Antiretroviral therapy has had a significant impact on improving the survival of patients infected with human immunodeficiency virus (HIV) with their survival now being similar to patients not infected with HIV. With improved long-term survival, the prevalence of chronic diseases such as end-stage kidney disease (ESKD) has increased in this population. However, studies have shown that the survival of HIV-infected patients with ESKD on dialysis is lower than that of matched HIV-negative patients on dialysis. HIV infection was previously considered to be a contraindication to kidney transplantation because of concerns about infection and malignancy.
A landmark study in 2010 demonstrated that patients with HIV and ESKD whose HIV infection was controlled (i.e. undetectable viral load, CD4 cell count>200/mm3 and stable ART regimen) could be transplanted safely. However, one of the concerns in the study was an alarmingly high rate of acute rejection (31% at one year). That was surprising given the previous belief that HIV-infected kidney transplant recipients were “over-immune suppressed” due to both HIV infection and transplant immunosuppression. The reason for the high risk of acute rejection was not fully understood but theories included immunomodulatory effects of HIV, difficulty achieving therapeutic calcineurin inhibitor (CNI) concentrations due to drug interactions with ART, and the reluctance to use T cell depleting agents for induction.
The South African experience brought back hope to kidney transplantation (KT) for patients with HIV when they showed excellent outcomes of HIV+ to HIV+ kidney transplantation. Following that, the HIV Organ Policy Equity (HOPE) act was passed in the United States in 2013 to allow research into HIV D+/R+ transplantation.
We now have a lot more data about KT in patients with HIV. An important study in 2015 showed patients with HIV monoinfection (i.e. without HCV) and ESKD who received kidney transplants had similar outcomes to matched HIV- patients. Another study showed that kidney transplantation was associated with improved survival in HIV+ KT recipients compared to remaining on dialysis, starting at about 6 months post-KT. Despite the data clearly showing a benefit to KT in this population, access to KT remains low in patients with HIV.
Why is there limited access to KT in patients with HIV?
There are likely multiple reasons. First of all, there seems to be low access to living donation.9 Second, there is still a concern about the high risk of acute rejection. Lastly, there is still concern about the effects of immunosuppression on HIV viral control, infections and malignancy.
What can we do about it?
- We need to increase the access of HIV-infected patients with KT through multiple mechanisms, including HIV donor+ and HCV donor+ KT.
- We need more studies confirming the safety of immunosuppression for KT in patients with HIV with regards to risks of malignancy. Data in that aspect are lacking, which results in some transplant centers continuing to hesitate to transplant patients with HIV. I focus here on malignancy because there is some data about safety with regards to infection
- We need to provide evidence-based care to HIV-infected KT recipients to improve their outcomes. This includes:
- Using anti-thymocyte globulin induction, which has clearly shown to be associated with lower risk of acute rejection in HIV-infected KT recipients
- Using tacrolimus-based maintenance immunosuppression regimens, which have also been shown to be associated with a lower risk of rejection. There is still controversy about steroid maintenance vs early withdrawal, which has yet to be settled.
- Collaborating with infectious disease specialists to switch patients to integrase inhibitor-based regimens if appropriate, since studies have shown that they are associated with a lower risk of death and allograft loss compared to patients on protease inhibitors. This is likely related to drug-drug interactions between calcineurin inhibitors and protease inhibitors.
In summary, kidney transplantation is the treatment of choice for patients with HIV and ESKD as it is associated with improved survival compared to remaining on dialysis. Despite reassuring data about the outcomes in these patients, issues of limited access and concerns about immunosuppression continue. The field has come a long way but more progress still needs to be made in taking care of these patients.
Ayman Al Jurdi, MD
Nephrology Fellow, Mass General, Brigham and Women’s