title: ARCHITECT® HIV Ag/Ab Combo assay: correlation of HIV-1 p24 antigen sensitivity and RNA viral load using genetically diverse virus isolates.
abstract: BACKGROUND
  HIV antigen/antibody (Ag/Ab) combination assays represent a significant advancement in assays used for diagnosing HIV infection based on their ability to detect acute and chronic infections. During acute HIV infection (AHI), detection depends on assay sensitivity for p24 Ag.
  
  
  OBJECTIVE
  To directly compare the Ag sensitivity of the ARCHITECT(®) HIV Ag/Ab Combo assay to RNA viral load using cell culture supernatants of virus isolates. HIV-1 isolates allow correlation in the total absence of an antibody response to infection and across genetically diverse HIV-1 group M strains.
  
  
  METHODS
  Thirty-five HIV-1 isolates comprising subtypes A-D, F and G, CRF01_AE, CRF02_AG, and unique recombinant forms were evaluated. Cell-free culture supernatant for each isolate was diluted to four levels and tested in the HIV Combo assay to determine a signal to cutoff ratio and the RealTime(®) HIV-1 assay to quantify RNA. The RNA copies/mL at the HIV Combo assay cutoff was determined.
  
  
  RESULTS
  The median RNA copies/mL at the HIV Combo assay cutoff was 57,900 for individual virus isolates (range 26,440-102,400). A single plot of all the data gave a value of 58,500RNA copies/mL. An analysis of data published for acute HIV infection in human subjects gave a similar result; HIV Combo detected 97% of AHIs with RNA copies/mL > 30,700.
  
  
  CONCLUSIONS
  Based on analysis of virus isolates, the ARCHITECT HIV Combo assay can detect p24 Ag when RNA is above approximately 58,000copies/mL. The correlation of viral load and Ag sensitivity was consistent across genetically diverse HIV-1 group M strains.
authors.affiliation: Infectious Diseases Research, Abbott Diagnostics, Abbott Park, IL, USA. catherine.brennan@abbott.com
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brennan
authors.forename: Julie
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Ana
authors.initials: A
authors.lastname: Vallari
authors.forename: Priscilla
authors.initials: P
authors.lastname: Swanson
authors.forename: John R
authors.initials: JR
authors.lastname: Hackett
mesh_terms: D000208:Acute Disease; D005260:Female; D014644:Genetic Variation; D015483:HIV Antibodies / Q000097:blood*; D016655:HIV Core Protein p24 / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D011933:Reagent Kits, Diagnostic; D011995:Recombination, Genetic; D012680:Sensitivity and Specificity; D019562:Viral Load
chemical_list: D015483:HIV Antibodies; D016655:HIV Core Protein p24; D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic