False-Positive Results for Human Immunodeficiency Virus Type 1 Nucleic Acid Amplification Testing in Chimeric Antigen Receptor T Cell Therapy.
Level 4 - case-series / case-control
Case series
PubMed 31694968 · doi:10.1128/JCM.01420-19
What was done
The authors described three clinical cases where patients who received chimeric antigen receptor (CAR) T-cell immunotherapy underwent human immunodeficiency virus type 1 (HIV-1) testing: a 16-year-old female with B-cell acute lymphoblastic leukemia screened prior to stem cell transplantation; a 65-year-old male with diffuse large B-cell lymphoma screened prior to a second CAR T-cell collection; and a 58-year-old male with multiple myeloma evaluated following an occupational exposure. Patient samples were tested via a fourth-generation HIV-1 enzyme immunoassay (targeting p24 antigen and anti-HIV-1 antibodies), the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test v2.0 (targeting gag and LTR sequences), and the Abbott m2000 RealTime HIV-1 assay (targeting integrase).
What was found
All 3 patients tested negative by fourth-generation HIV-1 enzyme immunoassay and positive by the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test v2.0. When retested with the Abbott m2000 RealTime HIV-1 assay, all 3 samples tested negative. The false-positive results on the Roche NAAT were attributed to cross-reactions between lentiviral vector sequences and LTR target regions.
Why it matters
Clinicians and diagnostic laboratories should be aware that lentiviral vector-based CAR T-cell products can cause false-positive HIV-1 viral load testing on LTR-targeting NAAT platforms. Switching to an alternative NAAT target, such as integrase, can clarify ambiguous results and prevent misdiagnosis.
Limits
This report is limited to a small descriptive case series (n = 3) and examines only two commercial NAAT platforms. Quantitative viral load values, assay analytical sensitivity, and the duration of false-positivity post-infusion were not reported in the abstract.
Cited by
- supports CAR-T cell therapy involves engineering a patient's T cells with an artificial chimeric antigen receptor using modified lentiviruses as gene delivery vectors.