title: Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Requena
authors.affiliation: Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Treviño
authors.affiliation: Hospital de Poniente, Almería, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabezas
authors.affiliation: Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Garcia-Delgado
authors.affiliation: Corporación Sanitaria Parc Taulí, Barcelona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Amengual
authors.affiliation: Hospital de Poniente, Almería, Spain.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Lozano
authors.affiliation: Son Espases Hospital, Palma de Mallorca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Peñaranda
authors.affiliation: Hospital de Poniente, Almería, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Fernández
authors.affiliation: La Paz University Hospital & Autonomous University, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics; D015498:HIV-2 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D014766:Viremia / Q000188:drug therapy; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D000099226:Dolutegravir