By: Jayoung Park, Pharm.D. Candidate c/o 2013
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Traditionally, human immunodeficiency virus (HIV)-infected patients have generally been excluded from organ transplantation.1 One of the principal concerns was that immunosuppression would accelerate HIV/acquired immune deficiency syndrome (AIDS), resulting in increased mortality and a “waste” of organs.1
A study entitled, “Opportunistic Infections and Neoplasms Following Liver and Kidney Transplantation in the HIV infected Recipient,” was presented at the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI) held by the National Institute of Health (NIH).1 It stated that although HIV does not progress in HIV-positive transplant recipients, there is a much higher incidence of organ rejection.1 As Peter Stock, MD, PhD, professor of surgery at the University of California at San Francisco reported, such two to threefold higher incidences of organ rejection in HIV-positive patients than in HIV-negative patients indicated the presence of a very dysregulated immune system rather than an absence of immunity.1
An NIH-funded multicenter trial evaluated the effect of HIV infection on graft function and survival, as well as the effects of transplantation and post-transplant immunosuppression on HIV progression and markers of immune function/activity.2 There were 150 kidney and 125 liver transplants at 18 centers across the United States who received three to four years of follow-up.2 Patients selected for the study had CD4+ T-cell counts greater than 200 cells/mm3 in kidney recipients and greater than 100 cells/mm3 in liver recipients.2 Of the 150 kidney transplant recipients, 20% were co-infected with hepatitis C virus (HCV) at baseline.2 The median follow-up was 3.6 years.2 Roughly 25% of patients had a history of opportunistic infections before transplantation.2 Among the 125 liver transplant recipients, 69% at baseline were co-infected with HCV, and the median duration of follow-up was four years.2
For the 150 kidney transplant recipients, researchers reported that HIV generally remained suppressed and CD4+ counts remained relatively stable.2 When given antithymocyte globulin (ATG), the patients’ CD4+ counts were depleted for one year; yet, there were minimal opportunistic infections during the time that it took for their CD4+ counts to increase again.2 The investigators did see a higher incidence of serious bacterial infections, about twofold greater, in the patients whose CD4+ counts were depleted.2 Both patient and graft survival were similar to that in the general population at one and three years.2
This high incidence of organ rejection in HIV-infected patients in an absence of HIV disease progression leads to an interesting message.2 It seems that HIV is not the issue, but rather, the presence of a very dysregulated immune system could be more responsible.2 Research is underway to explore the mechanism behind the high rate of rejection.2
Other observations worth attention are the differences in graft survival in HIV patients co-infected with Hepatitis B virus (HBV) or HCV compared with the mono-infected controls.3 Graft survival in co-infected patients at three years was 59%, while it was 67% in the mono-infected controls.3 Compared with patients mono-infected with HBV, HIV-positive liver transplant recipients co-infected with HBV did just as well with their transplants for five years, supporting the belief that HIV is not the problem but rather the co-pathogens are.3
However, the three-year survival rate in the HIV-HCV co-infected patients was a different story; it was 11% higher than with patients mono-infected with HCV.3 Also, the incidence of organ rejection in the HIV-HCV co-infected patients was twofold higher than that of HIV-HBV co-infected patients.3 Organ transplantations for co-infected patients with HCV (and not much for those with HBV) are opposed in many centers due to the low survival rates.3
As Dr. Stock stated, treating rejections creates another dilemma, as rejection becomes an independent predictor of graft loss and severe HCV recurrence (where control over the virus and the co-pathogen is lost when these patients are immunosuppressed).1 There has been no evidence of significant HIV disease progression on allograft function.1 A high incidence of organ rejection is a concern in kidney transplant recipients, as is the possible poor clinical outcome in HCV-co-infected liver transplant recipients.1 The data observed in the trial indicated that transplantation should not be absolutely excluded as a treatment option for patients with well-controlled HIV disease, whereas its practice is opposed in patients co-infected with HBV or HCV.1
The mechanisms behind the high rate of rejection in HIV-positive patients require further studies. In addition, the association between the current treatments for treating these viruses and the risk of cancer may be another valuable topic for further investigation.
SOURCES:
- Capital Consulting Corporation. 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies: Draft Agenda. Website. Available online: http://www.capconcorp.com/meeting/2011/13thICMAOI/agenda.asp. Nov 7, 2011. Accessed Apr 10, 2012.
- Yin S. No HIV Disease Progression in Transplant Recipients. Website. Available online: http://www.medscape.com/viewarticle/753922. Nov 11, 2011. Accessed Apr 10, 2012.
- Lie D. Co-infections and Co-therapies: Treatment of HIV in the Presence of Hepatitis C and Hepatitis B. Website. Available online: http://www.medscape.org/viewarticle/588909. Nov 11, 2011. Accessed Apr 10, 2012.
