Role for HCV antigen detection: a new generation of assays Blood Borne Virus Unit Virus Reference Department Centre for Infections HPA Colindale 13 May 2019

Samples used for the study Part 1: 94 acute phase seronegative plasma donors, 51 of which contained detectable RNA genotyped, titrated as appropriate Part 2: Plasma samples from 65 individuals in a randomised clinical trial of Ribavarin/IFN samples from first 14 days of treatment to assess early dynamics

Part 1 inferences to be drawn:- Proficient across limited selection of genotypes 1-3 available Linearity also maintained over 3 log10 Interpolated LOD in range 2-3 log10

Part 2: 300 samples from 65 patients HCV Ag log10 f/mole HCV RNA Viral load log10 iu/ml

Part 2: Pre- or D3 samples from 59 patients

49 RA 4.00 7.00 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 Base D3 D7 D10 D14 W12 Time log HCV Ag 5.00 6.00 7.00 log HCV RNA 3.50 6.00 3.00 5.00 2.50 4.00 2.00 log HCV RNA log HCV Ag 3.00 1.50 2.00 1.00 0.50 1.00 0.00 0.00 Base D3 D7 D10 D14 W12 Time 64 Time 0.00 0.50 1.00 1.50 2.00 2.50 3.00 BASE D7 D14 W12 log HCV Ag 4.00 5.00 6.00 log HCV RNA

257 292 0.5 1 1.5 2 2.5 3 3.5 4 Base D3 D7 D10 D14 W12 Time log HCV Ag 5 6 7 log HCV RNA 4 6 3.5 5 3 4 2.5 log HCV Ag 2 3 log HCV RNA 1.5 2 1 1 0.5 Base D3 D7 D14 W12 Time 268 4.5 8 4 7 3.5 6 3 5 2.5 log HCV RNA 4 log HCV Ag 2 3 1.5 1 2 0.5 1 Base D3 D7 D14 W12 Time

Part 2 inferences to be drawn:- Good correlation between HCV Ag quantitification and HCV RNA BUT NOT absolute, what is nature of the relationship? Response to R/IFN paralleled by both markers Idiosyncrasies rare but significant, reason? Qualitative therapy prediction possible early Need to pin antigenaemia against HCV RNA for each patient Positioning- adjunct or alternative? High risk population or resource-limited sites?

Thanks to: Prof Howard Thomas and colleagues for permission to use the “Mild Trial” samples Paul Grant, UCL for HCV RNA data Nigel Wallis, Phil Tuke, Siew Lin Ngui and colleagues in BBVU, VRD Abbott Diagnostics for Architect reagents and support