HIV and Transplantation: New Reasons for HOPE

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JAMA

Effective antiretroviral therapy has dramatically changed the health outcomes of people living with HIV. Although many HIV-positive patients now enjoy life expectancies similar to those of the general population, certain chronic diseases are more prevalent, and when present, these conditions appear to progress more rapidly. For example, co-infection with hepatitis C can result in liver failure, which is a major cause of death among people with HIV. Kidney disease is also common, with HIV-associated nephropathy being a leading cause of renal failure.

Preeti Malani, MD, MSJ

For many with end-stage organ disease, transplant offers the best clinical outcome. However, years ago, organ transplantation was not felt to be medically feasible in patients with HIV because of concerns about disease progression with the need for added immunosuppression to prevent graft rejection. Slowly, this prevailing consensus changed, and organ transplantation from HIV-negative donors to HIV-positive recipients is now routine.

Nonetheless, people living with HIV who were suitable transplant candidates faced another hurdle: a severe shortage of donor organs. Like others on the waiting list, many died awaiting transplant. For HIV-positive patients in need of a transplant, there existed an untapped potential donor pool: other HIV-positive patients. But due to a federal ban in place since 1984, HIV-positive individuals were not eligible to donate organs.

That changed in 2013, when Congress passed the HIV Organ Policy Equity Act, or HOPE Act, thanks to the efforts of many, including Dorry Segev, MD, PhD, a transplant surgeon and researcher at Johns Hopkins University. The HOPE Act made it possible for the first time to recover organs from HIV-positive donors and transplant the organs into HIV-positive recipients.

Segev, the director of the HIV transplant program at Hopkins, played an instrumental role in reversing the federal ban and helped draft the HOPE Act. Earlier this year, he also led the first team of US surgeons to successfully perform a liver and kidney transplant from an HIV-positive donor to HIV-positive recipients.

Recently, Segev spoke with JAMA about the advances and continued challenges in organ transplantation among patients with HIV. The following is an edited version of the interview.

JAMA:Let’s start by talking about the epidemiology of end-stage organ disease in the setting of HIV. Can you summarize some of the key issues, especially in relation to kidney and liver disease? What are the numbers, and how do they compare to the general population?

Dr Segev:We’re so good at treating and controlling HIV now that we are seeing chronic inflammatory diseases in patients, [such as] high blood pressure, diabetes, cardiovascular disease. We’re seeing manifestations of hepatitis co-infection and nonalcoholic fatty liver disease. The prevalence of kidney and liver disease in patients with HIV is higher than that of the general population, as are the morbidity and mortality. Up to one-third of patients with HIV will end up with some degree of chronic kidney disease related to the virus itself, HIV-associated nephropathy, hepatitis co-infection, [or] the medications we [use to] treat HIV. But more and more [kidney disease in patients with HIV is] related to chronic diseases like hypertension, diabetes, cardiovascular disease.

JAMA:Years ago, when the idea of transplantation in HIV was discussed in a purely theoretical manner, many clinicians believed wrongly that patients would die of overwhelming opportunistic infection. What’s happened during the past 10 to 15 years to allow transplantation to become feasible?

Dr Segev:[W]e’ve learned a lot about HIV, about the morbidity and mortality of end-stage renal disease, end-stage liver disease, and patients with HIV and about how best to transplant them. It turns out, for example, that the immune system of somebody with HIV who undergoes transplantation is intact. And so the rejection rates in kidney transplants are actually higher in patients with HIV than in their non–HIV-infected counterparts, making it important for us to provide the same level of immunosuppression.


JAMA:You were instrumental in the passage of the HOPE Act. How did this concept develop and what was the legislative process like?

Dr Segev:We were watching our patients with HIV wait for long periods of time before they could get an organ and [as a result] have a much higher risk of death on the waiting list. The problem was that we saw organ after organ being thrown away because the donor was HIV positive. And this was because of the National Organ Transplant Act, which, written in the ’80s during the AIDS scare, required standards for preventing the acquisition of organs infected with [HIV]. That gives you a sense of the era in which it was written.
[Given the] preliminary success that Elmi Muller had in South Africa using HIV-positive donors for HIV-to-HIV kidney transplants, it made sense that [the] law from the ’80s was antiquated and that we really need to be exploring the use of HIV-positive organs. The problem was that the National Organ Transplant Act was a congressional law, which requires Congress to change. [This meant] we had to write a bill and get [it] passed during a year that was the [worst] in the history of the United States for passing bills.
Fortunately, this was medically a no-brainer. Anyone we talked to on the Hill was very supportive of it. So we got a group together of AIDS and HIV advocacy societies, kidney societies, liver societies, et cetera. We [also] got a lot of help from the HIV Medicine Association, from the transplant societies, from the AMA [American Medical Association], from other professional societies. We talked to as many people as we possibly could on the Hill and built support.
By the time the bill was introduced [in February 2013], we had dozens of cosponsors from both sides of the aisle. President Obama signed it in November 2013, which was record speed for congressional bills.

