title: The effects of the Roche AMPLICOR HIV-1 MONITOR UltraSensitive Test versions 1.0 and 1.5 viral load assays and plasma collection tube type on determination of response to antiretroviral therapy and the inappropriateness of cross-study comparisons.
abstract: BACKGROUND
  Because there are limited head-to-head data comparing antiretroviral combinations, physicians are tempted to rely on cross-trial comparisons to evaluate the relative efficacy of HIV drugs. However, a variety of factors can confound these comparisons, resulting in misleading or invalid conclusions.
  
  
  OBJECTIVE
  To compare and evaluate the use of: (i) versions 1.0 and 1.5 of the Roche AMPLICOR HIV-1 MONITOR UltraSensitive assay, and (ii) ethylenediaminetetraacetic acid (EDTA) and plasma preparation (PPT) tubes on the proportion of HIV-infected patients who would be classified as virological responders in a multinational clinical trial.
  
  
  METHODS
  The study utilized was a randomized, double-blind trial comparing the efficacy and safety of atazanavir with efavirenz, each in combination with fixed-dose zidovudine/lamivudine, in antiretroviral-naïve patients. To evaluate the effect of monitor kit version, paired plasma samples from 634 patients at week 48 were analyzed using both versions 1.0 and 1.5 of the monitor kit. To evaluate the effect of collection tube type, paired plasma samples collected from 584 patients at week 52 using both EDTA and PPT tubes were assayed. Patients were classified as responders if HIV-1 RNA levels were below a pre-determined level of quantification (LOQ), both 400 and 50 copies/ml.
  
  
  CONCLUSIONS
  Substantially higher HIV-1 RNA levels were observed with monitor kit version 1.5, resulting in lower response rates. The version 1.0 monitor kit resulted in a 7% increase in patients classified as responders at the LOQ of 400 copies/ml and a 13% increase at the LOQ of 50 copies/ml. Consistently higher response rates (11% higher at the LOQ of 400 copies/ml and 34% higher at the LOQ of 50 copies/ml) were also observed when samples were collected in EDTA tubes compared with PPT tubes. Differences in monitor kit sensitivity and plasma collection procedures are key factors in study results and suggest caution when performing cross-study comparisons.
authors.affiliation: Pharmaceutical Research Institute, Bristol-Myers Squibb Company, 3 rue Joseph Monier, 92500 Rueil-Malmaison, Paris, France. Michael.Giordano@bms.com
authors.forename: Michael
authors.initials: M
authors.lastname: Giordano
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelleher
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Colonno
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Squires
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D001800:Blood Specimen Collection / Q000295:instrumentation* / Q000379:methods; D003521:Cyclopropanes; D017931:DNA Primers; D004359:Drug Therapy, Combination; D004492:Edetic Acid; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D038622:Internationality; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D009842:Oligopeptides / Q000627:therapeutic use; D010078:Oxazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D016032:Randomized Controlled Trials as Topic; D011933:Reagent Kits, Diagnostic; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017931:DNA Primers; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D010078:Oxazines; D011725:Pyridines; D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D004492:Edetic Acid; C098320:efavirenz