Antiretroviral therapy (ART) has transformed the lives of patients with HIV; AIDS-related deaths have declined dramatically and life expectancy of HIV-positive patients rivals that of patients without HIV.1-3 With longer life expectancy, however, comes the potential to develop chronic diseases. End-stage organ diseases, such as end-stage renal disease (ESRD) and liver disease from hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, are now the primary causes of mortality in HIV-positive patients.2,3
Although the incidence of ESRD has been declining, the prevalence has been increasing among patients with HIV.4,5 People living with HIV have an incidence of ESRD that is 2 to 4 times higher than that of people without HIV.5 Most patients with ESRD are treated with dialysis, but solid organ transplantation is the most effective treatment to improve quality of life and reduce mortality.5,6
More than 109,000 Americans are on a waitlist for an organ transplant.7 The organ shortage has led researchers to critically re-evaluate organ sources that previously were considered too risky.8,9 This has led to a number of advances in transplantation, such as the use of organs from HIV-positive donors for HIV-positive recipients and, more recently, a life-saving partial liver transplant from an HIV-positive mother to her HIV-negative child (See Case Study).10 These advances have the potential to improve the chance of survival for HIV-positive patients on organ transplantation waitlists.
Evolution of Transplantation in HIV+ Patients
The HIV Organ Policy Equity (HOPE) Act11 was proposed in 2011 after successful kidney and liver transplants were performed from HIV-positive cadavers to HIV-positive recipients in South Africa.12,13 In those early cases, there was no reported evidence of HIV superinfection; organ rejection rates at 1 and 3 years were 8% and 25%, respectively, and 1 of the 4 recipients developed idiopathic glomerulopathy.3,4,12,13
Under the HOPE Act, implemented in November 2013, HIV-positive donor to HIV-positive recipient transplants are permitted in the United States for clinical research under specific guidelines by the National Institutes of Health (NIH).3,8,10 The first such transplants in the United States were performed in 2016 at Johns Hopkins University Medical Center.2,3,10 In 2019, an HIV-positive living donor donated a kidney to an HIV-positive recipient at Johns Hopkins University Medical Center.8
Under the HOPE Act, donor selection, immunosuppression management, and postoperative management are reviewed carefully for both the donor and recipient. Donor screening is an integral step in the transplant selection process. A prospective donor’s medical history, physical examination, and laboratory results are gathered to determine if they meet entry criteria.14,15 Living and cadaver donors are screened using the same parameters.
All donors are assigned a Kidney Donor Profile Index (KDPI); higher scores indicate increased risk for the donor.9,16 Donor criteria vary depending on the study. For most studies, eligible donors must be free of active tuberculosis and opportunistic infections (OIs) and have an undetectable HIV viral load.10,13
Immunosuppression and HIV Treatments
All organ recipients require maintenance immunosuppression to prevent their body from rejecting the organ. In patients with HIV, this cocktail of agents must be given along with whatever ART the patient is taking. The optimal maintenance immunosuppression regimen for HIV organ recipients is not known. The potential for increased toxicity and drug interactions should be considered carefully when determining optimal immunosuppressive therapy (Table).17
Maintenance of immunosuppression can be achieved with calcineurin inhibitors (CNIs), but drug interactions between CNIs and some ART agents, such as protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), can create a challenge in maintenance of immunosuppression.2,12,13 Belatacept is an immunosuppressive agent that is organ safe, does not interact with ART, and has the added benefits of antiviral activity against HIV.2,17,18
Before a transplant, a patient should be on a stable ART regimen. Regimens with a pharmacokinetic booster such as cobicistat or a PI require significant dose adjustments. Tacrolimus, a commonly used CNI, should be added to the ART regimen for patients taking PIs or pharmacokinetic boosters during the peritransplant period.
Newer classes of ART, particularly integrase inhibitors, may allow for decreased drug monitoring with therapeutic benefits. For example, in clinical studies, raltegravir shows superior graft outcomes compared with other classes of ART; dolutegravir also provides a genetic barrier to the development of HIV resistance.2,6
Post-transplant (first 5-7 days), typical antibody induction therapy consists of weight-dosed antithymocyte globulin (rabbit), a polyclonal depleting antibody used to prevent and treat acute organ rejection in HIV-positive recipients. However, the long-term safety of rabbit therapy is considered controversial.
Maintenance immunosuppression therapy after transplantation includes prednisone tapered over 3 months, mycophenolate mofetil, and tacrolimus.13,17 Earlier protocols required lifelong antibiotic prophylaxis against Pneumocystis jirovecii.17 Post-transplant monitoring of lab values is crucial to prevent rejection. It is unknown whether an aggressive approach is needed in HIV-positive transplant recipients, but there have been reports of low incidence of OIs.17