Estimated Risk of Human Immunodeficiency Virus and Hepatitis C Virus Infection among Potential Organ Donors from 17 Organ Procurement Organizations in the United States

Abstract

To prevent unintentional transmission of bloodborne pathogens through organ transplantation, organ procurement organizations (OPOs) screen potential donors by serologic testing to identify human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Newly acquired infection, however, may be undetectable by serologic testing. Our objective was to estimate the incidence of undetected infection among potential organ donors and to assess the significance of risk reductions conferred by nucleic acid testing (NAT) versus serology alone. We calculated prevalence of HIV and HCV—stratified by OPO risk designation—in 13 667 potential organ donors managed by 17 OPOs from 1/1/2004 to 7/1/2008. We calculated incidence of undetected infection using the incidence-window period approach. The prevalence of HIV was 0.10% for normal risk potential donors and 0.50% for high risk potential donors; HCV prevalence was 3.45% and 18.20%, respectively. For HIV, the estimated incidence of undetected infection by serologic screening was 1 in 50 000 for normal risk potential donors and 1 in 11 000 for high risk potential donors; for HCV, undetected incidence by serologic screening was 1 in 5000 and 1 in 1000, respectively. Projected estimates of undetected infection with NAT screening versus serology alone suggest that NAT screening could significantly reduce the rate of undetected HCV for all donor risk strata. To prevent unintentional transmission of bloodborne pathogens through organ transplantation, organ procurement organizations (OPOs) screen potential donors by serologic testing to identify human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Newly acquired infection, however, may be undetectable by serologic testing. Our objective was to estimate the incidence of undetected infection among potential organ donors and to assess the significance of risk reductions conferred by nucleic acid testing (NAT) versus serology alone. We calculated prevalence of HIV and HCV—stratified by OPO risk designation—in 13 667 potential organ donors managed by 17 OPOs from 1/1/2004 to 7/1/2008. We calculated incidence of undetected infection using the incidence-window period approach. The prevalence of HIV was 0.10% for normal risk potential donors and 0.50% for high risk potential donors; HCV prevalence was 3.45% and 18.20%, respectively. For HIV, the estimated incidence of undetected infection by serologic screening was 1 in 50 000 for normal risk potential donors and 1 in 11 000 for high risk potential donors; for HCV, undetected incidence by serologic screening was 1 in 5000 and 1 in 1000, respectively. Projected estimates of undetected infection with NAT screening versus serology alone suggest that NAT screening could significantly reduce the rate of undetected HCV for all donor risk strata. Transmission of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) can occur through solid organ transplantation (1Tugwell BD Patel PR Williams IT et al.Transmission of hepatitis C virus to several organ and tissue recipients from an antibody-negative donor.Ann Intern Med. 2005; 143: 648-654Crossref PubMed Scopus (122) Google Scholar, 2Pereira BJ Milford EL Kirkman RL Levey AS Transmission of hepatitis C virus by organ transplantation.N Engl J Med. 1991; 325: 454-460Crossref PubMed Scopus (340) Google Scholar, 3Simonds RJ Holmberg SD Hurwitz RL et al.Transmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor.N Engl J Med. 1992; 326: 726-732Crossref PubMed Scopus (575) Google Scholar, 4CDCHuman Immunodeficiency virus infection transmitted from an organ donor screened for HIV antibody—North Carolina.Morbid Mortal Week Rep. 1987; 36: 306-308PubMed Google Scholar). Strategies to reduce transmission of these bloodborne pathogens from donor to recipient include assessing donor medical and behavioral risk, and laboratory testing for anti-HIV and anti-HCV seroreactivity in all potential organ donors. For most laboratory tests, there are window periods during which infection cannot be detected in donors with newly acquired infection. Compared with serologic testing, nucleic acid-amplification tests (NAT) shorten the window period through detection of the virus in plasma. In 2007 a donor, who was found to be nonreactive for HIV and HCV by routine serologic screening, was later found to be NAT-positive after four organ recipients were infected with HIV and HCV (5Ison et al. Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients. Am J Transplant, in press.Google Scholar). This incident underscored the need for a better understanding of the prevalence of HIV and HCV among potential organ donors and for evaluation of more sensitive screening tests to reduce the risk of undetected infection. Estimates of HIV and HCV infection rates during the window period for serologic testing (i.e. undetected infection) were recently reported in US blood and tissue donors but have not been estimated for organ donors. For first-time blood donors, 1 in 3.1 million donations for HIV and 1 in 270 000 for HCV were nonreactive by serology assays, but positive by NAT (6Stramer SL Glynn SA Kleinman SH et al.Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing.N Engl J Med. 2004; 351: 760-768Crossref PubMed Scopus (429) Google Scholar). The estimated risk of undetected infection among tissue donors for serologic testing is much higher: 1 in 55 000 for HIV and 1 in 42 000 for HCV (7Zou S Dodd RY Stramer SL Strong DM Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States.N Engl J Med. 2004; 351: 751-759Crossref PubMed Scopus (163) Google Scholar). The US Food and Drug Administration (FDA) currently mandates NAT screening for all blood and tissue donors for HIV and HCV, but no government agency mandates NAT screening for organ donors (8FDA. Tissue and tissue products compliance and regulation. http://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/default.htm.Google Scholar). As of 2008, approximately one-half of the 58 US organ procurement organizations (OPOs) voluntarily performed HIV and HCV NAT on all or at least some subset of their potential donors (9Kucirka LM Alexander C Namuyinga R Hanrahan C Montgomery RA Segev DL Viral nucleic acid testing (NAT) and OPO-level disposition of high-risk donor organs.Am J Transplant. 2009; 9: 620-628Crossref PubMed Scopus (58) Google Scholar). When transplant centers decide whether to accept an organ for transplantation, they rely on serologic test results as well as the ‘high risk’ designation assigned by OPOs during donor evaluations. OPOs are required to document the potential donor’s infectious risk status utilizing risk criteria for HIV transmission outlined in the PHS 1994 guidelines (10CDCGuidelines for preventing transmission of human immunodeficiency virus through transplantation of human tissue and organs.Morbid Mortal Week Rep. 1994; 43: 1-17Google Scholar). Many OPOs have also used these criteria to evaluate risk for hepatitis virus transmission, as indicated by donor medical-behavioral history questionnaires (Appendix 1). A 2008 survey of US OPOs reported that, on average, 7.7% of an OPO’s donors with organs recovered for transplantation, were designated as high risk, ranging from 2.3 to 26.1% (11Kucirka LM Namuyinga R Hanrahan C Montgomery RA Segev DL Provider utilization of high-risk donor organs and nucleic acid testing: Results of two national surveys.Am J Transplant. 2009; 9: 1197-1204Crossref PubMed Scopus (51) Google Scholar). Because transplants can be life saving, recipients and transplant surgeons may accept organs from high risk donors due to the shortage of available organs for transplantation; in 2008, 9465 candidates died or became too ill to benefit from transplantation while waiting for an available organ (12United Network for Organ Sharing. Latest Data. (Assessed December 7, 2009 at http://optn.transplant.hrsa.gov/latestData/rptData.asp).Google Scholar). Organ acceptance may be influenced by type of organ needed, type of risk factor identified, medical health status of the candidate and laboratory testing results. To appropriately weigh the risk of unintentional infection with HIV or HCV against the risk of delayed transplant, providers and patients must be able to reasonably assess risk. Currently there are no published studies that estimate the risk of undetected infection among potential organ donors by serologic testing in the United States. The objectives of this study were to (1) calculate the prevalence of HIV and HCV among a large subset of potential organ donors in the United States; (2) estimate the incidence of HIV and HCV among potential organ donors during the window periods for serologic and NAT screening. A sample of 17 of the 58 OPOs in the United States participated voluntarily in this study; these 17 OPOs manage over half of US organ donors (12United Network for Organ Sharing. Latest Data. (Assessed December 7, 2009 at http://optn.transplant.hrsa.gov/latestData/rptData.asp).Google Scholar). Participating OPOs constituted a convenience sample of OPOs that submitted serologic screening results through three large reference laboratories to the CDC for the designated study period. Serologic tests were performed at local OPO, hospital or reference laboratories. The geographic distribution of participating OPOs was concentrated in the northeast, mid-Atlantic and western states, including Alaska (Figure 1). Nucleic acid testing results were not available for the majority of participating OPOs and were available for only a fraction of donors within OPOs performing NAT; thus NAT results were not considered for analysis in this study. Demographic and serologic data from January 2004 to July 2008 were requested from participating OPOs for all potential organ donors, including those who were consented but subsequently had no organs recovered. Serologic data collected from participating OPOs included anti-HIV and anti-HCV test results. Western blot (WB) confirmatory testing results for anti-HIV and recombinant immunoblot assay (RIBA) confirmatory tests for anti-HCV were also collected when available. Data on high risk designation, as determined by the OPO based on criteria presented in Appendix I, were collected. Participating OPOs also submitted information on the assay and of the tests used over the study period. potential donors for data were requested had for organ and serologic test results. This study was determined to be from human by the at the for