Transplantation in the times of HIV infection: Thinking outside the box
© The National Medical Journal of India 2015.This paper describes the long-term results of kidney transplantation, giving kidneys from HIV-positive deceased donors to carefully selected HIV-positive recipients in Groote Schuur Hospital, Cape Town, South Africa. This was done to find a solution to the needs of renal replacement therapy of HIV-positive individuals with endstage kidney failure in South Africa. These patients were considered not suitable for kidney transplantation and, therefore, not accepted in dialysis programmes that preferentially accepted candidates who would eventually receive a kidney. The project was started in 2008. After encouraging results (100% graft survival and patient survival at 1 year),1 and with the approval of their hospital ethics committee, the authors extended this as a prospective study. The recipients were required to be on antiretoviral therapy (ART), and had a CD4 T-cell count of 200 per cmm or higher and an undetectable plasma HIV RNA at the time of transplantation. All donor kidneys were biopsied at the time of implantation. The recipients received depleting induction with antithymocyte globulin (ATG), and triple immunosuppression with tacrolimus, mycophenolate mofetil and prednisolone. Since the study was funded by Sanofi who market ATG, drugs were purchased at full cost to avoid any conflict of interest. After the transplant, patients were switched to a protease inhibitor-based regimen to ensure suppression of potential donorvirus replication. Since ritonavir is an inhibitor of cytochrome P450 system, a reduction in the dose of tacrolimus was needed to as low as 0.5 mg once every 7–10 days. However, concerns about nephrotoxicity of calcineurine inhibitors (CNI) led to abandoning this approach and return to non-protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART). All patients received lifelong cotrimoxazole and isoniazid prophylaxis and valgancyclovir for 3 months. The CD4 Tcell count and plasma HIV RNA viral load were monitored every 6 months. The paper describes the result of 27 people who received a transplant between September 2008 and February 2014. The donors were young (mean age 30 years). The patient survival rates were 84% (95% CI 62–94) at 1 year and 3 years and 74% (95% CI 45–89) at 5 years; and graft survival at 1 year was 93% (95% CI 74–98), decreasing to 84% at 3 years and 5 years (95% CI 55–95). These were comparable to the survival rate among HIV-negative patients in their unit. Acute rejection developed in 8% at 1 year and 22% at 3 years. The CD4 counts fell initially, perhaps secondary to the ATG therapy but rose later. The viral load remained undetectable throughout the follow-up period. In three patients, routine allograft biopsies revealed changes typical of early HIV-associated nephropathy, which were not present in the baseline biopsy specimens. The authors concluded that HIV-positive people can be considered a deceased kidney donor for HIV-positive recipients if they are either ART-naïve or on first-line treatment only with no resistance; have normal serum creatinine and no proteinuria. Donors with active infection, malignancies or possible HIV-associated nephropathy (HIVAN) were not used. Finally, the authors neither use, nor suggest the use of HIV-positive individuals for living kidney donation.