Analytical interference with most current commercial HIV molecular assays in patients treated by idecabtagene vicleucel, a recently approved lentivirus-based chimeric antigen receptor T-cell therapy

We report the case of a 65-year-old woman followed for multiple myeloma diagnosed in 2007. After multiple lines of therapy and relapses, she received idecabtagene vicleucel (a lentiviral-based vector chimeric antigen receptor [CAR] T-cell immunotherapy). At day 9 after infusion, HIV-1, HBV and HCV molecular testing were irrelevantly prescribed by the clinician, without any particular reason justifying them. A positive HIV-1 signal was detected by two commercial RT-PCR assays (Alinity m HIV-1, Abbott; 2.8 log cp/mL and Xpert HIV-1 Viral Load XC, Cepheid; 3.3 log cp/mL). Pretherapeutic HIV serology (fourth- and fifth-generation Enzyme-linked Immunosorbent Assays (EIAs)) and molecular testing were negative and no risk factor for HIV infection was reported by the patient. At day 11 after infusion, HIV serology remained negative, whereas HIV-1 RNA was still detected with Alinity m HIV-1 assay (3.5 log cp/mL) on a control sample. At day 21, HIV-1 RNA was quantified at 2.18 log cp/mL (Alinity m HIV-1 assay) and was no more detected 3 months after infusion. Finally, we concluded to a false HIV-RT-PCR-positive result, both assays targeting the long terminal region (LTR), because of an interference with the lentiviral-based vector LTR sequence used to manufacture idecabtagene vicleucel therapy. Cross-reactions between idecabtagene vicleucel and current commercial assays targeting the LTR region were expected but had not been reported to date.