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.

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.

• Authors: Marion Vermeulen, Charl Coleman, Josephine Mitchel, Ravi Reddy, Harry van Drimmelen, Tracy Fickett, Michael Busch, Nico Lelie
• Journal: Transfusion (Transfusion) Vol. 53 Issue 10 Pt 2 Pg. 2384-98 (Oct 2013) ISSN: 1537-2995 [Electronic] United States
• PMID: 23445273 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 American Association of Blood Banks.

Chemical References

• HIV Core Protein p24
• RNA, Viral

Topics

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