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    usmlemate is offline Junior Member
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    Acyclovir-Resistant Herpes Simplex Virus Infection

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    A 36-year-old HIV-infected man with a CD4 count of 4 cells/mm3 presents with a 2 week history of a lesion on his lip. He has a history of recurrent herpes simplex infection and has received multiple courses of oral acyclovir (Zovirax). He increased his acyclovir dose from 400 mg PO tid to 800 mg PO tid, but the lesion has expanded further (Figure 1). This lesion is now painful and culture of the lesion has grown herpes simplex virus type 1.

    Which of the following would be the most effective therapy at this point for presumptive acyclovir-resistant herpes simplex virus infection?

    A. Acyclovir (Zovirax) 10 mg/kg IV q8h.

    B. Famciclovir (Famvir) 500 mg PO tid.

    C. Foscarnet (Foscavir) 40 mg/kg IV q8h.

    D. Valacyclovir (Valtrex) 1000 mg PO tid.

  2. #2
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    Asclepius1 is offline Ultimate Member 537 points
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    Where is figure 1?

    I can't see picture of Figure 1? Where is it?

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    Asclepius1 is offline Ultimate Member 537 points
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    My guess is Famciclovir (Famvir) 500 mg PO tid.

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    is it?

    is it D?

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    usmle2005 is offline Newbie
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    Re: Where is figure 1?

    Quote Originally Posted by Anonymous
    I can't see picture of Figure 1? Where is it?
    I think you can not see that picture if you are a guest. I was surprised also when I logged out and did not see the pictures.

  6. #6
    usmlemate is offline Junior Member
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    Re: Acyclovir-Resistant Herpes Simplex Virus Infection

    Quote Originally Posted by usmlemate
    A 36-year-old HIV-infected man with a CD4 count of 4 cells/mm3 presents with a 2 week history of a lesion on his lip. He has a history of recurrent herpes simplex infection and has received multiple courses of oral acyclovir (Zovirax). He increased his acyclovir dose from 400 mg PO tid to 800 mg PO tid, but the lesion has expanded further (Figure 1). This lesion is now painful and culture of the lesion has grown herpes simplex virus type 1.

    Which of the following would be the most effective therapy at this point for presumptive acyclovir-resistant herpes simplex virus infection?

    A. Acyclovir (Zovirax) 10 mg/kg IV q8h.

    B. Famciclovir (Famvir) 500 mg PO tid.

    C. Foscarnet (Foscavir) 40 mg/kg IV q8h.

    D. Valacyclovir (Valtrex) 1000 mg PO tid.
    The correct answer is C. Foscarnet (Foscavir) is a pyrophosphate analog that directly inhibits viral DNA polymerase by reversibly blocking the pyrophosphate binding site of the viral polymerase (in addition to inhibiting the cleavage of pyrophosphate from deoxynucleotide triphosphates). Foscarnet does not require activation by viral thymidine kinase and thus retains activity against herpes simplex virus strains with absent or altered production of viral thymidine kinase.

    Answer A is incorrect. Using a very high dose of acyclovir (Zovirax) would not likely override the acyclovir resistance and thus intravenous acyclovir would not be an optimal choice.

    Answer B is incorrect. Most acyclovir-resistant herpes simplex virus infections result from decreased viral production of thymidine kinase, the enzyme responsible for the first phosphorylation step in converting acyclovir to its active triphosphorylated form acyclovir triphosphate. Famciclovir (Famvir) is a prodrug of penciclovir and because activation of penciclovir also depends on viral thymidine kinase, acyclovir resistance generally also causes famciclovir

    Answer D is incorrect. Valacyclovir (Valtrex) is an acyclovir prodrug (it is the L-valine ester of acyclovir). Following absorption of valacyclovir, it is almost completely converted to acyclovir during first-pass hydrolysis in the liver and intestines. Although oral valacyclovir has a relative bioavailability 3 to 5 times greater than acyclovir (and oral doses can generate relatively high serum levels of acyclovir), it would not likely override the acyclovir resistance.

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