AABB23: What the Latest TTIMS Data Says About Blood Safety

More than eight years have passed since the U.S. Food and Drug Administration introduced the Transfusion Transmissible Infections Monitoring System (TTIMS) as part of the effort to advance blood donor eligibility recommendations based on scientific data. Since then, TTIMS has been pivotal in shaping these recommendations, including FDA’s May 2023 approval of individual donor assessment.

While these changes have been welcomed by patients, donors and the blood community, many remain unfamiliar with the inner workings of TTIMS. During a Monday evening session at the 2023 AABB Annual Meeting, speaker provided attendees with a closer look at this vital blood safety system, alongside recent data regarding the incidence of transfusion transmissible infections (TTIs) in the United States.

Program chair Barbee I. Whitaker, PhD, lead general health scientist at FDA’s Center for Biologics Evaluation and Research, began the session with a brief overview of TTIMS. The system comprises four participating blood centers: American Red Cross, New York Blood Center, OneBlood and Vitalant. These centers collectively represent approximately 60% of the U.S. blood supply.

TTIMS gathers data on the prevalence and incidence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis infections from the screening of blood donors. In addition, the system compiles demographic data, behavioral risk factors, and biorepository samples from donors who test positive for markers of these infections.

Whitaker also clarified the organization and operation of the system. American Red Cross manages the Donor Database Coordinating Center (DDCC), which is responsible for acquiring and validating donor demographic data and testing results from Creative Testing Solutions. Vitalant Research Institute operates the Laboratory and Risk Factor Coordinating Center (LRCC), which serves as the repository for positive samples. It also conducts follow-up molecular sequencing and further testing.

During the session, Whitaker presented select TTIMS studies. One ongoing study examined risk factors in donors with TTIs through case control interviews. A second study focused on antiretroviral use in HIV-positive blood donors and found that 19.7% of the 869 tested samples showed evidence of antiretroviral medication.

Following Whitaker's presentation, Edward P. Notari, MPH, director of epidemiology at American Red Cross, provided insights into TTIMS data transfer and processing, along with an explanation of how consensus-positive donations are defined by TTIMS organizations.

Notari then showed TTIMS data on the prevalence, incidence, and residual risks of TTIs in donations from both first-time and repeat donors. The data indicated a downward trend for HCV, a steady trend for HBV, a slight downward trend for HIV, and an upward trend for syphilis. Notari stressed the overall low risk of TTIs, noting that there has been no observed increase in risk related to policy changes around blood donation by men who have sex with men (MSM).

The session concluded with a presentation from Eduard Grebe, PhD, affiliate investigator at Vitalant Research Institute, who focused on HIV incidence in first-time donors. Grebe noted that monitoring first-time donors for HIV incidence is challenging due to lack of inter-donation intervals but said that classifying infections as recently acquired or longstanding allows for estimation of incidence.

First, Grebe explained different types of testing that can help determine the recency of infection:

• HIV nucleic acid testing and HIV antibody (Ab) testing. NAT reactive and Ab nonreactive samples are classified as recently acquired HIV infections, while NAT nonreactive and AB reactive samples are classified as longstanding HIV infections.
• Sedia Limiting Antigen (LAg) Avidity EIA. This assay measure anti-HIV Ab activity, which increases over time after HIV infection. Normalized optical densit (ODn) below a threshold is classified as a recent infection.
• HIV-1 viral load. Viral suppression through antiretroviral therapy reduces antigenic pressure and leads to reduced Ab activity over time.

Grebe then reviewed data on HIV incidence among first-time blood donors after the reduction in the donor deferral period for MSM from 12 to 3 months. TTIMS data showed a decrease in HIV incidence from 2.74 to 1.86 per 100,000 person-years. Grebe noted that due to the rarity of recent infections, identifying changes in incidence rates is challenging. He concluded with a discussion of new methods to improve the detection of small changes in HIV incidence among first-time donors.