Comparison of human immunodeficiency virus assays in window phase and elite controller samples: viral load distribution and implications for transmission risk. Issue 10 (27th February 2013) - Vermeulen, Marion
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.