title: Comparison of human immunodeficiency virus assays in window phase and elite controller samples: viral load distribution and implications for transmission risk.
abstract: BACKGROUND
  After 3 years of individual-donation nucleic acid test (ID-NAT) screening by the South African National Blood Service (SANBS), a repository of 73 human immunodeficiency virus antibody (anti-HIV)-negative window period (WP)-yield samples and 28 anti-HIV-positive, HIV-RNA-negative elite controllers (ECs) became available for comparison of a p24 antigen (p24 Ag) assay (Innogenetics), two viral load assays (Siemens branch DNA [bDNA] 3.0 and Abbott real-time polymerase chain reaction [RT-PCR]), and three triplex NAT assays (Novartis Diagnostics Ultrio and Ultrio-Plus and Roche TaqScreen) by replicate testing of dilutions.
  
  
  METHODS
  Viral loads were assessed by bDNA and RT-PCR assays and if below 100 copies (cps)/mL, by Ultrio limiting dilution probit analysis. The probability of virus transmission by WP and EC donations was estimated for different levels of the 50% minimum infectious dose (ID50 ) using Poisson distribution statistics.
  
  
  RESULTS
  The equal distribution of WP donations plotted by log HIV-RNA levels indicated a random appearance of donors in the ramp-up phase. The HIV p24 Ag assay detected 45% of WP samples and the cutoff crossing point was estimated at 8140 (bDNA)/22,710 (RT-PCR) cps/mL. On replicate retesting of 40 HIV p24 Ag-negative ID-NAT WP-yield samples Ultrio minipool (MP)8, Ultrio-Plus MP8, and TaqScreen MP6 detected 79, 81, and 78%, respectively. Modeling with an estimated ID50 of 31.6 virions/RBC indicated that 15% of p24 Ag-negative ID-NAT WP-yield donations would have transmitted HIV if MP6-8 NAT had been used. Only 2% of RBC transfusions from ECs are estimated to be infectious with a worst-case ID50 estimate of 316 virions.
  
  
  CONCLUSIONS
  Our analysis of viremia and infectivity of WP and EC donations enables comparison of the efficacy of NAT options in preventing HIV transmission risk.
authors: South African National Blood Service (SANBS), Johannesburg, South Africa; BioQControl, DDL Laboratories, Rijswijk, Netherlands; Creative Testing Solutions, Tampa, Florida; Blood Systems Research Institute, San Francisco, California; Lelie Research Paris, Paris, France.
authors: Marion
authors: M
authors: Vermeulen
authors: Charl
authors: C
authors: Coleman
authors: Josephine
authors: J
authors: Mitchel
authors: Ravi
authors: R
authors: Reddy
authors: Harry
authors: H
authors: van Drimmelen
authors: Tracy
authors: T
authors: Fickett
authors: Michael
authors: M
authors: Busch
authors: Nico
authors: N
authors: Lelie
mesh_terms: D000465:Algorithms; D058070:Asymptomatic Diseases; D001782:Blood Donors / Q000706:statistics & numerical data; D016022:Case-Control Studies; D016655:HIV Core Protein p24 / Q000032:analysis / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D012367:RNA, Viral / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D012698:Serologic Tests / Q000379:methods; D013019:South Africa; D019562:Viral Load / Q000379:methods* / Q000502:physiology
chemical_list: D016655:HIV Core Protein p24; D012367:RNA, Viral