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Transplants in HIV patients should proceed, but drug interactions a concern

  [ 5 votes ]   [ Discuss This Article ] • August 29, 2002

MIAMI, Aug. 29 – While historically surgeons have been reluctant to transplant patients with the human immunodeficiency virus (HIV), in recent years, some centers have begun to accept patients with well-controlled HIV as candidates for liver or kidney transplantation. Based on results of three studies from the United States and one from France, which collectively reported on 34 kidney and 17 liver transplants in HIV-positive patients, researchers conclude that organ transplantation should indeed be considered a treatment option for such patients.

Reporting at the XIX International Congress of The Transplantation Society being held at the Westin Diplomat Resort and Spa in Hollywood, Fla., the researchers said that after more than one year of follow-up, outcomes in patients with HIV are very similar to outcomes in transplant patients without HIV, and importantly, the immunosuppressive drugs used to control organ rejection seem to have little effect on HIV progression.

But, the researchers added, managing these anti-rejection drugs and the anti-retroviral therapies for HIV presents quite a challenge. Mindful that the drugs may interact with each other or be toxic, transplant teams must achieve just the right balance between the two types of drugs. Suppressing the immune system too much with high doses of the anti-rejection drug may allow the HIV infection to worsen. Too low a dose, and the organ may be rejected.

Surgeons are seeing more patients with HIV needing liver or kidney transplants because the so-called highly active anti-retroviral therapies (HAART) are allowing patients with HIV to live longer with fewer HIV-related complications. Yet for HIV patients who also have liver disease, such as hepatitis B or hepatitis C, longer life expectancy also may allow progression of their chronic liver disease to end-stage liver failure. Some patients with HIV are developing end-stage kidney failure as a result of their HIV infection or from the anti-retroviral medications, some which can be toxic to the kidney.

In Philadelphia, where between 2 and 5 percent of patients on kidney dialysis have HIV, researchers at Hahnemann University Hospital performed 20 kidney transplants. One patient studied lost his graft to vascular rejection because a drug interaction with one of the medications in the HAART therapy made it difficult to achieve therapeutic levels of the anti-rejection drugs. According to Dr. Anil Kumar, more than one year after transplantation, 17 patients are alive and well and viral loads of HIV remain very low or undetectable, just as they were before surgery.

Drug interactions between the anti-rejection drug tacrolimus and protease inhibitors caused an acute rejection in one patient and toxic levels of tacrolimus in another, according to results presented by Dr. Didier Samuel of Paul Brousse Hospital in Villejuif, France. Six patients with HIV and hepatitis C received liver transplants. One patient died from liver failure, while the remaining five patients are alive more than a year following transplantation with negligible levels of HIV viral load and a significant improvement in quality of life.

The University of Pittsburgh examined the very issue of drug interactions and drug toxicity in a study of seven liver and four kidney transplant patients whose immunosuppression consisted of tacrolimus and steroids, and in one patient, rapamycin was also used. Profound drug interactions were observed in a liver transplant patient taking the anti-rejection drug tacrolimus and HAART therapy that included a protease inhibitor, reported Dr. Ashok Jain earlier this week. In contrast, regimens that included nucleoside reverse transcriptase inhibitors or non-nucleoside reverse transcriptase inhibitors produced less significant effects in the four kidney recipients and the other six liver patients.

At the University of California, San Francisco, four liver and 10 kidney transplants were performed in HIV-positive patients. HIV viral loads have remained undetectable in all patients on anti-retroviral therapy. The only death occurred in a 15-year-old child who underwent liver transplantation for hepatitis C who died as a result of a rapid recurrence of the hepatitis virus, said Dr. Peter Stock. Interestingly, patients on protease inhibitors required 25 percent of the dose of the anti-rejection drug cyclosporine compared to patients on non-nucleoside reverse transcriptase inhibitors.

There has been no evidence of significant HIV progression or any adverse effect of the virus on organ function, the researchers reported.

Held every two years, the International Congress of The Transplantation Society is recognized as the field's most important international scientific meeting. More than 1,600 abstracts covering basic and clinical science are being presented, and nearly 3,000 surgeons, physicians and researchers from 71 countries are in attendance. Co-chairs of the congress are Drs. Camillo Ricordi of the Diabetes Research Institute at the University of Miami School of Medicine and Domingo Casadei of the Instituto de Nefrologia in Buenos Aires.

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