Despite routine screening for HIV (human immunodeficiency virus) by live donors, a kidney transplant recipient became infected, according the New York City Department of Health and Mental Hygiene. An MMWR (Morbidity and Mortality Weekly Report) report, part of the CDC, highlights the need to re-examine national policy on HIV tests and their timing when screening living organ donors.

The report authors say donors should be screened for HIV as near as possible to the moment of organ recovery and transplantation. They add that serology and NAT (nucleic acid testing) should be used.

Doctors should also make sure their patients are aware of a potential disease transmission risk, as well as asking donors to avoid behaviors that would raise their risk of becoming infected with HIV.

In 2009, a patient with hemodialysis-dependent kidney failure was given a new kidney from a living donor at a New York City hospital - known in the report as "Hospital A". There was no trace of any STIs (sexually transmitted infections) in the individual's medical history, neither was there any history of high-risk activity, such as injection drug use or sexual encounters with injection drug users.

The patient had received blood transfusions in 2006, but none before that date. 12 days before the transplantation procedure started, the recipient tested negative for HIV.

After the operation the patient went through multiple hospitalizations, fevers, episodes of renal insufficiency, and evaluation of possible transplanted organ rejection.

The recipient did not take part in any behaviors which might have increased his/her risk of becoming infected with HIV.

The patient was hospitalized twelve months after the kidney transplant with refractory oral and esophageal candidiasis. An EIA screening for HIV tested positive, and confirmed with a positive Western blot. Initial CDY cell count was under 100 cells/µL. In a communiqué, the CDC added "The recipient's initial CD4 cell count was <100 cells/µL. The advanced immunosuppression was attributed, in part, to the recipient's induction with antithymocyte globulins (an immunomodulator that depletes T-lymphocytes to prevent graft-versus-host disease) and use of mycophenolic acid (a drug that suppresses lymphocyte proliferation, prescribed to prevent rejection of a transplanted kidney)."

The Donor

He was evaluated as a possible living kidney transplantation donor in 2009 in Hospital A. As is standard practice in that hospital, a multidisciplinary team determined his eligibility. They assessed donor-recipient immunologic compatibility, as well as his psychological state, willingness to donate, and general health. The team consisted of a coordinator, transplant surgeon, social worker, nutritionist, psychiatrist and nephrologist.

The donor was found to have had a history of participating in sex with male partners. He had had a previous diagnosis of syphilis. Initial HIV screening 79 days before the transplant operation showed no evidence of HIV infection by EIA, HBV (hepatitis B virus) by HBV surface antigen testing, or HCV (hepatitis C virus) by anti-HCV serology. A rapid plasma regain test for syphilis was reactive undiluted (1:1). Another test revealed he had had syphilis in the past.

The removal of his kidney was straightforward and no blood products were given to him during the procedure. Nothing unusual was detected by the transplant team six months after the operation. He visited his GP (general practitioner, primary care physician) twelve months after the operation for repeat STI screenings, which revealed HIV infection (serologic HIV antibody testing by EIA, confirmed with a positive Western blot).

One year after the transplant, the team learned about the donors new HIV status.

As both donor and recipient were diagnosed with HIV infection, this raised the possibility that the donor infected the recipient. New York City Department of Health and Mental Hygiene was told about this and a public investigation was ordered.

The Public Investigation

A standardized case interview form was used when interviewing both recipient and donor. The investigators looked at their medical records again, concentrating on their medical histories "before and after kidney transplantation, history of HIV testing and evidence of infection, pretransplant evaluation, posttransplant course, blood product transfusion history, other past medical history, history of substance use, sexual history, and other risk factors for HIV infection."

The investigators reviewed the transplant evaluation and medical course and interviewed the recipient's nephrologist, HIV doctor and transplant coordinator. They also interviewed the donor's GP and transplant nephrologist.

The donor told the investigator's he had engaged in unprotected sex with one male partner within 12 months before the transplant operation - he told them this had taken place after his initial evaluation and before his kidney was surgically removed. He had no idea what his male sexual partner's HIV status was. The donor said he had no history of tattoos, blood transfusions or injection drug use.

