Impact of Resistance Mutations on HIV-1 Replicative Fitness and INSTI Susceptibility

What is it about?

In this study, the effect of drug resistance mutations in multiple HIV-1 coding regions on susceptibility to integrase strand transfer inhibitors (INSTIs) and viral replicative fitness was analyzed using a novel HIV-1 phenotyping assay. The analysis showed that mutations in the protease and reverse transcriptase have limited effects on susceptibility to INSTIs. On the other hand, the replicative fitness of viruses harboring drug resistance mutations in these regions, along with integrase, was generally impaired compared to viruses carrying only INSTI-resistance mutations. These findings highlight the importance of understanding the collective effect of epistatic interactions in multidrug-resistant viruses, particularly in the context of antiretroviral treatment.

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Why is it important?

This research is important for several reasons. Firstly, it helps to understand the impact of drug resistance mutations in Gag, Protease, Reverse Transcriptase, and Integrase coding regions on susceptibility to integrase strand transfer inhibitors (INSTIs) and viral replicative fitness. This knowledge is crucial for developing effective treatment strategies for patients infected with multidrug-resistant HIV-1 strains. Key Takeaways: 1. The study demonstrates the effect of drug resistance mutations on susceptibility to INSTIs and viral replicative fitness, emphasizing the importance of analyzing patient-derived HIV-1 fragments in understanding the collective effect of epistatic interactions in multidrug-resistant viruses. 2. The use of a novel HIV-1 phenotyping assay, VIRALARTS TM HIV, allows for the study of the impact of drug resistance mutations on viral replication fitness, providing valuable insights into the replicative capabilities of drug-resistant viruses. 3. The study highlights the importance of analyzing the interactions among drug resistance mutations in the three HIV-1 enzymes (protease, reverse transcriptase, and integrase) to better understand the overall impact on viral replicative fitness and treatment response.