Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period

Context Current screening practices for blood donations have been successfu l in reducing human immunodeficiency virus (HIV) transmission through recei pt of contaminated blood products. However, HIV-infected blood donations ma de prior to seroconversion and before high levels of viral replication occu r could test negative using both serologic antigen and antibody tests, Test ing based on nucleic acid amplification (NAT) is being implemented to scree n for HIV-infected blood donated during this period, yet the issue of singl e vs minipool donation screening remains unresolved. Objectives To determine HIV-1 genetic linkage between virus in 2 HIV-1-infe cted recipients of blood components and virus in the donor, who was HIV ant igen and antibody negative at the time of donation; to screen the blood don or's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening. Design and Setting Case study conducted in October 1997 involving the Commu nicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore. Subjects The blood donor and the 2 recipients of donor platelets and red bl ood cells. Main Outcome Measures Genetic analysis of the HIV-1 p17 coding region of ga g and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative a ssays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts. Results Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitativ e and quantitative assay for HIV-1 RNA levels, a low level of viremia (rang e, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted b lood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels cu rrently used in minipool screening of blood donations in the United States. Conclusions Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window -period donations.