title: HIV type-1 drug resistance in treatment-naive patients monitored using minority species assays: a systematic review and meta-analysis.
abstract: BACKGROUND
  The detection of mutations associated with drug resistance in HIV type-1 might be increased by applying minority species assays capable of identifying low frequency mutations in comparison with the use of population sequencing alone. Because minority species assays are mutation-specific, the benefit of this approach differs depending on the mutation being detected.
  
  
  METHODS
  We performed a systematic review of published data reporting detection of genotypic drug resistance using allele-specific (AS)-PCR minority assays and by standard DNA sequencing in drug-naive populations. We calculated the fold increase of mutation detection for each study and pooled these via meta-analysis, displaying results using Forest plots.
  
  
  RESULTS
  Our studies revealed an increase in detection of 1.9-fold (95% confidence interval [CI] 1.3-2.7; P < 0.0005) for K103N, 4.4-fold (95% CI 1.2-16.6; P = 0.026) for Y181C, 4.8-fold (95% CI 1.5-15.1; P = 0.008) for L90M and 8.7-fold (95% CI 4.0-18.6; P < 0.0005) for M184V. We found no relationship between AS-PCR assay sensitivity and frequency of additional mutation detection.
  
  
  CONCLUSIONS
  Additional detection of drug resistance mutations using AS-PCR minority mutation assays vary significantly depending on the mutation examined; however, the most marked increase in detection of resistance mutations was observed for M184V, a mutation seldom detected by standard techniques in drug-naive patients. We suggest that the presence of drug resistance mutations can be more accurately estimated using a combination of AS-PCR and standard genotyping.
authors.affiliation: Centre for Infections, Health Protection Agency, London, UK. andrew.buckton@hpa.org.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Buckton
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Harris
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cane
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D058885:Multilocus Sequence Typing / Q000379:methods; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents