HIV status used to mean automatic exclusion from CAR T-cell therapy trials for B-cell lymphomas. That is changing. Research groups are now enrolling people with HIV in CAR T and bispecific antibody studies. The field is finally moving toward real inclusion and data-driven care.
Paul Rubinstein, MD, associate professor at the University of Illinois Chicago and member of the Big Ten Cancer Research Consortium, spoke about this shift at the 2026 Big Ten CRC Summit in Rosemont, Illinois. He pointed to new prospective data from the AIDS Malignancy Consortium (AMC) and Center for International Blood and Marrow Transplant Research (CIBMTR). These groups tracked 35 HIV-positive patients who received CD19-directed CAR T-cell therapy and compared them to 135 matched HIV-negative controls. Cytokine release syndrome (CRS) of any grade was less common in the HIV-positive group—68.6% versus 82.2% (P = .04). That finding goes against the old belief that HIV-positive patients face higher risks.
An independent analysis of 80 interventional CAR T-cell trials for non-Hodgkin lymphoma in the U.S. found that only 13.8% allowed people with HIV to participate, while 72.5% explicitly excluded them.
Breaking the exclusion barrier
Rubinstein was blunt. "No one should be excluded from any clinical trial." He said groups like the AMC matter because they refuse to accept outdated rules. The AMC-112 phase 1 trial (NCT05077527) is now prospectively testing axicabtagene ciloleucel (Yescarta; axi-cel) in patients with well-controlled HIV and relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. This is a big step. Earlier studies were mostly retrospective and left many questions open.
A University of Notre Dame research review found that excluding people with HIV from pivotal registration trials of CD19-directed CAR T-cell therapies forced the evidence base for this group to rely on post-approval and retrospective cohort studies. They were left out of the main trials. This exclusion also created real-world barriers. The median travel time for HIV-positive patients to reach an eligible clinical trial was 1.15 hours. For trials that excluded them, the median was just 0.84 hours.
Rubinstein explained the technical hurdle. CAR T therapy needs a patient's own T cells. In people with HIV, those T cells are infected. For years, that was the reason to keep them out of advanced therapies. But retrospective studies by the AMC and Stefan K. Barta, MD, MS, MRCPCUK, have shown that HIV-positive patients respond just as well as others. The field now needs time and more prospective data to confirm this.
The AMC-112 study (NCT05077527) remains an ongoing phase 1 prospective trial evaluating the safety and feasibility of axicabtagene ciloleucel in patients with controlled HIV infection and relapsed or refractory aggressive B-cell non-Hodgkin lymphoma; publicly available search results do not confirm study completion or publication of final results.
Expanding the therapeutic arsenal
The AMC is not stopping with CAR T. Rubinstein described ongoing and planned trials of bispecific antibodies. Some combine these drugs with chemotherapy for upfront diffuse large B-cell lymphoma. Others target plasmablastic lymphoma at the University of Illinois. These studies are built to make sure people with HIV are not left out as new immunotherapies change lymphoma care.
The number of HIV-positive lymphoma patients is small. But the momentum is real. Including these patients in advanced trials is not just about fairness. It is a scientific need. As reported earlier, CAR T-cell therapies are moving fast across blood cancers. The data must include all groups.
Rubinstein's message is simple. The era of exclusion is ending. But progress will take work. Early results show HIV status alone should not block access to advanced cell therapies or clinical studies. The next step is clear. The field must prove it can deliver equal access and strong evidence for every patient, no matter their HIV status. This is more than a technical milestone. It is a test of clinical research and the future of precision oncology.
