The HIV Type 1 Protease L10I Minor Mutation Decreases Replication Capacity and Confers Resistance to Protease Inhibitors

The effect of minor mutations in PR on treatment outcome has not been well established. We characterized the HIV protease minor mutations, L10I, compared to the minor mutation, L63P, and the major mutation D30N and their impact on viral fitness and resistance to protease inhibitors. Mutations were introduced individually and in combination by site-directed mutagenesis into the provirus pNL4.3ren and constructs used for replication capacity (RC) and resistance assays. A structure prediction of the protease carrying the L10I mutation was determined. The prevalence of the minor mutation L10I had a pattern similar to that found for major mutations D30N, with a low prevalence (4.9%) in naive patients and significantly higher prevalence in treated patients. Furthermore, viruses carrying the major mutation D30N or the minor mutation L10I showed a significant decrease in RC (p-value