Kidney transplant is a feasible option for HIV-positive patients with end-stage renal disease, US investigators report in the November 18th edition of the New England Journal of Medicine.
Three years after transplant 88% of patients were still alive, and the transplanted kidney was still functioning in 78% of individuals. Overall, transplant did not complicate HIV disease management.
“Kidney transplantation is highly feasible in HIV-infected recipients,” comment the investigators.
End-stage renal disease is a significant cause of illness in HIV-positive patients. Thanks to the success of antiretroviral therapy, many HIV-positive patients with severe renal disease are considered good candidates for transplant.
Investigators wanted to see how safe and effective kidney transplant was in patients with HIV. They therefore conducted a multicentre, prospective study involving 150 patients who received a new kidney at 19 transplant centres across the US. The patients were followed for up to three years.
To be eligible for transplant, patients were required to have a CD4 cell count of at least 200 cells/mm3, and an undetectable viral load while taking antiretroviral therapy. Patients who were co-infected with hepatitis B or hepatitis C were only eligible for transplant if they showed no sign of cirrhosis.
The patients had a median age of 46, most (78%) were men, and 69% were black. Median CD4 cell count at the time of transplant was 524 cells/mm3. A total of 19% of patients were co-infected with hepatitis C and 3% were co-infected with hepatitis B.
Enrolment occurred between 2003 and 2009. The median duration of follow-up was 1.7 years, but 53 patients contributed three or more years of follow-up.
Survival rates were good. One year after transplant 95% of patients were alive and the graft had survived in 90%. After three years, 90% of individuals were still alive, and the transplanted kidney was still functioning in 74%.
These survival rates were slightly poorer than those seen in HIV-negative kidney transplant recipients, but were better than the rates observed in older transplant patients.
A total of eleven patients died. Three of the deaths were attributed to cardiac causes, two to sepsis, two to lung infections, two to cancer in the non-transplanted kidney, and two to unknown causes. The new kidney was still functioning in eight patients at the time of their death.
In addition, 13 patients lost their transplanted kidney. For five patients the cause was long-term rejection or chronic graft nephropathy; in others, vascular thrombosis (three patients), acute rejection (three patients), technical reasons (one patient), and non-adherence to treatment (one patient).
Patients who received a kidney from a living donor were significantly less likely to lose their kidney than those whose donor was deceased (p = 0.02).
Antibody induction therapy with antithymocyte globulin was associated with an increased risk of graft rejection (p = 0.03).
A total of 49 patients experienced acute organ rejection. The incidence of rejection after one year was 31%, increasing to 41% after three years. Rejection responded to glucocorticoid therapy in 48% of patients.
Factors associated with an increased risk of rejection were receipt of a kidney from a deceased donor (p = 0.03), and use of the immunosuppressive drug cyclosporine (p = 0.02).
Patients whose donor was dead were more likely than those with a living donor to require dialysis during the first week after transplant (46 vs 15%).
Episodes of organ rejection were associated with poorer kidney function after one and three years of follow-up (p = 0.05 and p = 0.01 respectively).
HIV disease progression
One year after transplant, patients who received antithymocyte globulin had significantly greater falls in their CD4 cell counts than individuals who did not receive this drug (-238 vs. -135 cells/mm3, p < 0.001). A difference was still apparent after three years (-57 vs. -52 cells/mm3, p = 0.05).
Viral load became detectable in 48 (32%) of patients at least once. Most of these increases in viral load were transient and one patient had a detectable viral load three years after transplant.
There were seven new AIDS diagnoses.
Of the 150 transplant recipients, 57 had a total of 140 infections that required hospitalisation. Two-thirds of these were due to bacterial infections.
Patients co-infected with hepatitis C had a significantly higher rate of serious infections (p = 0.02). Infection rates were also significantly higher among patients treated with antithymocyte globulin (p = 0.002).
“The rates of patient survival and graft survival at 3 years were generally between the reported rates in the national database for older kidney-transplant recipients and for all kidney-transplant recipients,” comment the investigators.
They believe that these “favourable results were influenced by careful patient selection, adherence to clinical management protocols…and close coordination among the multidisciplinary teams”.
However, the investigators highlighted the difficulty of achieving “therapeutic and non-toxic levels of immunosuppressive drugs,” and they believe that this contributed to high rejection rates. The authors therefore caution: “antithymocyte globulin induction therapy should be restricted to patients at very high immunologic risk for rejection.”
Stock PG et al. Outcomes of kidney transplantation in HIV-infected recipients. New Engl J Med 363: 14-25, 2010.