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Treatment of drug-resistant genital herpes simplex virus infection in HIV-infected patients

Authors
Christine Johnston, MD, MPH
Anna Wald, MD, MPH
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

Genital herpes simplex is a common sexually transmitted viral infection that is found worldwide [1]. Most often genital herpes is secondary to herpes simplex virus type 2 (HSV-2), although about half of all new cases in developed countries are due to herpes simplex virus type 1 (HSV-1) [1].

Drug resistance to acyclovir and related drugs (eg, famciclovir or valacyclovir) is rare in immunocompetent hosts, but is seen more commonly among immunocompromised hosts, including HIV-infected patients and transplant recipients. This topic will review therapeutic options and strategies for prevention for drug-resistant infection in the HIV-infected patient. The epidemiology, natural history, clinical manifestations, and treatment of drug-sensitive HSV infection in the HIV-infected host are discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus in HIV-infected patients" and "Treatment of genital herpes simplex virus type 2 in HIV-infected patients" and "Effect of herpes simplex virus on HIV infection: Implications for HIV prevention".)

MECHANISMS OF DRUG RESISTANCE

Acyclovir, famciclovir, and valacyclovir are antiviral agents within the nucleoside analog class. After intracellular uptake, acyclovir is converted to acyclovir monophosphate by virally-encoded thymidine kinase [2]. The monophosphate derivative is subsequently converted by cellular enzymes to acyclovir triphosphate, which is a specific inhibitor of HSV DNA polymerase. HSV drug resistance to acyclovir infers broad cross-resistance to this entire class of antiviral agents. (See "Acyclovir: An overview", section on 'Mechanism of action'.)

Three mechanisms have been found that result in resistance to acyclovir [3,4]:

Reduced or absent thymidine kinase

                    

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Literature review current through: Nov 2016. | This topic last updated: Thu Mar 17 00:00:00 GMT 2016.
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