title: Anti-retrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in vivo increases when it is less frequently administered.
abstract: Different treatment schedules have been investigated when evaluating the inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 3'-azido-2',3'-dideoxythymidine (AZT) on the replication of human immunodeficiency virus type I (HIV-I) in MT-4 cells, transformation of C3H/3T3 cells by Moloney murine sarcoma virus (MSV), and MSV-induced tumor formation in newborn NMRI mice. Shortening the exposure time of HIV-I-infected MT-4 cells to PMEA or AZT led to an increase in the selectivity index of both compounds. PMEA proved markedly more efficient in suppressing MSV-induced tumor formation in mice when administered as a single dose on the day of infection than when these doses were spread over 2, 4 or 7 administrations within 1 week after the virus infection. This was not observed when the total dose of AZT was fractionated. While the infrequent dosage regimen increased the anti-retrovirus activity of PMEA, it did not increase its toxicity for the host. This unique property makes PMEA an attractive candidate for the treatment of retrovirus infections, including AIDS.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: L
authors.initials: L
authors.lastname: Naesens
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000633:toxicity; D002472:Cell Transformation, Viral / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015497:HIV-1 / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008980:Moloney murine sarcoma virus / Q000187:drug effects; D009368:Neoplasm Transplantation; D063065:Organophosphonates; D012190:Retroviridae / Q000187:drug effects*; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D015215:Zidovudine; C053001:adefovir; D000225:Adenine