Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice

Sarisky, Robert T.; Bartus, H Ron; Dennis, Shelley A; Quail, Matthew R.; Nguyen, Tammy T.; Wittrock, Robert J.; Halsey, Wendy S.; Bacon, Teresa H.; Leary, Jeffry J.; Sutton, David

doi:10.1186/1471-2334-1-24

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…The effect of serial passage of HSV in immunocompetent mice treated with suboptimal doses of oral valacyclovir or the similar prodrug famciclovir has been studied by means of plaque-reduction and plating-efficiency assays in parallel to monitor the emergence of resistance [85]. Only 1 of 140 virus isolates from mice treated with the antivirals was drug-resistant, by the plaque-reduction assay, during 7 sequential passages of either HSV-1 or HSV-2.…”

Section: Antiviral Selective Pressure and Emergence Of Resistant Hsvmentioning

confidence: 99%

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Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

2004

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Antiviral treatment of herpes simplex virus (HSV) infections with nucleoside analogues has been well established for >2 decades, but isolation of drug-resistant HSV from immunocompetent patients has remained infrequent (0.1%-0.7% of isolates) during this period. Even when drug-resistant HSV is isolated from an immunocompetent patient, this virus, with rare exceptions, is cleared normally without adverse clinical outcome. Although drug-resistant HSV is more commonly isolated from immunocompromised patients (4%-7% of isolates) and is more likely to be clinically significant, the prevalence of drug-resistant HSV even among these patients, has been stable over the past 2 decades. Despite this stable prevalence, disease due to drug-resistant HSV remains an important problem for many immunocompromised patients, including those with HIV infection. This article reviews the prevalence, pathogenesis, and implications of drug-resistant HSV infections in HIV-infected patients.

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Section: Antiviral Selective Pressure and Emergence Of Resistant Hsvmentioning

confidence: 99%

“…Two relatively recent publications attempt to address effects of selective pressure on HSV resistance in humans and an animal model [54,85].…”

Section: Antiviral Selective Pressure and Emergence Of Resistant Hsvmentioning

confidence: 99%

Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

2004

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“…The effect of serial passage of HSV in immunocompetent mice treated with suboptimal doses of oral famciclovir or valaciclovir has been studied by using the plaque reduction and plating efficiency assays in parallel to monitor the emergence of resistance (76). Mice were infected in the ear pinnae with 10 5 PFU of HSV-1 or HSV-2 and treated with the antivirals for 4 days via the drinking water (0.2 mg/ml, providing an estimated daily dose of 15 mg/kg).…”

Section: Proportion Of Resistant Virus Within Mixed Populationsmentioning

confidence: 99%

Herpes Simplex Virus Resistance to Acyclovir and Penciclovir after Two Decades of Antiviral Therapy

et al. 2003

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Acyclovir, penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections. In spite of the distribution of over 2.3 × 106 kg of these nucleoside analogues, the prevalence of acyclovir resistance in herpes simplex virus isolates from immunocompetent hosts has remained stable at approximately 0.3%. In immuncompromised patients, in whom the risk for developing resistance is much greater, the prevalence of resistant virus has also remained stable but at a higher level, typically 4 to 7%. These observations are examined in the light of characteristics of the virus, the drugs, and host factors

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“…A single mutation in DNA pol enzyme may confer resistance to many anti-HSV agents. 53 , 54 , 55 For example, most ACV-resistant HSV isolates are also resistant to penciclovir because of a mutation in viral DNA polymerase.…”

Section: Herpes Simplex Virus and Drug Resistancementioning

confidence: 99%

New strategies against drug resistance to herpes simplex virus

et al. 2016

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Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV.

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Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice

Cited by 5 publications

References 25 publications

Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

Herpes Simplex Virus Resistance to Acyclovir and Penciclovir after Two Decades of Antiviral Therapy

New strategies against drug resistance to herpes simplex virus

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