title: Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure.
abstract: BACKGROUND
  In our study, we have hypothesized that proviral DNA may show the history of mutations that emerged at previous failures to a Raltegravir containing regimen, in patients who are currently undetectable and candidates to simplification to a Dolutegravir containing regimen, in order to decide on once a day or twice a day dosing.
  
  
  METHODS
  We have performed a pilot, observational, retrospective, non interventional study, including 7 patients infected by HIV-1, all with a history of previous failure to a RAL containing regimen, that were successfully salvaged and had reached viral suppression. A genotypic viral Integrase region study was available for each patient at the moment of RAL failure. After an average (IQR) time of 48 months (29-53) Integrase resistance mutations in proviral DNA were studied.
  
  
  RESULTS
  All the patients were infected by HIV-1 B subtypes, with a mean age of 55 (range 43 to 56), originating from Spain, and 4 were women. Median viral load (log) and CD4 count at the moment of the study on proviral DNA was of 1.3 log cp/ml (range 0-1.47) and 765.5 cells/μL (range; 436.75-1023.75). The median time (IQR) between previous failure to RAL and the study on proviral DNA was 48 (29-53) months. At Raltegravir failure, N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). In proviral DNA, N155H was detected by population sequencing in three patients (42.8 %), and UDS demonstrated a 9.77 % relative abundance of N155H in the remaining patient. Sanger sequencing correctly identified all the secondary mutations.
  
  
  CONCLUSIONS
  This is a pilot study that demonstrates the possibility of properly identifying N155H and some secondary mutations 29-53 months after failure.
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain. jose.angel.fernandez.caballero@gmail.com.|, Domicilio: C/Divan del Tamarit, 4, CP: 18198, Huetor, Vega (Granada), Spain. jose.angel.fernandez.caballero@gmail.com.
authors.forename: Jose Ángel
authors.initials: JÁ
authors.lastname: Fernández-Caballero
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Chueca
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Álvarez
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Mérida
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: López
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Sánchez
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: David
authors.initials: D
authors.lastname: Vinuesa
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Martínez
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: José
authors.initials: J
authors.lastname: Hernández
authors.affiliation: Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: García
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010078:Oxazines; D010865:Pilot Projects; D010879:Piperazines; D011728:Pyridones; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000068898:Raltegravir Potassium; D000099226:Dolutegravir
keywords: Dolutegravir; HIV; Integrase; Proviral DNA; Raltegravir