Snoeck R, Andrei G, Gérard M, Silverman A, Hedderman A, Balzarini J, Sadzot-Delvaux C, Tricot G, Clumeck N, De Clercq E
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Clin Infect Dis. 1994 Apr;18(4):570-8. doi: 10.1093/clinids/18.4.570.
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.
无环核苷膦酸酯（S）-1-（3-羟基-2-膦酰甲氧基丙基）胞嘧啶（HPMPC）被局部用于治疗两例持续性黏膜皮肤感染。一名艾滋病患者因感染2型单纯疱疹病毒（HSV-2）出现会阴病变，对阿昔洛韦无反应且不耐受膦甲酸钠。一名骨髓移植受者因感染1型单纯疱疹病毒（HSV-1）出现口腔面部病变，对阿昔洛韦和膦甲酸钠治疗均无反应。局部应用HPMPC后，HSV-2病变完全消退。然而，3周后病变复发，再次用HPMPC治疗后消退。复发时发现病毒对阿昔洛韦敏感，遂给予该患者阿昔洛韦。之后又出现了对阿昔洛韦耐药的HSV-2；在另一轮HPMPC治疗后也有类似观察结果。HSV-1分离株对阿昔洛韦和膦甲酸钠耐药。局部应用HPMPC治疗后，病变消退，但1周后，因复发感染不得不进行第二轮局部HPMPC治疗。病变再次消退，由于复发病毒对阿昔洛韦敏感，该患者用该药成功治愈。本研究结果表明，局部应用HPMPC对于治疗对阿昔洛韦和/或膦甲酸钠治疗难治的免疫功能低下的HSV相关黏膜皮肤感染具有潜在的应用价值。
