Successful treatment of progressive mucocutaneous infection due to acyclovir- and foscarnet-resistant herpes simplex virus with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC).
The acyclic nucleoside phosphonate (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was used topically for the treatment of persistent mucocutaneous infections in two cases. One patient with AIDS suffered from a perineal lesion due to infection with herpes simplex virus type 2 (HSV-2) and did not respond to acyclovir and was intolerant of foscarnet. A bone marrow transplant recipient developed orofacial lesions due to infection with herpes simplex virus type 1 (HSV-1) that failed to respond to therapy with both acyclovir and foscarnet. After topical application of HPMPC, the HSV-2 lesions completely resolved. However, the lesions recurred 3 weeks later, and, upon subsequent treatment with HPMPC, regressed. On recurrence, the virus was found to be sensitive to acyclovir, which the patient was given. Again HSV-2, which was resistant to acyclovir, emerged; similar observations were made after another cycle of HPMPC therapy. The HSV-1 isolates were resistant to acyclovir and foscarnet. Following local HPMPC treatment, the lesions regressed, but after 1 week, a second course of topical HPMPC therapy had to be instituted for recurrent infection. The lesions again regressed, and as the recurrent virus was sensitive to acyclovir, the patient was successfully treated with the drug. The results of this study point to the potential usefulness of topical HPMPC in the treatment of immunocompromised patients with HSV-related mucocutaneous infections that are refractory to therapy with acyclovir and/or foscarnet.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
R
R
Snoeck
G
G
Andrei
M
M
Gérard
A
A
Silverman
A
A
Hedderman
J
J
Balzarini
C
C
Sadzot-Delvaux
G
G
Tricot
N
N
Clumeck
E
E
De Clercq
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy; D000212:Acyclovir / Q000494:pharmacology; D000287:Administration, Topical; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000235:genetics; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy*; D006561:Herpes Simplex / Q000150:complications / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications; D008297:Male; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D017193:Skin Diseases, Viral / Q000150:complications / Q000188:drug therapy*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017245:Foscarnet; D003596:Cytosine; D013937:Thymidine Kinase; D004262:DNA Restriction Enzymes; D000077404:Cidofovir; D000212:Acyclovir