and in To calculate prevalence for HIV and HCV among potential donors, the of positive results for a serologic test was by the of potential donors To for positive serologic were from data submitted by OPOs from of donors with or confirmatory tests available. For within the subset of serologic tests with the of positive anti-HIV with positive results was by the of all with or results to calculate a a more factor using positive and results as the was The was for HCV, using available testing to and For HIV, there were 11 for which confirmatory tests were had positive and had results. For HCV, there were with confirmatory tests were and 11 were The were determined to be the of the and for HIV and for The prevalence of HIV and HCV among potential organ donors was calculated for all potential donors and for donors by OPO risk included risk’ (i.e. designated as not ‘high ‘high risk’ and risk’ (i.e. risk status was not or not available for this The prevalence was by an factor to prevalence for positive serologic the prevalence estimates were using for and risk For the the of tests by serology was assigned a The were assigned with and the and factor for HIV and for were from these for 000 in of undetected HIV and HCV infection in potential organ donors was calculated using the incidence-window period for blood donors, which the incidence of infection (i.e. the rate of newly acquired infection) in the donor by the of the window period C A et risk of HIV, HBV, HCV and HTLV infection among tissue donors in J Transplant. PubMed Scopus Google Scholar, Kleinman SH The risk of The donor Engl J Med. PubMed Scopus Google Scholar, et of detection of and serologic human immunodeficiency virus type 1 for screening of blood and tissue PubMed Scopus Google Scholar, S and estimated incidence of infection in organ and tissue donors from J Transplant. PubMed Scopus Google Scholar). The infectious window period is as the after when the virus a in to be to the of detection by NAT or serologic screening Kleinman SH The risk of The donor Engl J Med. PubMed Scopus Google S and estimated incidence of infection in organ and tissue donors from J Transplant. PubMed Scopus Google Stramer SL et testing to HIV-1 infection for in incidence estimates and for and PubMed Scopus Google Scholar). The incidence-window period was recently for of undetected infection in the tissue donor in the United States and to organ and tissue donor in (7Zou S Dodd RY Stramer SL Strong DM Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States.N Engl J Med. 2004; 351: 751-759Crossref PubMed Scopus (163) Google S and estimated incidence of infection in organ and tissue donors from J Transplant. PubMed Scopus Google Scholar). in the blood donor can be determined by in blood donors there are no donations in the potential organ donor incidence must be estimated by from blood donor the incidence of HIV and HCV among potential organ donors required from incidence estimates in blood donors during the period. was that prevalence the organ donors in this study and blood donors in published in the of organ donor prevalence to published blood donor prevalence was by the published incidence in blood donor to the incidence in the study of organ donors. incidence and prevalence rates from a of blood donors who had to from 2007 and 2008 were used to this S et and risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors the of nucleic acid PubMed Scopus Google Scholar). To incidence were used to the in including organ donor prevalence as calculated in this blood donor prevalence and incidence as reported in the and window periods for serologic and NAT tests the window period was with were assigned to thus distribution and incidence estimates were from 000 in a the incidence were calculated with and in Serologic data were submitted for 13 potential donors 13 for anti-HIV and 13 for 1). For prevalence was with a of was for normal risk donors 11 at 0.10% and for donors with risk status at For high risk donors prevalence was 0.50% The prevalence for anti-HCV was The anti-HCV prevalence was for normal risk donors at 3.45% and for high risk donors at For donors with risk the HCV prevalence was of anti-HIV and anti-HCV in potential organ donors by risk status and for test status of potential donors were designated as risk’ the OPO designated the donor as high with no risk status designated by the OPOs were risk by by factor was determined by the by an factor determined by donors with confirmatory tests blot for HIV and recombinant immunoblot assay for The factor for potential positive results from serologic prevalence prevalence for prevalence for the prevalence were using to for in the by serology a and in the a risk potential risk potential were designated as risk’ the OPO designated the donor as high with no risk status designated by the OPOs were risk by was determined by the by an factor determined by donors with confirmatory tests blot for HIV and recombinant immunoblot assay for The factor for potential positive results from serologic prevalence for the prevalence were using to for in the by serology a and in the a in a of all potential organ donors not have organs recovered. of the donors, 58 not have organs recovered. the donors with organs were designated as normal risk and was risk were