Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine.
The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of Moloney murine sarcoma virus-induced tumor formation in mice. In the latter system PMEA has stronger antiretroviral potency and selectivity than 3'-azido-3'-thymidine (AZT). We have now investigated the effect of the drug in cats infected with the feline immunodeficiency virus (FIV). In vitro, PMEA was found to efficiently block FIV replication in feline thymocytes (50% effective dose, 0.6 microM). When administered to cats at doses of 20, 5, or 2 mg/kg per day, PMEA caused a dose-dependent suppression of FIV replication and virus-specific antibody production. Seropositive field cats with signs of opportunistic infection (gingivitis, stomatitis, and diarrhea) showed clinical improvement during PMEA therapy (5 mg/kg per day) and recurrence of the disease after treatment was discontinued. Thus, FIV infection in cats is an excellent model to test the efficacy of selective anti-human immunodeficiency virus agents in vivo.
Egberink
H
H
Department of Infectious Diseases and Immunology, School of Veterinary Medicine, State University of Utrecht, The Netherlands.
Borst
M
M
Niphuis
H
H
Balzarini
J
J
Neu
H
H
Schellekens
H
H
De Clercq
E
E
Horzinek
M
M
Koolen
M
M
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002415:Cats; D002460:Cell Line; D006678:HIV / Q000187:drug effects / Q000502:physiology; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D009894:Opportunistic Infections / Q000517:prevention & control*; D063065:Organophosphonates; D012190:Retroviridae / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D012192:Retroviridae Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013601:T-Lymphocytes / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D063065:Organophosphonates; D015215:Zidovudine; C053001:adefovir; D000225:Adenine