Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients

Background HIV infection is associated with high rates of acute rejection following kidney transplantation. The underlying mechanisms for such predisposition are incompletely understood. Pathological immune activation is a hallmark of chronic HIV infection that persists despite effective antiretroviral therapy. We hypothesized that the baseline levels of T cell activation in HIV⁺ candidates would correlate with their risk of acute rejection following kidney transplantation. Methods Single-center retrospective cohort analysis of HIV⁺ adult kidney transplants performed between October 2006 and September 2013. The frequency of CD3⁺ HLA-DR⁺ cells measured by flow cytometry served as a surrogate marker of immune activation. Patients were categorized into tertiles of activation, and the rates of biopsy-proven acute rejection were compared across groups. Results (1) Compared to matched HIV⁻ controls, the baseline number of CD3⁺ HLA-DR⁺ cells was higher in HIV⁺ kidney transplant candidates. (2) Abnormally high levels of activation did not decrease with transplant-associated immunosuppression. (3) Patients categorized within the lower and middle CD3⁺ HLA-DR⁺ tertiles had higher probability of rejection during the first 3 years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P = 0.04). Conclusions Pathological immune activation in HIV⁺ transplant candidates does not explain their increased susceptibility to allograft rejection. Paradoxically, those with the highest levels of immune activation seem to be less prone to rejection.