Treatment of drug-resistant genital herpes simplex virus infection in HIV-infected patients
- Christine Johnston, MD, MPH
Christine Johnston, MD, MPH
- Assistant Professor of Medicine
- University of Washington
- Anna Wald, MD, MPH
Anna Wald, MD, MPH
- Professor of Medicine, Epidemiology, and Laboratory Medicine
- University of Washington
Genital herpes simplex is a common sexually transmitted viral infection that is found worldwide . 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) .
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 . 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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- MECHANISMS OF DRUG RESISTANCE
- PREVALENCE OF DRUG RESISTANCE
- Epidemiologic studies of drug resistance
- Clinical importance of drug resistance
- Risk factors
- WHEN TO SUSPECT HSV-RELATED DRUG RESISTANCE
- DIAGNOSIS OF DRUG RESISTANCE
- AVAILABLE AGENTS FOR ACYCLOVIR-RESISTANT HSV INFECTION
- Topical therapies
- - Cidofovir
- - Other therapies
- MANAGEMENT OF DRUG-RESISTANT ULCERATIVE DISEASE
- Intravenous acyclovir
- Intravenous foscarnet
- Intravenous cidofovir
- Patients with intolerance to foscarnet
- PATIENT MANAGEMENT AFTER RESOLUTION OF LESIONS
- Antiviral suppression of genital HSV infection
- Optimization of HIV therapy
- SUMMARY AND RECOMMENDATIONS