Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus–Infected Kidney Allograft Recipients

Abstract

In current practice HIV+ candidates with CD4 >200 cells/mm3 are eligible for kidney transplantation. However, the optimal pre-transplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm3 among 38 anti-thymocyte globulin (ATG)-treated HIV- to HIV+ kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection, patient and graft survival were not different between groups. However, occurrence of severe CD4 lymphopenia (<200 cells/mm3) was more common among individuals with a baseline CD4 count 200–349 cells/mm3 compared to those transplanted at higher counts (75% vs 30% at 4 weeks [p=0.04] and 71% vs 5% at 52 weeks [p=0.001] post-transplant, respectively). After adjusting for age, baseline CD4 count of 200–349 cells/mm3 was an independent predictor of severe CD4 lymphopenia at 4 (RR, 2.6; 95% CI, 1.3–5.1) and 52 weeks (RR, 14.3; 95% CI, 2–100.4) post-transplant. Patients with CD4 <200 cells/mm3 at 4 weeks had higher probability of serious infections during first 6 months post-transplant (19% vs. 50%; log-rank 0.05). These findings suggest that ATG must be used with caution in HIV+ kidney allograft recipients with a pre-transplant CD4 count <350 cells/mm3.

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

“…We recently showed that ATG-treated HIV + kidney transplant recipients with a baseline CD4<350 cells/mm 3 have higher risk of severe lymphopenia (CD4<200 cells/mm 3 ) and associated infectious complications [21]. Given the narrow therapeutic window of ATG in this population, it has been proposed that administration of this agent should be restricted to patients at very high immunologic risk for rejection [5, 21].…”

“…Given the narrow therapeutic window of ATG in this population, it has been proposed that administration of this agent should be restricted to patients at very high immunologic risk for rejection [5, 21]. Considering the null rates of acute rejection at 3 years we observed among HIV + recipients categorized to the upper CD3 + HLA-DR + tertile, it is conceivable that individuals with high pre-transplant immune activation levels, particularly those with CD4<350 cells/mm 3 , might benefit of less intense lymphodepletion during induction therapy.…”

Clinical outcomes in HIV+/HCV+ coinfected kidney transplant recipients in the pre‐ and post‐direct‐acting antiviral therapy eras: 10‐Year single center experience

“…Maintenance IS included tacrolimus, mycophenolate mofetil, and prednisone. Additional details about IS and antimicrobial prophylaxis protocols at our center have been previously described …”

“…Outcomes assessed at 1 year post‐transplant in each group were as follows: patient survival, death‐censored graft survival, and acute rejection. We also assessed the incidence of serious infections within the first 6 months post‐transplant, defined as infections requiring admission to the intensive care unit during initial transplant hospitalization or re‐admission to the hospital after discharge …”

“…In a follow‐up study, the authors directly evaluated the magnitude of the adverse impact of HIV+/HCV+ coinfection relative to HCV and determined that HIV+/HCV+ coinfection had a negative impact on death‐censored graft survival (adjusted HR 1.63; 95% CI 1.14‐2.34) and patient survival (adjusted HR 2.32; 95% CI 1.71‐3.16) compared to HCV monoinfection . The incidence of serious infections is also higher in HIV+/HCV+ coinfected than HIV‐monoinfected patients . Similarly, HIV+ liver transplant recipient outcomes have been reported to be superior to HCV+ and HIV+/HCV+ coinfection …”