title: Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study.
abstract: OBJECTIVE
  Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL.
  
  
  METHODS
  A total of 16 511 HIV-1 reverse transcriptase and protease sequences from 11 492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs.
  
  
  RESULTS
  Overall, 2500/16 511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL.
  
  
  CONCLUSIONS
  Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases.
authors.affiliation: Clinic of Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy. ahnven@yahoo.it
authors.forename: Mattia C F
authors.initials: MC
authors.lastname: Prosperi
authors.forename: Nicola
authors.initials: N
authors.lastname: Mackie
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camacho
authors.forename: Iuri
authors.initials: I
authors.lastname: Fanti
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Anders
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Codoñer
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
authors.forename: Loveleen
authors.initials: L
authors.lastname: Bansi
authors.forename: David A M C
authors.initials: DA
authors.lastname: van de Vijver
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005060:Europe; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D014764:Viral Proteins