Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response

J Antimicrob Chemother. 2017 Jul 1;72(7):2083-2088. doi: 10.1093/jac/dkx090.


Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir.

Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded.

Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R.

Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Integrase / genetics
  • HIV Integrase Inhibitors / therapeutic use
  • HIV-1 / genetics
  • HIV-2 / drug effects
  • HIV-2 / enzymology
  • HIV-2 / genetics*
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral / blood
  • Raltegravir Potassium / administration & dosage
  • Raltegravir Potassium / therapeutic use*
  • Treatment Failure
  • Viremia / drug therapy


  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral
  • Raltegravir Potassium
  • dolutegravir
  • HIV Integrase