Kidney Transplant Leads to HIV Infection
Published: March 17, 2011
A New York kidney transplant patient contracted HIV in 2009 from a living organ donor, the first such case known in the U.S. since screening for the virus became possible in 1985, the CDC reported.
It's also the first documented case since a 1989 kidney transplant from a living donor in Italy, the agency reported in the March 18 issue of Morbidity and Mortality Weekly Report.
Rare cases of infection from deceased donors in the U.S. have occurred since then, most notably in 2007, when transplants from a single high-risk donor transmitted both HIV and hepatitis C to four organ recipients.
The current case has prompted new guidelines from the State of New York Department of Health that call for more sensitive and timely testing of prospective donors.
In that current case, the CDC reported, an adult with hemodialysis-dependent renal failure received a kidney transplant from a living donor at a New York City hospital, identified only as "hospital A."
The recipient tested negative for HIV by enzyme immunoassay 12 days before the transplant and did not have a history of sexually transmitted infections, injection drug use, sex with injection drug users, or other high-risk sexual activity, the agency reported.
The patient was frequently ill during the year after the procedure, with fevers, episodes of renal insufficiency, and fears of organ rejection.
On day 375 after the transplant, the patient was admitted to the hospital for refractory oral and esophageal candidiasis and tested positive for HIV.
The donor, an adult male, had reported a previous diagnosis of syphilis and a history of sex with male partners but laboratory screening 79 days before the transplant showed no evidence of HIV (by enzyme immunoassay), hepatitis B, or hepatitis C.
A year after the transplant, after seeking screening for sexually transmitted infections, the donor was found to be HIV-positive.
Retrospective analysis of stored blood samples by the CDC, using nucleic acid testing, showed that the donor was HIV-negative 57 days before the transplant, but positive 11 days before.
The recipient, on the other hand, was negative by nucleic acid testing 11 days before the procedure but positive 12 days afterward.
HIV genetic sequences from the donor and recipient were nearly identical, the CDC reported, suggesting the viruses were closely related.
The time lag between the original evaluation of the donor and the transplant opened a window for infection, the CDC suggested.
But that window could have been at least partly closed by a repeat test -- involving both serologic and nucleic acid methods -- of the donor no more than seven days from the scheduled procedure, the agency argued.
Such testing should become standard across the country, the agency suggested.
The new guidelines in New York call for transplant centers to test prospective living donors for HIV within 14 days of the procedure, using nucleic acid testing and blood tests for antibodies.
The key factor in the current case was the fact that the donor was tested 10 weeks before the transplant, but not again, according to Colin Shepard, MD, of the New York City Department of Health and Mental Hygiene, who led a public health probe into the matter.
"The gap is critical," Shepard told MedPage Today. "But it highlights the fact the guidelines for living donors don't specify the type and timing of testing."
Blood tests for HIV start to detect the virus between three and eight weeks after infection, while nucleic acid testing reduces the "eclipse" period in which the virus is not yet detectable to eight or 10 days.
But, the CDC noted, nucleic acid testing is not used consistently by organ procurement agencies across the country.
"What we're recommending (in the new state advisory) is that the most sensitive tests be done as close as possible to the time of donation," Shepard said.
The CDC has also suggested that clinicians should make sure donors know they have an obligation to avoid high-risk behavior in the run-up to the transplant.
Primary source: Morbidity and Mortality Weekly Report
Centers for Disease Control and Prevention "HIV transmitted from a living organ donor -- New York City, 2009" MMWR 2011; 60: 297-301.
HIV Transmitted from a Living Organ Donor --- New York City, 2009
March 18, 2011 / 60(10);297-301
Routine screening of organ donors for human immunodeficiency virus (HIV) infection has made transmission of HIV through organ transplantation rare in the United States. However, despite routine screening, transmission of HIV can be an uncommon complication of organ transplantation and is a public health concern. In 2010, the New York City (NYC) Department of Health and Mental Hygiene (NYC DOHMH) was notified of a potential transplant-related HIV infection. This report summarizes the results of the subsequent public health investigation, which confirmed HIV transmission through transplantation of an organ from a living donor. To reduce the risk for transmission of HIV through living-donor organ transplantation, transplant centers should screen living donors for HIV as close to the time of organ recovery and transplantation as possible, using sensitive tests for both chronic and acute infections, namely, serology and nucleic acid testing (NAT). Furthermore, clinicians should inform transplant candidates of the potential risks for disease transmission and advise donors during evaluation of their obligation to avoid behaviors that would put them at risk for acquiring HIV before organ donation.
An adult with hemodialysis-dependent renal failure received a kidney transplant from a living donor at hospital A in NYC in 2009. The recipient did not have any history of sexually transmitted infections (STIs), injection drug use, sex with injection drug users, or other high-risk sexual activity. The recipient received blood transfusions in 2006, but none previously. The recipient tested negative for HIV infection by enzyme immunoassay (EIA) 12 days before the transplant (Figure). The posttransplant clinical course was complicated by multiple hospitalizations for febrile illness, episodes of renal insufficiency, and evaluation for possible rejection of the transplanted kidney. During the year after kidney transplantation, the recipient did not engage in any behaviors that would increase the risk for acquiring HIV. One year after transplant, the recipient was hospitalized with refractory oral and esophageal candidiasis; screening for HIV infection by EIA was positive, and HIV infection was confirmed with a positive Western blot. The recipient's initial CD4 cell count was <100 cells/ÁL. 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 was an adult male who underwent evaluation as a potential living donor for kidney transplantation at hospital A in 2009. Consistent with the hospital's protocol, a multidisciplinary team (consisting of a living donor coordinator, nephrologist, transplant surgeon, psychiatrist, social worker, and nutritionist) determined the donor's eligibility by assessing his immunologic compatibility with the recipient, his general health, his psychosocial status, and his willingness to donate. His evaluation revealed a previous diagnosis of syphilis and a history of sex with male partners. Laboratory testing conducted during the initial evaluation 79 days before transplant showed no evidence of infection with HIV by EIA, hepatitis B virus (HBV) by HBV surface antigen testing, or hepatitis C virus (HCV) by anti-HCV serology; a rapid plasma reagin test for syphilis was reactive undiluted (1:1) with a fluorescent treponemal antibody absorption test, also positive, consistent with previously treated syphilis. The donor's kidney was removed without complication; no blood products were administered around the time of transplant. Routine medical evaluation by the transplant team 6 months after the transplant was unremarkable. Approximately 1 year after the transplant, the donor visited his primary-care physician requesting repeat screening for STIs. Serologic testing for HIV antibody by EIA with confirmatory Western blot was positive. The transplant team learned of the living donor's new HIV diagnosis during his follow-up visit 1 year after the transplant.
