- The Study
- The Results
- Where Do We Go From Here?
- The Bottom Line
- We Must Have Presumed Consent
As people with HIV are living longer due to advances in HIV medicines, there is a rise in death rates from conditions not historically associated with HIV. This includes an increase in risks and rates of both liver and kidney failure, often caused by hepatitis B or C, and underlying kidney disease or HIV-related harm to the kidneys (called HIV-associated nephrotoxicity or HIVAN).
Anti-HIV therapies that are processed through the liver or kidney can also, in some cases, worsen these conditions and there have been some instances where the damage to the organ has been wholly caused by the side effects of therapies to treat HIV. For people with very advanced liver disease, liver transplantation is often the only option. People with kidney disease have slightly greater options, including dialysis, which involves being hooked up periodically to a machine to circulate and cleanse the blood. It is critical to assess the effectiveness of organ transplantation in people with HIV in order to determine if it prolongs life, improves quality of life and if so then costs should be covered by third-party payers (insurance, Medicaid/MediCal, etc.). The answers to these questions are not obvious since the kind of surgery associated with organ transplants can be very hard on anyone, let alone people suffering from HIV infection.
Historically HIV has been a contraindication for organ transplantation, meaning that if a person were living with HIV they were not considered a candidate to receive an organ. Transplant surgeons were often unwilling to perform the surgery and third-party payers were not willing to pay the costs for the required supportive long-term care, as they considered the transplants unproven and "experimental" in HIV-positive people. A number of years ago AIDS activists, including activists from Survive AIDS in San Francisco and Project Inform, got involved with this issue. With the support and leadership of two researchers at the University of California San Francisco, HIV specialist Michelle Roland and transplant surgeon Peter Stock, a local pilot project has blossomed into a national project providing important information to move this field forward.
Dr. Roland presented an overview of findings from 53 people undergoing kidney or liver transplantation in the setting of potent anti-HIV therapy. To be eligible people must have:
no prior history of opportunistic infections,
a CD4+ cell count greater than 200 for kidney transplant candidates and greater than 100 for liver transplant candidates, and
a viral load below 50 copies/ml for kidney transplant candidates and either a viral load below 50 copies/ml for liver transplant candidates
or if the person is unable to tolerate anti-HIV therapies due to their liver condition, a protocol HIV specialist must determine that after transplantation the individual will be able to construct an effective anti-HIV regimen that will result in maximal viral suppression.
Of the 53 patients reported on at the conference, 45 fit the above eligibility criteria and 8 did not. The reason it's important to include the information on the 8 ineligible people is it helps to determine whether or not the eligibility criteria is appropriate, or if it is perhaps too rigid.
Focusing first on the 45 eligible study participants, 26 received kidneys and 19 received livers. There were six deaths among eligible volunteers receiving transplants, two among those receiving kidney and four among liver transplant recipients. For the most part deaths were happening at similar rates and were due to the same causes that would typically be seen among HIV-negative transplant recipients, such as recurrent HCV disease or post-operative pancreatitis.
In one instance, death was deemed to be caused by a person stopping their anti-HIV medication without consulting the study team. When a person undergoes organ transplantation, they are given immune-suppressive therapy for the rest of their life in order to prevent their body from rejecting the new organ. Anti-HIV therapies have notable interactions with these anti-rejection medications. A great deal of care is taken in monitoring levels of anti-rejection medications and adjusting doses as needed. When the individual stopped anti-HIV medication abruptly, their blood levels of the anti-rejection medication fell dramatically and they died due to a serious organ rejection event. The important lesson here is that when a person receives an organ transplant, they have less flexibility in implementing choices around anti-HIV therapy. Moreover, adherence to medications has even more critical and potentially life-threatening consequences. Implementing a decision to discontinue the use of anti-HIV therapy, for example, must be done in careful consultation with the transplant team so that dose adjustments for anti-rejection drugs can be made and carefully monitored. Even the simple act of switching anti-HIV drugs can alter blood levels of anti-rejection drugs and must be done with a higher degree of care.
For the most part, liver and kidney transplantation had little to no effect on either viral load or CD4+ cell counts. CD4+ cell counts among kidney transplant recipients were about 441 pre-transplant and about 436 post-transplant. CD4+ cell counts were about 280 pre-transplant for liver recipients and about 218 afterwards. Viral loads were basically undetectable in both groups pre-transplant and remained so afterwards. In terms of the short-term safety issues, this is all good news. The median follow up on the entire group is about 314 days, so almost 1 year (with some people having been followed only 3 days but others having been followed for close to 1,700 days -- nearly five years).
When comparing the outcomes of the transplant recipients to the larger population of people receiving kidney and liver transplants, survival outcomes thus far appear to be very similar after one year. Some scientists have worried that a higher rate of organ rejection would be seen among people with HIV compared to transplant recipients in the general population. So far, this has not occurred. Among the kidney transplant recipients there was a 38% rejection rate and among liver patients the rate was 21%. Rates of patient survival appear to be similar among the study observations and survival rates observed in the UNOS registry (a registry of outcomes for transplantation in the general population).
Among the eight ineligible subjects who also received transplants, two have died of severe neurologic condition associated with HIV infection called progressive multifocal leukoencepthalopathy (PML). There is currently no way to know whether this was in any way related to the transplants. The reasons folks were deemed ineligible included: one was undiagnosed with HIV at the time of transplantation, a few kidney transplant recipients had viral load above the requisite 50 copies/ml, low CD4+ cell counts and altered mental status (which is also disallowed by the protocol). Of note, those with detectable viral load prior to study entry are currently doing fine as are those with CD4+ cell counts lower than the required threshold. The deaths occurred in the individual with altered mental status and the individual who was not known to be HIV-positive at the time of transplantation.
NIH funding is pending for the formal national multi-center study. Results to date are quite encouraging and may already be enough to begin dialog with third-party payers around reimbursement policies. In the meantime, the study is enrolling and providing an option for people with HIV who are or may be in need of kidney or liver transplantation. It is critical that the community push for this study to be expanded to include other organ transplantation approaches, such as heart transplants, as well. While there may be openness by investigators to include such approaches in the study, there remain barriers to overcome. For more details about these study results, and for a list of transplant sites participating in the multi-center study, call the Project Inform hotline. Moreover, your help is needed in political action to insure that organs are available to all those who need them.
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