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Table 102-1

Antiviral Chemotherapy for Herpes Simplex Virus (HSV) Infection

  • Mucocutaneous HSV infections
    • Infections in immunosuppressed pts
      1. Acute symptomatic first or recurrent episodes: IV acyclovir (5 mg/kg q8h) or oral acyclovir (400 mg qid), famciclovir (500 mg bid or tid), or valacyclovir (500 mg bid) is effective. Treatment duration may vary from 7 to 14 days. IV therapy may be given for 2-7 days until clinical improvement and followed by oral therapy.
      2. Suppression of reactivation disease (genital or oral-labial): IV acyclovir (5 mg/kg q8h) or oral valacyclovir (500 mg bid) or acyclovir (400-800 mg 3-5 times per day) prevents recurrences during the 30-day period immediately after transplantation. Longer-term HSV suppression is often used for persons with continued immunosuppression. In bone marrow and renal transplant recipients, oral valacyclovir (2 g/d) is also effective in reducing cytomegalovirus infection. Oral valacyclovir at a dose of 4 g/d has been associated with thrombotic thrombocytopenic purpura after extended use in HIV-positive persons. In HIV-infected persons, oral acyclovir (400-800 mg bid), valacyclovir (500 mg bid), or famciclovir (500 mg bid) is effective in reducing clinical and subclinical reactivations of HSV-1 and HSV-2.
    • Infections in immunocompetent pts
      1. Genital herpes
        • First episodes: Oral acyclovir (200 mg 5 times per day or 400 mg tid), valacyclovir (1 g bid), or famciclovir (250 mg bid) for 7-14 days is effective. IV acyclovir (5 mg/kg q8h for 5 days) is given for severe disease or neurologic complications such as aseptic meningitis.
        • Symptomatic recurrent genital herpes: Short-course (1- to 3-day) regimens are preferred because of low cost, likelihood of adherence, and convenience. Oral acyclovir (800 mg tid for 2 days), valacyclovir (500 mg bid for 3 days), or famciclovir (750 or 1000 mg bid for 1 day, a 1500-mg single dose, or 500 mg stat followed by 250 mg q12h for 2 days) effectively shortens lesion duration. Other options include oral acyclovir (200 mg 5 times per day), valacyclovir (500 mg bid), and famciclovir (125 mg bid for 5 days).
        • Suppression of recurrent genital herpes: Oral acyclovir (400-800 mg bid) or valacyclovir (500 mg daily) is given. Pts with >9 episodes per year should take oral valacyclovir (1 g daily or 500 mg bid) or famciclovir (250 mg bid or 500 mg bid).
      2. Oral-labial HSV infections
        • First episode: Oral acyclovir is given (200 mg 5 times per day or 400 mg tid); an oral acyclovir suspension can be used (600 mg/m2 qid). Oral famciclovir (250 mg bid) or valacyclovir (1 g bid) has been used clinically. The duration of therapy is 5-10 days.
        • Recurrent episodes: If initiated at the onset of the prodrome, single-dose or 1-day therapy effectively reduces pain and speeds healing. Regimens include oral famciclovir (a 1500-mg single dose or 750 mg bid for 1 day) or valacyclovir (a 2-g single dose or 2 g bid for 1 day). Self-initiated therapy with 6-times-daily topical penciclovir cream effectively speeds healing of oral-labial HSV infection. Topical acyclovir cream has also been shown to speed healing.
        • Suppression of reactivation of oral-labial HSV: If started before exposure and continued for the duration of exposure (usually 5-10 days), oral acyclovir (400 mg bid) prevents reactivation of recurrent oral-labial HSV infection associated with severe sun exposure.
      3. Surgical prophylaxis of oral or genital HSV infection: Several surgical procedures, such as laser skin resurfacing, trigeminal nerve-root decompression, and lumbar disk surgery, have been associated with HSV reactivation. IV acyclovir (3-5 mg/kg q8h) or oral acyclovir (800 mg bid), valacyclovir (500 mg bid), or famciclovir (250 mg bid) effectively reduces reactivation. Therapy should be initiated 48 h before surgery and continued for 3-7 days.
      4. Herpetic whitlow: Oral acyclovir (200 mg) is given 5 times daily (alternative: 400 mg tid) for 7-10 days.
      5. HSV proctitis: Oral acyclovir (400 mg 5 times per day) is useful in shortening the course of infection. In immunosuppressed pts or in pts with severe infection, IV acyclovir (5 mg/kg q8h) may be useful.
      6. Herpetic eye infections: In acute keratitis, topical trifluorothymidine, vidarabine, idoxuridine, acyclovir, penciclovir, and interferon are all beneficial. Debridement may be required. Topical steroids may worsen disease.
  • Central nervous system HSV infections
    • HSV encephalitis: IV acyclovir (10 mg/kg q8h; 30 mg/kg per day) is given for 10 days or until HSV DNA is no longer detected in cerebrospinal fluid.
    • HSV aseptic meningitis: No studies of systemic antiviral chemotherapy exist. If therapy is to be given, IV acyclovir (15-30 mg/kg per day) should be used.
    • Autonomic radiculopathy: No studies are available. Most authorities recommend a trial of IV acyclovir.
  • Neonatal HSV infections: IV acyclovir (60 mg/kg per day, divided into 3 doses) is given. The recommended duration of IV treatment is 21 days. Monitoring for relapse should be undertaken. Continued suppression with oral acyclovir suspension should be given for 3-4 months.
  • Visceral HSV infections
    • HSV esophagitis: IV acyclovir (15 mg/kg per day) is given. In some pts with milder forms of immunosuppression, oral therapy with valacyclovir or famciclovir is effective.
    • HSV pneumonitis: No controlled studies exist. IV acyclovir (15 mg/kg per day) should be considered.
  • Disseminated HSV infections: No controlled studies exist. IV acyclovir (5 mg/kg q8h) should be tried. Adjustments for renal insufficiency may be needed. No definite evidence indicates that therapy will decrease the risk of death.
  • Erythema multiforme associated with HSV: Anecdotal observations suggest that oral acyclovir (400 mg bid or tid) or valacyclovir (500 mg bid) will suppress erythema multiforme.
  • Infections due to acyclovir-resistant HSV: IV foscarnet (40 mg/kg IV q8h) should be given until lesions heal. The optimal duration of therapy and the usefulness of its continuation to suppress lesions are unclear. Some pts may benefit from cutaneous application of trifluorothymidine or 1% cidofovir gel, both of which must be compounded at a pharmacy. These preparations should be applied once daily for 5-7 days. Topical imiquimod can be considered. The helicase primase inhibitor pritelivir is being studied for treatment of acyclovir-resistant HSV infection. IV cidofovir (5 mg/kg weekly) may be considered.
  • Acyclovir and pregnancy: No adverse effects to the fetus or newborn have been attributable to acyclovir. Acyclovir can be used in all stages of pregnancy and among women who are breastfeeding (the drug can be found in breast milk). Suppressive acyclovir treatment in late pregnancy reduces the frequency of cesarean delivery among women with recurrent genital herpes. Such treatment may not protect against transmission to neonates.