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.
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.
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.
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