{
  "abstract": "Background Chimeric Antigen Receptor T cells (CAR-T) are genetically engineered T lymphocytes expressing a chimeric receptor that targets tumor cells. They represent an effective immunotherapy for onco-hematological malignancies. Data on CAR-T use in people living with HIV (PLWH) and non-Hodgkin lymphoma (NHL) remain limited, as these patients were historically excluded from clinical trials. However, emerging evidence is redefining this scenario.Case Description A 49-year-old man was diagnosed with stage IIIA diffuse large B-cell lymphoma (DLBCL), ABC subtype, with submandibular involvement and PET hypermetabolism with colliquative features. During staging, he was newly diagnosed with HIV-1 infection - AIDS. Baseline HIV RNA was 270,000 copies/mL, CD4+ T cells 154/mmc (22%), CD4/CD8 ratio 0.3. Antiretroviral therapy (ART) with darunavir/cobicistat/tenofovir alafenamide/emtricitabine (DRV/c/TAF/FTC) was started concomitantly with six cycles of R-CHOP and standard prophylaxis, achieving metabolic partial response. Virological suppression was obtained after approximately six weeks. Three months later, disease progression occurred. The patient was referred for CAR-T therapy with axicabtagene ciloleucel (axi-cel). Bridging therapy with polatuzumab plus rituximab, followed by Axi-cel infusion after a standard lymphodepletion with fludarabine / cyclophosphamide (FLUCY). Treatment was well tolerated. No cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or infectious complications occurred. ART was continued without any occurrence of drug-drug interactions. Post-infusion monitoring showed maintained viroimmunological control: HIV RNA, EBV DNA, and CMV DNA remained undetectable. Absolute lymphocyte count varied from 1700/mmc (CD4 272/mmc, 16%) day 0, to 2400/mmc (CD4 240/mmc, 16%) at day +60 and 2700/mmc (CD4 243/mmc, 9%, CD4/CD8 ratio 0.1) at day +90. To date, PET imaging documented disease progression with increased SUV and lesion volume. Management of relapse is ongoing.Discussion In this case, CAR-T therapy showed an excellent safety profile, without typical toxicities or opportunistic infections. Available literature, although limited to case reports and small series, suggests a safety profile comparable to HIV-negative individuals. Reported complete remission rates are approximately 50%, though evidence remains scarce. Sustained virological suppression and strict ART adherence appear crucial.Future Perspectives Further evaluation of CAR-T cell expansion kinetics and investigation of HIV genetic material within the CAR-T genome are planned. Collection of additional cases will be essential to better define the safety and efficacy of CAR-T therapy in PLWH in the field of onco-hematological malignancies.",
  "authors": [
    {
      "affiliations": [
        "Infectious and Tropical Diseases Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "G Formica"
    },
    {
      "affiliations": [
        "Infectious and Tropical Diseases Unit, Villa Sofia - Cervello Hospital, Palermo, Italy",
        "Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties G. D’Alessandro, University of Palermo, Palermo, Italy"
      ],
      "name": "MC Gagliano"
    },
    {
      "affiliations": [
        "Infectious and Tropical Diseases Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "V Li Vecchi"
    },
    {
      "affiliations": [
        "Infectious and Tropical Diseases Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "R La Sala"
    },
    {
      "affiliations": [
        "Bone Marrow Transplant Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "G Sapienza"
    },
    {
      "affiliations": [
        "Microbiology and Virology Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "GME Colomba"
    },
    {
      "affiliations": [
        "Microbiology and Virology Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "O Diquattro"
    },
    {
      "affiliations": [
        "Cytogenetic and Oncohematological Laboratory Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "A Santoro"
    },
    {
      "affiliations": [
        "Bone Marrow Transplant Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "L Castagna"
    },
    {
      "affiliations": [
        "Bone Marrow Transplant Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "R Bono"
    },
    {
      "affiliations": [
        "Infectious and Tropical Diseases Unit, Villa Sofia - Cervello Hospital, Palermo, Italy"
      ],
      "name": "G Mazzola"
    }
  ],
  "title": "CC4 CAR-T therapy in a person living with HIV and refractory DLBCL: safety, virological control and multidisciplinary management",
  "uid": "de54b523-a29e-570a-bc89-7172dadc3d50"
}