title: Drug resistance is rarely the cause or consequence of long-term persistent low-level viraemia in HIV-1-infected patients on ART.
abstract: BACKGROUND
  The introduction of highly sensitive HIV-1 viral load assays with a lower quantification limit of 20 copies/ml uncovered that in a number of patients on ART, the viral load systematically fluctuates around or slightly above the detection limit of the assays. This study aimed to analyse the presence or occurrence of drug resistance mutations in HIV-1-infected patients during long-term persistent low-level viraemia (PLLV) under ART.
  
  
  METHODS
  A retrospective study was carried out in which baseline and on-therapy presence of drug resistance mutations in the HIV-1 protease and reverse transcriptase genes were analysed in patients with PLLV between 20 and 250 copies/ml. For all available plasma samples collected during PLLV, resistance analysis was attempted with an ultrasensitive amplification and sequencing protocol.
  
  
  RESULTS
  Resistance analysis was successful for 154 samples collected longitudinally from 23 patients over a median period of 4.7 years (IQR 3.3-5.7). Twenty of these patients were on a boosted protease inhibitor (PI)-based regimen (87%). Single drug resistance mutations were detected in isolated samples of 4 patients, 2 of the 3 patients who initiated a non-nucleoside reverse transcriptase inhibitor-based regimen and 2 of the 20 on a PI-based regimen. Only one of the detected mutations decreased susceptibility to the therapy regimen taken at the time of sample collection. Drug resistance mutations were not found in the three patients who developed virological failure (viral load >250 copies/ml) during the study.
  
  
  CONCLUSIONS
  Long episodes of PLLV in patients on boosted PI-based regimens rarely result in the selection of new drug-resistant variants.
authors.affiliation: AIDS Reference Laboratory, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Vancoillie
authors.forename: Virginie
authors.initials: V
authors.lastname: Mortier
authors.forename: Els
authors.initials: E
authors.lastname: Demecheleer
authors.forename: Marlies
authors.initials: M
authors.lastname: Schauvliege
authors.forename: Linos
authors.initials: L
authors.lastname: Vandekerckhove
authors.forename: Dirk
authors.initials: D
authors.lastname: Vogelaers
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents