Viral Mutants and Tenofovir Therapy in Rhesus Macaques
Author Information
Author(s): Koen K.A. Van Rompay, Jeffrey A. Johnson, Emily J. Blackwood, Raman P. Singh, Jonathan Lipscomb, Timothy B. Matthews, Marta L. Marthas, Niels C. Pedersen, Norbert Bischofberger, Walid Heneine, Thomas W. North
Primary Institution: California National Primate Research Center, University of California, Davis, USA
Hypothesis
How do viral mutants with K70E and K65R mutations emerge during prolonged tenofovir therapy in rhesus macaques?
Conclusion
Tenofovir therapy can select for K70E viral mutants in vivo, and the presence of K65R mutants suggests that both immune responses and drug therapy are important for controlling viremia.
Supporting Evidence
- Tenofovir treatment led to a significant decrease in viral RNA levels.
- K70E mutants emerged within 4 weeks of therapy, followed by K65R mutants.
- One animal suppressed K65R viremia to undetectable levels for over 4 years.
- CD8+ cell-mediated immune responses were crucial for controlling viremia.
- Continued tenofovir therapy was necessary for optimal suppression of K65R viremia.
Takeaway
This study shows that a medicine called tenofovir can change viruses in monkeys, making them different and sometimes harder to treat, but the monkeys' immune systems can still help fight the virus.
Methodology
Rhesus macaques were inoculated with RT-SHIV and treated with tenofovir; viral RNA levels and mutations were monitored over time.
Potential Biases
Potential bias due to the limited number of animals and the specific conditions of the study.
Limitations
The study had a small sample size and results may not fully extrapolate to human HIV-1 infections.
Participant Demographics
Juvenile rhesus macaques from a specific colony.
Statistical Information
P-Value
0.001
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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