Parallel increase of viral nucleic acid and antigen load in ramp up phase

Studies with seroconversion panels, infected chimpanzees and NAT yield window period samples have shown that there is a log linear increase of the viral concentration in the ramp up phase of viremia. Careful quantification of the HBV-DNA and HBsAg concentration in seroconversion panels shows a parallel increase of the nucleic acid and antigen concentration (at a HBV to HBsAg particle ratio of approximately 1:1000) (figure below).

Figure. Parallel kinetics of HBV-DNA and HBsAg in ramp up phase of five seroconversion panels


There is also a clear correlation between p24 antigen and HIV-RNA concentration in antibody negative window period ramp up samples. For these viruses we used regression analysis to estimate the HBV-DNA and HIV-RNA concentration in copies/mL at the 50% NAT and antigen seroconversion point in ramp up samples. Since the viral doubling times for the viruses are known the lengths of the diagnostic window periods for NAT and antigen testing could be estimated and these were confirmed in seroconversion panels. Hence for NAT and antigen testing there is no need to use seroconversion panels from US plasma donors for evaluation of the diagnostic sensitivity. One can better use viral standard dilution panels of different genotypes to estimate 50% LODs in copies/mL and so ensure that diagnostic window periods of a NAT system are comparable in different regions of the world.