HIV+ Donors Might Add To Available Kidney Donor Pool

Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa MedicalResearch.com Interview with:
Elmi Muller, M.B., Ch.B., M.Med.
University of Cape Town–Surgery
Groote Schuur Hospital Observatory Cape Town
Cape Town, South Africa

Medical Research: What is the background for this study?

Dr. Muller: South Africa currently offers dialysis and transplantation as a treatment option for patients with End Stage Renal Disease (ESRD). However, dialysis is not freely available to everyone, but severely limited and only available to a selected group of patients. This means that patients get assessed when they present with ESRD and they only get accepted onto a dialysis programme if they fulfill certain criteria. These criteria are criteria to assess the patient’s medical fitness in general as well as social criteria to assess whether the patient will be compliant with follow-up. In most state hospitals, patients will only be accepted onto a dialysis program if they are also fit to receive a transplant in the long run. The idea is that dialysis programs should naturally feed into transplant programs. Therefore a patient who is not a suitable transplant candidate will normally be turned down for dialysis.

In 2008, when the HIV positive-to-positive program started, patients with ESRD and HIV would be turned down for dialysis. The reason was that they were seen as unfit for transplantation and therefore not suitable dialysis patients. This meant that anybody with HIV and ESRD was doomed to die. This situation remained unchallenged for a number of years, especially as the rollout of antiretroviral therapy was quite slow in the state sector.

Because of very high HIV rates in the country, more and more HIV positive brain-dead donors presented to the Groote Schuur Hospital Transplant team. These donors were mostly braindead people who were worked up for organ donation (after consent was obtained from the family) and who then turned out to be HIV positive. In 2008 it made sense to try and marry this supply of donors with the group of HIV positive patients without any treatment options in the country.

Medical Research: What are the main findings?

Dr. Muller: In the study report on 27 patients who received kidneys form HIV positive donors over the last five years. Five patients died after transplant. The reasons for death were myocardial infarction, lung squamous cell cancer, pancreatitis with a duodenal perforation, disseminated Aspergillosis and Klebsiella Pneumonia sepsis. Two patients lost their grafts in the first week after transplantation: one with venous thrombosis of the graft and one with acute severe rejection within one week after transplantation. A third patient lost her graft with chronic vascular rejection and fibrosis of the graft 2 years after her transplant. The risk of rejection in this patient population group is higher than expected in HIV negative patients. In the Cape Town study rejection took place on 8 occasions in 5 of the patients, which gives an acute rejection rate of 18%. This happened despite induction therapy with Thymogloglobuline. A dysregulated immune response might be the reason for high rejection rates despite potent immunosuppression and similar high rejection episodes were reported in the NIH study using HIV negative donors for HIV positive recipients. (11)

Medical Research: What should clinicians and patients take away from your report?

Dr. Muller: Using HIV positive donors might resolve some of the problems we are experiencing in getting enough donors for our patients wit ESRD. In the USA the HOPE act was accepted in 2014 and this might now also impact on the use of HIV positive donors elsewhere in the world.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Concerns about a second viral strain remain a problem. In the literature the outcomes and reports of HIV positive patients with superinfections are difficult to interpret as there are a lot of methodological difficulties which often yield conflicting results. (4,5) When a patient with low viral load gets exposed to a second viral strain, a superinfecting strain may be detectable for only a short period of time. Viral fitness and the ability of a viral strain to replicate effectively in a given environment, may play a role to determine whether the two different strains will eventually become undetectable in standard resistance tests or whether outgrowth of a different virus from the baseline or whether a novel recombinant virus will become detectable. We are currently investigating this question at UCT.

Furthermore, in South Africa we have a unique situation in view of the fact that we have low antiretroviral therapy resistance rates. Most patients who failed second-line ART in South Africa, have wild-type virus and resistance rates remain less than 5% in our HIV population. So in our setting the issues transplanting HIV positive patients are mostly that they have very high rejection rates, that they need powerful and expensive immunosuppression as these patients have a dysregulated immunosystem rather than a suppressed one. They also have a high infection risk as opportunistic infections are more common in immunosuppressed and HIV positive patients and in Africa opportunistic infection remain a major reason why transplant patients might run into trouble. All these things needs to be followed up and investigated in more detail in the future.

Citation:

HIV-Positive–to–HIV-Positive Kidney Transplantation — Results at 3 to 5 Years

Elmi Muller, M.B., Ch.B., M.Med., Zunaid Barday, M.B., Ch.B., Marc Mendelson, M.D., Ph.D., and Delawir Kahn, M.B., Ch.B., Ch.M.

N Engl J Med 2015; 372:613-620
February 12, 2015 DOI: 10.1056/NEJMoa1408896

 

MedicalResearch.com Interview with:, & Elmi Muller, M.B., Ch.B., M.Med. (2015). HIV+ Donors Might Add To Available Kidney Donor Pool MedicalResearch.com