Organ transplants and HIV/AIDS

BACKGROUND

Highly active antiretroviral therapy (HAART), a combination of drugs used to suppress HIV, enables HIV-infected individuals to live longer lives. Today, most patients are dying from end-stage organ disease and organ failure rather than AIDS-associated opportunistic infections. Since HAART prolongs the lives of HIV patients, it is possible for chronic conditions to progress to organ failure.

For instance, HIV patients may experience end-stage liver disease as a complication of chronic hepatitis C virus. Glomeruli diseases are also common among HIV patients, and they may lead to kidney failure. In advance stages of liver or kidney damage, organ transplants may be the patient's only chance of survival

In general, about 92,000 people who need kidneys, livers, pancreases, intestines, hearts and lungs are on the U.S. organ transplant waiting list. About 6,500 people died while waiting for an organ transplant in 2005 (almost 18 people a day).

Until recently, people who had HIV were not considered good candidates for organ transplantations. Many patients were denied transplants under the assumption that they had shorter life expectancies and less favorable survival rates than other patients in need of transplants. However, now that patients are living longer lives, many groups are reconsidering whether HIV patients should be transplant candidates.

Although the United Network for Organ Sharing (UNOS) does not consider HIV infection a contraindication for organ transplantation, the decision to perform transplantation in an HIV-positive individual rests with individual centers. Some centers will not provide organ transplants to good candidates who are HIV-positive.

Some health insurance companies are reluctant to cover transplantation in HIV-positive candidates because they consider it to be an experimental procedure. Currently, only a few medical centers worldwide perform organ transplants in HIV-positive patients. However, transplantation in HIV-negative patients is considered a well-established, reimbursable procedure.

Recent legislation in California and a ruling in Arizona may help increase HIV patients' access to transplant surgery. In October 2005, an administrative law judge declared that Medicaid had to pay for a liver transplant for an Arizona woman who was HIV-positive. In the same month, California Governor Arnold Schwarzenegger signed a law that prohibits health insurance companies from denying coverage for organ transplants in HIV patients solely on the basis of their HIV-status. The law is the first of its kind to target such denials.

The limited number of transplants that have been performed in HIV patients have produced encouraging results. However, organ transplants for people with HIV/AIDS have not gained widespread medical support, and there are still concerns regarding the long-term prognosis for HIV-positive transplant recipients.

GENERAL TRANSPLANT REQUIREMENTS

The United Network for Organ Sharing (UNOS) maintains a computer network that links all organ procurement organizations and transplant centers in the United States. This network is accessible 24 hours a day, seven days a week.

Once a doctor refers a patient, a transplant center evaluates the potential transplant candidate. Members of the transplant center conduct medical tests and consider the patient's mental and physical health, as well as his/her personal support system. Prospective transplant candidates are then added to the national patient waiting list. The patient is not placed on a ranked list at that time. Instead, the patient is added to the pool of patients who are waiting.

When a deceased organ donor is identified, a transplant coordinator from an organ procurement organization accesses the UNOS database. The computer creates ranked lists of patients for each organ that is procured from that donor in ranked order, based on organ allocation policies.

Rank is determined by factors such as blood type, length of time on the waiting list, immune status and the geographical distance between the candidate and donor. For organs such as the heart, liver and intestines, the patient's degree of medical urgency is also considered.

The organ is offered to the transplant team of the first person on the list. In most cases, the top patient does not end up receiving the organ. This is because when the patient is selected, he/she must be healthy enough to undergo major surgery and willing to receive the transplant immediately. In addition, a test that measures the compatibility between the donor and recipient may be necessary. For instance, patients who have high antibody levels are often incompatible with the donor because the patient's immune system is likely to reject the organ.

Once an organ recipient is selected and contacted, and testing is complete, surgery is scheduled.

HIV TRANSPLANT RESEARCH

Preliminary data from a prospective study on the outcomes of HIV-infected liver or kidney transplant recipients was presented at the XVI International AIDS Conference.

Subjects in the study were HIV-infected patients who had CD4 cell counts higher than 200cells/mm3, an undetectable viral load (with the exception of liver transplant candidates who could not tolerate antiretroviral therapy) and no history of certain opportunistic infections. Eleven patients received liver transplants and 18 received kidney transplants. The average patient was 45 years old. Fifty-five percent of liver and 28% of kidney transplant recipients tested positive for hepatitis C virus (HCV) coinfection.

The researchers reported similar rates of patient and graft survival that has been reported in patients who are not infected with HIV. Three patients in the liver transplant group died. Despite relatively high rates of rejection, organ function remained high in the transplant recipients. None of the patients experienced HIV disease progression and most patients maintained stable CD4 cell counts. Lower CD4 cell counts were reported in older patients who had episodes of rejection and received the immunosuppressant anti-thymocyte globulin (Thymoglobulin©).

Ninety-two percent of the liver transplant recipients lived one year after surgery, and 72% lived three years after surgery. Ninety-four percent of the kidney transplant recipients lived one year after surgery, and 94% lived three years after surgery.

The researchers reported that two out of the three deaths among liver transplant recipients were the result of recurrent HCV disease. The third patient also experienced recurrent HCV, although it was not the cause of death. The researchers concluded that transplant risks appear to be similar in HIV-infected and non-infected patients. However, more studies are necessary to determine the proper management of HCV-coinfection after liver transplants.

