Varicella-zoster virus infection acyclovir

Jacobson M, Berger T, Fikrig S, et al. Acyclovir-resistant varicella-zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1990 112 187-191. 

Shepp DH, Dandliker PS, Meyers ID. Treatment of varicella-zoster virus infection in severefy immunocompromised patients arandomizedcompaiisonof acyclovir and vidarabine. NEr l JMed 9 314,208-12. 

Acyclovir (ACV) is not a true nucleoside, because the guanine residue is attached to an open-chain structure, but it mimics deoxyribose well enough for the compound to be accepted as a substrate by a thymidine kinase specified by certain herpes-type viruses. The normal thymidine kinase in mammalian cells does not recognize ACV as a substrate, however, so only virus-infected cells convert ACV to its monophosphate. Once the first phosphate has been added, the second phosphate is added by cellular guanylate kinase several other cellular kinases can add the third phosphate. The triphosphate is a more potent inhibitor of the viral DNA polymerases than of cellular DNA polymerases and also inactivates the former but not the latter. The net result is that ACV has been an effective treatment of, and prophylaxis for, genital herpes. Also it can result in dramatic relief of pain associated with shingles caused by reactivation of latent varicella-zoster virus, and has been successful in many patients with herpes encephalitis. 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Cidofovir is an acyclic nucleotide analogue of the monophosphate of cytosine. When phosphorylated by host cellular enzymes, the active compound cidofovir diphosphate has broad activity against the herpes viruses, including CMV, herpes simplex viruses 1 and 2, varicella zoster virus and Epstein-Barr virus. Cidofovir is used primarily in treatment of CMV retinitis in patients who have failed treatment with ganciclovir or foscamet and in acyclovir-resistant herpes simplex infections. 

Famciclovir, the oral formulation of penciclovir, is a new antiherpes agent that is well absorbed following oral administration with little intersubject variability, and is rapidly converted to penciclovir with a bioavailability of 77%. Furthermore, although the activities of penciclovir and acyclovir against varicella-zoster virus (VZV) in infected cell lines appear to be comparable, penciclovir-triphosphate persists in virus-infected cells far longer than acyclovir-triphosphate, resulting in more prolonged antiviral activity. The intracellular half-life of penciclovir-triphosphate in VZV-infected cells is reported to be 9 hours, whereas that of... 

Foscamet is an antiviral agent that inhibits replication of all known herpes viruses, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV). It is indicated in the treatment of CMV retinitis in patients with AIDS treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and as combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

The first systemically administered antiherpesvirus agent, vidarabine, was approved by the Food and Drug Administration (FDA) in 1977. However, its toxicities restricted its use to life-threatening infections of HSV and varicella-zoster virus (VZV). The discovery and development of acyclovir, approved in 1982, provided the first effective treatment for less severe HSV and VZV infections in ambulatory patients. Intravenous acyclovir is superior to vidarabine in terms of efficacy and toxicity in HSV encephalitis and in VZV infections of immunocompromised patients. Acyclovir is the prototype of a group of antiviral agents that are phosphorylated intraceUularly by a viral... 

Vidarabine Vidarabine is an adenine analog and has activity against HSV, VZV, and CMV. Its use for systemic infections is limited by rapid metabolic inactivation and by marked toxic potential. However, it has been used intravenously for severe HSV infections, including those resistant to acyclovir, and it also prevents the dissemination of varicella-zoster virus in immunocompromised patients. Vidarabine is used topically for herpes keratitis, but it has no effect on genital lesions. Toxic effects with systemic use include gastrointestinal irritation, paresthesias, tremor, convulsions, and hepatic dysfunction. Vidarabine is teratogenic in animals. 

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV) is clinically useful in the treatment of infections caused by several members of the herpes virus (e.g., herpes simplex, varicella zoster and Epstein-Barr virus [2,38,39]). An enzyme coded for by the virus phosphorylates ACV to a monophosphate intermediate. This species in turn undergoes further phosphorylation to a triphosphate with the aid of normal cell enzymes. Then, ACV triphosphate inhibits the herpes virus DNA... 

Herpes simplex virus (HSV) infections in transplant patients are most commonly the result of reactivation of a previous infection. Symptomatic HSV infection usually presents as labial or oral lesions in the first 1 to 3 months after transplantation, but patients also may present with reactivation of varicella-zoster as shingles. Prophylactic therapy with low-dose oral acyclovir delays the development of HSV infections in patients following transplantation. 

Vidarabine is a purine nucleoside analogue active against herpes viruses, influenza viruses, and some RNA viruses. Use of vidarabine for treatment of herpes simplex and varicella-zoster infections has largely been supplanted by acyclovir because of the superior efficacy, fewer adverse effects, and easier administration of the latter agent. Vidarabine has been associated with significant gastrointestinal, neurologic, and hematopoietic toxicities. Patients with renal insuffi-... 

Parenteral acyclovir (e.g., 5 mg/kg infused at a constant rate over 1 hour every 8 hours for 7 days) may be used in mucosal and cutaneous herpes simplex virus infections, and in varicella zoster infections (shingles) in immunocompromised patients and in herpes simplex encephalitis. 

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