Results of donor screening with nucleic acid amplification tests (NAT) and implications for HIV research, diagnosis and surveillance

Michael P. Busch, MD, PhD Professor of Laboratory Medicine, UCSF Director, Blood Systems Research Institute

Issues: Highly sensitive, qualitative tests for rapid detection of nucleic acids of HIV and other blood-borne viruses (HCV, HBV and WNV) were developed and implemented as minipool (MP)-NAT assays in blood, plasma and organ donor screening settings beginning in the late 1990s. This presentation will review the design of donor NAT assays, summarize the yield of MP-NAT screening of U.S. donors, discuss the impact MP vs. single-sample NAT on window period closure and blood safety, and illustrate applications of donor NAT assays in HIV research, diagnostic and public health surveillance settings.

Description: NAT assays with sensitivities of <15 copies/mL have been developed by several manufacturers and licensed by FDA for donor screening. Over the first 3 years of donor NAT screening HIV-1 RNA yield was 12 confirmed-positive donors in 37 million donations screened, or 1 in 3.1 million, of which only two were detected by HIV-1 p24 antigen. For HCV, the yield was 170 RNA confirmed-positive donors in 40 million donations screened, or 1 in 230,000. WNV NAT was quickly implemented following documented transfusion cases in 2002, and resulted in detection of ~1000 viremic units in 2003 and over 500 in 2004. HBV MP-NAT implementation is now under consideration.

Lessons Learned: Although MP-NAT screening of donor was successfully implemented and has enhanced transfusion safety, this technology is expensive and the cost effectiveness of NAT is low (>$1,000,000 per QALY) due to very low incidence of HIV and other agents in blood donors. There is continued pressure to expand NAT to both additional established agents, as well as in response to threats from emerging viruses. Advances in technology, including automation allowing for high throughput individual sample NAT and increased multiplexing of multiple targets, are evolving rapidly.

Recommendations: The experience with donor NAT screening has been positive, with excellent performance of assays and yields as predicted by incidence-window period models. Preliminary applications of donor NAT assays to HIV research, diagnostic, therapeutic monitoring and vaccine trial settings have shown promise. Research is critical to establish a rational, cost-effective role for NAT screening outside the donor screening context.