title: Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients.
abstract: OBJECTIVE
  The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients.
  
  
  METHODS
  We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing.
  
  
  METHODS
  Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.
  
  
  RESULTS
  Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.
  
  
  CONCLUSIONS
  As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.
authors.affiliation: aDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich bInstitute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich cLaboratory of Virology and AIDS Center, University Hospital Geneva, Geneva dDepartment of Biomedicine, Haus Petersplatz, University of Basel, Basel eDivision of Immunology, University Hospital Lausanne, Lausanne fDepartment of Infectious Diseases, Bern University Hospital and University of Bern, Bern gDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel hDivision of Infectious Diseases, Cantonal Hospital St. Gallen, St. Gallen iInfectious Diseases Service, University Hospital Lausanne, Lausanne jDivision of Infectious Diseases, Geneva University Hospitals, Geneva kDivision of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland. *Karin J. Metzner, Alexandra U. Scherrer and Viktor Von Wyl contributed equally to this work.
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Vincent
authors.initials: V
authors.lastname: Aubert
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Vernazza
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000328:Adult; D000483:Alleles; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D060005:Genotyping Techniques / Q000379:methods*; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D020125:Mutation, Missense; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase