Michel Frank Ferrazo, Purchased Materials Technician at ABL Antibióticos do Brasil Ltda, shared a post on LinkedIn:
“CAR-T altered HIV rebound without measurably shrinking the viral reservoir.
Riley et al. report a first-in-human preprint of autologous CD4BBζ CAR-T cells engineered in two ways: CD4-based recognition of HIV Env and CCR5 editing intended to make the cells more resistant to infection.
Ten men receiving suppressive antiretroviral therapy received a single infusion, followed by an analytical treatment interruption either one day or at least eight weeks later. Nine of 10 participants experienced viral rebound within one to six weeks. One had no detectable rebound during the planned 16-week interruption, although treatment was resumed before the durability of that control could be established.
Among the nine participants who rebounded, six later maintained viral loads below their historical pre-treatment set point through the end of the interruption. One participant remained below 1,000 HIV RNA copies/mL for 90 weeks without antiretroviral therapy.
The product was also well tolerated. No serious adverse events, cytokine release syndrome, ICANS, or clinically significant neurologic toxicity were reported. But the reservoir did not measurably contract.
Adjusted intact proviral DNA analysis, near-full-length sequencing, and integration-site profiling showed no consistent reduction in intact HIV proviruses after infusion.
That changes how I read the result. The signal may reflect immune containment of viral rebound rather than eradication of the latent reservoir. In selected participants, the treatment was also associated with broader endogenous HIV-specific CD8 T-cell responses, including one documented escape mutation that abolished recognition of a Gag peptide.
This remains an uncontrolled 10-person preprint. All participants were men, and the participant with 90-week control had previously received CCR5-edited CD4 T cells.
Should HIV CAR-T be judged primarily by how much reservoir it removes, or by whether it can maintain ART-free control despite the reservoir that remains?”
Title: HIV-specific and resistant CAR T cells promote control of HIV replication in people with HIV
Authors: James Riley, Pablo Tebas, Julie Jadlowsky, Yuepeng Zhang, M. Betina Pampena, Jake Robinson, Lucia Baquero, Andrea Brennan, Irina Kulikovskaya, Vanessa Gonzalez, Amanda Kotch, Max Eldabbas, Chungdhak Tsang, Ola Mohamed, Gregory Laird, Honghong Sun, Zhenyu Huang, Eline Luning Prak, Gabriela Plesa, Katherine Bar, Joseph Fraietta, Donald Siegel, Elizabeth Hexner, James Hoxie, Mary Putt, Michael Betts, Xu Yu, Mathias Lichterfeld
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