Effect of PMPA and PMEA on the kinetics of viral load in simian immunodeficiency virus-infected macaques.
In this study we compared the effect of postexposure treatment of the acyclic nucleoside analogs 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) and 9-(2-phosphonylmethoxypropyl)-adenine (PMPA) on the kinetics of viral load in the blood and lymph nodes of rhesus macaques chronically infected with SIVmac251 for 18 weeks. Two of the four macaques treated with PMPA (20 mg/kg per day) for 28 consecutive days had demonstrable reductions in viral loads of 1.5 and 3 logs. Three of four macaques given the same dosing regimen of PMEA had viral load reductions ranging from 1.25 to 2.8 logs. Furthermore, treatment with either drug caused a reduction in virus burden in the lymph nodes by 2 weeks posttreatment. However, in both PMEA- and PMPA-treated animals, viral loads rebounded to day of treatment levels by 2 weeks after termination of treatment. The extent to which viral load was suppressed was similar for both drugs. In contrast, viral loads in three of four mock-treated animals remained persistently high throughout the study. This study has demonstrated that postexposure treatment with these acyclic nucleoside analogs could modulate the kinetics of viral load reduction in some animals.
Silvera
P
P
Henry Jackson Foundation, Rockville, Maryland 20850, USA. silvera@sri.org
Racz
P
P
Racz
K
K
Bischofberger
N
N
Crabbs
C
C
Yalley-Ogunro
J
J
Greenhouse
J
J
Jiang
J B
JB
Lewis
M G
MG
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D012367:RNA, Viral; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine