title: Treatment with intravenous (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine of acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with AIDS.
abstract: (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is a nucleotide analogue with potent in vitro and in vivo activity against a broad range of herpesviruses, including acyclovir-resistant herpes simplex virus (HSV). A patient with severe acyclovir-resistant perineal HSV infection received intravenous HPMPC at 5 mg/kg/week, with concomitant oral probenecid and prehydration, and had 95% healing after four infusions. The patient developed a hypersensitivity reaction to probenecid and discontinued HPMPC after the fourth infusion. Recurrence of the perineal lesions 2 weeks later prompted initiation of an oral desensitization program to probenecid and enabled the patient to resume therapy. The lesions again responded to infusions of HPMPC, but the drug was discontinued before complete healing because of transient nephrotoxicity (proteinuria, 2+; creatinine, 1.7 mg/dL). HPMPC is a potent antiviral agent that holds promise as a potential treatment for acyclovir-resistant HSV infection.
authors.affiliation: Mount Zion Medical Center, University of California, San Francisco.
authors.forename: J P
authors.initials: JP
authors.lastname: Lalezari
authors.forename: W L
authors.initials: WL
authors.lastname: Drew
authors.forename: E
authors.initials: E
authors.lastname: Glutzer
authors.forename: D
authors.initials: D
authors.lastname: Miner
authors.forename: S
authors.initials: S
authors.lastname: Safrin
authors.forename: W F
authors.initials: WF
authors.lastname: Owen
authors.forename: J M
authors.initials: JM
authors.lastname: Davidson
authors.forename: P E
authors.initials: PE
authors.lastname: Fisher
authors.forename: H S
authors.initials: HS
authors.lastname: Jaffe
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000212:Acyclovir / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D006561:Herpes Simplex / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D018139:Simplexvirus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D000212:Acyclovir