title: In vivo emergence of drug-resistant mutations at less than 50 HIV-1 RNA copies/mL that are maintained at viral rebound in longitudinal plasma samples from human immunodeficiency virus type-1-infected patients on highly active antiretroviral therapy.
abstract: OBJECTIVE
  Emergence of human immunodeficiency virus type-1 (HIV-1) genotypic drug resistance is generally attributed to noncompliance, poorly absorbed drugs, or drug-to-drug interaction. Attempts to determine emerging genotypic drug resistance from study subjects on highly active antiretroviral therapy (HAART) relied on insensitive polymerase chain reaction (PCR) techniques, revealing wild type HIV-1 or precursor resistant genotypes from few plasma samples successfully amplified with <50 copies/mL.
  
  
  METHODS
  In this analysis, using Applied Biosystems' ViroSeq HIV-1 Genotyping Systems, Version 2.0 (Applied Biosystems, Foster City, CA, USA) and the supplemental, for research use only, nested PCR primers, genotypic drug resistance was determined in longitudinal plasma samples from 11 study subjects on HAART.
  
  
  RESULTS
  In 4 of 11 study subjects, newly emerging genotypic primary resistant mutations were detected in plasma samples with <50 copies/mL. Most of these primary drug-resistant mutations were detected in subsequent longitudinal samples with detectable viral load (viral breakthrough).
  
  
  CONCLUSIONS
  This analysis suggests sufficient viral replication <50 copies/mL to generate genotypic drug resistance in study subjects on suppressive HAART.
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, Clinical Laboratories at San Francisco General Hospital, San Francisco, California, USA. elbeik@itsa.ucsf.edu
authors.forename: T
authors.initials: T
authors.lastname: Elbeik
authors.forename: B S
authors.initials: BS
authors.lastname: Hoo
authors.forename: M E
authors.initials: ME
authors.lastname: Campodonico
authors.forename: J
authors.initials: J
authors.lastname: Dileanis
authors.forename: F F
authors.initials: FF
authors.lastname: Fay
authors.forename: R L
authors.initials: RL
authors.lastname: Bortolozzi
authors.forename: M S
authors.initials: MS
authors.lastname: Benetti
authors.forename: O H
authors.initials: OH
authors.lastname: Fay
authors.forename: N
authors.initials: N
authors.lastname: Marlowe
authors.forename: O
authors.initials: O
authors.lastname: Petrauskene
authors.forename: D
authors.initials: D
authors.lastname: Chernoff
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: V L
authors.initials: VL
authors.lastname: Ng
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D019259:Lamivudine / Q000494:pharmacology; D008137:Longitudinal Studies; D009154:Mutation; D012367:RNA, Viral / Q000187:drug effects*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019438:Ritonavir / Q000494:pharmacology; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D019438:Ritonavir