potential donors, not have organs recovered. the donors who have organs were considered high risk donors, were considered normal risk donors and were risk were not able to information whether recovered organs were incidence estimates for HIV among all potential organ donors was approximately 000 for normal risk, high risk and risk donors the incidence was and 000 respectively. The incidence estimate for HCV was approximately 000 for normal risk, high risk and risk donors, incidence was and 000 respectively. For normal risk donors, the estimated incidence of undetected HIV infection during the window period for serologic testing was approximately 000 and 000 for the window period for NAT screening. For high risk donors, undetected HIV incidence 000 during the window periods for serologic and NAT screening were and respectively. The for undetected HIV infection during serologic and NAT window periods all donor risk incidence of HIV and HCV for potential organ donors 000 and estimated incidence of undetected infection during the window period for serologic and NAT were designated as risk’ the OPO designated the donor as high with no risk status designated by the OPOs were risk for organ donors in estimates for organ donors from OPO data blood donors estimates for blood donors with 2007 by et al. as a for blood donors estimates 000 for blood donors and by et al. in organ 000 in Organ among Organ in in in in in is reported with using period for periods determined from published risk of undetected infection among potential donors during window period for risk of undetected infection among organ donors in Organ in is reported with using period for periods determined from published risk of undetected infection among potential donors during window period for risk of undetected infection among organ donors in Organ in is reported with using were designated as risk’ the OPO designated the donor as high with no risk status designated by the OPOs were risk estimates for organ donors from OPO data estimates for blood donors with 2007 by et al. as a estimates 000 for blood donors and by et al. 000 in Organ among Organ in in in in in is reported with using periods determined from published risk of undetected infection among organ donors in Organ in is reported with using in a For normal risk donors, the estimated incidence of undetected HCV infection during the window period for serologic testing was approximately 000 and 000 for the window period for NAT testing. For high risk donors, undetected HCV incidence 000 during the window periods for serologic and NAT screening were and respectively. The for undetected HCV infection during serologic and NAT window periods not for risk potential reductions conferred by NAT screening as to serology alone for In prevalence study of over 13 000 potential organ donors, approximately 1 in were positive for anti-HIV after for serologic testing, with prevalence among high risk donors in versus normal risk donors in in of all potential donors were positive for anti-HCV after for serologic the prevalence among high risk donors was in and that among normal risk donors was in suggest that organ donors are at risk of undetected infection by serologic screening (i.e. incident infection during the window to tissue donors. In tissue donors were reported to have a 1 in 55 000 risk of undetected HIV and 1 in 42 000 risk of undetected HCV infection by serologic screening (7Zou S Dodd RY Stramer SL Strong DM Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States.N Engl J Med. 2004; 351: 751-759Crossref PubMed Scopus (163) Google Scholar). In this normal risk organ donors had an estimated 1 in 000 risk of undetected HIV infection by serologic screening, which is to tissue donors; however, high and risk organ donors were at of undetected HIV infection in 000 and 1 in Organ donors of all risk had a risk of undetected HCV infection by serologic testing to tissue donors. In this normal risk organ donors had an estimated 1 in 5000 risk of undetected HCV infection by serologic testing, and high risk donors had a 1 in risk. For HCV, in the window period for NAT screening the risk by of undetected infection to 1 in 50 000 for normal risk donors and 1 in 000 for high risk donors. for HCV incidence during the window period for serologic versus NAT screening not for of the risk risk reductions conferred by NAT screening serology for for HIV incidence during serologic and NAT window periods for all risk this is a of HIV prevalence and incidence in and a in the window period for serology versus NAT for HIV with HCV (i.e. a a The prevalence estimates of anti-HCV in high risk and normal risk donors in this study are to those reported in a analysis of donors reported to during the period (9Kucirka LM Alexander C Namuyinga R Hanrahan C Montgomery RA Segev DL Viral nucleic acid testing (NAT) and OPO-level disposition of high-risk donor organs.Am J Transplant. 