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This study compares the sensitivities of two US-licensed NAT systems in detecting viremia in early HIV and HCV infections. The research highlights the analytical sensitivities and clinical yields of these assays, emphasizing the differences in performance on seroconversion panels. Findings suggest minimal differences in window periods and yield rates, supporting the use of NAT for accurate detection. The study also discusses discrepancies between assays, differential yields per million units, and the accuracy of TMA and PCR for resolving reactive samples.
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Relative Sensitivities of US Licensed NAT Assays for Detection of Viremia in Early HIV and HCV Infection MP Busch, SA Glynn, DJ Wright, D Hirschkorn, ME Laycock, JD McAuley, Y Tu, C Giachetti, J Gallarda, J Heitman, S Kleinman NHLBI-REDS NAT Study Group (submitted to Transfusion)
Background and Rationale • Two licensed NAT Systems in US • Roche Ampliscreen (Multi/Std-Prep / PCR) • Gen-Probe/Chiron Procleix (TC / TMA) • Manufacturer licensure trials and previous blood industry studies have documented analytical sensitivities and WP closure relative to serology • Comparable clinical yields (NAT-only donations) in US screening (Stramer et al. NEJM 2004), but limited power to detect differences • No previous head-to-head study of performance on SC panels in ID- and MP-NAT contexts
HIV Panel Testing Algorithm 44 HIV Panels 145 Serial Samples Sample Selection >1 PCR(+), Ab(-) >2 PCR(-), Ab(-) >2 wk pre-quantification <7 days between samples Discrepancies ? SuperQuant [TM] RT PCR X 1 RNA Quantifiable Samples Non-Quantifiable Samples (<100 copies/mL) YES NO 12 Panels 116 Serial Samples END >5000 copies / mL <5000 copies / mL Ultra Qual RT PCR X 5-10 Neat & MP x1 Neat & MP x 3 20 add'l replicates for a given assay and dilution.
HCV Panel Testing Algorithm 55 HCV Panels 629 Serial Samples Sample Selection >1 PCR(+), Ab(-) >2 PCR(-), Ab(-) > 2 wks pre-quantification <7 days between samples Discrepancies ? COBAS Amplicor HCV Monitor v2.0 PCR X 1 RNA Quantifiable Samples Non-Quantifiable Samples <1,620 copies/mL YES NO 12 Panels 180 Serial Samples END >5000 copies / mL <5000 copies / mL d-HCV TMA X 4 Neat & MP x 1 Neat & MP x 3 20 add'l replicates for a given assay and dilution.
Representative Discrepancies between G-P TMA and Roche PCR on HIV Panels
Representative Discrepancies between G-P TMA and Roche PCR on HIV Panels
Odds Ratios (OR) and 95% CIs Comparing Assays Performed Neat or in Mini-Pools (MP)
Differential WP (ΔWP *) in Days and Differential Yields of Viremic Donations per 10,000,000 Donations ‡ (95% CI) for Comparisons of NAT Assays Performed Neat or on Mini-Pool (MP) Dilutions * based on doubling times: HIV, 20.5 hrs; HCV, 10.8 hrs. ‡ based on US incidence rates: HIV, 2.16 per 100,000 person-years; HCV, 2.80 per 100,000 person-years.
Conclusions • Findings reassuring with respect to comparability of licensed NAT systems • Differences in MP-NAT sensitivity translated into extremely small window period and yield differences • 12 and 14 hours for HIV and HCV, respectively • 1 infected donation per 20 million (HCV) or 33 million (HIV) units • Support Stramer et al. (NEJM 2004) finding of similar HIV and HCV MP-NAT yields for Gen-Probe/Chiron and Roche NAT users • Differences in sensitivity of ID- vs MP-NAT consistent with previous estimates based on viral doubling time models • 2 to 4 day WP closure and 1 to 2 ID-only yield cases per 10 million units for HIV and HCV, respectively • Data supports accuracy of dTMA and PCR for resolution of reactive MPs, and for “cross-supplemental” testing for counselling/reinstatement
