A cluster of human immunodeficiency virus Type 1 recombinant form escaping detection by commercial genomic amplification assays

BACKGROUND: Nucleic acid testing (NAT)-based methods for the detection and quantification of human immunodeficiency virus Type 1 (HIV-1) RNA are used to increase transfusion safety and to diagnose and manage HIV-1-infected patients. We describe a novel HIV-1 recombinant form associated with lack of reactivity or substantial underestimation of viral load by commercial NAT assays. STUDY DESIGN AND METHODS: We observed a repeat blood donor seroconverting to anti-HIV in whom HIV RNA was initially undetectable with routine NAT was observed. During donor follow-up, HIV RNA became detectable, but the viral load was 2 to 3 log lower than measured with other NATs targeting different genome regions. Genome sequencing revealed a novel B/F recombinant with mutations affecting primers and probe annealing accounting for the poor performance of routine NAT. A total of 553 HIV-1-infected patients attending the hospital clinic were subsequently tested prospectively using the routine assay and an in-house assay specifically designed to detect the B/F strains. RESULTS: The routine assay substantially underestimated viremia (1-5 log) in 19 cases (3.5%), 11 (58%) of which were infected with the same B/F strain observed in the index donor samples. Two other non-B circulating recombinant forms of HIV-1 (A/G, B/G subtypes) were identified as poorly detected. Newly introduced NATs targeting two HIV-1 regions improved assay performance. CONCLUSION: HIV-1 increasing heterogeneity affects the efficiency of NATs and consequently the safety of the blood supply as well as diagnosis and patient management.