How safe is safe: new human immunodeficiency virus Type 1 variants missed by nucleic acid testing

Area of Science:

• Virology
• Molecular Biology
• Public Health

Background:

• Nucleic acid amplification techniques (NAT) are crucial for reducing the window period of infectious diseases in blood donation screening.
• Despite NAT's effectiveness, false-negative results for human immunodeficiency virus Type 1 (HIV-1) RNA have been reported, posing a risk to blood transfusion safety.

Observation:

• This study investigated four cases of HIV-1 RNA-positive blood donations that were initially missed by routine NAT screening.
• Comparative analysis involved 12 CE-marked NAT assays and sequencing of target regions in suspected HIV-1 variants.

Findings:

• Many single-target NAT assays, particularly those using the 5'-long terminal repeat (LTR) region, showed deficiencies in detecting viral variants and low-viral-load donations.
• Sequence analysis identified deletions and insertions within the 5'-LTR, as well as primer mismatches, contributing to false-negative results.
• Dual-target assays successfully detected the viral variants in these cases, and two cases had viral loads below the limit of detection for standard NAT.

Implications:

• The high mutation rate of HIV-1 necessitates robust screening methods to account for emerging viral variants.
• Employing multi- and dual-target NAT assays in routine blood donor screening is recommended to minimize the risk of false-negative results and enhance blood safety.
• Further optimization of NAT assays is essential to ensure comprehensive detection of diverse HIV-1 strains.