JAMA:It’s taken several years, but you and your team performed the first transplants made possible under the HOPE Act in March 2016. How did that go? Were there any surprises?

Dr Segev:The law was signed in 2013, and it took until 2016 to do [the first transplant]. A lot of that was because the NIH [National Institutes of Health], CDC [Centers for Disease Control and Prevention], HERSA [Health Resources and Services Administration], and a bunch of other groups got together to try to figure out the best criteria for patient and donor selection. The transplants that we did in March of 2016 went beautifully. The issues were nothing different from what we would normally deal with [when] HIV-positive patients receive HIV-negative organs.

JAMA:One of the theoretical risks of transplanting HIV-positive organs into HIV-positive recipients is the risk of superinfection, acquisition of an HIV strain from a donor that differs from the strain infecting the recipient. What’s the current thinking on this?

Dr Segev:One of the things that we’re doing [to avoid superinfection] is getting as much detailed information as we possibly can on the HIV treatment of both the donor and the recipient. For example, if the recipient has a strain that’s been very easy to control on first-line therapy and we get a donor who’s had some resistance problems, that may not be the right donor for [that recipient]. But if that patient’s in trouble and really needs the transplant, it may be something that we can do. So it’s basically an issue of donor-recipient matching, of resistance patterns, and aggressiveness of the HIV strain, balanced against the transplant candidate’s need.

JAMA:So far, implementation of the HOPE Act has focused on deceased donors. Can you comment on using living donors?

Dr Segev:I think there actually is a future to HIV-infected patients becoming living donors. Let’s take the example of living kidney donors. We’re already very careful about selection of living kidney donors in terms of making sure we only allow people with adequate kidney function who are free from diabetes and other evidence of ongoing injury to their kidney. And we would just need to add that to the HIV equation.
We’ve been doing some studies to get a better sense of which HIV-infected patients are at risk for chronic kidney disease and ESRD [end-stage renal disease]. It turns out the risk of ESRD attributable to the HIV in some patients is no higher than the risk of ESRD attributable to something like, say, smoking, which is generally not considered a contraindication to live kidney donation.
As we do more research on ESRD risk in patients with HIV, we will find appropriate low-risk populations in whom it would be safe to donate a kidney. We will be allowing some patients with HIV to be live kidney donors, and we’re in the process of planning a perspective trial.

JAMA:I remember hearing estimates in regards to the number of organs that might be provided by the HOPE Act. Three years later, what are your thoughts on those initial estimates?

Dr Segev:As we were writing the HOPE Act, the estimates were somewhere on the order of about 300 to 500 [HIV-positive] donors per year. Recent estimates look similar. [But] the use of HIV-positive donors has been illegal for so long that it will take us probably a year or maybe even longer to get the word to every doctor in the United States. It takes long enough to spread the word to 300 transplant centers and to get protocols in place. But there are thousands of hospitals in this country, and all of them need to be aware that HIV-positive individuals can be donors. We also need every single person with HIV to be aware that they can sign their donor card. I think it’s going to take a couple years for this to disseminate across the country.

JAMA:The HOPE Act clearly benefits individuals with HIV who are waiting for organ transplant. What are some of the other less obvious benefits?

Dr Segev:There are actually 2 groups of people who will benefit: the first one is people without HIV. Remember in the past, those with HIV were drawing from the HIV-negative organ supply. Now, every single time we transplant somebody with HIV using an HIV-positive organ, they are removed from the waiting list, and everybody else moves forward. The other population that benefits is every single person living with HIV. Before the HOPE Act, people living with HIV were told, “You’re not going to be able to be a donor.” That’s very stigmatizing. Now, with the HOPE Act, we encourage [all] people who are interested in leaving a living legacy to sign their donor cards.

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