2009; 9: 620-628Crossref PubMed Scopus (58) Google Scholar). of anti-HIV in this study are most potential donors not have organs and thus may not be reported to This study included potential donors who had for testing, but who had no organs recovered of their HIV this study and the study are to the prevalence of HIV among potential organ donors are from by HIV positive are to be consented for testing. A of donors for anti-HIV and anti-HCV were risk status by This was not to or 13 of the 17 participating OPOs submitted serologic testing results for donors with risk with risk’ status had a high prevalence of HIV A is that this study included all potential donors who serologic testing including those organs were not recovered due to HIV no considered for transplantation are reported to which that the OPO the risk designation, and thus OPO may not risk for these donors. in for organ versus blood and tissue may be to in the of risk for the recipient of organs from high risk donors to be is of several at the for organs are from donors with as well as after of organs from these donors is of the potential life by the recipient or recipients A et acid testing of organ the test the A J Transplant. PubMed Scopus Google Scholar). In donors with behavioral risk are from the blood and tissue to and transplant organs are based on several designated as high risk may not have their organs recovered or of their high risk designation or of medical or organs are in high the high risk designation may or may not a transplant from an A survey of transplant surgeons that NAT screening in organs from high risk donors, undetected infection were (11Kucirka LM Namuyinga R Hanrahan C Montgomery RA Segev DL Provider utilization of high-risk donor organs and nucleic acid testing: Results of two national surveys.Am J Transplant. 2009; 9: 1197-1204Crossref PubMed Scopus (51) Google Scholar). a recently published that there to routine NAT the benefit may not the of organs for transplantation of NAT results A et acid testing of organ the test the A J Transplant. PubMed Scopus Google Scholar). Our study that of NAT screening for HCV could significantly reduce the incidence of undetected infection during the window period with a high for high risk donors; thus NAT screening could organ acceptance from high risk donors with results. The as to whether the donor through acceptance of organs or organ from rates for NAT screening are NAT screening could be to the organ organs are the NAT more on the and of is and for NAT screening this study was not to assess the rate of NAT this be considered in with the results from this study when to NAT screening. This study is to a of the geographic distribution of OPOs participating in this study is on the of that results may not be of the results be on the that most of the serologic tests used in this study 2004 and were The of more sensitive serologic also shorten window periods and thus may be a to NAT screening for of window periods by when the of serology may large reference and and may the rate of results. The results of study suggest that undetected infection, and transmission, can occur with testing transmission have been may be several for this is that occur a recipient the infection is may also occur a transplant is to identify the donor as the of recipient infection, after the of to was not of and that This study is also to the of the incidence in which the incidence of undetected infection among potential organ donors is estimated from incidence in the blood donor by an donor prevalence This that the donor prevalence the donor incidence This was by using prevalence and incidence estimates from the all estimates used to calculate the of undetected infection of HIV and HCV among potential organ donor incidence blood donor prevalence data and organ donor prevalence collected from 2004 through that NAT is as is performed by OPOs on some donors for at least bloodborne the is This is of as high risk donor also is and may not be with of Because the risk of bloodborne infections through transplantation is to be and can be to for donor, recipients and providers have a understanding of the risk and through at in the transplantation and SD A of transplant to organs to patients infected with HBV, HCV or J Transplant. 2005; PubMed Scopus Google Scholar). and analysis of donor testing results as performed in a better of transmission risk is in a that for most of a organ The of Organ of of Organ and Tissue of Organ and Tissue of Organ of The and from Organ from from of and from The of this have no of to as by the of for who have had with in the who or of in the with or who have factor and who have in in for or in the who have had in the with in or with a or to have HIV who have been in the to or blood through or through with an or of for of the criteria for to with HIV infection or who the behavioral or laboratory criteria for donors of their HIV HIV infection can be in the as of who are to with or at risk for HIV infection, who have not been within the and HIV tests, and of medical not of HIV infection can be as or to of who are to with or at risk for HIV infection or who have been within the not be as donors of their HIV test for or on the or of 1 for and of transmitted or or of of reported in of PHS criteria by OPOs included hepatitis as a risk factor of the in the with or to have hepatitis or HIV The PHS who participated in risk during the or on the For these PHS some OPOs of of used as the for behavioral risk the PHS criteria of OPOs or more as whether the was a in the currently in the or in or more of the as or are considered in the of the donor’s medical and behavioral history to risk in a