Effects of (R)-9-(2-phosphonylmethoxypropyl)adenine monotherapy on chronic SIV infection in macaques.
(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA) acts as a reverse transcriptase inhibitor of retroviruses and has been shown to be effective against acute simian immunodeficiency virus (SIV) infection in macaques. To study its efficacy at different stages of infection, we tested PMPA in cynomolgus macaques (Macaca fascicularis) that had been chronically infected with SIVMne for at least 19 weeks before treatment was begun. PMPA was administered subcutaneously in a single daily dose of either 30 or 75 mg/kg body weight for 28 days. Within < or = 2 weeks of treatment, PMPA in both dosing regimens reduced SIV levels by >99% in the plasma or peripheral blood mononuclear cells; in some macaques SIV levels were reduced to below the lower quantitation limit. At a dose of 30 mg/kg/day PMPA was well tolerated, causing no side effects while increasing the mean CD4+ cell counts in animals that received this dose. Thus PMPA seems to be a promising agent for use against retroviral infections.
Tsai
C C
CC
Washington Regional Primate Research Center, Seattle 98195, USA.
Follis
K E
KE
Beck
T W
TW
Sabo
A
A
Bischofberger
N
N
Dailey
P J
PJ
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004341:Drug Evaluation; D018655:Lymphocyte Count / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000166:cytology; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D008252:Macaca fascicularis / Q000821:virology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use* / Q000633:toxicity; D012192:Retroviridae Infections / Q000097:blood / Q000188:drug therapy*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D000068698:Tenofovir
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine