November 20, 2011

No HIV Disease Progression in Transplant Recipients

Sandra Yin

November 18, 2011 (Bethesda, Maryland) — Now that people infected with HIV are living longer, physicians are seeing a growing number who need kidney or liver transplants because of comorbid conditions. But what happens when you take patients in an immunosuppressed population, give them new organs, and further immunosuppress them with drugs to prevent rejection of those organs?

HIV does not progress in HIV-positive transplant recipients, according to findings from a study titled "Opportunistic Infections and Neoplasms Following Liver and Kidney Transplantation in the HIV Infected Recipient," which was presented at the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI) here at the National Institutes of Health (NIH).

But there is a much higher incidence of organ rejection, indicating a dysregulated immune system rather than an absence of immunity, investigators said.

"The take-home message is that HIV is not the issue," Peter Stock, MD, PhD, professor of surgery at the University of California at San Francisco. He was the principal investigator of a multicenter trial in patients with HIV who received liver or kidney transplants.

"It's the comorbidities that are the issue. In other words, we did not see progression of HIV in any of the transplantations. Nor did we see an increase in the incidence of AIDS-related malignancies."

The aim of the trial was to evaluate the effect of HIV infection on graft function and survival, study the effect of transplantation and post-transplant immunosuppression on HIV progression and markers of immune function and activity, and describe the pharmacokinetic interactions between immunosuppressive agents and antiretroviral agents.

The NIH-funded trial involved 150 kidney and 125 liver transplants at 18 centers across the United States, with 3- to 4-year follow up. Patients selected for the study had CD4+ T-cell counts greater than 200 cells/mm3 for kidney recipients and greater than 100 cells/mm3 for liver recipients. For kidney patients, the HIV viral load had to be undetectable while the patients were receiving a stable antiviral regimen. A detectable HIV viral load was permitted in liver recipients as long as the HIV providers said that the virus could be suppressed after transplantation. Researchers excluded patients with opportunistic infections that could not be treated, such as cryptosporidiosis and visceral Kaposi's sarcoma. Post-treatment management included prophylaxis against opportunistic infections, immunosuppression, management of rejection, and antiretroviral therapy.

Of 150 kidney transplant recipients, 20% were co-infected with hepatitis C virus (HCV) at baseline. The median follow-up was 3.6 years. One in 4 patients had a history of opportunistic infections before transplantation.

For the 150 kidney transplant recipients, researchers reported that HIV generally remained suppressed and CD4 counts remained relatively stable. When they used antithymocyte globulin, patients' CD4 counts were wiped out for a year and they still saw minimal opportunistic infections in the year it took for the CD4 counts to come back. The investigators did see a higher incidence of serious bacterial infections, about 2-fold greater, in the patients whose CD4+ counts were deleted. Both patient and graft survival were similar to that in the general population at 1 and 3 years.

The main problem, Dr. Stock said, was a high incidence of organ rejection, 2- to 3-fold higher than what they saw in HIV-negative patients. Research is underway to explore the mechanism behind the high rate of rejection. "But it is real," he said. "It clarifies to me that this is not the absence of an immune system, it is the presence of a very dysregulated immune system."

Among 125 liver transplant recipients, 69% at baseline were co-infected with HCV, 36% had hepatocellular carcinoma, and 12% had a history of opportunistic infections before transplantation. Median duration of follow-up was 4 years.

Compared with patients mono-infected with hepatitis B virus (HBV), HIV-positive liver transplant recipients co-infected with HBV did just as well with their transplants 5 years out. "I think this is the proof that HIV is not the problem," said Dr. Stock. "It's the co-pathogens that are the problem after transplantation. We do a pretty good job of controlling HIV."

HCV was a different story, he said. The 3-year survival rate for the HCV-HIV co-infected group was 64%, compared with 75% for the group with HCV infection only.

Not surprisingly, many centers are balking at transplantations for co-infected patients with HCV, but not those with HBV, because the low survival rate is affecting center-specific results, Dr. Stock said. Those rates could endanger Medicare funding and scare third-party payer referrals away.

Graft survival in co-infected patients at 3 years was 59%, compared with 67% in the mono-infected controls.

The incidence of rejection in the HIV-HCV co-infected patients was 2-fold higher, and 50% of those rejection episodes happened early on.

Treating those rejections is problematic because rejection becomes an independent predictor of graft loss and severe HCV recurrence, Dr. Stock said. Control over the virus and the co-pathogen is lost when these patients are immunosuppressed. "That begs the question of what we're doing to all the viruses that may be associated with cancer," he observed.

"I think the striking thing about the cancer risk in those patients, which is what Dr. Stock was presenting, is that it's not a lot higher than what he observed," Eric Engels, MD, MPH, senior investigator at the National Cancer Institute's Division of Cancer Epidemiology and Genetics, told Medscape Medical News.

There certainly are some cancers, but no more than you would probably expect in a transplant population that did not have HIV infection, Dr. Engels said.

13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI); Abstract #P6. Presented November 8, 2011.