Prevalence of Darunavir Resistance in the United States from 2010 to 2017

AIDS Res Hum Retroviruses. 2018 Dec;34(12):1036-1043. doi: 10.1089/AID.2018.0100. Epub 2018 Oct 31.

Abstract

The emergence and transmission of antiretroviral drug resistance have been and remain a concern among people living with human immunodeficiency virus (HIV)-1 infection. The protease inhibitor (PI) darunavir has been approved for use in the United States for more than 10 years and has demonstrated a high barrier to resistance. Previous analyses identified significant reductions in the prevalence of samples with darunavir resistance-associated mutations (RAMs) and with phenotypic resistance to darunavir and other PIs between 2006 and 2012. This analysis extends those findings by evaluating darunavir and PI resistance among clinical samples submitted for routine drug resistance testing (combined genotyping and phenotyping) in the United States from 2010 to 2017. Frequencies of 11 darunavir and 23 primary PI RAMs, and phenotypic susceptibility, were assessed yearly among all samples and in a subset of samples with distinct phenotypic resistance to one or more PIs. Among all samples (N = 60,760), the proportion with 0 darunavir RAMs was 91.7% in 2010 and 95.8% in 2017. The proportions of all samples with phenotypic susceptibility to darunavir, atazanavir, and lopinavir were, respectively, 97.4%, 94.2%, and 94.7% in 2010 and 98.6%, 97.7%, and 97.5% in 2017. Among the 4,799 samples with phenotypic resistance to one or more PIs, the proportions with phenotypic susceptibility to darunavir, atazanavir, and lopinavir were, respectively, 73.3%, 41.5%, and 46.0% in 2010 and 70.7%, 53.7%, and 48.8% in 2017. The prevalence of darunavir RAMs among commercially tested HIV-1 samples remained low and generally stable from 2010 to 2017, and high proportions showed phenotypic darunavir susceptibility.

Keywords: antiretroviral; darunavir once daily; genotypic resistance; human immunodeficiency virus-1; phenotypic resistance; resistance-associated mutations.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Darunavir / pharmacology*
  • Drug Resistance, Viral / genetics*
  • HIV Protease Inhibitors / pharmacology*
  • History, 21st Century
  • Humans
  • Inhibitory Concentration 50
  • Mutation*
  • United States

Substances

  • HIV Protease Inhibitors
  • Darunavir