title: Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels.
abstract: BACKGROUND
  We evaluated reliability and clinical usefulness of genotypic resistance testing (GRT) in patients for whom combination antiretroviral therapy (cART) was unsuccessful with viremia levels 50-1000 copies/mL, for whom GRT is generally not recommended by current guidelines.
  
  
  METHODS
  The genotyping success rate was evaluated in 12 828 human immunodeficiency virus type 1 (HIV-1) plasma samples with viremia >50 copies/mL, tested using the commercial ViroSeq HIV-1 Genotyping System or a homemade system. Phylogenetic analysis was performed to test the reliability and reproducibility of the GRT at low-level viremia (LLV). Drug resistance was evaluated in 3895 samples from 2200 patients for whom treatment was unsuccessful (viremia >50 copies/mL) by considering the resistance mutations paneled in the 2013 International Antiviral Society list.
  
  
  RESULTS
  Overall, the success rate of amplification/sequencing was 96.4%. Viremia levels of 50-200 and 201-500 copies/mL afforded success rates of 67.2% and 88.1%, respectively, reaching 93.2% at 501-1000 copies/mL and ≥97.3% above 1000 copies/mL. A high homology among sequences belonging to the same subject for 96.4% of patients analyzed was found. The overall resistance prevalence was 74%. Drug resistance was commonly found also at LLV. In particular, by stratifying for different viremia ranges, detection of resistance was as follows: 50-200 copies/mL = 52.8%; 201-500 = 70%; 501-1000 = 74%; 1001-10 000 = 86.1%; 10 001-100 000 = 76.7%; and >100 000 = 63% (P < .001). Similar bell-shaped results were found when the GRT analysis was restricted to 2008-2012, although at a slightly lower prevalence.
  
  
  CONCLUSIONS
  In patients failing cART with LLV, HIV-1 genotyping provides reliable and reproducible results that are informative about emerging drug resistance.
authors.affiliation: University of Rome Tor Vergata.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Santoro
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fabeni
authors.forename: Daniele
authors.initials: D
authors.lastname: Armenia
authors.forename: Claudia
authors.initials: C
authors.lastname: Alteri
authors.forename: Domenico
authors.initials: D
authors.lastname: Di Pinto
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.forename: Domenico
authors.initials: D
authors.lastname: Di Carlo
authors.forename: Caterina
authors.initials: C
authors.lastname: Gori
authors.forename: Stefania
authors.initials: S
authors.lastname: Carta
authors.forename: Valentina
authors.initials: V
authors.lastname: Fedele
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Arrigo
authors.forename: Giulia
authors.initials: G
authors.lastname: Berno
authors.forename: Adriana
authors.initials: A
authors.lastname: Ammassari
authors.forename: Carmela
authors.initials: C
authors.lastname: Pinnetti
authors.forename: Emanuele
authors.initials: E
authors.lastname: Nicastri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Latini
authors.forename: Chiara
authors.initials: C
authors.lastname: Tommasi
authors.forename: Evangelo
authors.initials: E
authors.lastname: Boumis
authors.forename: Nicola
authors.initials: N
authors.lastname: Petrosillo
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral; D060005:Genotyping Techniques / Q000379:methods*; D015658:HIV Infections / Q000175:diagnosis* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015203:Reproducibility of Results; D012189:Retrospective Studies; D019562:Viral Load
keywords: HIV-1 genotyping; HIV-1 low viremia; clinical outcome; drug resistance; phylogenesis