Are HIV-Infected Donors Suitable for Renal Transplantation?

Abstract

Recent studies confirm that outcome of renal transplantation (RT) in adequately selected HIV-infected patients receiving kidneys from HIV-negative donors is similar to that of HIV-negative RT recipients (1). Main challenges in the clinical management of HIV-infected RT recipients are the pharmacologic interactions between immunosuppressive agents and some classes of antiretroviral drugs and a higher rate of acute rejection in comparison with HIV-negative RT recipients. Currently, organ transplantation from HIV-infected donors is an absolute contraindication in Western countries (2,3), but its potential utility is under consideration (4). Recently, Muller et al. (5) reported the outcome of four HIV- infected RT recipients who received their grafts from two HIV-infected donors in South Africa, being the first clinical experience published involving this type of transplants. After 12 months of follow-up, all recipients had a functioning renal allograft with a good renal function, and HIV infection was controlled under different antiretroviral regimens. South Africa is a country with a high HIV prevalence in the general population, and HIV infection is an absolute exclusion criterion for access to dialysis or RT. Muller et al. (5) suggested that the use of HIV-infected donors would increase the donor pool, providing renal allografts to HIV-infected patients otherwise sentenced to death as a consequence of end-stage renal disease. It is likely that organ transplantation from HIV-infected donors will generate considerable controversy. The situation is similar to what occurred a decade ago in relation to hepatitis C virus RNA-positive donors, who are now accepted for hepatitis C virus-positive recipients in international guidelines (2,3). The strategy under consideration is bold and implies difficult decisions. Nonetheless, it must be evaluated with caution and based on several considerations. First, there are ethical implications stemming from the lack of long-term safety data. In countries with a resource-limited health system, HIV infection is an exclusion criterion for access to dialysis or RT. We agree that in these cases, the balance between justice and equity is more difficult. Second, recipients might acquire a more aggressive HIV strain from the donor (e.g., different clade or recombinant virus, or X4 tropism), including drug- resistant strains, which could lead to superinfection, virologic failure, and HIV progression to death. Previous reported experiences do not provide donor's virologic information (5), which, moreover, is difficult to obtain during organ procurement (3). Third, HIV-infected donors are at high risk for transmitting other infections that could increase morbidity and reduce recipient survival. Finally, there are nephrologic issues that must also be considered. HIV-associated nephropathy is the leading cause of end-stage renal disease in HIV-infected patients in South Africa; it is caused by direct viral infection of kidney cells (particularly the visceral epithelial cells of the glomerulus and the tubular epithelial cells), and it is more common in patients with high plasma HIV-RNA viral load (6). Moreover, HIV is associated with other renal diseases: immune-mediated glomerulonephritis, postinfectious glomerulonephritis, and thrombotic microangiopathies. Muller et al. (5) reported that the two HIV-infected donors had normal kidney biopsies, and no proteinuria was observed. However, technical limitations of renal allograft biopsy during procurement may misdiagnose subclinical renal disease, which could have a negative impact on allograft survival. To accelerate acquisition of evidence enabling resolution of these considerations, we suggest evaluating this approach in a prospective, controlled, pilot clinical trial of RT in HIV-infected recipients, containing two arms (HIV-positive and -negative donors) with virologic and histologic (protocolled renal biopsy) assessment and biochemical markers of renal injury and clinical outcome. Thus, the effectiveness and safety of this type of transplantation can be established. We believe that this strategy must initiate an intense scientific debate because of different ethical, nephrologic, virologic, and clinical considerations, and an international consensus conference could be of interest to analyze the controversies of this interesting and emerging issue. Federico Cofan1 Joan-Carles Trullas2 Carlos Cervera3 Federico Oppenheimer1 Asuncion Moreno3 Josep-Maria Campistol1 Jose-Maria Miró3 1 Renal Transplant Unit Nephrology Department Hospital Clinic–IDIBAPS University of Barcelona Barcelona, Spain 2 Internal Medicine Service Hospital Sant Jaume Olot, Universitat de Girona, Girona, Spain 3 Infectious Diseases Service Hospital Clinic–IDIBAPS University of Barcelona Barcelona, Spain