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

D. Armenia, L. Fabeni, C. Alteri, D. Di Pinto, D. Di Carlo, A. Bertoli, C. Gori, S. Carta, V. Fedele, F. Forbici, R. D'Arrigo, V. Svicher, G. Berno, D. Pizzi, E. Nicastri, L. Sarmati, C. Pinnetti, A. Ammassari, G. D'Offizi, A. LatiniM. Andreoni, A. Antinori, F. Ceccherini-Silberstein, C. F. Perno, M. M. Santoro

Research output: Contribution to journalArticle

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, 1001-10000, 10001-100000 and >100000 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%; 1001-10000=53.7%; 10001-100000=30.0%; and >100000=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.

Original languageEnglish
Article numberdkv029
Pages (from-to)1865-1873
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number6
DOIs
Publication statusPublished - Nov 12 2014

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Keywords

  • Dolutegravir
  • Drug resistance
  • Elvitegravir
  • HIV-1 genotyping
  • INSTI
  • Integrase
  • Low-level viraemia
  • Raltegravir

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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