HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia

J Antimicrob Chemother. 2015;70(6):1865-73. doi: 10.1093/jac/dkv029. Epub 2015 Feb 23.

Abstract

Objectives: Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients.

Methods: An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10 000, 10 001-100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients.

Results: Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10 000 = 53.7%; 10 001-100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL.

Conclusions: Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.

Keywords: HIV-1 genotyping; INSTI; dolutegravir; drug resistance; elvitegravir; integrase; low-level viraemia; raltegravir.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Genotyping Techniques / methods*
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Integrase / genetics*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Microbial Sensitivity Tests / methods*
  • Middle Aged
  • Mutation, Missense*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Viral Load
  • Viremia / virology

Substances

  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1