The diagnosis of HIV in both the donor and recipient raised the possibility of transplant-transmitted HIV infection. NYC DOHMH was notified of the possible transmission, and a public health investigation was initiated.
Public Health Investigation
The donor and recipient each were interviewed in person using a standardized case interview form. Medical records were reviewed, focusing on relevant medical history 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 recipient's transplant coordinator, nephrologist, and HIV physician were interviewed separately to review the transplant evaluation and medical course. The donor's primary-care physician and transplant nephrologist also were interviewed.
During the public health investigation, the donor reported unprotected sex with one male partner during the 1 year before the transplant, including the time between his initial evaluation and organ recovery. He did not know his partner's HIV status. He did not report any history of injection drug use, tattoos, or blood transfusions.
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.
On posttransplant day 404, whole blood specimens were obtained from the donor and recipient for phylogenetic analysis at CDC (Figure). The donor had initiated antiretroviral therapy 2 weeks before the specimen was obtained, whereas the recipient had not yet initiated antiretroviral therapy. HIV DNA sequences from donor and recipient peripheral blood lymphocytes collected on day 404 were 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.
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.
This report describes the first confirmed case of HIV transmission through organ transplantation from a living donor reported since 1989 (1) and the first such transmission documented in the United States since laboratory screening for HIV infection became available in 1985. 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.
Reports of confirmed, donor-derived HIV transmission are rare but notable and have important implications for public health when they occur despite screening. The annual number of living donors increased from 1,829 to 6,609 during 1988--2009.* 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.
Deceased organ donors typically are screened for HIV infection at the time of the donor's cardiac death or brain death, which occurs within hours of organ recovery. In contrast, living donors undergo a longer and more comprehensive physical and psychological evaluation (2). In the case described in this report, the time between initial donor evaluation and transplant surgery was 10 weeks. This longer evaluation process for prospective living donors allows potential for acquisition of infections after initial evaluation, emphasizing the need for repeat testing before organ recovery to rule out recently acquired infections. Prospective living donors and transplant candidates frequently have a personal relationship (e.g., they are relatives or friends), which might make a donor less likely to disclose potential risk factors for HIV infection. Therefore, all living donors should be informed about modes of transmission and risk factors for HIV infection and should be counseled to avoid behaviors that would place them at risk for acquiring HIV infection before organ recovery (3). For persons with a history of previous high-risk behavior (e.g., high-risk sexual activity or injection drug use) identified during evaluation (3), individualized counseling and a detailed discussion of specific strategies to avoid risk behaviors should be provided.
The availability of NAT now permits detection of HIV infection before antibodies develop and are detectable by serology. The window between time of HIV infection and time of development of detectable HIV-specific antibodies ranges from 3 to 8 weeks, whereas with NAT, the window (i.e., the "eclipse period" for the time from infection to detection of virus in blood) is estimated to be 8--10 days (4,5). For blood and tissue donation, the combination of HIV NAT and serology is used to screen all donors. However, HIV NAT is not consistently used for organ donor screening. A recent survey of organ procurement organizations (OPO) found that 52% of OPOs report always performing HIV NAT on deceased donors, whereas 24% of OPOs never perform HIV NAT (6). For deceased potential donors who screen negative by HIV serology, NAT can reduce the risk for HIV transmission from an undetected infection during the window period by approximately 68% (7,8). This reduction reflects differences in the timeframe of detection between the two tests. U.S. Public Health Service guidelines have recommended serologic screening for HIV infection in potential organ donors since 1994 (3). A forthcoming updated revision to those guidelines, currently in draft form, likely will include consideration of NAT in addition to serology to screen for HIV infection in all potential organ donors, living and deceased.
In the case described in this report, the donor was screened for HIV infection by EIA 10 weeks before organ procurement but was not rescreened closer to the date of transplant surgery. Despite an initial negative EIA screening and counseling for behavioral risk reduction, living donors can acquire HIV infection between the initial evaluation and organ recovery. To reduce the risk for transplant-transmitted HIV infection, living donors should be rescreened with both HIV serologic tests and NAT as close to the time of organ recovery as logistically feasible, but no longer than 7 days before organ donation (Box). In addition, clinicians should advise living donors of their obligation to avoid behaviors that would put them at risk for acquiring HIV before organ donation. Because NAT cannot detect HIV infections during the eclipse period, all transplant candidates should be informed during the evaluation process that despite donor screening, a very small risk remains that they could acquire HIV or other infections as a result of transplantation. All suspected cases of transplant-associated HIV transmission should be reported to appropriate public health authorities and to OPTN.