Anti-CD4 monoclonal antibody(Immunotech)

Porcine islet xenotransplantation is limited by the availability of clinically applicable immunosuppressive regimens. We tested four depletional induction strategies and maintenance regimens in a non‐human primate (NHP) islet xenotransplant model.

Genetically modified or wild‐type neonatal porcine islets were transplanted via portal vein infusion in diabetic NHPs. Induction consisted of rhesus anti‐thymocyte globulin (rhATG) (Group 1, n = 4), anti‐CD4 monoclonal antibody (mAb, Group 2, n = 3), or human anti‐thymocyte globulin (huATG) tocilizumab (Groups 3 and 4; n = 3 and n = 4, respectively). Maintenance consisted of B7 (Groups 1–3) or anti‐CD154 (Group 4) costimulation blockade, tacrolimus transitioned to sirolimus (sirolimus only in Group 4), and mycophenolate mofetil. Xenografts were monitored for blood glucose and porcine c‐peptide.

Median graft survivals were <14 days (Group 1), <14 days (Group 2), 99 days (Group 3), and 119 days (Group 4). Insulin independence was achieved in one animal in Group 4. Graft survival significantly correlated with islet dose >40,000 IEQ/kg. Rejection was predominately CD3 + T‐cell mediated. Selective depletion of CD4 + T cells led to increased proliferation of CD8 + T cells and CD8 + infiltrates.

Induction with huATG/tocilizumab and maintenance with 5c8 led to the best functional outcomes. CD4 T‐cell depletion with anti‐CD4 mAb induced compensatory CD8 T‐cell proliferation and graft infiltration.

HIV-1 pan-resistance refers to a reduced susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and integrase strand tranfer inhibitors. Although still anecdotal, its management remains a concern both for affected people living with HIV (PLWH) and for public health.

We described genotypic resistance testing (GRT) of three PLWH with a documented poor virological response to previous antiretroviral therapies, who started ibalizumab, an anti-CD4 monoclonal antibody, combined with an optimized background therapy. Both historical and most recent GRT on plasma RNA and peripheral blood mononuclear cell DNA were interpreted according to the Stanford HIVDb version 9.0 (last updated on 22 February, 2021). After the switch to a regimen including the monoclonal antibody, HIV-1 RNA has been quantified biweekly (PCR Cobas® HIV-1 test 6800 Systems, Roche Diagnostics). Follow-up was censored at data freezing (16 January, 2021).

We report findings from heavily treatment-experienced PLWH with a pan-resistant HIV-1 infection, who achieved virological control once introduced injections of ibalizumab, that is free from cross-resistance with all the antiretroviral drugs available and ensures patient adherence due to a close monitoring attributable to the route of administration, combined with recycled enfuvirtide and an optimized background regimen, selected on the basis of an accurate evaluation of resistance mutations.

In these cases, this new approach has revealed to be a turning point in achieving virological control.

None, this research was supported by internal funding.