Detection of HIV RNA after CAR T-Cell Therapy in a Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patient: Possibility of False Positivity and Clinical Implications.

Chimeric antigen receptor (CAR) T-cell therapy using lentiviral vectors can lead to false-positive human immunodeficiency virus (HIV) RNA detection, making distinguishing true infection from vector-related signals challenging. A 64-year-old male with relapsed/refractory diffuse large B-cell lymphoma underwent multiple lines of treatment, including R-CHOP, R-ICE, autologous stem cell transplantation, and tisagenlecleucel (tisa-cel, Kymriah). Infectious disease screening before CAR T-cell therapy was negative for HIV. However, 4 months post-infusion, during evaluation for second-line CD20-targeted CAR T-cell therapy, HIV RNA was detected in Roche Cobas HIV-1 assay targeted dual target, 5' long terminal repeat (5' LTR) and gag gene (48 copies/mL). Serial testing showed persistent but low-level positivity of HIV RNA. Retrospective analysis of stored serum samples revealed HIV RNA negativity before tisa-cel infusion but positivity post-infusion in Roche Cobas HIV-1 assay. Additional testing using the Alinity m HIV-1 assay (dual target: 5' LTR and pol gene) and the Abbott RealTime HIV-1 assay (single-target: pol gene) confirmed that only the dual-target assay yielded positive results, suggesting lentiviral vector cross-reactivity rather than actual HIV infection. This case underscores the potential for false-positive HIV-1 RNA detection in CAR T-cell treatment recipients due to vector-derived sequences, emphasizing the need for cautious interpretation of HIV-1 testing.