Role of Gag mutations for PI resistance in the Swiss HIV cohort – bystander or contributor? Journal of Antimicrobial Chemotherapy
Kletkenov et al. aimed to describe for HIV infections in Switzerland the potential role of the C-terminus of Gag (NC–p6) in HIV protease inhibitor (PI) resistance. Resistance information on plasma samples from 2004–12 was collected for patients treated by two diagnostic centres of the Swiss HIV Cohort Study. Sequence information on protease and the C-terminal Gag region was paired with the corresponding patient treatment history. The prevalence of Gag and protease mutations was analysed for PI treatment-experienced patients versus PI treatment-naive patients.
More than half of all PI treatment-experienced patients in the analzyed sample set carried HIV variants with at least one of the known Gag mutations, and 17.9% (66/369) carried at least one Gag mutation for which a phenotypic proof of PI resistance by in vitro mutagenesis has been reported. The authors identified several novel Gag mutations that were associated with PI exposure and therapy failure.
In conclusion, this analysis of data from the SHCS confirmed the association of Gag mutations with PI exposure. In addition, the study revealed new, potentially important mutations in Gag that could have clinical implications. However, further phenotypic analyses and clinical correlates of drug failure will be needed before such information is suitable for amending existing resistance algorithms that are used for genotypic HIV resistance testing.