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

Bacon, Teresa H.; Levin, Myron J.; Leary, Jeffry J.; Sarisky, Robert T.; Sutton, David

doi:10.1128/cmr.16.1.114-128.2003

Cited by 434 publications

(388 citation statements)

References 105 publications

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“…In fact, Kreisel and coworkers reported only the third case of recurrent disease caused by a resistant virus in an immunocompetent patient 19 . Drug-resistant strains are generally less virulent and less able to reactivate from latency and replicate, reducing their potential of transmission; wild-type susceptible virus typically causes relapses 20 .…”

Section: Discussionmentioning

confidence: 99%

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Bodsworth¹,

Fife

Koltun

et al. 2009

Current Medical Research and Opinion

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Background Episodic therapy of genital herpes is usually recommended for patients with infrequent symptomatic recurrences and where transmission is not a concern. While shorter courses are as effective as standard 5-day regimens, it is unknown whether abbreviated therapy has detrimental effects on natural history and the development of antiviral resistance. Objectives To assess time to next recurrence and development of antiviral resistance in patients with recurrent genital herpes treated with either single-day famciclovir (1 g twice-daily) or 3-day valacyclovir (500 mg twice-daily). Methods Longer-term, follow-up data on the time to next recurrence and antiviral sensitivity were collected from a previously reported multicenter, multinational, double-blind, parallel group study in which 1179 immunocompetent adults were randomized 1:1 to receive either single-day famciclovir or 3-day valacyclovir. Treatment was self-initiated within 6 hours of a recurrence. Swabs for viral culture and sensitivity testing were collected for two sequential recurrences. Results The median time to next recurrence from treatment initiation was 33.5 days for famciclovir and 38.0 days for valacyclovir. No drug resistance to penciclovir, the active metabolite of famciclovir, was observed at baseline nor did any develop by the time of the next recurrence. Limitations The study had no placebo arm, typing of viral isolates was not performed and viral resistance testing was restricted to penciclovir only. Conclusion Treatment with single-day famciclovir for recurrent genital herpes did not shorten the time to the next recurrence. Drug resistance to penciclovir continues to be a rare event in immunocompetent patients.

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Section: Discussionmentioning

confidence: 99%

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Bodsworth¹,

Fife

Koltun

et al. 2009

Current Medical Research and Opinion

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show abstract

“…Moreover, the lack of a complete correlation between in vitro susceptibility of viral isolates and clinical response implicates other factors in the clinical outcome. These include the antiviral medication (dose, dose frequency, route of administration and level of compliance), absorption and metabolism of the antiviral, immunological response of the patient and heterogeneity of the virus population [45]. Hence, data on HIV viral load in the blood or at genital level during HSV-2 suppressive therapy with aciclovir could be underestimated by the presence of aciclovir-resistant strains or reduced intestinal absorption of aciclovir in this population.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely to be quite high among HIV patients, reducing the effect of the suppressive therapy at population level. It is known that aciclovir-resistant HSV can emerge rapidly during the course of antiviral therapy in immunocompromised patients [45]. Moreover, a continuing survey of HSV isolates from HIV-positive patients in the USA and Canada from 1998 to 2000 indicates that the prevalence of resistant HSV is approximately 6% [46].…”

Section: Discussionmentioning

confidence: 99%

Aciclovir, herpes viruses and HIV: a never-ending story

Volpi¹,

Sarrecchia

Sordillo

2009

Expert Review of Anti-infective Therapy

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HIV infection continues to be among the leading causes of morbidity and mortality, especially in Africa. The prevalence of herpes simplex virus type 2 (HSV-2) has already reached high seroprevalence of up to 90% in HIV-seropositive individuals, and HSV-2 is now the leading cause of genital ulcer disease in both developing and developed countries. The role of HSV-2 as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV diffusion, also facilitating HIV spread among the low-risk population who have stable long-term sexual partnerships. To date, no vaccine to prevent HSV-2 acquisition or reactivation has been developed, although antivirals have been shown to be safe and effective in reducing HSV-2 shedding frequency and the duration of genital ulcer disease. The paper under evaluation confirms the favorable effect of therapies aimed at suppressing HSV-2 reactivation in HIV-seropositive patients on HIV plasma and vaginal load. In this study, aciclovir 400 mg twice daily was able to significantly reduce plasma and genital HIV RNA, the frequency of HIV shedding, genital HSV-2 DNA and the frequency of genital ulcerations. These results suggest that HSV-2 control with low-cost aciclovir can play an important role in reducing HIV spread, mainly in developing countries, where costs limit the use of highly active antiretroviral therapy

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“…This was important because suboptimal concentrations of antiviral drugs are likely to promote selection of drug-resistant viral strains. 33 We evaluated 2 PK-PD indices (T > IC 50 and AUC 24 :IC 50 ) that have been extensively used in antimicrobial research to facilitate determination of optimal dosages and thereby improve antimicrobial efficacy and reduce the emergence of resistance. 34 The C max :IC 50 was not evaluated in the present study because the C max varied greatly among cats, which might have affected interpretation of that index.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

Sebbag

Thomasy

Woodward

et al. 2016

ajvr

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TitlePharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir OBJECTIVESTo determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS7 male domestic shorthair cats. PROCEDURESIn a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTSCompared with penciclovir concentrations, BRL42359 concentrations were 5-to 11-fold greater in plasma and 4-to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCEIn cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus. (Am J Vet Res 2016;77:833-845)

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

Cited by 434 publications

References 105 publications

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Single-day famciclovir for the treatment of genital herpes: follow-up results of time to next recurrence and assessment of antiviral resistance

Aciclovir, herpes viruses and HIV: a never-ending story

Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

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