Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients

J Antimicrob Chemother. 2015 May;70(5):1507-12. doi: 10.1093/jac/dku535. Epub 2015 Jan 3.


Objectives: The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).

Patients and methods: Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).

Results: Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004).

Conclusions: This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.

Keywords: inhibitors; integrase; mutations; patterns.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Drug Resistance, Viral*
  • Female
  • France
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Integrase / genetics
  • HIV Protease / genetics
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Mutant Proteins / genetics
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones / pharmacology*
  • Raltegravir Potassium / therapeutic use*
  • Sequence Analysis, DNA


  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Mutant Proteins
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones
  • Raltegravir Potassium
  • elvitegravir
  • dolutegravir
  • HIV Integrase
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • HIV Protease