HSV infection

Acyclovir is more effective the more serious the disease and the earher it is given. It has been shown to be efficacious when used systemicaHy in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephaUtis in humans (68). 

The antiviral mechanism of action of acyclovir has been reviewed (72). Acyclovir is converted to the monophosphate in herpes vims-infected cells (but only to a limited extent in uninfected cells) by viral-induced thymidine kinase. It is then further phosphorylated by host cell guanosine monophosphate (GMP) kinase to acyclovir diphosphate [66341 -17-1], which in turn is phosphorylated to the triphosphate by unidentified cellular en2ymes. Acyclovir triphosphate [66341 -18-2] inhibits HSV-1 viral DNA polymerase but not cellular DNA polymerase. As a result, acyclovir is 300 to 3000 times more toxic to herpes vimses in an HSV-infected cell than to the cell itself. Studies have shown that a once-daily dose of acyclovir is effective in prevention of recurrent HSV-2 genital herpes (1). HCMV, on the other hand, is relatively uninhibited by acyclovir. 

Active labial HSV infection. Prescribe prophylaxis with oral antivirals in patients with relapsing HSV (2 days pre- and 5 days post-operatively)... 

Li+ has significant inhibitory effects upon DNA viruses, in particular HSV which has been studied in depth. It was originally shown that Li+ inhibits viral replication in a dose-dependent, reversible manner in HSV-infected baby hamster kidney cells [240], and this has been found to be due to a Li+-induced decrease in the synthesis of viral DNA [241]. It is now well established that Li+ inhibits DNA synthesis in HSV types 1 and 2 and in several other DNA viruses, including measles, vaccinia, adenovirus, poxvirus, pseudorabies virus, Epstein-Barr virus, and the bovine, equine, and canine HV s [241]. Interestingly, Li+ has no effect on the replication of RNA viruses, such as influenza or encephalomyo-carditis virus. 

Although Li+ inhibits the synthesis of viral DNA in HSV-infected cells, it has no effect on that of the host cell DNA, making it an ideal drug for this infection. The synthesis of both viral and host cell polypeptides continues in, but is influenced by, the presence of Li+. In uninfected cells, the synthesis of the host cell polypeptides is unaffected by Li+. However in HSV-infected cells, the virus itself suppresses protein synthesis in the host and it appears that Li+ has the ability to reduce this suppression slightly [242]. Li+ has both stimulatory and inhibitory effects upon the synthesis of the viral polypeptides. For instance, the synthesis of HSV glycoprotein C is significantly decreased by approximately 90% by Li+ treatment. 

Li+ is currently administered topically for the relief of HSV and, in addition, it has been demonstrated that the recurrence of HSV infection is inhibited in Li+-treated patients, indicating another potential prophylactic effect of Li+ [245]. Ointment containing 8% lithium succinate has been shown to reduce the severity and the incidence of recurrent genital HSV infection in man [246]. It has also been proposed that Li+ might be efficacious in treating HIV-infected patients, although any benefits have not yet been demonstrated [247]. While HTV is a RNA virus and as such might not be predicted to be affected by Li+, it is a retrovirus and utilizes a DNA intermediate for its replication and it uses a DNA polymerase. 

Bonneau, R. H. et al., Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection, Brain Behav. Immun., 5, 170, 1991. 

Yorty, J.L. and Bonneau, R. H., Prenatal transfer of low amounts of herpes simplex vims (HSV)-specific antibody protects newborn mice against HSV infection during acute maternal stress, Brain Behav. Immun., 18, 15, 2004. 

Herpes simplex virus (HSV) /nfecf/ons Treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. 

HSV infections Foscarnet is not a cure for HSV infections. While complete healing may occur, relapse occurs in most patients. 

Mucosal and cutaneous HSV infections in immuno-compromised patients 5 mg/kg infused at a constant rate over 1 hour every 8 hours (15 mg/kg/ day) for 7 days- 10 mg/kg infused at a constant rate over 1 hour every 8 hours for 7 days... 

Neonatal HSV infections NA 10 mg/kg infused at a constant rate over 1 hour every 8 hours for 10 days-... 

Intravenous acyclovir is used in the treatment of herpes simplex encephalitis, neonatal HSV infection, and mucocutaneous HSV infection in immunocompromised individuals. Acyclovir ointment is used in the treatment of initial genital herpes but is not effective for recurrent disease. Ophthalmic acyclovir formulations, although not available in the United States, are effective in the treatment of herpes keratoconjunctivitis. 

Acyclovir reduces the extent and duration of VZV lesions in adults and children, although higher doses are required than for the treatment of HSV infection. Although not recommended for the routine treatment of uncomplicated varicella in children, acyclovir may be used for chickenpox treatment and prophylaxis in high-risk individuals. Acyclovir accelerates healing in patients with herpes zoster (shingles), but it does not affect postherpetic neuralgia. 

Cidofovir is approved for the treatment and prophylaxis of CMV retinitis in AIDS patients. It has also been used in the treatment of acyclovir-resistant (viral thymidine kinase-dehcient) HSV infections, polyomavirus-associated progressive multifocal leukoencephalopathy, condylomata acuminata (anogenital warts), and mollus-cum contagiosum. 

Famciclovir is indicated for the treatment of acute herpes zoster (shingles) it is at least as effective in reducing pain and healing time. Famciclovir is generally as effective as acyclovir in the treatment of HSV. In immunocompetent patients, famciclovir is approved for the treatment and prophylaxis of recurrent genital herpes. For HIV-infected individuals, famciclovir is approved for the treatment of all recurrent mucocutaneous HSV infections. 

Foscarnet is approved for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised individuals. A clinical study indicated that it is more effective than vidarabine. Foscarnet has also been used for the treatment of acyclovir-resistant VZV and nonretinitis forms of CMV infection, although its efficacy is not so well established. 

The most commonly observed side effects associated with vidarabine are lacrimation, burning, irritation, pain, and photophobia. Vidarabine has oncogenic and mutagenic potential however, the risk of systemic effects is low because of its limited absorption. It should not be used in conjunction with ophthalmic corticosteroids, since these drugs increase the spread of HSV infection and may produce side effects such as increased intraocular pressure, glaucoma, and cataracts. 

Acyclovir-resistant HSV infection Thin film covering lesion 5 times daily until healed... 

Intravenous acyclovir is the treatment of choice for herpes simplex encephalitis, neonatal HSV infection, and serious HSV or VZV infections (Table 49-1). In immunocompromised patients with VZV infection, intravenous acyclovir reduces the incidence of cutaneous and visceral dissemination. 

Topical acyclovir is substantially less effective than oral therapy for primary HSV infection. It is of no benefit in treating recurrent genital herpes. 

Trifluridine (trifluorothymidine) is a fluorinated pyrimidine nucleoside that inhibits viral DNA synthesis in HSV-1, HSV-2, CMV, vaccinia, and some adenoviruses. It is phosphorylated intracellularly by host cell enzymes, and then competes with thymidine triphosphate for incorporation by the viral DNA polymerase (Figure 49-3). Incorporation of trifluridine triphosphate into both viral and host DNA prevents its systemic use. Application of a 1% solution is effective in treating keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 or HSV-2. Cutaneous application of trifluridine solution, alone or in combination with interferon alfo, has been used successfully in the treatment of acyclovir-resistant HSV infections. 

Acyclovir Mucosal and Cutaneous HSV Infection in Immunocompromised Patients ... 

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