Case report
Successful treatment of acyclovir-resistant herpes simplex virus type 2 proctitis with leflunomide in an HIV-infected man

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Abstract

Human herpes simplex virus infections are very common and represent significant morbidity in the immunocompromised host. Patients with acyclovir resistant strains of HSV based on viral thymidine kinase gene mutations need alternative therapeutic approaches. Leflunomide has been shown to possess antiviral activity against several viruses. Herein we describe a case of acyclovir resistant HSV-2 proctitis in an HIV patient successfully treated with leflunomide without significant side effects.

Section snippets

Why this case is important

HSV infections are traditionally treated with acyclovir, an agent that is phosphorylated to its active moiety by virally encoded thymidine kinase (TK+) which acts by inhibition of viral DNA replication. Acyclovir-resistant HSV due to thymidine-kinase deficient (TK−) mutants has been found in both HIV-infected and non-infected individuals.1, 2, 3 Agents that do not require phosphorylation to their active moiety include foscarnet and cidofovir. While these antivirals have excellent activity

Case description

In January of 2006, a 42-year old male HIV positive since 1989 on HAART (highly active antiretroviral therapy) consisting of abacavir/lamivudine and boosted darunavir with a CD4 count of 240/μl (normal range: 323–1546/μl) (nadir of 11/μl) and an HIV RNA of 81 copies/ml (normal range < 48 copy/ml) presented to the University of Colorado Denver for follow up care, having relocated from an outside state. His course had been complicated by cryptospodiosis with cholangiopathy and pancreatitis, right

Other similar and contrasting cases in the literature

While no controlled clinical trials have as yet been conducted, two reports by John et al. (total of 21 patients),7, 8 as well as several case studies9, 10, 11, 12 have documented reductions in viral load and improvement of CMV-related symptoms in human transplant recipients or AIDS patients suffering CMV disease and treated with leflunomide, including individuals who developed resistance to traditional antiviral drugs or were non-responsive to them initially. In addition, several reports have

Discussion

Persistent herpes simplex virus (HSV) is a common scenario in HIV positive patients. The virus can cause recurrent extensive, deep, non-healing perineal ulcerations. The primary therapy for those lesions is acyclovir and its related compounds (famciclovir and valacyclovir); however acyclovir resistant strains are well characterized, especially in the setting of previous prolonged acyclovir exposure.15, 16 Treatment options for resistant acyclovir strains are intravenous foscarnet and cidofovir

Funding

No funding agencies had role in the preparation, review, or approval of the manuscript. The views expressed in this article are those of the author and do not necessarily represent the views of the University of Colorado Denver or the Ohio State University.

Competing interests

No conflicts of interest were reported by Drs. Andrés F. Henao-Martínez, Adriana Weinberg and Marilyn E. Levi. W. James Waldman is named as a co-inventor on US Patent 7,691,890, European Patent 1 169 036 B1, Antiviral uses of leflunomide products.

Ethical approval

Not required. Advice has been properly sought and the approval has been deemed unnecessary.

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