The authors added:

"Two samples of frozen leukocyte specimens collected from the organ donor 57 and 11 days pretransplant and two frozen serum specimens collected from the recipient 11 days pretransplant and 12 days posttransplant were sent to CDC for HIV testing. HIV NAT on the donor leukocytes collected 57 days pretransplant was negative; however, DNA sequences for three HIV genes (envelope gp41, polymerase, and group-specific antigen p17) were amplified from donor leukocytes collected 11 days pretransplant and sequenced at CDC. Recipient serum collected 11 days pretransplant was nonreactive for HIV-1 RNA by Aptima (Gen-Probe). Recipient serum collected 12 days post transplant was reactive for HIV RNA by Aptima."

404 days after the transplant operation, whole blood specimens were taken from both recipient and donor for phylogenetic analysis at CDC. Two weeks before his kidney was surgically removed, the donor was initiated antiretroviral therapy, at that moment the recipient had not been initiated on such therapy. Donor and recipient peripheral blood lymphocytes and HIV DNA sequences were gathered on the 404th day and amplified and sequenced. "Sequences from these two specimens were analyzed phylogenetically together with HIV sequences obtained from the donor's frozen leukocyte specimen collected 11 days pretransplant. The gp41, polymerase, and p17 sequences from the donor and recipient were nearly identical, with greater than 98% identity and tight phylogenetic clustering, suggesting that the two viruses are highly related."

The authors explain that this is the first confirmed case of a living donor infecting an organ transplant recipient since 1989. It is also the first such transmission documented in America since 1985, when laboratory screening for HIV infection became available.

The authors wrote:

"The time sequence in which HIV was isolated from frozen specimens, tight phylogenetic clustering of HIV sequences from the donor and recipient, and lack of other HIV exposure risk in the recipient confirmed that HIV was transmitted by transplantation of a kidney from a living donor who was infected after screening negative for HIV infection during his initial evaluation. This case highlights the need for repeat HIV screening for all living donors using a combination of HIV serology and NAT, as close to the time of organ donation as logistically feasible, to rule out acute or recent HIV infection in living donors before organ donation."

The authors stress that cases of donors infecting organ transplant recipients with HIV are extremely rare in the USA - however, they do occur, despite thorough screening. In 1988 there were 1,829 live donors in the USA, compared to 6,609 in 2009.

The authors added:

"Although the Organ Procurement and Transplantation Network (OPTN) sets national policies for organ allocation, including screening potential donors for HIV and other infections, current OPTN policies do not address screening and counseling for HIV infection in living potential donors."

In cases where the donor is dead, he/she is screened for HIV infection at the time of cardiac or brain death - this occurs within hours of the organ being surgically removed. Living donors, on the other hand, undergo a more lengthy and comprehensive physical-psychological evaluation. In this case, there was a 10-week gap between donor evaluation and the removal of the donor's organ.

This longer gap between initial evaluation of live donors and the moment of transplant removal is long enough for potential infections to occur. The authors believe repeat testing should occur very close to the moment of organ removal to rule out any newly acquired infections.

As many donor candidates and recipients have close personal relationships - often relatives or very good friends - the donor may be less likely to reveal his/her potential HIV infection risk factors. Consequently, living donors should be made fully aware of HIV infection risk factors, as well as any other infections. They should receive counseling which includes education on avoiding behaviors which increase the risk of becoming infected before their organ is removed. Those with a history of high-risk behaviors should receive individualized counseling with detailed discussions on how to avoid behaviors which may increase infection risks.

"HIV Transmitted from a Living Organ Donor - New York City, 2009"
MA Bernard, MD, J Eavey, MSPH, HW Gortakowski, MPH, C Sabharwal, MD, C Shepard, MD, L Torian, PhD, New York City Dept of Health and Mental Hygiene; L McMurdo, LC Smith, MD, K Valente, New York State Dept of Health. JT Brooks, MD, WM Heneine, PhD, MP Joyce, MD, SM Owen, PhD, A Shankar, MS, W Switzer, MPH, Div of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; E Farnon, MD, M Kuehnert, MD, D Seem, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infections; T Al-Samarrai, MD, P Gounder, MD, CK Kwan, MD, EIS officers, CDC.
MMWR March 18, 2011 / 60(10);297-301

Written by Christian Nordqvist