title: Low concordance and resistance mutation emergence in the HIV protease gene among circulating and cell-associated viruses at viral replication episodes during darunavir/ritonavir monotherapy.
abstract: OBJECTIVE
  To assess the changes on the HIV protease gene in plasma and peripheral blood mononuclear cell (PBMC) compartments during viral replication episodes in patients on boosted-darunavir monotherapy (mtDRV/rtv).
  
  
  METHODS
  A prospective study was carried out in which adult HIV-1-infected patients who started mtDRV/rtv after viral suppression for ≥ 6 months with no major darunavir-related resistance mutations were enrolled. Patients with two consecutive plasma HIV RNA measurements >200 HIV-1 RNA copies/mL were considered as having virological failure (VF), while patients with two consecutive plasma HIV RNA measurements >50 copies/mL without meeting the VF criteria were considered to have virological rebound (VR). HIV protease genotypic profiles from plasma and PBMCs were performed at baseline and at VF and VR episodes.
  
  
  RESULTS
  One hundred and fifty patients were included in the study, with overall VF and VR rates of 14% (n=21) and 14.7% (n=22), respectively. No major darunavir resistance mutations were observed in the plasma or PBMC samples. Circulating and cell-associated viruses showed a wild-type protease gene sequence in 54% and 23% of patients, respectively while the remainder patients only harboured minor protease inhibitor-associated mutations. Full concordance between plasma RNA and PBMC DNA protease genotypes was found in 23% of the sequences.
  
  
  CONCLUSIONS
  No darunavir-related mutations were found in patients with VF or VR, either in plasma or in PBMCs; thus, simplification to mtDRV/rtv does not comprise future antiretroviral treatment options.
authors.affiliation: Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: O J
authors.initials: OJ
authors.lastname: Benmarzouk-Hidalgo
authors.forename: A
authors.initials: A
authors.lastname: Gutierrez-Valencia
authors.forename: R
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: P
authors.initials: P
authors.lastname: Viciana
authors.forename: L F
authors.initials: LF
authors.lastname: López-Cortés
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015331:Cohort Studies; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011446:Prospective Studies; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D054301:gag Gene Products, Human Immunodeficiency Virus; D016333:HIV Protease; D019438:Ritonavir; D000069454:Darunavir
keywords: HIV protease gene; HIV reservoir; HIV-1 therapy; resistance mutation; ritonavir-boosted darunavir monotherapy