Another study presented at the conferences examined the pharmacokinetics of protease inhibitor use in six HIV patients who received liver transplants and received immunosuppressive therapy. The patients received the protease inhibitor nelfinavir (Viracept©). Three of the patients required a dose adjustment. The study suggests that HIV patients require close monitoring and individualized treatment regimens when they receive immunosuppressants.

TREATMENT

General: It is recommended that HIV patients continue highly active antiretroviral therapy (HAART) to suppress HIV after they receive organ transplants. It is unclear whether immunosuppressants are beneficial for HIV patients, who are already immunocompromised. Research is currently being conducted to determine if immunosuppressive therapy is safe, and whether it effectively prevents transplant rejection in HIV patients. Patients who receive immunosuppressants may also receive medication to prevent infections. Patients should tell their healthcare providers if they are taking any drugs (prescription or over-the-counter), herbs or supplements.

Highly active antiretroviral therapy (HAART): It is recommended that HIV/AIDS patients continue to receive highly active antiretroviral therapy (HAART) after receiving an organ transplant. While these drugs cannot cure HIV infection or AIDS, they can suppress the virus. HAART combines drugs from at least two different classes of antiretroviral drugs.

Currently, the FDA has approved 28 antiretroviral drugs to treat HIV. These drugs fall into three major classes - reverse transcriptase (RT) inhibitors, fusion inhibitors and protease inhibitors. In July 2006, the U.S. Food and Drug Administration (FDA) approved a multi-class combination called Atripla©.

Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA into HIV DNA. There are two main types of RT inhibitors - non-nucleoside RT inhibitors and nucleoside/nucleotide RT inhibitors. Non-nucleoside RT inhibitors bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Rescriptor©, Sustiva© and Viramune©.

Nucleoside/nucleotide RT inhibitors serve as faulty DNA building blocks. Once they are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved drugs include Combivir©, Emtriva©, Epivir©, Epzicom©, Hivid©, Retrovir©, Trizivir©, Truvada©, Videx EC©, Videx©, Viread©, Zerit© and Ziagen©.

Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. Only one fusion inhibitor, Fuzeon©, is FDA-approved.

Protease inhibitors (PIs) interfere with the protease enzyme that HIV uses to produce infectious viral particles. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the virus to cleave nascent proteins for final assembly of new virons. FDA-approved protease inhibitors include Agenerase©, Aptivus©, Crixivan©, Invirase©, Kaletra©, Lexiva©, Norvir©, Prezista©, Reyataz© and Viracept©.

Immunosuppressants: The most common oral immunosuppressants prescribed in the United States include tacrolimus (Prograf©), mycophenolate mofetil (CellCept©), sirolimus (Rapamune©), prednisone, cyclosoporine (Neoral©, Sandimmune© or Gengraf©) and azathioprine (Imuran©). Depending on the transplant, some patients may need to take different combinations and doses of the drugs. In general, patients are typically prescribed two to three medications for long-term immunosuppression.

Preventing infections: Since immunosuppressants inhibit the body's ability to fight off infections, medications may also be prescribed to prevent illness. Antivirals like acyclovir (Zovirax©) or valganciclovir (Valcyte©) have been used to prevent viral infections. Antifungals like fluconazole (Diflucan©), nystatin (Mycostatin© or Nilstat©) or itraconazole (Sporanox©) have been used to prevent fungal infections. Antibiotics like sulfamethoxazole/trimethoprim (Bactrim© or Septra©) have been used to prevent bacterial infections.

INTEGRATIVE THERAPIES

Unclear or conflicting scientific evidence :

L-arginine : Dietary supplementation with L-arginine and canola oil has been associated with decreased rejection rates after the first month in kidney transplant recipients. Due to reductions in cardiac events, long-term benefits for patient survival may be particularly important. Further research is needed to confirm these results.

Art therapy : There is some evidence suggesting that art therapy may help bone marrow transplant patients strengthen positive feelings, alleviate distress and clarify their existential/spiritual issues. It may be beneficial for patients who need to deal with emotional conflicts and feelings about life and death. Further research is needed before a firm conclusion can be made.

Fair negative scientific evidence :

Omega-3 fatty acids : There are multiple studies of heart transplant and kidney transplant recipients taking cyclosporine (Neoral©) who were administered fish oil supplements. The majority of trials report improvements in kidney function (glomerular filtration rate, serum creatinine), and less hypertension (high blood pressure) compared to patients not taking fish oil. However, several recent studies report no benefits on kidney function, and no changes have been found in rates of rejection or graft survival.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• AIDS info NYC. www.aidsinfonyc.org. Accessed March 5, 2007.
• International AIDS Society. www.iasociety.org. Accessed March 5, 2007.
• McGee F, English K, and the HIV and Organ Transplantation Working Group. HIV and organ transplantation: improving access in Ontario. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract WEPE0894.
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2008.
• Roland M, Barin B, Carlson L, et al. HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract WEPE0052.
• The Foundation for AIDS Research. Organ Transplants for HIV+ Patients Controversial. www.amfar.org. Accessed March 5, 2007.