Comparison of human immunodeficiency virus assays in window phase and elite controller samples: viral load distribution and implications for transmission risk

Transfusion. 2013 Oct;53(10 Pt 2):2384-98. doi: 10.1111/trf.12117. Epub 2013 Feb 27.

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.

Study design and 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.

Conclusion: Our analysis of viremia and infectivity of WP and EC donations enables comparison of the efficacy of NAT options in preventing HIV transmission risk.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Asymptomatic Diseases
  • Blood Donors / statistics & numerical data
  • Case-Control Studies
  • HIV Core Protein p24 / analysis
  • HIV Core Protein p24 / blood
  • HIV Core Protein p24 / immunology*
  • HIV Infections / blood
  • HIV Infections / diagnosis*
  • HIV Infections / transmission*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / isolation & purification*
  • Humans
  • RNA, Viral / blood*
  • Real-Time Polymerase Chain Reaction / methods
  • Risk Factors
  • Serologic Tests / methods
  • South Africa
  • Viral Load / methods*
  • Viral Load / physiology

Substances

  • HIV Core Protein p24
  • RNA, Viral