Low Frequency of Protease Inhibitor Resistance Mutations and Insertions in HIV-1 Subtype C Protease Inhibitor-Naïve Sequences.

Abstract

Human immunodeficiency virus-1 (HIV-1) protease sequences from 2,225 protease inhibitor (PI)-naïve HIV-1 subtype C-infected individuals collected over a 14-year period were analyzed for polymorphisms. Over 50% of sequences differed from an HIV-1 subtype B consensus sequence at 8 of the 99 amino acids at residues 12, 15, 19, 36, 41, 69, 89, and 93, but not in the functionally important regions. The frequency of primary resistance and accessory mutations occurred in <1% of the sequences. Of note, 11 sequences (0.5%) harbored amino acid insertions between residues 36 and 39, located in the elbow of the flap region. The insertions were found throughout the 13-year period. Occurrence of insertions in subtype C viruses is rare and viruses remain sensitive to currently used PIs (lopinavir/r, atazanavir/r, and darunavir/r). However, ongoing characterization of isolates is required to identify changes that may impact PI treatment since PIs are part of standard SA regimens.