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False-Positive Results for Human Immunodeficiency Virus Type 1 Nucleic Acid Amplification Testing in Chimeric Antigen
Jocelyn R Hauser1, Hong Hong1, N Esther Babady1
1Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Abstract:
Chimeric antigen receptor (CAR) T cell immunotherapy has been a major advancement in cancer therapeutics. Reprogramming of T cells is achieved by using gammaretroviral or lentiviral vectors, which may interfere with human immunodeficiency virus type 1 (HIV-1) nucleic acid amplification testing (NAAT). Here, we describe three clinical scenarios in which CAR T cell immunotherapy interfered with HIV-1 testing, including (i) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B cell acute lymphoblastic leukemia, post CAR T cell treatment; (ii) routine infectious disease screening prior to second CAR T cell collection in a 65-year-old male with diffuse large B cell lymphoma who failed initial CAR T cell treatment; and (iii) routine infectious risk assessment following an occupational health exposure from a 58-year-old male with multiple myeloma, who received CAR T cell treatment. In each case, patients initially tested negative by the "fourth-generation" HIV-1 screening enzyme immunoassay (targeting the p24 antigen and anti-HIV-1 antibodies), but positive by the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test v2.0 (targeting gag and the long terminal repeat [LTR]). These samples subsequently retested negative using the Abbott m2000 RealTime HIV-1 assay, which targets the integrase gene. These results indicated that cross-reactions between lentiviral vectors and LTR genomes targeted in the HIV-1 NAAT caused the HIV-1 NAAT false-positive results.
Insights
Chimeric antigen receptor (CAR) T cell therapy can cause false positives in HIV-1 nucleic acid amplification tests. Lentiviral vectors used in CAR T cell reprogramming cross-react with HIV-1 testing targets, leading to inaccurate results.
Area of Science:
- Oncology
- Immunotherapy
- Infectious Disease Diagnostics
Background:
- Chimeric antigen receptor (CAR) T cell immunotherapy represents a significant breakthrough in cancer treatment.
- CAR T cells are generated by genetically modifying T cells using viral vectors, typically gammaretroviral or lentiviral vectors.
- These viral vectors are essential for CAR T cell reprogramming but can potentially interfere with diagnostic tests.
Observation:
- Three clinical cases are presented where CAR T cell immunotherapy interfered with human immunodeficiency virus type 1 (HIV-1) testing.
- Patients undergoing CAR T cell treatment showed false-positive results in HIV-1 nucleic acid amplification tests (NAAT).
- Initial screening with fourth-generation HIV-1 enzyme immunoassays was negative, but subsequent NAAT (Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test v2.0) yielded positive results.
Findings:
- The false-positive HIV-1 NAAT results were attributed to cross-reactions between the lentiviral vectors used for CAR T cell reprogramming and the targeted HIV-1 genetic sequences (gag and long terminal repeat [LTR]).
- Specific NAAT assays targeting different viral genes, such as the integrase gene (Abbott m2000 RealTime HIV-1 assay), correctly identified the samples as HIV-1 negative.
- This highlights a critical issue of assay specificity in the context of advanced gene therapies.
Implications:
- The findings necessitate a re-evaluation of HIV-1 testing protocols for patients who have undergone or are undergoing CAR T cell therapy.
- Development of more specific diagnostic assays or modified testing algorithms is crucial to avoid misdiagnosis and unnecessary patient anxiety.
- Understanding these cross-reactivities is vital for the safe and effective clinical application of CAR T cell immunotherapies.
