HIV-1 Gag Mutations and Resistance to Protease Inhibitors
Author Information
Author(s): Dam Elisabeth, Quercia Romina, Glass Bärbel, Descamps Diane, Launay Odile, Duval Xavier, Kräusslich Hans-Georg, Hance Allan J., Clavel François
Primary Institution: Inserm U552, Paris, France
Hypothesis
How do mutations in the Gag protein contribute to HIV-1 resistance to protease inhibitors?
Conclusion
Gag mutations play a significant role in HIV-1 resistance to protease inhibitors by compensating for fitness loss and directly contributing to resistance.
Supporting Evidence
- Gag mutations were found to directly contribute to protease inhibitor resistance.
- Mutations in the NC-SP2-p6 region of Gag were particularly significant.
- Removing specific Gag mutations resulted in reduced resistance to protease inhibitors.
- Patient-derived Gag sequences significantly improved viral replicative capacity.
- Resistance levels were markedly lower in viruses lacking patient-derived Gag sequences.
Takeaway
HIV-1 can become resistant to treatments because of changes in its proteins, especially the Gag protein, which helps the virus survive even when medicines are trying to stop it.
Methodology
The study involved constructing recombinant viruses with different Gag-Pol segments from HIV-1 infected patients and testing them for resistance and replicative capacity.
Potential Biases
Potential bias due to the specific patient population studied, which may not reflect broader HIV-1 populations.
Limitations
The study focused on a small number of patients and may not represent all HIV-1 variants.
Participant Demographics
Patients were highly drug-experienced individuals with multiple lines of treatment failure.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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