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 3years 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.