after the uptake of acyclovir.
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 five times per day for 10 days, and for recurrent herpes the same dose can be used for 5 days. For greater convenience, 400 mg of ACV three times per day can be used in place of 200 mg five times per day. Acyclovir has a greater effect on first episode genital herpes than on recurrent disease, but if initiated during the prodrome of a recurrence, it may show significant benefit. If taken daily, acyclovir suppresses the signs and symptoms of genital herpes as well as reduces asymptomatic viral shedding of HSV2 by 95%. For patients with significantly severe or frequently recurring outbreaks, ACV suppression with 400 mg twice daily reduces the frequency of genital herpes by 80% to 90% and herpes labialis by 50% to 78%.
The recommended oral dose of acyclovir for chickenpox is 20 mg/kg four times daily; in adults, the average dose is 800 mg five times per day. Treatment needs to be initiated early for it to be effective. Viral replication usually starts about 2 weeks prior to the development of signs and symptoms. The initiation of acyclovir does not affect the humoral response to VZV, hence there is an adequate antibody response to VZV in patients treated with acyclovir.