Outcomes of kidney transplantation in HIV-infected recipients

Abstract

Background: The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.

Methods: We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.

Results: Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.

Conclusions: In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

Figure 1. Kaplan–Meier Estimates of Patient and Graft Survival and First Acute Kidney-Allograft Rejection

Rates of patient survival (Panel A) and graft survival (Panel B) were generally within those rates reported in the national Scientific Registry of Transplant Recipients (SRTR) for older kidney-transplant recipients (≥65 years) and for all kidney-transplant recipients in the United States during a similar time frame. The rate of graft survival was calculated on the basis of graft failure from any cause. The 1-year and 3-year cumulative incidences of graft rejection in the study recipients were 31% (95% confidence interval [CI], 24 to 40) and 41% (95% CI, 32 to 52), respectively. The 1-year SRTR rejection rate was estimated to be 12.3% (95% CI, 11.9 to 12.7) (Panel C).

Figure 2. Kaplan–Meier Estimates of Patient and Graft Survival and First Acute Kidney-Allograft Rejection According to Presence or Absence of Hepatitis C Virus (HCV) Infection

Panel A shows the rate of patient survival, Panel B the rate of graft survival, and Panel C the rate of rejection according to HCV status. Seven deaths occurred among 122 HCV-negative patients (6%) and 4 among 28 HCV-positive patients (14%). Among HCV-positive recipients, the 1-year product-limit estimates for patient survival and graft survival were 88.3% (95% CI, 67.9 to 96.1) and 88.6% (95% CI, 68.6 to 96.2), respectively. Among HCV-negative recipients, the corresponding estimates were 96.1% (95% CI, 90.0 to 98.5) and 90.9% (95% CI, 83.7 to 95.0). The hazard of death was marginally higher in the HCV-positive patients than in the HCV-negative patients (P = 0.09 by the log-rank test) (Panel A). Time-to-event curves for graft loss (Panel B) and for graft rejection (Panel C) did not differ significantly between HCV-positive and HCV-negative patients (P = 0.91 and P = 0.36, respectively, by the log-rank test).

Figure 3. Changes in CD4+ T-Cell Count and Percentage of CD4+ T Cells after Transplantation, According to Antithymocyte Globulin Induction Status

The mean (±SE) CD4+ T-cell counts and the mean (±SE) percentages of CD4+ T cells are plotted over time in Panels A and B, respectively. At year 0.2, the mean changes from baseline in numbers and percentages of CD4+ T cells were significantly greater in patients who received antithymocyte globulin induction therapy early than in those who did not (P = 0.004 and P = 0.048, respectively). After the initial drop, there was an increase in the CD4+ T-cell count (P<0.001), but the percentage of CD4+ T cells did not change significantly over time (P = 0.66).