OA4-AM24-ST-06 - Inflammatory Profile Among Kidney Donors with HIV and Without HIV to Recipients with HIV

Kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+) can increase access to transplants. Under the HIV Organ Policy Equity (HOPE) Act, HIV D+/R+ transplants are made possible under research conditions. HIV infection is associated with heightened immune activation, and therefore, organs from HIV D+ may have an increased likelihood of causing increases in underlying immune activation verse D- organs. However, it is unknown if the inflammatory profile varies among HIV D+ vs. D- or whether the recipients’ inflammation varies post-transplantation by whether they received an organ from an HIV D+ vs. D-.

Study

Design/Methods: Between April 2018 and September 2022, 198 R+ underwent kidney transplantation under the multicenter quasi-randomized controlled clinical HOPE in Action trial. There were 99 transplants in each trial arm of either HIV D+/R+ or HIV D-/R+. Cytokine production was detected by utilizing a multiplexed electrochemiluminescence assay from MSD to quantify Eotaxin, Eotaxin-3, GM-CSF, BCA-1/BLC, IFN-γ, IL-10, IL-12/IL-23p40,  IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-1α, IL-1β,  IL-2, IL-29/IFNg1, IL-4,  IL-5, IL-6,  IL-7, IL-8, IL2RA, IP-10 , MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, and VEGF in the plasma of donors and recipients to evaluate both pro-inflammatory and anti-inflammatory state. Donor time points were all pre-transplantation.  Recipients' time points were pre-transplant, week 13, week 26, and week 52. Mann Whitney U tests determined differences between donors by HIV status and recipients by trial arms (HIV D+/R+ and HIV D-/R+) for each analyte at each time point. Bonferroni correction was used to account for multiple comparison.

Results/Findings: There were 146 donors who participated in the trial, including 64 HIV D+ and 82 HIV D- (of which 27 had false-positive HIV tests). Of these individuals, 103 donors (63 HIV D+ and 40 HIV D-) had plasma available to evaluate. There were no significant differences observed in 32 cytokines between the D+ vs. D- groups pre-transplantation. All 198 recipients had plasma available at least for one time point to evaluate. Comparing HIV D+/R+ to HIV D-/R+ transplants, no significant differences were observed between the 32 cytokines at baseline pre-transplantation, week 13, week 26, and week 52. One-year rejection was similar between the two groups (13% vs 20%) and the incidence of opportunistic infections and cancer were similar between groups.

Conclusions: Previous literature suggests higher levels of inflammation in HIV-positive individuals despite ART and low viral load. In this study, the data suggests that there is no significant difference in the inflammatory state between HIV D+ vs. HIV D-. The data also demonstrates that there is no significant difference in the inflammatory state between the recipients who received an organ from an HIV D+ vs. D-.