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Preexposure prophylaxis with 9-(2-phosphonylmethoxyethyl)adenine against simian immunodeficiency virus infection in
1Regional Primate Research Center, University of Washington, Seattle.
Abstract:
A reverse transcriptase inhibitor, 9-(2-phosphonylmethoxyethyl)adenine (PMEA), was evaluated for efficacy against acute simian immunodeficiency virus (SIV) infection in juvenile macaques (Macaca fascicularis). Macaques were pretreated subcutaneously with PMEA for 48 h before SIV inoculation. Drug treatment continued for an additional 28 days. Efficacy of PMEA was determined by detection of SIV in blood, SIV DNA in peripheral blood mononuclear cells, and SIV antibodies. Protection from acute SIV infection occurred in 83% of macaques treated with 20 mg/kg/day versus 50% of macaques treated with 10 mg/kg/day. Several PMEA-treated macaques developed mild dermatitis that disappeared when the 4-week therapy ended. The results of these experiments indicate that preexposure prophylaxis with PMEA can prevent acute SIV infection in macaques. Since PMEA demonstrates profound inhibition of retrovirus infection, it may have utility as a chemoprophylactic agent for humans exposed to SIV or human immunodeficiency virus.
Insights
Preexposure prophylaxis with 9-(2-phosphonylmethoxyethyl)adenine (PMEA) prevented simian immunodeficiency virus (SIV) infection in macaques. This antiviral agent shows promise for preventing human immunodeficiency virus (HIV) exposure.
Area of Science:
- Virology
- Pharmacology
- Primatology
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a model for human immunodeficiency virus (HIV) infection.
- Antiviral agents are crucial for managing and preventing retroviral infections.
Purpose of the Study:
- To evaluate the efficacy of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) as a preexposure prophylaxis against acute simian immunodeficiency virus (SIV) infection.
- To determine the protective effect of PMEA in a macaque model.
Main Methods:
- Juvenile macaques (Macaca fascicularis) were pretreated with PMEA subcutaneously for 48 hours before SIV inoculation.
- Drug treatment continued for 28 days post-inoculation.
- Efficacy was assessed by detecting SIV in blood, SIV DNA in peripheral blood mononuclear cells, and SIV antibodies.
Main Results:
- Preexposure prophylaxis with PMEA demonstrated significant protection against acute SIV infection.
- 83% of macaques treated with 20 mg/kg/day and 50% treated with 10 mg/kg/day were protected.
- Mild, transient dermatitis was observed in some PMEA-treated animals.
Conclusions:
- Preexposure prophylaxis with PMEA can effectively prevent acute SIV infection in macaques.
- PMEA exhibits potent retroviral inhibition, suggesting potential utility as a chemoprophylactic agent for human retroviral exposure.
- Further research into PMEA's role in preventing SIV and HIV infection is warranted.